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Responding effectively to people with long term breathlessness

Introduction, Methodology, Scope and Definitions

This programme of work from IMPRESS includes:

• Impressions Blog 31: breathlessness • The Introduction • Methodology, Scope and Definitions • Breathlessness prevalence modelling for COPD, heart failure, anxiety, obesity

and anaemia • The algorithm • Breathlessness IMPRESS Tips BITs for clinicians • Breathlessness IMPRESS Tips BITs for patients • Breathlessness IMPRESS Tips BITs for commissioners • Breathlessness IMPRESS Tips BITs for researchers

All the documents are available at http://www.impressresp.com/index.php?option=com_docman&task=cat_view&Itemid=82 Introduction Following on from our groundbreaking work that analysed the relative value of interventions for a COPD population1 2, IMPRESS decided to take on a new project. It decided to work with the London School of Economics again to apply the same STAR methodology3 to identify the relative value of interventions for a common symptom that matters to patients. We hypothesised that a symptom-based approach would:

• Be a more patient-focused approach than a disease-based approach

• Be more aligned to a holistic patient-centred approach

1 Gray M. Optimising the value of interventions for populations BMJ 2012;345:e6192 doi: http://dx.doi.org/10.1136/bmj.e6192 2 Williams S Getting value from COPD interventions 14 December, 2012 accessed http://www.hsj.co.uk/home/innovation-and-efficiency/-getting-value-from-copd-interventions/5052249.article and www.impressresp.com 3 http://www.health.org.uk/areas-of-work/star/

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• Introduce multiple morbidities into the discussions

• Engage a wider range of clinicians from more than one specialty

• Take everyone “out of the box” and therefore potentially lead to innovative thinking about how best to practise population medicine and achieve the greatest health gain/improvement in health outcomes

• Answer some of the questions that commissioners are already asking about the right balance of generic and disease-specific services for people with long term conditions and how best to address the issues of comorbidities where, for example, it has been estimated only 14-18% of people with COPD only have COPD and when actively assessed for co-morbidities it may be as low as 3%.4 5 6

There were a number of common respiratory symptoms that we could have chosen, but we decided that the one that is a high priority on patient agendas, is closest to our previous work and sufficiently prevalent in the population to warrant a service, was chronic breathlessness in adults.

The few epidemiological studies available seem to point in the direction that chronic breathlessness affects about 10% of the general population7, but the magnitude of the problem is greater in specific groups of the population, such as the elderly with about 30% of them being breathless8. Despite these significant prevalence rates, breathlessness is mentioned as a reason for encounter in primary care in about 1% of the recorded consultations in general practice9. Whether this figures is affected by coding behaviour in primary care or under-reporting of the symptom by patients is for discussion.

It has been an intellectually challenging piece of work. The cost-effectiveness evidence-base that we found for COPD does not exist for chronic and disabling breathlessness and therefore there is significant uncertainty. We needed to agree on a definition of breathlessness, identify the main underlying causes and bring together prevalence and incidence data for these causes: COPD, uncontrolled asthma, heart failure, anaemia, and obesity, singly or in combination and with or without anxiety, and distinguish between chronic and acute breathlessness. It seems as though some basic truths have been “blind-spots” in the research literature. For example, most patients and clinicians would say that breathlessness is a relatively common symptom for obese people (a belief also confirmed by the epidemiological data available, which show that about 50% of obese patients are breathless and up to 70% of obese elderly complain of some 4 Smith SM, Soubhi H, Fortin M, Hudon C, O’Dowd T. Managing patients with multimorbidity: systematic review of interventions in primary care and community settings. BMJ. 2012 2012-09-03 12:34:34;345. 5 Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. The Lancet. 2012. 6 Vanfleteren LE et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728-35 7 Based on (i) Currow DC, Plummer JL, Crockett A, Abernethy AP. A community population survey of prevalence and severity of dyspnea in adults. Journal of pain and symptom management. 2009; 38(4):533–45 and (ii) Bowden J, To THM, Abernethy AP, Currow DC. Predictors of chronic breathlessness: a large population study. BMC public health. 2011; 11(1):33. 8 See for example Ho SF, O'Mahony MS, Steward JA, Breay P, Buchalter M, Burr ML. (2001) Dyspnoea and quality of life in older people at home. Age Ageing. 2001 Mar;30(2):155-9. 9 Charles J, Ng A, Britt H. Presentations of shortness of breath in Australian general practice. Australian family physician. 2005;34(7):520–1.

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degree of breathlessness) and yet the recent excellent Royal College of Physicians Action on Obesity report has one mention and no discussion of breathlessness.10 In heart failure breathlessness may not be the cardinal symptom, which might be tiredness, however, the literature suggests up to 93% of people with heart failure, mainly elderly, suffer from breathlessness. The sensation may be perceived by the individual as part of their normal ageing process. We had many debates about when breathlessness is disabling and warrants an intervention and what that intervention should be.

The interaction between breathlessness and anxiety is complex and so this is another reason why this project has been worth doing, because it forces discussions about the interaction between mental and physical health and highlights the need for healthcare professionals to have skills to promote both. For example, panic disorder is ten times more common in the population with COPD than in the general population.11 However, anxiety is under-diagnosed and under-treated in primary care despite strong evidence of the effectiveness of talking therapies.12 13 14

There are few straightforward answers when you combine general practice, community and hospital clinicians from different specialties and disciplines to reach consensus about coding, symptom-scoring, patient and population interventions though much learning. It is also challenging when you bring together literature from medicine, psychology, and public health. There are also few examples of symptom-based services in operation and even fewer examples of how these are commissioned; that is, how they are paid for or monitored. However, we have reached some conclusions that could make a difference today to people with chronic and disabling breathlessness. We also have a reasonably long list of research questions that we encourage academic health science networks to investigate. We see this as the beginning of a debate about how to best set up a breathlessness service for a population. We welcome feedback, examples of good practice, and case studies and urge those setting up services to evaluate their cost and their outcomes, and to publish their findings.

One of our conclusions is that local breathlessness services and pathways will need to grow from what already exists provided by health and local authorities, and also will depend on the local populations’ needs and health status. Disabling breathlessness is more common in deprived populations. Therefore we would encourage the local stakeholders involved in developing, approving and implementing joint strategic needs assessments to use our work as the basis for a local (and ultimately electronic) version.

What is certain is that the service will need to integrate mental and physical health pathways and services, and a common and consistent approach to behaviour change across a number of health specialties and public health. It is also certain that the normal consultation arrangements are not fit for purpose to assess a breathless person. We strongly recommend that services review the tests of change that a number of areas are undertaking to provide longer appointments in long term conditions in both primary and out-patients settings. We also want to reinforce the power of taking time with the patient 10 Royal College of Physicians. Action on obesity: comprehensive care for all. Report of a working party. London: RCP, 2013. 11 Livermore N, Sharpe L, McKenzie D. Prevention of panic attacks and panic disorder in COPD. Eur Respir J. 2010 Mar;35(3):557-63. 12 Tylee A, Walters P. Under recognition of anxiety and mood disorders in primary care: why does the problem exist and what can be done? J Clin Psychiatry. 2007;68Suppl 2:27-30. 13 Kroenke, K. (2007) Efficacy of Treatment for Somatoform Disorders: A Review of Randomised Controlled Trials. Psychosomatic Medicine, 69: 881-888 14 Tyrer P et al Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial. The Lancet, Available online 18 October 2013

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to take a full history, once the immediate decision about whether to admit a patient has been made. At an individual level, always be mindful of three dimensions: the person’s mental health, their social context as well as their physical health, remember that breathlessness is not always caused by one single factor and that all breathlessness is stressful to some extent; the question is to what extent.

How these resources are organized This is the introduction and methodology in which we review the definitions for breathlessness, and the main causes of breathlessness including COPD, heart failure, obesity, anxiety and anaemia, which are the terms around which we developed our work, as well as an exploration of the association between obesity and asthma.

We also propose an algorithm and Breathlessness IMPRESS Tips (BITs) organized for four main groups of stakeholders: patients, clinicians, commissioners and researchers.

For each BIT, we give the rationale for suggesting it and reference the claim with currently available evidence.

We have taken a symptom-based approach, therefore our focus was not on asymptomatic patients but on finding and treating people with symptoms in an integrated way that increase value. However, it would be irresponsible to ignore primary prevention at either a population or individual level. Therefore we recommend that NICE public health guidance is followed about smoking, physical activity and weight management (see Appendix for a full list).

Method We worked with a team from the London School of Economics including two academics from the School of Management who are experts in decision-making, a director of public health and the programme lead for the North West London Integrated Care Pilot. We invited our multi-disciplinary IMPRESS Implementation Group that had worked on our Relative Value work and represents general practice, community and hospital services and supplemented their knowledge and expertise with key informants from other specialties:

• Two primary care cardiovascular experts

• Two consultant cardiologists

• One Royal College of Physicians nominee from the Action on Obesity programme

• One health psychologist

The full list of contributors is available here.

The first task was to review the literature in order to complete a grid of the cost-effectiveness literature on interventions for breathlessness. Whilst this had to be abandoned due to the lack of evidence, it did create helpful dialogue about definitions, the scope of the work and what might be possible and meaningful.

Following substantial email debate between sub-groups looking at different causes of breathlessness, we organised a one-day workshop with key informants to debate the evidence that was available, using case studies to tease out different approaches and clinical behaviours to diagnose and manage chronic disabling breathlessness.

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Subsequently, we created a web platform and email exchange to collect further evidence, refine the claims and agree on the content of this report.

Limitations of the methodology The review of the literature for the collection of evidence available on breathlessness has not been systematic. We rather embraced a less structured and more opportunistic approach which anyway highlighted some main problems in the literature about breathlessness.

To start with, we faced problems around how breathlessness can be defined and assessed, as different scales have been used. Data on epidemiology of breathlessness is scarce, suggesting that a common and noticeable problem felt by a significant number of a local population is somehow under the radar of researchers. In the attempt of overcoming the lack of data on the epidemiology of breathlessness, we developed an algorithm for extracting these data from the electronic systems currently used in primary care. This attempt confirmed that coding of breathlessness in primary care is inconsistent.

We did not perform the same analysis on hospital data as coding in secondary care is driven by diagnosis and so was only helpful insofar as it described the impact of COPD and heart failure on hospital services. Similarly, if we look at QOF data15, we cannot discover the prevalence of breathlessness, but only the prevalence of relevant conditions that may be associated with breathlessness in general practice.

Also the prevalence of breathlessness as a symptom reported by patients already diagnosed with a particular condition seems to be unevenly studied. For COPD and HF data are fairly available, but for other conditions (eg anxiety and anaemia) knowledge appears scarce. This affects whether and how the symptom is managed and treated in different conditions.

Scope of the work, definitions

In the literature, there are a number of words that are used for referring to breathlessness, such as shortness of breath, dyspnoea (literally “disordered breathing”)16. There is no one definition of breathlessness from the patient or clinician perspective because patients use an array of terms to describe their breathing sensation and the term can represent a number of qualitatively distinct sensations17,18,19,20

“I just feel I can’t get my breath”

“I never seem to have any breath when I try and do things”

15 2011-12 GP QOF submissions www.gpcontract.co.uk 16 Sarkar S, Amelung P J. Evaluation of the dyspneic patient in the office. Primary care. 2006;33:643–57. 17 Sarkar S, Amelung P J. Evaluation of the dyspneic patient in the office. Primary care. 2006;33:643–57. 18 Ambrosino N, Serradori M. Determining the cause of dyspnoea: linguistic and biological descriptors. Chronic Respiratory Disease. 2006;3:117. 19 Elliott MW, Adams L, Cockcroft A, MacRae KD, Murphy K, Guz A. The language of breathlessness. Use of verbal descriptors by patients with cardiopulmonary disease. Am Rev Respir Dis. 1991 Oct;144(4):826-32. 20 Mahler DA, Harver A, Lentine T, Scott JA, Beck K, Schwartzstein RM. Descriptors of breathlessness in cardiorespiratory diseases. Am J Respir Crit Care Med. 1996 Nov;154(5):1357-63.

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“No matter how big a breath I take, it doesn’t feel enough”

“I can never catch my breath”

“It feels as if there is no air in the room”

“I feel as though I am so breathless I will die”

“It makes you very frightened”

These different sensations will depend on personally-felt interactions between physiological, psychological, social and environmental factors.21 Breathlessness can also be described by the individual in terms of time course, frequency and triggers22, its intensity and the distress it evokes23 24 25 and impact on function, psychological, social and spiritual well-being.26 Qualitative studies on the experience of breathlessness show that the range of descriptors used by patients varies across the underlying conditions causing their breathlessness.27 28 29 30

According to the American Thoracic Society breathlessness is a “subjective experience of breathing discomfort that derives from interactions among multiple physiological, psychological, social, and environmental factors, that may induce secondary physiological and behavioural responses”. (…)Potentially it warns of a critical threat to homeostasis thus frequently leading to adaptive responses (such as resting or seeking medical care). Protracted or intractable breathlessness causes suffering and impaired performance and quality of life”. 31 In health it is not always unpleasant and not associated with anxiety or fear, but fear and anxiety also may give rise to or amplify

21 Parshall MB. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435–452. 22 Simon ST, Higginson IJ, Benalia H, Gysels M, Murtagh FE, Spicer J, Bausewein C. Episodic and Continuous Breathlessness: A New Categorization of Breathlessness. J Pain Symptom Manage. 2013 Jun;45(6):1019-29. 23 Banzett RB, Mossavi S. Dyspnea and pain: similarities and contrasts between two very unpleasant sensation. APS Bulletin. 2001;11,:1–8. 24 Wilson RC, Jones PW. Differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise. Clinical science. 1991; 80: 65–70. 25 Banzett RB, Pedersen SH, Schwartzstein RM, Lansing R W. The affective dimension of laboratory dyspnea: air hunger is more unpleasant than work/effort. American journal of respiratory and critical care medicine. Am J Respir Crit Care Med. 2008;177:1384–90. 26 Bausewein C, Farquhar M, Booth S, Gysels M, Higginson IJ. Measurement of breathlessness in advanced disease�: A systematic review. Respir Med. 2007 Mar;101(3):399-410. 27 Edmonds PM, Rogers A, Addington-Hall JM, McCoy A, Coats AJ, Gibbs JS. Patient descriptions of breathlessness in heart failure. Int J Cardiol. 2005 Jan;98(1):61-6. 28 Ekman I, Boman K, Olofsson M, Aires N, Swedberg K., Gender makes a difference in the description of dyspnoea in patients with chronic heart failure. Eur J Cardiovasc Nurs. 2005 Jun;4(2):117-21. 29 Elliott MW, Adams L, Cockcroft A, MacRae KD, Murphy K, Guz A. The language of breathlessness. Use of verbal descriptors by patients with cardiopulmonary disease. Am Rev Respir Dis. 1991 Oct;144(4):826-32. 30 Gysels MH, Higginson IJ, The lived experience of breathlessness and its implications for care: a qualitative comparison in cancer, COPD, heart failure and MND. BMC Palliative Care. 2011;10:15. 31 Parshall MB. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435–452.

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breathlessness.32 Virtually all people will feel breathless on relatively mild exertion when at altitude so environment makes a difference.

The American College of Chest Physicians defines breathlessness as a complex sensation with a wide range of factors that can generate and sustain it33. The efferent drive to breathe is mediated through the phrenic nerves and nerves supplying the intercostal muscles. When these pathways are stimulated out of proportion to their ability to respond by afferent signals from chemo- and mechano-receptors, the mismatch between the two systems generates the feeling of breathlessness.

Therefore to exclude shortness of breath caused by an acute condition and the normal – and healthy - feeling of being out of breath after physical activity, we chose to limit our scope to long-term or chronic breathlessness that develops over weeks or months and that might or might not have a physiological basis. How long “chronic” is, it is subjective.

Assessing breathlessness to determine its impact and guide intervention As with other symptoms like pain, breathlessness can and should be measured to assess it adequately. There have been many efforts to develop and validate measures and instruments over the last few years. Some of these come from the respiratory community, and others from the cardiovascular community and they are not the same. For example, the first response from a cardiology colleague might be to use the New York Heart Association (NYHA) functional classification which includes breathlessness, whereas the first response from a respiratory colleague might be to use the Medical Research Council (MRC) dyspnoea scale which is also a functional classification and limited to breathlessness. They are very similar although not validated against each other in other conditions. There are also a number of versions of the MRC scale, which is important particularly at Grade 3 because this is currently used as the threshold for referral to pulmonary rehabilitation.

Table 1 - Medical Research Council dyspnoea scale34

Grade Degree of breathlessness related to activities

1 Not troubled by breathlessness except on strenuous exercise 2 Short of breath when hurrying or walking up a slight hill 3 Walks slower than contemporaries on level ground because of breathlessness, or has to

stop for breath when walking at own pace 4 Stops for breath after walking about 100m or after a few minutes on level ground 5 Too breathless to leave the house, or breathless when dressing or undressing

In order to determine the best course of therapy, physicians often assess the stage of heart failure according to the New York Heart Association (NYHA) functional

32 Parshall MB. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435–452. 33 Mahler DA, Selecky PA, Harrod CG, Benditt JO, Carrieri-Kohlman V, Curtis JR, et al. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest. 2010 Mar;137(3):674-91. 34 Adapted from Fletcher CM, Elmes PC, Fairbairn AS et al. (1959) The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. British Medical Journal 2:257-66, available at http://www.nice.org.uk/usingguidance/commissioningguides/pulmonaryrehabilitationserviceforpatientswithcopd/mrc_dyspnoea_scale.jsp accessed on 21st October 2013

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classification system. This system relates symptoms to everyday activities and the patient's quality of life.

Table 2 - NYHA Classification - The symptoms of Heart Failure35

Class Patient Symptoms

Class I (Mild) No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath).

Class II (Mild) Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea.

Class III (Moderate) Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.

Class IV (Severe) Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

Instruments may ask what breathing feels like (as with the Borg Scale or its modified version36), whereas others may ask how distressing it is (eg. the Medical Research Council dyspnoea scale37, and its modified version38, the numerical Rating Scale (NRS)39) or how it impacts performance (such as the Baseline Dyspnea Index (BDI) - Transitional Dyspnea Index (TDI)40 41) or quality of life (eg, the Chronic Respiratory Disease Questionnaire (CRQ)42 – , the rating task (i.e., what patients or research subjects are instructed to rate), and whether measurements are real-time or involve recall of a specific episode, some defined interval, or how things usually are. Some measures are unidimensional (i.e. measuring the severity of breathlessness), others are multidimensional, and of these some are breathlessness-specific and others disease-

35 http://www.abouthf.org/questions_stages.htm accessed 25 July 2013 36 Boezen HM, Rijcken B, Schouten JP, Postma D S. Breathlessness in elderly individuals is related to low lung function and reversibility of airway obstruction. European Respiratory Journal. 1998;12(4): 805–810. 37 Fletcher CM, Elmes PC, Fairbairn AS et al. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. British Medical Journal. 1959;2:257-66. 38 Bowden J, To TH M, Abernethy AP, Currow DC. Predictors of chronic breathlessness: a large population study. BMC public health. 2011;11(1):33. 39 Peel ET, Burns GP. Breathlessness. In: Bourke SJ, Peel ET, editors. Integrated Palliative Care of Respiratory Disease. London: Springer; 2013. 40 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011;105(7):1014–21. 41 Crisafulli E, Clini EM. Measures of dyspnea in pulmonary rehabilitation. Multidisciplinary Respiratory Medicine. 2010;5:202-210. 42 Peel ET, Burns GP. Breathlessness. In: Bourke SJ, Peel ET, editors. Integrated Palliative Care of Respiratory Disease. London: Springer; 2013.

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specific43. Reviews on instruments for breathlessness assessment can be found in 44 and 45.

Therefore our conclusion, confirmed by many46 47, is that no single measure of breathlessness covers all its possible domains, and there is no reason not to use the NYHA or MRC scales as long as their purpose and how to use them is understood to increase inter-rater reliability and reproducibility48 (see Appendix).

We have also proposed an IMPRESS definition:

Proposed IMPRESS definition Breathlessness is the sensation of not getting enough air, and may be the result of anything that interferes with the extraction of oxygen from air and its delivery to the tissues. Therefore any of: altitude, asthma, rib fracture, COPD, heart failure, exercise or anaemia may be the cause. It can also be caused, or contributed to, by anxiety.

Long-term or chronic breathlessness is experienced by an individual over a period of months and may develop without them noticing.

Diagnosis associated with breathlessness

The underlying causes of long-term breathlessness can be manifold. In the case of chronic breathlessness, the condition is most often due to respiratory or cardiac problems, such as49 50 51

• Asthma • Cardiomyopathy • COPD • Croup • Heart arrhythmias • Heart dysfunction • Heart failure • Interstitial lung disease • Lung cancer • Pericarditis • Pleurisy • Pulmonary oedema • Pulmonary fibrosis • Pulmonary hypertension • Sarcoidosis • Tuberculosis

43 Bausewein C, Farquhar M, Booth S, Gysels M, Higginson IJ. Measurement of breathlessness in advanced disease�: A systematic review. Respir Med. 2007 Mar;101(3):399-410. 44 Parshall MB. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435–452. 45 Ries AL. Impact of chronic obstructive pulmonary disease on quality of life: the role of dyspnea. Am J Med. 2006 Oct;119(10 Suppl 1):12-20. 46 Parshall MB. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. 2012; 185(4): 435–452. 47 Harty H, Adams L. Assessment of dyspnoea in research. In: Ahmedzai SH, Muers MF, editors. Supportive Care in Respiratory Disease. 1st ed. New York: Oxford University Press; 2005. 48 Raphael C. Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure. Heart. 2007 April;93(4):476–482. 49 Based on http://www.mayoclinic.com/health/shortness-of-breath/MY00119/DSECTION=causes 50 Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: Dyspnea, Can Fam Physician. August 2007;53(8):1333. 51 Karnani NG, Reisfield GM, Wilson GR. Evaluation of Chronic Dyspnea. American Family Physician. 2005;71(8):1529-1537.

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In addition to these cardio-respiratory causes (which represent two thirds of patients with breathlessness52), other possible conditions associated with breathlessness are53 54

• Anaemia • Hyperthyroidism • Obesity • Deconditioning • Chest wall pathology • Neuromuscular disease • Broken ribs • Epiglottitis • Foreign object inhaled: First aid • Guillain-Barre syndrome

• Thromboembolic disease • Psychogenic causes (GAD, PTSD, panic disorders)

• Gastroesophageal reflux disease • Metabolic conditions (acidosis, uremia)

• Liver cirrhosis • Thyroid disease • Neuromuscular disorders

(myasthenia gravis, amyotrophic lateral sclerosis)

• Chest wall deformities (kyphoscoliosis)

• Mental health problems • Upper airway obstruction

(laryngeal disease, tracheal stenosis)

Breathlessness can be caused by a single underlying condition or by the interaction of two or more underlying conditions (complex multi-morbidity breathlessness).

In some cases the diagnosis or contribution of various components to the breathlessness remains uncertain, if not unexplained. A study of a sample of 72 patients referred because unexplained breathlessness had been present for more than 1 month, a definite diagnosis could be established only in 81%.55

It is worth mentioning also that diagnosing breathlessness can be difficult. The concordance between the clinical diagnosis on referral and the final diagnosis at the breathlessness clinic was found in less than 40% of the patients studied by Nelson and colleagues in their study of 284 breathless patients referred from the GPs to a hospital-based breathlessness clinic.56 A slightly higher rate of accurate first diagnosis was reported by Pratter and colleagues. According to this study, physicians’ predictions following history and physical examination were accurate 55% of the time compared with final diagnoses. When results of pulmonary function tests were added, accuracy increased to 72%.57

The brief account made by Mustchin and Tiwari about the emergency admissions in which breathlessness was recorded as a prominent presenting symptom showed that in only 8% of the cases there was a discrepancy between the admission and the final

52 Gillespie DJ, Staats BA. Unexplained dyspnea. Mayo Clin Proc. 1994 Jul;69(7):657-63. 53 http://www.mayoclinic.com/health/shortness-of-breath/MY00119/DSECTION=causes 54 Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: Dyspnea, Can Fam Physician. August 2007;53(8):1333. 55 DePaso WJ, Winterbauer RH, Lusk JA, Dreis DF, Springmeyer SC. Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience. Chest. 1991 Nov;100(5):1293-9. 56 Nielsen LS, Svanegaard J, Wiggers P, Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. J Intern Med. Nov 2001;250(5):422-8. 57 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011;105(7):1014–21.

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diagnosis or no diagnosis was made during the hospital stay.58 In some cases it is not the presenting symptom.

Identifying the underlying aetiology of breathlessness is essential in determining its management and the most appropriate treatment for the patient. This may require the coordinated intervention of a number of experts. However, in some people, particularly frail elderly people, it may not be appropriate to make a diagnosis: the point of tests and diagnosis being to plan interventions.

Besides being affected by a physical problem and/or a particular psychological state, breathlessness can be shaped by an individual’s particular life situation. Therefore in addition to other causal factors, sex, ageing, pregnancy, menopause have been reported to be often associated with breathlessness.59

Prevalence and incidence of breathlessness There are only a few large scale epidemiological studies on breathlessness. In addition, comparability across them is not straightforward because of the heterogeneity of definitions and measurements of breathlessness used, study populations included, time horizons and study designs adopted. In this section we briefly review and compare the results of the studies on breathlessness which have been realized in different settings: in the general population, in primary care, in ED departments, among the elderly, and among end-of-life patients.

General population

Two community-based Australian studies are available using data collected in two editions of the South Australian Health Omnibus. Currow found an overall prevalence of 8.9% in a population of 5,473 participants over 15 years in South Australia using 2006/2007 survey data. More marked impairment from breathlessness (MRC 3-5) was seen in 2.6% of the total population. The results by age group show that prevalence rates increase with age: 6.7% in people aged less than 35, 4.9% in people aged 35-49, 9.8% in those aged 50-64, 16.9% in those aged 65 or above.60

In a similar sample of 5,331 participants from the 2007-2008 survey, there was an increase. Overall 11.1% of the population sampled reported breathlessness and 3.4% of them had an MRC score between 2 and 4. Prevalence was reported in 15% of the respondents aged 50 years or over61.

In a general population sample (2,306 participants) in Sweden, breathlessness, defined as grade 2, was reported by 20,5% of women and 12% of men, giving an overall prevalence rate of 16.4%.62

58 Mustchin CP, Tiwari I. Diagnosing the breathless patient. Lancet. 1982 Apr 17;1(8277):907-8. 59 Hayen A, Herigstad M, Pattinson KT. Understanding dyspnea as a complex individual experience. Maturitas. 2013 Sep;76(1):45-50. 60 Currow DC, Plummer JL, Crockett A, Abernethy AP. A community population survey of prevalence and severity of dyspnea in adults. Journal of pain and symptom management. 2009;38(4):533–45. 61 Bowden J, To THM, Abernethy AP, Currow DC. Predictors of chronic breathlessness: a large population study. BMC public health. 2011;11(1):33. 62 Voll-Aanerud M, Eagan TM, Wentzel-Larsen T, Gulsvik A, Bakke PS. Respiratory symptoms, COPD severity, and health related quality of life in a general population sample. Respir Med. 2008 Mar;102(3):399-406.

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The Vlagtwedde/Vlaardingen study based in the Netherlands on a general population cohort of 7,360 exclusively Caucasian individuals of Dutch descent found moderate and severe breathlessness respectively in 5% and 1% of the study sample.63

Primary care

Prevalence has been studied more extensively in primary care settings, as it appears to be a common symptom in general practice.64

Jolly reported an annual incidence and an annual prevalence of 7.3 and 15.4 per 1,000 patients at risk per year65 in a sample of 121 patients in Canada in 1974-1975.

In a larger sample of a thousand patients over a 3-year period (1984-1987) in the USA, Kroenke estimated a three-year incidence of 3.7%.66

More recently, Charles used the data available through the BEACH program, a national study of general practice activity in Australia from April 1998 to March 2004, to conclude that in 5,215 encounters the patient gave breathlessness as one of their reasons for the encounter, that is 0.9 per 100 encounters.67

Older people

Breathlessness is a common experience for older people and therefore it is often associated not only with specific conditions but more in general with the process of ageing.

Abramson studied self-reported breathlessness measured by the MRC scale in a random sample of 4,276 adults aged between 45 and 69 years drawn from electoral rolls for Melbourne, Australia. The prevalence rate of exertional breathlessness was estimated at about 27%.68 A similar prevalence rate (24%) was found in a random sample of 210 55-year and older subjects in the Netherlands with a Borg score higher than 069.

In a group of 152 patients with MRC grade > 1 and aged 60-79 living at home, 31% had breathlessness confirmed at examination.70

In a large community-based study performed in France in a sample of more than 4,000 residents aged 65 and over, breathlessness was found in about 60% of them, with women reporting higher rates than men (63.8% vs 58.3%).71

63 Figarska SM, Boezen HM, Vonk JM. Dyspnea severity, changes in dyspnea status and mortality in the general population: the Vlagtwedde/Vlaardingen study. Eur J Epidemiol. 2012 Nov;27(11):867-76. 64 Frese T, Sobeck C, Herrmann K, Sandholzer H. Dyspnea as the reason for encounter in general practice. Journal of clinical medicine research. 2011;3(5):239–46. 65 Jolly DT. Dyspnea in Primary Care. Can.Fam.Physician. 1978;24:983–988. 66 Kroenke K, Mangelsdorff AD. Common symptoms in ambulatory care: incidence, evaluation, therapy, and outcome. The American journal of medicine. 1989;86(3):262–6. 67 Charles J, Ng A, Britt H. Presentations of shortness of breath in Australian general practice. Australian family physician. 2005;34(7):520–1. 68 Abramson M, Matheson M, Wharton C, Sim M, Walters EH. Prevalence of respiratory symptoms related to chronic obstructive pulmonary disease and asthma among middle aged and older adults. Respirology. 2002;7(4):325–31. 69 Boezen HM, Rijcken B, Schouten JP, Postma D S. Breathlessness in elderly individuals is related to low lung function and reversibility of airway obstruction. European Respiratory Journal. 1998;12(4):805–810. 70 Pedersen F, Mehlsen J, Raymond I, Atar D, Skjoldborg US, Hildebrandt PR. Evaluation of dyspnoea in a sample of elderly subjects recruited from general practice. International journal of clinical practice. 2007;61(9):1481–91.

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In a UK-based study, 32.3% of the study population of 1,169 subjects aged 70 and over living at home in Barry, South Wales interviewed by Ho and colleagues had breathlessness (MRC grades 3-5) confirmed72. As the only UK study we found, it is important to have these data but it is not certain to what we might attribute these higher rates.

Another European study among 114 patients over 70 found a higher prevalence rate of breathlessness (55%): 32% (n = 27) had mild breathlessness complaints (MRC 1 or 2) and moderate to severe symptoms (MRC > 3) were reported by 23% of the respondents. In the subsample that completed the BDI interview, 37% reported moderate to severe breathlessness. According to the Authors of the study discrepancies between these two figures may reflect differences in the two instruments and the mode of administration (questionnaire versus interview), the interval of approximately three months between the two assessments, and differences in the composition of the sample due to exclusion or drop-out in that interval.73

People with advanced disease A recent comparison of symptom prevalence among people with five advanced, life-limiting diseases found that breathlessness is one of the core symptoms which are particularly persistent and frequent towards the end of life. Breathlessness is a symptom which affects patients with many conditions. It is very common in patients with advanced cancer of any primary site, occurring in 78% of patients with lung cancer74 and 50-70% of all cancer patients.75 It affects up to 95% of chronic obstructive pulmonary disease (COPD) patients76 and 88% cardiac failure patients.77

Usually it is associated with a great level of distress – Edmonds et al. (2001) reported that 60% of breathless patients with lung cancer described it as “very distressing”).78

It can also be a major factor in causing emergency hospital admissions. Escalante et al. found that 7% of a sample of cancer patients was admitted to the ED with a complaint of

71 Barberger-Gateau P, Chaslerie A, Dartigues JF, Commenges D, Gagnon M, Salamon R. Health measures correlates in a French elderly community population: the PAQUID study. J Gerontol. 1992 Mar;47(2):S88-95. 72 Ho SF, O’Mahony MS, Steward JA, Breay P, Buchalter M, Burr ML. Dysponea and quality of life in older people at home. Age Ageing. 2001 Mar;30(2):155-9. 73 Huijnen B, van der Horst F, van Amelsvoort L, Wesseling G, Lansbergen M, Aarts P, Nicolson N, Knottnerus A. Dyspnea in elderly family practice patients. Occurrence, severity, quality of life and mortality over an 8-year period. Fam Pract. 2006 Feb;23(1):34-9. 74 Edmonds P, Karlsen S, Khan S, Addington-Hall J. A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer. Palliat Med. 2001 Jul;15(4):287-95. 75 Thomas S, Bausewein C, Higginson I, Booth S. Breathlessness in cancer patients - implications, management and challenges. Eur J Oncol Nurs. 2011 Dec;15(5):459-69. 76 Solano JP, Gomez B, Higginson IJ: A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease (COPD), and renal disease. J Pain Symptom Management. 2006;31(1):58-69. 77 Solano JP, Gomez B, Higginson IJ: A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease (COPD), and renal disease. J Pain Symptom Management. 2006;31(1):58-69. 78 Edmonds P, Karlsen S, Khan S, Addington-Hall J. A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer. Palliat Med. 2001 Jul;15(4):287-95.

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breathlessness.79 Its incidence increases in the last six weeks of life80 81 and is associated with a poor prognosis.82 83 84

Some studies report that breathlessness is a contributing factor to the need for palliative sedation at the end of life. For example, Mercadante found that in 25 patients out of 77 terminally ill patients breathlessness was the indication for sedation.85 In a multicentre observational study investigating the efficacy of palliative sedation for end-of-life patients, the Authors found that almost 60% of the study population reported intolerable dyspnoea requiring sedation.86

Emergency Department (ED)

Sudden shortness of breath, or breathing difficulty, is the most common reason for visiting ED.87 Breathlessness has been examined across diagnoses in a general ED in the United States, revealing a prevalence of 2.7% of all visits.88 In a UK-based study the prevalence of breathlessness resulted much higher rate as was found in 25% of all patients admitted as medical emergencies.89 Mustchin reported a similar rate: according to his results, in 21% of all emergency admissions breathlessness was recorded as the prominent presenting symptom.90

79 Escalante CP, Manzullo EF, Lam TP, Ensor JE, Valdres RU, Wang XS. Fatigue and its risk factors in cancer patients who seek emergency care. J Pain Symptom Manage. 2008 Oct;36(4):358-66. 80 Booth S, Silvester S, Todd C. Breathlessness in cancer and chronic obstructive pulmonary disease: using a qualitative approach to describe the experience of patients and carers. Palliat Support Care. 2003 Dec;1(4):337-44. 81 Escalante CP, Martin CG, Elting LS, Price KJ, Manzullo EF, Weiser MA, Harle TS, Cantor SB, Rubenstein EB. Identifying risk factors for imminent death in cancer patients with acute dyspnea. J Pain Symptom Manage. 2000 Nov;20(5):318-25. 82 Maltoni M, Caraceni A, Brunelli C, Broeckaert B, Christakis N, Eychmueller S, Glare P, Nabal M, Viganò A, Larkin P, De Conno F, Hanks G, Kaasa S; Steering Committee of the European Association for Palliative Care. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations--a study by the Steering Committee of the European Association for Palliative Care. J Clin Oncol. 2005 Sep 1;23(25):6240-8. 83 Viganò A, Dorgan M, Buckingham J, Bruera E, Suarez-Almazor ME. Survival prediction in terminal cancer patients: a systematic review of the medical literature. Palliat Med. 2000 Sep;14(5):363-74. 84 Bausewein C, Booth S, Gysels M, Kühnbach R, Haberland B, Higginson IJ. Understanding breathlessness: cross-sectional comparison of symptom burden and palliative care needs in chronic obstructive pulmonary disease and cancer. J Palliat Med. 2010 Sep;13(9):1109-18. 85 Mercadante S, Intravaia G, Villari P, Ferrera P, David F, Casuccio A. Controlled sedation for refractory symptoms in dying patients. J Pain Symptom Manage. 2009 May;37(5):771-9. 86 Morita T, Chinone Y, Ikenaga M, Miyoshi M, Nakaho T, Nishitateno K, et al. Efficacy and safety of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan. J Pain Symptom Manage. 2005 Oct;30(4):320-8. 87 http://www.nhs.uk/Conditions/shortness-of-breath/Pages/Introduction.aspx accessed on 21st October 2013 88 Fedullo AJ, Swinburne AJ, McGuire-Dunn C. Complaints of breathlessness in the emergency department. The experience at a community hospital. N Y State J Med. 1986 Jan;86(1):4-6. 89 Pearson SB. The diagnosis and management of patients admitted to hospital with acute breathlessness. Postgraduate medical journal. 1981;57(669):419. 90 Mustchin CP, Tiwari I. Diagnosing the breathless patient. Lancet. 1982 Apr 17;1(8277):907-8.

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Conclusion

To conclude, the epidemiology of breathlessness seems to be an under-researched area of study. When studies are available, methodological differences compromise any possible direct comparisons. There are substantial differences between studies in the general population, primary care the elderly and end-of-life patients, and ED. Community studies by Currow in South Australia quantified breathlessness prevalence rates between 9 and 11%. Breathlessness as a reason for an encounter is reported in 1-4% of the patients attending primary care. A 4% three-year incidence rate is reported in one study and another one found an annual incidence of 7.3 per 1,000 patients at risk. Calculations of prevalence rates of breathlessness in older people vary between 24 and 32%.

Breathlessness is one of the core symptoms which are persistent and frequent towards the end of life. Depending on the underlying conditions it can affect up to the whole population of the end-of-life patients.

Sudden shortness of breath, or breathing difficulty, is the most common reason for visiting an ED – 25% of all patients admitted as medical emergencies reported also breathlessness.

Therefore breathlessness is a problem that would benefit from a population approach as well as a consistent approach by clinicians in general practice, community and hospital settings.

Breathlessness in different conditions In this section we now review the epidemiology of breathlessness in different conditions. We consider heart failure, COPD, obesity, anaemia and anxiety which are responsible for about 50% of the burden of disease associated with breathlessness.91

For each of this condition we investigate (i) how often patients presenting with breathlessness are diagnosed with a specific condition and (ii) how often patients who already have been diagnosed with that condition complain of breathlessness. This is supported by detailed modelling, available at http://www.impressresp.com/index.php?option=com_content&view=article&id=172:impressions-31-breathlessness&catid=11:impressions&Itemid=3.

These data allow us to start describing who the breathless patients are and how the breathless population as a whole looks like. In order to do so, for each condition we have chosen data available from studies realized in the general population, when available, or in primary care. Therefore we have deliberately not included results from studies performed in special groups, such as the elderly or patients admitted to the hospital, or in particular settings, eg tertiary care centres, as not representative of the general population.

Available prevalence rates have been used to estimate the expected number of patients with breathlessness and of breathless patients with a specific condition already diagnosed both at the CCG level (under the assumption that there the median number of

91 Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: Dyspnea, Can Fam Physician. August 2007; 53(8):1333.

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patients in a CCG is 251,700, of whom about 173,000 adults92) and for a GP (assuming an average list size of 1,520 patients, of whom 1,140 adults93).

Heart failure Heart failure (HF) is a complex clinical syndrome of symptoms and signs that suggest impairment of the heart as a pump supporting physiological circulation. It is caused by structural or functional abnormalities of the heart. The demonstration of objective evidence of these cardiac abnormalities is necessary for the diagnosis of heart failure to be made. The symptoms most commonly encountered are breathlessness, fatigue and ankle swelling.94

Heart failure can be classified according to New York Heart Association criteria, where class I (i.e. no symptoms) is the mildest grade and class IV (symptoms of cardiac insufficiency at rest) is the most severe grade.95 The American College of Cardiology/American Heart Association (ACC/AHA) has proposed an alternative staged heart failure classification, listed from stage A identifying the patient who is at high risk for developing heart failure but has no structural disorder of the heart to stage D designating the patient with end-stage disease who requires specialized treatment strategies such as mechanical circulatory support, cardiac transplantation, or hospice care.96

The prevalence of heart failure has been estimated at 1-2% of the adult population and approximately 6-10% in the elderly97, and the incidence approaches 5-10 per 1000 persons per year.98 99 According to the QOF statistical bulletin, in 2011-12 in England the prevalence of diagnosed HF was 0.7%.100

Breathlessness is a hallmark symptom of HF, common and distressing for patients.101

92 Median CCG population. Available at ONS, http://www.ons.gov.uk/ons/rel/sape/clinical-commissioning-group-population-estimates/mid-2011--census-based-/stb---clinical-commissioning-groups---mid-2011.html, accessed on 21st October 2013 93 Average patient list size of medical practitioner in general practice in England, year 2009. Available at http://www.ohe.org/page/health-statistics/access-the-data/health-service/data.cfm accessed on 21st October 2013 94 National Clinical Guideline Centre. Chronic heart failure: the management of chronic heart failure in adults in primary and secondary care. 2010. London: National Clinical Guideline Centre. Available from: http://guidance.nice.org.uk/CG108/Guidance/pdf/English 95 http://www.abouthf.org/questions_stages.htm 96 Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. J Heart Lung Transplant. 2002 Feb;21(2):189-203. 97 Blinderman CD, Homel P, Billings JA, Portenoy RK, Tennstedt SL. Symptom distress and quality of life in patients with advanced congestive heart failure. J Pain Symptom Manage. 2008 Jun;35(6):594-603. 98 Mosterd A, Hoes AW. Clinical Epidemiology of Heart Failure. Heart. 2007;93:1137–1146. 99 For a review of epidemiological studies on heart failure see McMurray J, Stewart S. Epidemiology, aetiology, and prognosis of heart failure. Heart; 2000;83:596-602. 100 Health and Social Car Information Centre. Quality and Outcomes Framework - 2011-12, England level. Publication date: October 30, 2012. Available from http://www.hscic.gov.uk/catalogue/PUB08661 accessed on 27th September 2013. 101 Johnson MJ, Oxberry SG, Cleland JG, Clark AL. Measurement of breathlessness in clinical trials in patients with chronic heart failure: the need for a standardized approach: a systematic review. Eur J Heart Fail. 2010 Feb;12(2):137-47.

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Studies on the prevalence of symptoms in HF patients have been realized in different settings (primary care vs secondary care vs ED), including a variety of study populations (eg. the community, the elderly and end-of-life patients), with methods which varied from medical records reviews to surveys to interviews. A comparative analysis of these studies is therefore quite challenging.

Studies performed in patients of every ages living in the community found prevalence of breathlessness of 57%102, whereas among the hospitalized this rate was about 76-100%.103 104

These data are also confirmed by the latest National Heart Failure Audit on about 44,000 hospital admissions for acute heart failure across England and Wales. According to this audit about 80% of patients on first admission and 84% of those readmitted were breathless on minimal exertion or at rest105, hence confirming the findings from previous audits.

Among the elderly breathlessness was reported in 54 to 66% of the HF patients recruited in the community106, a prevalence rate lower when compared to elderly patients hospitalized among whom breathlessness was reported in 89-95% of the cases studied. 107 108 109 110 111

The results of the Olmsted County study which reported breathlessness in 93% of the 216 new cases of definite HF112 mainly among elderly patients living in the community seems to be an outlier when compared to this stream of research, which may be partially explained by the high proportion (49%) of patients over 80.

102 Mayou R, Blackwood R, Bryant B, Garnham J. Cardiac failure: symptoms and functional status. J Psychosom Res. 1991;35(4/5):399e407. 103 Albert N, Trochelman K, Li J, Lin S. Signs and Symptoms of Heart Failure: Are You Asking the Right Questions?,Am J Crit Care. September 2010;19(5): 443-452. 104 Evangelista LS, Dracup K, Doering LV. Treatment-seeking delays in heart failure patients. J Heart Lung Transplant. 2000;19(10):932e938. 105 National Institute for Cardiovascular Outcomes Research (NICOR). National Heart Failure Audit 6th annual report April 2012 - March 2013. Available from http://www.ucl.ac.uk/nicor/nicor/NHFAreport2013 106 Walke LM, Byers AL, Tinetti ME, Dubin JA, McCorkle R, Fried TR. Range and severity of symptoms over time among older adults with chronic obstructive pulmonary disease and heart failure. Arch Intern Med. 2007 Dec 10;167(22):2503-8. 107 Krumholz HM, Wang Y, Parent EM, Mockalis J, Petrillo M, Radford MJ. Quality of care for elderly patients hospitalized with heart failure. Arch. Intern. Med. 1997;157: 2242–2247. 108 Vaccarino V, Chen YT, Wang Y, Radford MJ, Krumholz HM. Sex differences in the clinical care and outcomes of congestive heart failure in the elderly. Am Heart J. 1999 Nov;138(5 Pt 1):835-42. 109 Friedman M. Older adults’ symptoms and their duration before hospitalisation for heart failure. Heart Lung. 1997;26(3):169e176. 110 Ahmed A, Allman RM, Aronow WS, DeLong JF. Diagnosis of heart failure in older adults: predictive value of dyspnea at rest. Arch Gerontol Geriatr. 2004;38:297e307. 111 Weil E, Tu JV. Quality of congestive heart failure treatment at a Canadian teaching hospital. Can. Med. Assoc. J. 2001;16:284–287. 112 Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998 Nov 24;98(21):2282-9.

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A large US-based study of emergency visits for cardiorespiratory disease found that 62% out of 320 HF patients reported breathlessness as primary reason for the ED visit.113

Another group of studies looked at patients with advanced HF, finding breathlessness in 45 to 85% of the study samples.114 115 116

The last group of studies investigated symptoms prevalence in hospitalized end of life patients. A systematic review of studies on patients with end-stage chronic organ failure found that 42-79% (median 62%) HF patients at the terminal stage of their disease (eg in the last 2 weeks of life, the last week, the last 3 days, the last 24 hours) experienced breathlessness. Among those not at the terminal stage the same symptom was assessed in the range of 18-88% (median 72%)117. Also Solano and colleagues who reviewed 64 original studies reporting the prevalence of 11 common symptoms among end-stage patients, including HF patients in whom breathlessness was reported in the range of 60-88%118. The variability in the results of both these reviews reflects the heterogeneity in methodology used across studies.

In addition to these systematic reviews, we retrieved a few large population-based studies that measured the prevalence of breathlessness in HF patients near the end of life between 60 and 80%.119 120 121 122

Reported prevalence rates of breathlessness with heart failure as underlying cause vary between 4 and 27% depending on the characteristics of the study populations.

In a study aiming at understanding the patient-perceived causes of breathlessness, people in the community reporting being breathless were directly asked to what they attributed their breathlessness. 17% of the respondents (more than 2,800 Australians) self-reported that the daily experienced of this symptom for at least 3 months within the last 6 months was caused by HF.123

113 Parshall MB. Adult emergency visits for chronic cardiorespiratory disease: does dyspnea matter?, Nurs Res. 1999 Mar-Apr;48(2):62-70. 114 Dracup K, Walden J, Stevenson LW, Brecht L. Quality of life in patients with advanced heart failure. J Heart Lung Transplant. 1992;11:273–9. 115 Zambroski CH, Moser DK, Bhat G, Ziegler C. Impact of symptom prevalence and symptom burden on quality of life in patients with heart failure. Eur J Cardiovasc Nurs. 2005 Sep;4(3):198-206. 116 Blinderman CD, Homel P, Billings JA, Portenoy RK, Tennstedt SL. Symptom distress and quality of life in patients with advanced congestive heart failure. J Pain Symptom Manage. 2008 Jun;35(6):594-603. 117 Janssen DJ, Spruit MA, Wouters EF, Schols JM. Daily symptom burden in end-stage chronic organ failure: a systematic review. Palliat Med. 2008 Dec;22(8):938-48.

118 Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage. 2006 Jan;31(1):58-69. 119 Levenson JW, McCarthy EP, Lynn J, Davis RB, Phillips RS. The last six months of life for patients with congestive heart failure. J Am Geriatr Soc. 2000 May;48(5 Suppl):S101-9. requested 120 McCarthy M, Lay M, Addington-Hall J.J R, Dying from heart disease. Coll Physicians Lond. 1996 Jul-Aug;30(4):325-8. 121 Sullivan MD, O'Meara ES. Heart Failure at the End of Life: Symptoms, Function, and Medical Care in the Cardiovascular Health Study. Am J Geriatr Cardiol. 2006 Jul-Aug;15(4):217-25. 122 Zambroski CH, Moser DK, Roser LP, Heo S, Chung ML. Symptoms Experienced by Heart Failure Patients in Hospice Care. Am Heart J. 2005 Mar;149(3):558-64. 123 Johnson MJ, Bowden JA, Abernethy AP, Currow DC. To what causes do people attribute their chronic breathlessness? A population survey. J Palliat Med. 2012 Jul;15(7):744-50.

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According to the data collected through the BEACH program, a continuous national study of general practice activity in Australia, 18.2% encounters at which the patient gave breathlessness as one of their reasons for encounter received a diagnosis of HF.124 Studies performed in specialist clinics found controversial results. In a study of 123 patients with a chief complaint of breathlessness of unknown cause present for >8 weeks referred to a university pulmonary practice, 6% received a final diagnosis of heart failure/ cardiomyopathy (includes diastolic dysfunction, systolic dysfunction, and ischemic heart disease).125 In a similar study performed in a sample of 284 consecutive patients referred from general practice to hospital with breathlessness, heart failure was found to be the final diagnosis in 27% of them, a much higher proportion.126

Finally, a study realized in an Emergency Department in the US hospital reported that 26% of 162 patients who gave breathlessness as primary complaint for visiting the ED was then diagnosed with HF.127

It is worth mentioning also a couple of studies about cardiac diagnoses in general which have been found associated with breathlessness. The first one is the study by Jolly on 50 primary care patients newly presenting with breathlessness which found that cardiovascular disorders was found in 16.7% of males and 31.3% of females.128 The second study aimed at testing a diagnostic algorithm for evaluating breathlessness in 152 elderly patients recruited from general practice and 21% of them were diagnosed with heart disease.

The prevalence rates collected from published studies allow thus to estimate that in an English CCG we would expect about 5,800 patients suffering from CF, half of them above the age of 65. Of the HF patients, about 3,750 would complain of some level of breathlessness (almost 2,100 in the older age group). The number of patients presenting with breathlessness and in whom HF would be found as the cause of their symptom would be about 3,400.

Table 3 – Estimate of the burden of disease of breathlessness associated with HF in a CCG

No. patients per CCG Prevalence rates Baseline

population MIN MAX AVG MIN MAX AVG Median CCG population 251,700 Median CCG population (total adult) 172,730

Median CCG population - adult 18-65 135,454

Median CCG population – elderly 65+ 35,411

Prevalence of HF - adult 18- 65 1,354 2,709 2,031 1% 2% 1.5%

124 Charles J, Ng A, Britt H. Presentations of shortness of breath in Australian general practice. Australian family physician. 2005;34(7):520–1. 125 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011;105(7):1014–21. 126 Nielsen LS, Svanegaard J, Wiggers P, Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. J Intern Med. Nov 2001;250(5):422-8. 127 Fedullo AJ, Swinburne AJ, McGuire-Dunn C. Complaints of breathlessness in the emergency department. The experience at a community hospital. N Y State J Med. 1986 Jan;86(1):4-6. 128 Jolly DT. Dyspnea In Primary Care. Can Fam Physician. 1978 October; 24:983-984.

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Prevalence of HF - elderly 65+ 2,125 3,541 2,833 6% 10% 8%

HF cases – total 3,479 6,250 4,865 QOF diagnosed prevalence for HF 1,209 0.7%

Breathless patients in the general population 15,373 19,173 17,273 9% 11% 10%

Breathless patients diagnosed with HF 2,798 3,489 3,144 18.2%

HF patients complaining of breathlessness - adult 18- 65

772 1,544 1,158 57% 57% 57%

HF patients complaining of breathlessness - elderly 65+ 1,147 3,293 2,082 54% 93% 74%

HF patients complaining of breathlessness – total 1,919 4,837 3,240

Similarly, we can estimate that a GP with a patient list of 1,140 adult patients would have 32 patients with HF in total [23-41] and the majority of them will be elderly. More than 70% of them would complain of breathlessness, and again the elderly will be the most affected by it. This GP would see in total 114 patients complaining of breathlessness [101-127] and in 21 [13-32] of them HF will be found as the underlying cause for their breathlessness.

Table 4 – Estimate of the burden of disease of breathlessness associated with HF at the GP level

No. patients per GP Prevalence rates Population

baseline MIN MAX AVG MIN MAX AVG

Average patients list per GP in England (adult only) 1,140

Average GP population - adult 20-65 912 80%

Average GP population – elderly 65+ 228 20%

Prevalence of HF - adult 20-65 9 18 14 1% 2% 2% Prevalence of HF - elderly 65 + 14 23 18 6% 10% 8% Cases of HF – total 23 41 32 QOF diagnosed prevalence for HF 8 1%

Breathless patients in the general population 101 127 114 9% 11% 10%

Breathless patients diagnosed with HF 18 23 21 18%

HF patients complaining of breathlessness - adult 15- 65 5 10 8 57% 57% 57%

HF patients complaining of breathlessness - elderly 65 + 7 21 13 54% 93% 74%

HF patients complaining of breathlessness – total 13 32 21

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COPD Chronic obstructive pulmonary disease (COPD) is an umbrella term for chronic lung diseases. It is now the preferred term for the conditions in patients with airflow obstruction who were previously diagnosed as having chronic bronchitis or emphysema.

COPD is characterised by airflow obstruction that is not fully reversible. The airflow obstruction does not change markedly over several months and is usually progressive in the long term. COPD is predominantly caused by smoking. Other factors, particularly occupational exposures, may also contribute to the development of COPD. Smoking or inhaled dust leads to blockage or narrowing of the airways. COPD symptoms include breathlessness and a chronic cough. As the disease progresses over time, patients experience poorer lung health, worse breathlessness and more frequent exacerbations of their condition, where there is a rapid and sustained worsening of symptoms beyond normal day-to-day variations.129 This often leads to emergency hospital admissions.130

COPD produces symptoms, which may respond to pharmacological and other therapies (eg pulmonary rehabilitation) that have limited or no impact on the airflow obstruction.

COPD is increasingly recognised as an important long-term lung condition with a high burden for patients in terms of disability and impaired quality of life and a large cost to the healthcare systems.131

The complexity of the disease calls for a multidimensional assessment: several aspects of the clinical presentation of the disease, such as symptom perception, limitation in physical activity, lung function, and exacerbations, interrelate to configure the final disease expression.132 There is no single diagnostic test for COPD. Making a diagnosis relies on clinical judgement based on a combination of history, physical examination and confirmation of the presence of airflow obstruction using spirometry.133 Spirometry is required to diagnose COPD patients according to international guidelines.

The working definition of COPD, as noted in the 2013 update of the Global Initiative for Obstructive Lung Disease (GOLD) guidelines, goes as follows “COPD is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients”.134

This classification, which has been used in many studies and publications on COPD in the last year, has been now updated with a new classification system (A-D) based on symptoms, airflow obstruction, and exacerbation history. Symptom burden is measured by either the modified Medical Research Council questionnaire (mMRC) or the COPD 129 NICE. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update). 2010. London: NICE: Available from http://publications.nice.org.uk/chronic-obstructive-pulmonary-disease-cg101/working-definition-of-copd 130 http://www.hta.ac.uk/project/2569.asp accessed on 24th September 2013 131 http://www.hta.ac.uk/project/2569.asp accessed on 24th September 2013 132 Lopez-Campos JL, Calero C, Quintana-Gallego E. Symptom variability in COPD: a narrative review. Int J Chron Obstruct Pulmon Dis. 2013;8:231-8. 133 NICE. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update). 2010. London: NICE: Available from http://publications.nice.org.uk/chronic-obstructive-pulmonary-disease-cg101/working-definition-of-copd 134 The Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Available from: http://www.goldcopd.org/

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assessment test (CAT). The assessment starts with categorization by symptom burden, and then is refined by “risk” evaluation using FEV1 and/or exacerbation history. Patients can be categorized in to the higher risk groups (C and D) by either low FEV1 or frequent exacerbations, or both.

This approach reflects the complexity of COPD better than the unidimensional analysis of airflow limitation assessed with spirometry previously used for staging the disease.

Despite the importance of this disease, the general perception is that the prevalence of COPD is not well measured. Potential sources of inter-study variation that could affect reported prevalence estimates have been identified.135

It is currently estimated that in the UK over 3 million people have the disease and that an estimated 2 million have undiagnosed COPD (“the missing millions”) and data available seem to show that the problem in England, analyzed in this paragraph, is even more serious.

The study by Shahab and colleagues found out that spirometry-defined COPD was present in 13.3% of 8,200 adults over the age of 35 who participated in the Health Survey for England. Over 80% of them reported no respiratory diagnosis. Even among people with severe or very severe COPD by spirometric assessment, only 46.8% reported any diagnosed respiratory disease.136

According to the Quality Outcome Framework (QOF) statistical bulletin approximately 939,000 out of 55 million people in England have been diagnosed with COPD in 2011-12, for a diagnosed prevalence of 1.7%.137 In 2004/2005 there were 717,000 patients diagnosed with COPD, and prevalence was about 1.4%.138

Approximately 1 person in 59 has received a diagnosis of COPD at some point in their lives. In the most socio-economically deprived quintile, 1 in 32 patients was diagnosed with COPD, compared with 1 in 98 patients in the most affluent quintile. Most deprived patients represent about the 30% of the COPD patients, whereas the most affluent ones are about the 15%.139

According to the NHS Atlas of Variation, respiratory disease is the third leading cause of death in England after circulatory disease and cancer. In England, around 23,000 people die from COPD each year. Acute exacerbation of COPD is itself a high-mortality condition: 1 in 12 patients will die during an emergency admission; 1 in 6 will die within 3 months.140 COPD is the second most common reason for emergency admission to hospital, accounting for 1 in 8 non-elective admissions. Local audit data suggests that a third of patients admitted for the first time with acute exacerbations of COPD have

135 Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic review and meta-analysis. Eur Respir J. 2006 Sep;28(3):523-32. 136 Shahab L, Jarvis MJ, Britton J, West R. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006;61:1043-1047. 137 The Health and Social Care Information Centre, Prescribing Support Unit, http://www.hscic.gov.uk/catalogue/PUB08661 accessed on 10th September 2013 138 The Health and Social Care Information Centre, Prescribing Support Unit, http://www.hscic.gov.uk/catalogue/PUB05951 accessed on 10th September 2013 139 Simpson CR, Hippisley-Cox J, Sheikh A. Trends in the epidemiology of chronic obstructive pulmonary disease in England: a national study of 51 804 patients. Br J Gen Pract. 2010 Jul;60(576):277-84. 140 RightCare. Atlas of Variation in Healthcare for People with Respiratory Disease. 2012. Available from http://www.rightcare.nhs.uk/index.php/atlas/respiratorydisease/

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severe disease and have had no prior diagnosis.141 Re-admissions are a substantial problem in the treatment of patients with COPD. Of all emergency re-admissions to hospital, COPD is the fifth most common cause. At any one time, around one-third of all people admitted as an emergency with COPD have been treated in hospital for the same condition within the preceding 30 days.

Mortality from COPD in England shows a strong urban/rural gradient: lower mortality rates were seen in rural and mixed areas, while higher event ratios were seen in conurbations. The same analysis showed a north/south divide, with higher COPD rates seen in northern areas of England.142

Smoking accounts for approximately 80% of COPD cases and is the cause of 85% of all deaths from COPD143 COPD is an important co-morbidity in those dying from other smoking related diseases, most commonly ischaemic heart disease and lung cancer144 and yet smoking is rarely cited on death certificates, even in cases where the causal link with smoking is very strong.

Prevalence of current smokers among COPD-diagnosed patients has been found at 35% in the study realized by Shahab and colleagues. 29.5% of patients were diagnosed with mild COPD, 38.3% with moderate COPD and 40.5% with severe/very severe COPD. A similar rate of smoking was found in a group of 307 patients with COPD enrolled in a London-bases study (32.9%).145 Among the ever-smokers Shahab’s figures increase dramatically. 70.5% of the ever smokers received a diagnosis of COPD, of whom 60.4% of mild, 75.8% moderate and 83.5% severe/very severe COPD.146

Interestingly, more recent avenues of research have started bringing into question the myth that COPD is only for smokers and showed that the burden of COPD in non-smokers is much higher than supposed. It is now recognized that never smokers may account for between one-fourth and one-third of all COPD cases.147

The most common symptoms for COPD are breathlessness, chronic cough and chronic sputum production. COPD symptoms are often under-reported by patients148 149 150 151 141 Bastin AJ, Starling L, Ahmed R, et al. High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation. Chron Respir Dis 2010;7:91e7. 142 Hansell A, Hollowell J, McNiece R, Nichols T, Strachan D. Validity and interpretation of mortality, health service and survey data on COPD and asthma in England. Eur Respir J. 2003;21(2):279–286. 143 NICE. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update). 2010. London: NICE: Available from http://publications.nice.org.uk/chronic-obstructive-pulmonary-disease-cg101/working-definition-of-copd 144 Hansell AL, Walk JA, Soriano JB. What do chronic obstructive pulmonary disease patients die from? A multiple cause coding analysis. Eur Respir J. 2003; 22(5):809-814. 145 Donaldson GC, Goldring JJ, Wedzicha JA. Influence of season on exacerbation characteristics in patients with COPD. Chest. 2012 Jan;141(1):94-100. 146 Shahab L, Jarvis MJ, Britton J, West R. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006;61:1043-1047. 147 For a review of studies on COPD in nonsmokers, see Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009 Aug 29;374(9691):733-43. 148 Gysels M. The experience of breathlessness: the social course of chronic obstructive pulmonary disease. Journal of pain and symptom management. 2010;39(3):555. 149 Gysels M. Access to services for patients with chronic obstructive pulmonary disease: the invisibility of breathlessness. Journal of pain and symptom management. 2008;36(5):451. 150 Rennard S. Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. The European respiratory journal. 2002; 20(4):799.

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and not recognized by physicians, especially in the early stage of the disease.152 153 154 As a consequence, COPD is largely undiagnosed. Halbert et al. estimated that the ratio of true COPD cases to self-reported diagnoses ranged from approximately 1.5 to 4.155

In addition to problems of under-diagnosis, there might be also problems with misdiagnosis. A review of the diagnoses or suspected diagnoses of the patients referred for spirometry in primary care showed that more than half of the patients referred for asthma or COPD or both, had no evidence of airway obstruction on testing. In 6 of them with BMI of more than 30, obesity seemed to rather be the cause for their breathing problems.156

Breathlessness represents the most disabling symptom of COPD and its prevalence increases with the severity of COPD.157

A number of studies have been performed in order to estimate the prevalence of breathlessness among COPD patients. Comparability across studies is undermined by the heterogeneity of study populations included and criteria adopted for assessing breathlessness. A number of studies investigated the prevalence of breathlessness (any level) in patients with COPD, finding rates between 3.8 and 53%. Moderate or severe level of breathlessness have been reported in 7-61% of patients with any severity of COPD.

We retrieved a couple of studies investigating the prevalence of breathlessness in the outpatient setting. In the study by Viejo-Banuelos, out of almost 12,000 patients with a previous diagnosis of COPD - confirmed by history and spirometry – 54% of patients presented with breathlessness as reason for consultation.158 Another study performed in the US, including patients at least 60 years old with a primary diagnosis of COPD or HF, found that 74 out of a total sample of 133 COPD patients reported shortness of breath.159

In a US-based study of emergency visits for cardiorespiratory disease found that 78.2% out of 239 COPD patients reported breathlessness as main presenting symptom for the

151 Britton M. The burden of COPD in the U.K.: results from the Confronting COPD survey. Respir Med. 2003 Mar;97 Suppl C:S71-9. 152 Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance—United States, 1971–2000. MMWR Surveill Summ. 2002;51:1–16. 153 Rabe K. Outcome measures in COPD. Primary care respiratory journal. 2004;13(4):177. 154 Britton M. The burden of COPD in the U.K.: results from the Confronting COPD survey. Respir Med. 2003 Mar;97 Suppl C:S71-9. 155 Halbert RJ, Isonaka S, George D, Iqbal A. Interpreting COPD Prevalence Estimates: What Is the True Burden of Disease?. Chest. 2003;123(5):1684-1692. 156 Wolfenden H, Bailey L, Murphy K, Partridge MR. Use of an open access spirometry service by general practitioners. Prim Care Respir J. 2006 Aug;15(4):252-5. 157 Steuten LM, Creutzberg EC, Vrijhoef HJ, Wouters EF.COPD as a multicomponent disease: inventory of dyspnoea, underweight, obesity and fat free mass depletion in primary care, Prim Care Respir J. 2006 Apr;15(2):84-91. 158 Viejo-Bañuelos JL, Pueyo-Bastida A, Fueyo-Rodríguez A. Characteristics of outpatients with COPD in daily practice: The E4 Spanish project. Respir Med. 2006 Dec;100(12):2137-43. 159 Walke LM, Byers AL, Tinetti ME, Dubin JA, McCorkle R, Fried TR. Range and severity of symptoms over time among older adults with chronic obstructive pulmonary disease and heart failure. Arch Intern Med. 2007 Dec 10;167(22):2503-8.

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ED visit. Among patients with COPD, breathless patients were nearly twice as likely to be admitted as those who were not.160

The prevalence of breathlessness caused by COPD has been reported in a few studies performed both in primary, in secondary care and in ED. Results showed some degree of variation, depending on the characteristics of the populations studied: high rates were found in primary care (19-36%) and lower rates in secondary care (9-14%) and ED (14-17%).

In a study aiming at understanding the patient-perceived causes of breathlessness, people in the community reporting being breathless were directly asked to what they attributed the cause of their breathlessness. 64% of the sample (more than 4,000 Australians) self-reported that the daily experienced of this symptom for at least 3 months within the last 6 months was caused by COPD.161

According to the data collected through the BEACH program, a continuous national study of general practice activity in Australia, among the 602,100 encounters recorded from April 1998 to March 2004, there were 5215 at which the patient gave shortness of breath as one of their reasons for encounter (RFE), therefore presenting at a rate of 0.9 per 100 encounters. Of these, 19.2% received a diagnosis of COPD.162

It is worth mentioning also the study by Jolly on 50 primary care patients newly presenting with breathlessness which found that respiratory disorders (not specifically COPD) was found in 39% of males and 35% of females (aggregated 36%).163

A couple of study realized in specialist clinics reported prevalence rates in the range of 9-14%. In order to test diagnostic approach based on objective confirmation of suspected diagnoses, Pratter et al. prospectively studied 85 patients with a primary complaint of breathlessness seen in a pulmonary subspecialty clinic and found that 14% of the study sample was diagnosed with COPD.164

In another study, Pratter analysed data from a group of 123 patients with a chief complaint of breathlessness of unknown cause present for >8 weeks referred to a university pulmonary practice. Patients underwent an algorithmic approach to breathlessness which was treated at any time that data supported a treatable diagnosis. Whenever possible, accuracy of diagnosis was confirmed with an improvement in breathlessness after therapy. 9% of patients enrolled received a final diagnosis of COPD.165

Similar rates have been found in a study realized in an Emergency Department in the US: 14% of 162 patients who gave breathlessness as primary complaint for visiting the ED were diagnosed with COPD.166 A similar study which found 21% of emergency 160 Parshall MB. Adult emergency visits for chronic cardiorespiratory disease: does dyspnea matter?, Nurs Res. 1999 Mar-Apr;48(2):62-70. 161 Johnson MJ, Bowden JA ; Abernethy AP, Currow DC. To what causes do people attribute their chronic breathlessness? A population survey. Journal of palliative medicine. 2012;15(7):744. 162 Charles J, Ng A, Britt H. Presentations of shortness of breath in Australian general practice. Australian family physician. 2006; 34(7): 520–1. 163 Jolly DT. Dyspnea In Primary Care. Can Fam Physician. 1978 October; 24:983-984. 164 Pratter MR. Cause and evaluation of chronic dyspnea in a pulmonary disease clinic. Archives of internal medicine. 1989;149(10): 2277. 165 Pratte MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011; 105(7): 1014–21. 166 Fedullo AJ, Swinburne AJ, McGuire-Dunn C. Complaints of breathlessness in the emergency department. The experience at a community hospital. New York state journal of medicine. 1986;86(1):4.

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admissions being related to breathlessness, reported that 17% of them then received a diagnosis of COPD.167

In light of the data collected in the review, we are be able to quantify the burden of COPD and breathlessness at the CCG level and for a GP.

At the CCG level168, a COPD prevalence rate of 13%, as reported by Shahab and colleagues169, would correspond to about 23,000 adults, and about a third of them (about 8,000, 4,400-12,000)) would report some level of breathlessness. Assuming that 10% of the CCG population would complain of breathlessness (about 17,300 patients, 15,400-19,000), we can estimate that in 19% of them (about 3,500) their breathlessness may be caused by COPD.

Table 5 – Estimate of the burden of disease of breathlessness associated with COPD at the CCG level

No. patients per CCG Prevalence rates     Population baseline MIN MAX AVG MIN MAX AVG

Median CCG population (adult only) 172,730

Prevalence of spirometry-based COPD

2,973 13.3%

QOF diagnosed prevalence for COPD 2,936 1.7%

Prevalence of smokers in COPD patients 9,189 40%

Breathless patients in the general population 15,373 19,173 17,273 9% 11% 10%

Breathless patients diagnosed with COPD 3,316 19%

COPD patients complaining of breathlessness

4,360 12,176 7,848 19% 53% 34%

Scaling down these data at the level of a single GP, we estimate that s/he would see roughly 150 COPD patients per year, and a third of them (about 52, 29-80) would be breathless. Of the 115 patients (101-126) presenting with breathlessness, in 19 their breathlessness would be explained by COPD.

Table 6 – Estimate of the burden of disease of breathlessness associated with COPD at the GP level

No. patients per GP Prevalence rates Population baseline MIN MAX AVG MIN MAX AVG

167 Mustchin CP, Tiwari I. Diagnosing the breathless patient. Lancet. 1982 Apr 17;1(8277):907-8. 168 We used the median annual mid-year population estimates for Clinical Commissioning Groups, 2011 available at http://www.ons.gov.uk/ons/rel/sape/clinical-commissioning-group-population-estimates/mid-2011--census-based-/stb---clinical-commissioning-groups---mid-2011.html 169 Shahab L, Jarvis MJ, Britton J, West R. Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample. Thorax 2006;61:1043-1047.

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No. patients per GP Prevalence rates Population baseline MIN MAX AVG MIN MAX AVG

Average patients list per GP in England (adult over 20) 1,140

Prevalence of spirometry-based COPD 152 13.3%

QOF diagnosed prevalence for COPD 19 1.7%

Prevalence of smokers in COPD patients 61 40%

Breathless patients in the general population 101 126 114 9% 11% 10%

Breathless patients diagnosed with COPD 19 19%

COPD patients complaining of breathlessness 29 80 52 19% 53% 34%

Obesity Obesity has become major public health problem worldwide. The UK in particular has been defined the ‘fat man’ of Europe.170 Obesity, which is sometimes a lifelong condition which should be preventable, is increasing in prevalence in the UK such that approximately 25% of adults are obese. The rate of increase may be slowing but projections remain valid – namely that by 2050 the population of Britain will be mainly obese.171

According to the 2011 Health Survey for England (HSE) data analyzed by the National Obesity of Observatory around 62% of adults were overweight or obese (BMI ≥ 25). Men and women have a similar prevalence of obesity (25%), but men are more likely to be overweight (33% for women and 41 % for men). The adult prevalence of severe obesity (obesity III: BMI ≥ 40) is around 2.5%.172

According to the Quality Outcome Framework (QOF) statistical bulletin, in 2011-12 approximately 5 million out of 55 million people in England could be defined obese173, for a prevalence of 10.7%.174 In 2006/2007 there were almost 4 million obese patients, and the prevalence at that time was about 7.4%.175

Breathlessness on exertion is common in people with obesity. Nevertheless, there is no reference to breathlessness in the recent report by the Academy of Medical Royal Colleges “Measuring Up”, which aims to be “the medical profession's prescription for the 170 Academy of Medical Royal Colleges. Measuring Up The Medical Profession's Prescription For The Nation's Obesity Crisis; 2013. Available from http://www.aomrc.org.uk/publications/statements/doc_view/9673-measuring-up.html 171 Royal College of Physicians. Action on obesity: comprehensive care for all. Report of a working party. London: RCP; 2013. 172 National Obesity Observatory. NOO data factsheet. Adult Weight. February 2013. Available from http://www.noo.org.uk/uploads/doc/vid_17925_AdultWeightFactsheetFeb2013.pdf 173 i.e. they are aged 16 and over with a BMI greater than or equal to 30 in the previous 15 months 174 The Health and Social Care Information Centre, Prescribing Support Unit, http://www.hscic.gov.uk/catalogue/PUB08661 accessed on 16th September 2013 175 The Health and Social Care Information Centre, Prescribing Support Unit, http://www.hscic.gov.uk/catalogue/PUB05997 accessed on 16th September 2013

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nation's obesity crisis”.176 Similarly, the RCP’s Action on obesity report mentions breathlessness only marginally.177

Many overweight or obese people suffer from breathlessness that impairs their ability to be physically active, and stay or gain physical fitness.178 179 Quite a few patients are unable to exert sufficiently to feel breathless because of other musculoskeletal or mobility problems.

In a large epidemiological study, 80% of obese middle aged subjects reported shortness of breath after climbing two flights of stairs compared with only 16% of similarly aged non-obese controls, and this was despite smoking being significantly less frequent in the obese.180 The large population study conducted by Bowden et al. in Australia, among the adults who were classified as obese (1,063 out of a study sample of 5,331 participants), 18.1% experienced breathlessness compared to 8.7% of those who were not obese. Among adults aged 50 years and over, breathlessness was experienced by 22.2% of those who were obese, compared to 12.3% who were not obese.181 In another study of 23 obese but otherwise healthy men (with normal spirometry), two thirds reported breathlessness.182 According to Ho and colleagues183 among obese elderly subjects, it occurs in about 40% of them. In another large study of patients with non-insulin dependent diabetes, one third reported troublesome breathlessness and its severity increased with BMI.184

A relationship between obesity and asthma has been established in the literature: obesity has been associated with an increased risk of asthma and increased prevalence of physicians diagnosed and self-reported asthma has been observed in obese subjects185 186, mainly in women.187 Both asthma and obesity cause breathlessness and there is a risk of misdiagnosis of asthma in patients who are obese. Scott and

176 Academy of Medical Royal Colleges. Measuring Up The Medical Profession's Prescription For The Nation's Obesity Crisis; 2013. Available from http://www.aomrc.org.uk/publications/statements/doc_view/9673-measuring-up.html 177 Royal College of Physicians. Action on obesity: comprehensive care for all. Report of a working party. London: RCP; 2013. 178 Babb TG, Buskirk ER, Hodgson JL. Exercise end-expiratory lung volumes in lean and moderately obese women. Int J Obes; 1989:13(1):11–19. 179 Babb TG, Korzick D, Meador M, Hodgson JL, Buskirk ER. Ventilatory response of moderately obese women to submaximal exercise. Int J Obes. 1991;15(1):59–65. 180 Sjöström L, Larsson B, Backman L, Bengtsson C, Bouchard C, Dahlgren S, Hallgren P, Jonsson E, Karlsson J, Lapidus L, et al., Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state, Int J Obes Relat Metab Disord. 1992 Jun;16(6):465-79. 181 Bowden JA, To THM, Abernethy AP, Currow DC. Predictors of chronic breathlessness: a large population study. BMC Public Health. 2011;11:33. 182 Sahebjami H. Dyspnea in Obese Healthy Men. Chest. 1998;114(5):1373-1377. 183 Ho SF, O'Mahony MS, Steward JA, Breay P, Buchalter M, Burr ML. (2001) Dyspnoea and quality of life in older people at home. Age Ageing. 2001 Mar;30(2):155-9. 184 Bulpitt CJ, Palmer AJ, Battersby C, Fletcher AE.Association of symptoms of type 2 diabetic patients with severity of disease, obesity, and blood pressure. Diabetes Care. 1998 Jan;21(1):111-5. 185 Rönmark E, Andersson C, Nyström L, Forsberg B, Järvholm B, Lundbäck B. Obesity increases the risk of incident asthma among adults. Eur Respir J. 2005 Feb;25(2):282-8. 186 Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immunol. 2005 May;115(5):897-909. 187 Chen Y, Dales R, Tang M, Krewski D. Obesity may increase the incidence of asthma in women but not in men: longitudinal observations from the Canadian National Population Health Surveys. Am J Epidemiol. 2002 Feb 1;155(3):191-7.

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colleagues studied a group of subjects who were overweight with physician-diagnosed asthma and found that of 91 subjects (mean BMI, 38 kg/m2) 36.3% had a possible misclassification of asthma diagnosis.188 Similarly, in a study of 16,171 patients, subjects in the highest weight quintile had an odds ratio of 2.66 for breathlessness on exertion compared with the rest of the population, and they were more likely to report a diagnosis of asthma or to be on bronchodilators despite no evidence of obstruction on PFTs, thus raising the possibility that some obese people with breathlessness are misdiagnosed as having asthma.189 Obesity has a first diagnosis for breathlessness has been studies in different settings.

Obesity is a very common cause of breathlessness, and the study by Johnson and colleagues seems to confirm that obese patients are aware of and accept breathlessness as part of their condition.190

Remarking one of the main results of the study by Ho et al., Berner reinforces that obesity is the main contributory factor in breathlessness in the elderly.191 In fact, about 30% of the study population had been breathless, of whom 33% were obese. In another study of breathlessness in the elderly, 50 patients out of 210 reported breathlessness (Borg score > 0). Of them, 78% were categorized as overweight according to the Quetelet Index (QI=weight/height).192

In a study performed in primary care patients in order to document the relationship between obesity and breathlessness found that obesity was not significantly related to the presence of breathlessness in male or female presenting with new or persistent breathlessness. For males with continuing complaints of breathlessness, 46% were obese, and the same proportion of the controls was obese. Likewise, 55.6% of males newly presenting with breathlessness were obese, compared to the same proportion of controls. In women with persistent breathlessness, 55.6% of patients were obese, as were 42.2% of controls. For women with new cases of breathlessness 37.5% were obese compared to 56.3% of the controls.193

Prevalence rates of obesity in patient complaining of breathlessness vary between 4% in a group of 284 patients referred with breathlessness from their GPs to a breathlessness diagnostic clinic194 and 16% among a study group of 148 patients with a chief complaint of breathlessness of unknown cause present for more than 8 weeks.195 The same prevalence rate (16%) was found in a group of 152 patients aged 60-79, for whom

188 Scott S, Currie J, Albert P, Calverley P, Wilding JP. Risk of misdiagnosis, health-related quality of life, and BMI in patients who are overweight with doctor-diagnosed asthma. Chest. 2012 Mar;141(3):616-24. 189 Sin DD, Jones RL, Man SF. Obesity is a risk factor for dyspnea but not for airflow obstruction. Arch Intern Med. 2002 Jul 8;162(13):1477-81. 190 Johnson MJ, Bowden JA, Abernethy AP, Currow DC. To what causes do people attribute their chronic breathlessness? A population survey. J Palliat Med. 2012 Jul;15(7):744-50. 191 Berner Y.N. The contribution of obesity to dyspnoea in elderly people. Age Ageing. 2001 Nov;30(6):530. 192 Boezen HM, Rijcken B, Schouten JP, Postma DS. Breathlessness in elderly individuals is related to low lung function and reversibility of airway obstruction. Eur Respir J. 1998 Oct;12(4):805-10. 193 Jolly DT. Dyspnea In Primary Care. Can Fam Physician. 1978 October; 24:983-984. 194 Nielsen LS, Svanegaard J, Wiggers P, Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. Journal of Internal Medicine. 2001; 250(5),422-428. 195 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011; 105(7):1014-21.

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obesity appeared to be the only explanation of their breathlessness.196 A much lower proportion of patients with chronic unexplained breathlessness referred by their GPs to a pulmonary clinic was found in an American study. Out of 77 study participants, only two were found to have breathlessness in association with significant weight gain and lack of physical exercise.197

The data available help us understand the burden of breathlessness in obesity. At the CCG level, we would expect about 43,200 patients being obese. 18 to 80% of them (average about 50%) would complain of some level of breathlessness. Obesity would be found as the underlying cause of breathlessness in 1-16% (average 7%) breathless patients in the CCG population.

Table 7 – Estimate of the burden of disease of breathlessness associated with obesity in a CCG

No. patients per CCG Prevalence rates Population

baseline MIN MAX AVG MIN MAX AVG Median CCG population (adult only) 172,730

Prevalence of obesity 43,182 25% Breathless patients in the general population

15,373 19,173 17,273 9% 11% 10%

Breathless patients diagnosed with obesity

154 2,460 1,076 1% 16% 7%

Obese patients complaining of breathlessness

7,816 34,546 21,131 18.1% 80% 48.9%

A GP would have 285 obese patients on his list. Of them, 140 [52-228] would report also breathlessness. Among the breathless patients, about 114 [101-126], 7 [1-16] would have obesity as the reason for their breathlessness.

Table 8 – Estimate of the burden of disease of breathlessness associated with obesity at the GP level

No. patients per GP Prevalence rates Population

baseline MIN MAX AVG MIN MAX AVG Average patients list per GP in England (adult only)

1.140

Prevalence of obesity 285 25% Breathless patients in the general population

101 126 114 9% 11% 10%

Breathless patients diagnosed with obesity

1 16 7 1% 16% 7%

196 Pedersen F, Mehlsen J, Raymond I, Atar D, Skjoldborg US, Hildebrandt PR. Evaluation of dyspnoea in a sample of elderly subjects recruited from general practice. International journal of clinical practice. 2007;61(9):1481-91. 197 DePaso WJ, Winterbauer RH, Lusk JA, Dreis DF, Springmeyer SC. Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience. Chest. 1991 Nov;100(5):1293-9.

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No. patients per GP Prevalence rates Population

baseline MIN MAX AVG MIN MAX AVG Obese patients complaining of breathlessness

52 228 139 18.1% 80% 49%

Anxiety Anxiety is a feeling of unease, such as worry or fear, which can be mild or severe.198 It is considered an adaptive process until its magnitude or persistence renders it a dysfunctional response that can have negative consequences.199 It exists on a continuum from normal to pathologic and it is considered the generalized symptom of a myriad of abnormal and pathological fear and anxiety states, including generalised anxiety disorder (GAD), panic disorder (PD), agoraphobia, neurocirculatory asthenia, obsessive-compulsive disorder (OCD), and phobic disorders.200

The main diagnostic criteria for anxiety are (i) the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders published by the American Psychiatric Association (DSM-5) – also adopted by NICE guidelines on GAD and on anxiety disorders and depression – and (ii) the ICD-10 Classification of Mental and Behavioural Disorder published by the World Health Organization (WHO).

According to the DSM-5, people with generalized anxiety disorder (GAD) experience constant, chronic, and unsubstantiated worry, often about health, family, money, or work. This worrying goes on every day, possibly all day. It disrupts social activities and interferes with work, school, or family. Physical symptoms of GAD include the following:

• muscle tension

• fatigue

• restlessness

• difficulty sleeping

• irritability

• edginess

• gastrointestinal discomfort or diarrhoea

It requires two major symptoms (6 months or more of excessive anxiety and worry, occurring on more days than not, about a number of events and activities and difficulty controlling the worry) and two or additional symptoms.201

ICD-10 focuses more on somatic symptoms of anxiety, particularly autonomic reactivity and tension. For a diagnosis of GAD it requires 6 months or more prominent tension, worry and feelings of apprehension, and four from a list of 22 symptoms, of which at least one must be from a list of four autonomic symptoms (palpitations, sweating, trembling, dry mouth).

198http://www.nhs.uk/conditions/Anxiety/Pages/Introduction.aspx 199 Konstam V, Moser DK, De Jong MJ. Depression and anxiety in heart failure. J Card Fail. Aug 2005;11(6):455-63. 200 Usmani ZA, Carson KV,Heslop K, Esterman AJ, De Soyza A, Smith BJ. Psychological therapies for the treatment of anxiety disorders in chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2013. 201http://www.dsm5.org/Pages/RecentUpdates.aspx accessed on 9th October 2013

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A number of measures and instruments have been developed in order to measure the presence of symptoms and to calibrate the severity of general symptoms of anxiety. Some of them, such as the Generalised Anxiety Disorder Assessment, the State-trait Anxiety Inventory (STAI), the Beck Anxiety Inventory (BAI) and the Hospital Anxiety and Depression Inventory (HADS) are self-reported.

The Generalised Anxiety Disorder Assessment (GAD 7) is a self-administered patient questionnaire used as a screening tool and severity measure for anxiety. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of “not at all,” “several days,” “more than half the days,” and “nearly every day,” respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut off points for mild, moderate, and severe anxiety, respectively. When used as a screening tool, further evaluation is recommended when the score is 10 or greater.202

The State-Trait Anxiety Inventory (STAI) is used to measure the self-reported presence and severity of current symptoms of anxiety and a generalized propensity to be anxious. There are 2 subscales within this measure. First, the State Anxiety Scale (S-Anxiety) evaluates the current state of anxiety, asking how respondents feel “right now,” using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system. The Trait Anxiety Scale (T-Anxiety) evaluates relatively stable aspects of “anxiety proneness,” including general states of calmness, confidence, and security. Scores range from 20 to 80, with higher scores correlating with greater anxiety. A cut off score of 40 detects patients suspected of suffering from significant anxiety symptoms.

The Beck Anxiety Inventory (BAI) is a brief measure of anxiety with a focus on somatic symptoms of anxiety that was developed as a measure adept at discriminating between anxiety and depression. It includes assessment of symptoms such as nervousness, dizziness, inability to relax, etc. For each of the 21 items patients indicate how much they have been bothered by each symptom over the past week. The BAI has a maximum score of 63: scores between 16 and 25 indicates moderate anxiety, scores above 63 signal severe anxiety.

The Hospital Anxiety and Depression Scale (HADS) is commonly used to identify caseness (possible and probable) of anxiety disorders and depression among patients in medically ill patients in secondary care settings. It is divided into an Anxiety subscale (HADS-A) and a Depression subscale (HADS-D) both containing seven intermingled items. To prevent ‘noise’ from somatic disorders on the scores, all symptoms of anxiety or depression relating also to physical disorder, such as dizziness, headaches, insomnia, anergia and fatigue, were excluded.203 The HADS-A includes items that assess generalized anxiety such as tension, worry, fear, panic, difficulty in relaxing and restlessness.204 Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. According to Bjelland’s literature review, anxiety or depression are identified by a cut-off point of 8/21.

Latest estimates of the current global prevalence of anxiety disorders ranged between 0.9% and 28.3% and past-year prevalence between 2.4% and 29.8%. After adjusting for methodological differences across studies, the global current prevalence of anxiety

202 The GAD-7 originates from Spitzer RL, Kroenke K, Williams JB, et al; A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May;166(10):1092-7. 203 Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002 Feb;52(2):69-77. 204 Julian LJ. Measures of Anxiety. Arthritis Care & Research. 2011 November;63(S11):S467–S472.

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disorders was 7.3%, suggesting that one in 14 people around the world at any given time has an anxiety disorder and one in 9 (11.6%) will experience an anxiety disorder in a given year. Regional burden estimates ranged from 5.3% in African countries to 10.4% in Euro/Anglo cultures.205The results of the World Mental Health Surveys of the WHO confirm this same pattern.206

According to the most recent Adult Psychiatric Morbidity in England207 the estimated proportion of English people (including adults between 16 and 74 years of age living in private households) with GAD was 4.4%, a figure that has been almost constant across the last three surveys (1993, 2000, 2007).208 209

This figure is almost in line with the American rate (4.3%), but higher than rates reported from other European countries.

Anxiety is the most common anxiety disorder seen in primary care, and one of the most neglected.210 211 A number of studies have reported its under-detection or under-reporting by GPs.212 213 214 215 216 People with anxiety disorders are often frequent users of primary care resources, but if the anxiety component of their problem is not detected they may not receive the correct treatment and may undergo unnecessary and costly investigations, in particular for their physical symptoms.217

205 Baxter AJ, Scott KM, Vos T, Whiteford HA. Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychol Med. 2013 May;43(5):897-910. 206 Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel J, Ustün TB, Wang PS. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc. 2009 Jan-Mar;18(1):23-33. 207 The Adult Psychiatric Morbidity Survey is run every 7 years, the 2007 report is currently the most recent available. An alternative source of information is the IAPT Quarterly reports which provide information on activity in IAPT services – see http://www.hscic.gov.uk/pubs/iapt1314q1exp. However, the quality of the data available in this report remains low, as only 48.4% of records were valid in the July final data (http://www.hscic.gov.uk/searchcatalogue?productid=12554&q=Improving+Access+to+Psychological+Therapies&sort=Relevance&size=10&page=1#top ) 208 McManus S, Meltzer H, Brugha T, Bebbington P, Jenkins R. Adult Psychiatric Morbidity in England, 2007: results of a household survey London: National Centre for Social Research; 2009 209 Prevalence rates were as follows: 4.4% in 1993, 4.7% in 2000 and 4.7% in 2007. Estimates were based on those aged 16 to 64 and living in England. 210 Wittchen HU. Generalized anxiety disorder: Prevalence, burden, and cost to society. Depression and anxiety. 2002;16:162–171. 211Tylee A, Walters P. Under-recognition of anxiety and mood disorders in primary care: why does the problem exist and what can be done? J Clin Psychiatry. 2007;68(Suppl 2):27-30. 212Kroenke K, Spitzer RL, Williams JBW, Monahan PO, Lowe B. Anxiety Disorders in Primary Care: Prevalence, Impairment, Comorbidity, and Detection. Ann Int Med. 2007;146:317–325. 213 Grant BF, Goldstein RB, Chou SP, Huang B, Stinson FS, et al. Sociodemographic and psychopathologic predictors of first incidence of DSM IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Mol Psychiatry. 2009;14:1051–1066. 214 Wittchen HU, Kessler RC, Beesdo K, Krause P, Hofler M, et al. Generalized anxiety and depression in primary care: prevalence, recognition and management. J Clin Psychiatry. 2002;63(Suppl 8): 24–34. 215 Jameson JP, Blank MB. Diagnosis and treatment of depression and anxiety in Rural and Non-rural Primary Care: National Survey Results. Psychiatric Services. 2010;61:624–627. 216 King M, Nazareth I, Levy G, Walker C, Morris R, et al. Prevalence of common mental disorders in general practice attendees across Europe. Br J Psychiatry. 2008;192:362–367. 217 Hales RE, Hilty DA, Wise MG.A treatment algorithm for the management of anxiety in primary care practice. Journal of Clinical Psychiatry.1997;59(Suppl. 3):76–80.

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A study performed in a large sample of UK general practices found that incidence of GP recorded anxiety diagnosis fell from 7.9 to 4.9/1000 person years at risk from 1998 to 2008, thus conflicting the increasing prevalence rates reported in the Adult Psychiatric Morbidity Survey in England 2007. The reasons for this under-recording seem to be manifold. Patients may have symptoms of anxiety, worry, tension, irritability or tiredness, about which they feel reluctant to complain to their GP because they do not view these symptoms as being ‘medical’. Moreover, anxious patients tend not to report somatic symptoms (such as dizziness and breathlessness) which are seldom attributed to psychological causes, and the focus for clinical examination is kept on somatic conditions.218 GPs, on their side, may see these as symptoms of a more general malaise and not specifically consider or ask about anxiety as a possible cause.219 220 221 There may be also some issues about coding behaviour of physicians, reluctant to appropriately disclose or document anxiety.222

Anxiety has been studied also in particular population groups. Wolitzky-Taylor’s review found that prevalence estimates of anxiety disorders in late age (not strictly defined) range from 3.2% to 14.2%, whereas prevalence estimates for GAD more specifically range from 1.2% to 7.3%. Studies comparing different age groups generally find a decrease in prevalence with age.223

Anxiety and smoking are often interrelated problems. Data from the 2007 Adult Psychiatric Morbidity Survey for England showed that among the 23% of the population with any of the mental disorders covered by the survey, the smoking rate was 33%, higher than the rate for the English population (22%). Real rates of smoking rates among people with a mental disorder might be underestimated in the Adult Psychiatric Morbidity Survey, which surveyed people living in private households. Certain groups such as prisoners224 or homeless people225, among whom mental disorders are more prevalent, were not represented.

Patients with anxiety experience a high-degree of comorbidity, with 80-90% presenting at least one additional current psychiatric diagnosis226. Moreover, anxiety disorders are strongly and independently associated with chronic medical illness such as cardiovascular disorders, stroke, diabetes, hyperthyroidism, gastrointestinal disorders,

218 Marple RL, Kroenke K, Lucey CR, Wilder J, Lucas CA. Concerns and expectations on patients presenting with physical complaints: frequency, physician perceptions and actions, and two-week outcome. Arch Intern Med 1997;157:1482–8. 219 Arroll B, Kendrick T. Anxiety. In: Gask L, Lester H, Kendrick T, Peveler R, editors. Primary Care Mental Health. Glasgow: Bell and Bain Ltd; 2009. 220 Kim HFS, Braun U, Kunik ME. Anxiety and depression in medically ill older adults. Journal of Clinical Geropsychology 2001;7:117–30. 221 Kirmayer LJ, Robbins JM, Dworkind M, Yaffe MJ. Somatization and the recognition of depression and anxiety in primary care. Am J Psychiatry. 1993 May;150(5):734-41. 222 Walters K, Rait G, Griffin M, Buszewicz M, Nazareth I. Recent Trends in the Incidence of Anxiety Diagnoses and Symptoms in Primary Care. 2012; PLoS ONE 7(8): e41670. 223 Wolitzky-Taylor KB, Castriotta N, Lenze EJ, Stanley MA, Craske MG. Anxiety disorders in older adults: a comprehensive review. Depress Anxiety. 2010 Feb;27(2):190-211. 224 Singleton N, Meltzer H, Gatward R. Psychiatric morbidity among prisoners in England and Wales. London: The Stationery Office; 1998. 225 Gill B, Meltzer H, Hinds K, Petticrew M. OPCS Surveys of Psychiatric Morbidity in Great Britain, Report 7: Psychiatric morbidity among homeless people. London: HMSO; 1996. 226 Roy-Byrne PP, Davidson KW, Kessler RC, Asmundson GJ, Goodwin RD, Kubzansky L, Lydiard RB, Massie MJ, Katon W, Laden SK, Stein MB. Anxiety disorders and comorbid medical illness. Gen. Hosp. Psychiatry. 2008;30: 208–225.

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migraine headaches, thyroid disease, osteoarthritis.227 228 229 230 231 232 233 234 235 236 237 238 239

240 241 242 243 244 245

227 Härte MC. Associations between anxiety disorders and physical illness. European archives of psychiatry and clinical neuroscience. 2003; 253(6): 313. 228 Rogers MP, White K, Warshaw MG, Yonkers KA, Rodriguez-Villa F, Chang G, Keller MB. Prevalence of medical illness in patients with anxiety disorders. Int J Psychiatry Med. 1994;24(1):83-96. 229 Scott KM, Browne MAO, McGee MA, Wells JE. Mental–physical comorbidity in Te Rau Hinengaro: the New Zealand Mental Health Survey. Aust N Z J Psychiatry. 2006;40:882-888. 230 Teesson M. Affective and anxiety disorders and their relationship with chronic physical conditions in Australia: findings of the 2007 National Survey of Mental Health and Wellbeing. Australian and New Zealand journal of psychiatry. 2011;45(11):939. 231 Clarke DM, Currie KC. Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med J Aust. 2009;190(S7):54–60. 232 Kessler RC, McGonagle KA, Zhao S e t al . Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19. 233 Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:617–627. 234 Compton WM, Thomas YF, Stinson FS, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry. 2007;64:566–576. 235 Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64:830–842. 236 Gratzer D, Levitan RD, Sheldon T, Toneatto T, Rector NA, Goering P. Lifetime rates of alcoholism in adults with anxiety, depression, or co-morbid depression/anxiety: a community survey of Ontario. J Affect Disorder. 2004;79:209–215. 237 deGraaf R, Bijl RV, Smit F, Vollebergh WA, Spijker J. Risk factors for 12-month comorbidity of mood, anxiety, and substance use disorders: findings from the Netherlands Mental Health Survey and Incidence Study. Am J Psychiatry. 2002;159:620–629. 238 John U, Meyer C, Rumpf HJ, Hapke U. Smoking, nicotine dependence and psychiatric comorbidity: a population-based study including smoking cessation after three years. Drug Alcohol Depen. 2004;76:287–295. 239 Farrell M, Howes S, Bebbington P, Brugha T, Jenkins R, Lewis G, Marsden J, Taylor C, Meltzer H. Nicotine, alcohol and drug dependence and psychiatric comorbidity: results of a national household survey. Br J Psychiatry. 2001;179:432–437. 240 Wells JE, Browne MAO, Scott KM, McGee MA, Baxter J, Kokaua J. Te Rau Hinengaro: The New Zealand Mental Health Survey: overview of methods and findings. Aust N Z J Psychiatry. 2006;40:835–844. 241 Andrews G, Hall WD, Henderson S. Prevalence, comorbidity, disability and service utilisation: overview of the Australian National Mental Health Survey. Br J Psychiatry. 2001;178:145–153. 242 Teesson M, Hall WD, Lynskey M, Degenhardt L. Alcohol- and drug use disorders in Australia: implications of the National Survey of Mental Health and Wellbeing. Aust N Z J Psychiatry. 2000;34:206–213. 243 Sareen J, Jacobi F, Cox BJ, Belik SL, Clara I, Stein MB. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med. 2006 Oct 23;166(19):2109-16. 244 Fava GA, Porcelli P, Rafanelli C, Mangelli L, Grandi S. The spectrum of anxiety disorders in the medically ill. J Clin Psychiatry. 2010 Jul;71(7):910-4. 245 Chou SP, Huang B, Goldstein R, Grant BF. Temporal associations between physical illnesses and mental disorders--results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Compr Psychiatry. 2013 Aug;54(6):627-38.

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Such comorbidities are associated with poorer clinical outcomes, with higher morbidity, higher mortality, increased disability, higher healthcare utilization.246 Furthermore, the comorbidity between medical and psychiatric conditions poses difficulties for differential diagnosis, detection and treatment. In turn, many physical conditions can mimic the symptoms of anxiety, making it difficult to establish the underlying diagnosis.247

Costs to the health care system are also significant – by interacting with and exacerbating physical illness, co-morbid mental health problems raise total health care costs by at least 45 per cent for each person with a long-term condition and co-morbid mental health problem. It has been calculated that the presence of poor mental health increases the average cost of NHS service use by each person with a long-term condition from approximately £3,910 to £5,670 a year. This suggests that between 12 per cent and 18 per cent of all NHS expenditure on long-term conditions is linked to poor mental health and wellbeing.248

People with respiratory conditions experience increased levels of psychosocial morbidity, when compared with those associated with other chronic physical disease groups.249

Rates of anxiety disorders in patients with COPD, particularly generalized anxiety disorder (GAD) and panic disorder, are much higher than in the general public.250 A meta-analysis of 13 studies (900 patients) found that the prevalence of anxiety was 36%, significantly higher than those observed in the general population (4.4%).251

The recent meta-analysis conducted by Willgoss and colleagues found that the rates of clinical anxiety reported in 8 studies ranged from 10-55%. Four studies examined the prevalence of clinical anxiety in inpatient settings, which varied from 10-55%, whereas in the 4 studies that reported the prevalence of clinical anxiety in outpatient samples, prevalence ranged from 13-46%.252 A recent study comparing psychiatric comorbidity between hospitalized COPD patients and a hospitalized clinical control group without pulmonary dysfunction showed that 55% of patients with COPD received a diagnosis of a mental disorder compared to 30% of the control group.253

246 Teesson M. Affective and anxiety disorders and their relationship with chronic physical conditions in Australia: findings of the 2007 National Survey of Mental Health and Wellbeing. Australian and New Zealand journal of psychiatry. 2011;45(11):939. 247 Wolitzky-Taylor KB, Castriotta N, Lenze EJ, Stanley MA, Craske MG. Anxiety disorders in older adults: a comprehensive review. Depress Anxiety. 2010 Feb;27(2):190-211. 248 Naylor C, Galea A, Parsonage M, McDaid D, Knapp M, Fossey M. Long-term conditions and mental health. The cost of co-morbidities. London: The King’s Fund and Centre for Mental Health; February 2012. Available from http://www.kingsfund.org.uk/sites/files/kf/field/field_publication_file/long-term-conditions-mental-health-cost-comorbidities-naylor-feb12.pdf 249 Kim HFS, Braun U, Kunik ME. Anxiety and depression in medically ill older adults. Journal of Clinical Geropsychology. 2001;7:117–30. 250 Mikkelsen RL, Middelboe T, Pisinger C, Stage KB. Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). A review. Nord J Psychiatry. 2004;58(1):65-70. 251 Yohannes AM, Baldwin RC, Connolly MJ. Depression and anxiety in elderly patients with chronic obstructive pulmonary disease. AgeAging. 2006;35:457–9. 252 Willgoss TG, Yohannes AM. Anxiety disorders in patients with COPD: a systematic review. Respir Care. 2013 May;58(5):858-66. 253 Vogele C, von Leupoldt A. Mental disorders in chronic obstructive pulmonary disease. Respir Med 2008;102: 764–773.

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Similar results have been found in older age patients with COPD: between 18 and 50% of older age patients with COPD report significant symptoms of anxiety.254 255

Anxiety has also been found to be related to the disease characteristics of COPD, including breathlessness. Gift’s pilot study reported that COPD patients had greater anxiety during times of higher breathlessness levels.256 257

In their primary care based study of about 250 COPD patients assessed for their health status and perceived breathlessness, Falker and colleagues found that regardless of the severity of COPD, patients with COPD and comorbid depressive/anxiety disorder have worse perceived breathlessness and physical health-related quality of life than patients with COPD alone.258

Not only is anxiety highly common among COPD patients but the reverse is also true. The lifetime prevalence of respiratory disease is higher in people with panic disorder (47%) than with other psychiatric diagnoses.259

Anxiety appears to be a significant problem also among patients with cardiovascular disease (CVD). Findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) in the USA suggest that anxiety disorders, mood disorders, and CVD are highly comorbid in the community, and CVD was associated with increased likelihood of any anxiety disorder (OR=1.43).260

Yohannes and colleagues who reviewed the literature around HF and anxiety found that few studies have examined co-morbid anxiety in HF patients. In the 8 studies available they found that anxiety has been found in 11% to 45% of the HF patients studied.261

It is important also to mention the difficulty of differentiating between anxiety and cardiac disease. A number of studies have reported that 43% to 61% of patients with a negative cardiovascular diagnostic test receive in the end a diagnosis of anxiety.262

Research on the relationship between obesity and mental health has traditionally explored the first as a consequence of an underlying psychopathology. More recently

254 Yohannes A, Baldwin R, Connolly M. Depression and anxiety in elderly outpatients with chronic obstructive pulmonary disease: prevalence, and validation of the BASDEC screening questionnaire. Int J Geriatr Psychiatry. 2000;15:1090–1096. 255 Dowson C, Laing R, Barraclough R, Town I, Mulder R, Norris K, Drennan C. The use of the Hospital Anxiety and Depression Scale (HADS) in patients with chronic obstructive pulmonary disease: a pilot study. New Zeal Med J 2001;114:454–457. 256 Gift AG. Psychophysiologic aspects of dyspnea in chronic obstructive pulmonary disease: a pilot study. Heart & lung. 1990;19(3): 252. 257 Gift AG. Psychologic and physiologic factors related to dyspnea in subjects with chronic obstructive pulmonary disease. Heart & lung. 1986;15(6): 595 258 Felker B. Added burden of mental disorders on health status among patients with chronic obstructive pulmonary disease. Primary care companion to the Journal of clinical psychiatry. 2010;12(4). 259 Zandbergen J. Higher lifetime prevalence of respiratory diseases in panic disorder?.The American journal of psychiatry. 1991; 148(11): 1583. 260 Goodwin RD. Mental disorders and cardiovascular disease among adults in the United States. Journal of psychiatric research. 2009; 43(3): 239. 261 Yohannes AM, Willgoss TG, Baldwin RC, Connolly MJ. Depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease: prevalence, relevance, clinical implications and management principles. Int J Geriatr Psychiatry. 2010 Dec;25(12):1209-21. 262 Kim HFS, Braun U, Kunik ME. Anxiety and depression in medically ill older adults. Journal of Clinical Geropsychology. 2001; 7:117–30.

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work has investigated the causal relationship between body weight and psychological distress, which can influence also treatment outcome. A systematic review pointed to a weak but positive association between obesity and anxiety, (with a pooled odds ratio from published cross-sectional studies of 1.4). The work done by Baumeister and Härter showed that the prevalence rates of anxiety disorders significantly increased in the individuals who are overweight and obese. In their sample of 2,955 individuals the 12-month prevalence rates of anxiety were 17.2% in overweight patients, 20.4% in the obese and 26% in the obese rehabilitation patients groups, contrasting the lower rate (10.2%) among the healthy patients.

In a study group of 253 patients referred to two UK weight management specialist centres preliminarily assessed also for their psychiatric or psychological disorders, Tuthill and colleagues found that 56% exceeded the minimum criteria for an anxiety disorder (HADS >8). The likelihood of exceeding the cut-off points for probable or severe anxiety (HADS > 11 and HADS > 15, respectively) increased as BMI increased.263

A relation between asthma and anxiety appears to be established in the literature, not only for severe asthma patients but also for milder cases. In a cohort of patients with predominantly mild asthma, Gada and colleagues found a 43.5% increased risk of anxiety.264 In other studies, anxiety was found in ranges between 21% and 45% in asthmatic patients.265 266 267 268

Comorbid anaemia was found in 4.4% of men and 22.5% of women from a total of 169 patients diagnosed with anxiety.269

Patients who are anxious report more physical symptoms than do patients who are not.270 271 One hypothesis is that these patients experience specific distress related physical symptoms. This makes sense because mental disorders have specific physiological aspects, which are part of the definition. Anxiety disorders can be accompanied by autonomic arousal, e.g., palpitations and sweating, or breathlessness. The number of physical symptoms rather than the specific type of symptom is found to be predictive for depression or anxiety.272 273 274 275 276

263 Tuthill A, Slawik H, O'Rahilly S, Finer N. Psychiatric co-morbidities in patients attending specialist obesity services in the UK. QJM. 2006 May;99(5):317-25. 264 Gada E, Khan DA, DeFina LF, Sherwood Brown E. The relationship between asthma and self-reported anxiety in a predominantly healthy adult population. Annals of Allergy, Asthma & Immunology. 2013; in press. 265 Nascimento I, Nardi AE, Valença AM, Lopes FL, Mezzasalma MA, Nascentes R, Zin WA. Psychiatric disorders in asthmatic outpatients. Psychiatry Res. 2002;110:73–80. 266 Lavoie KL, Bacon SL, Barone S, Cartier A, Ditto B, Labrecque M.What is worse for asthma control and quality of life: depressive disorders, anxiety disorders, or both? Chest. 2006;130:1039–47. 267 Feldman JM, Siddique MI, Morales E, Kaminski B, Lu SE, Lehrer PM. Psychiatric disorders and asthma outcomes among high-risk inner-city patients. Psychosom Med. 2005;67:989–96. 268 Cooper CL. Anxiety and panic fear in adults with asthma: prevalence in primary care. BMC family practice. 2007; 8(1): 62. 269 Härter MC. Associations between anxiety disorders and physical illness. European archives of psychiatry and clinical neuroscience. 2003;253(6):313. 270 Kroenke K, Jackson JL, Chamberlin J. Depressive and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome. Am J Med. 1997;103(5):339– 47. 271 Chetta A, Foresi A, Marangio E, Olivieri D. Psychological implications of respiratory health and disease. Respiration. 2005 Mar-Apr;72(2):210-5. 272 Simon G, Gater R, Kisely S, Piccinelli M. Somatic symptoms of distress: an international primary care study. Psychosom Med. 1996;58(5):481–8.

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Research has usually focused on clinical predictors of anxiety disorders in patients presenting with physical complains, thus estimating the ORs of anxiety associated with breathlessness between 2.13 and 18.6.277 278 279 The study by Leivseth found also that having symptoms of anxiety increased the adjusted ORs for reporting breathlessness within ppFEV1 level or COPD stages.280

Data on the prevalence of breathlessness in patients with anxiety seems to be less available. The study by de Waal and colleagues reported the breakdown of prevalence rates for different symptoms experienced by 1,458 patients in general practice. Breathlessness was found in about 15% of the patients with mental distress, and the same rate was also found in patients with mental distress and a known somatic disease.281

Dales and colleagues studied the association between respiratory symptoms and psychological problems in a sample of 600 healthy subjects. A consistent trend toward higher respiratory symptom reporting by subjects with higher scores for psychopathology was present for all respiratory symptoms. In total, 42% of the patients with anxiety reported some sort of breathlessness that could be associated exclusively with their psychological status, given the sampling method adopted in the study which minimized possible confounding factors.282

Janson et al. found a clear association between psychological disturbances, such as anxiety and depression, and the report of respiratory symptoms in subjects with or without lung diseases, thereby confirming the previous results in healthy subjects.283

The HUNT study realized in Norway in 1995-1997 representing a large sample from the general population aimed at examined the association of lung function, anxiety symptoms and breathlessness in different situations. According to its results, 13.5% of women and 11.5% of men with anxiety (HADS 11-21) reported breathlessness when

273 Kroenke K, Jackson JL, Chamberlin J. Depressive and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome. Am J Med. 1997;103(5):339–47. 274 Kroenke K, Spitzer RL, Williams JB, Linzer M, Hahn SR, deGruy FV, et al. Physical symptoms in primary care. Predictors of psychiatric disorders and functional impairment. Arch Fam Med. 1994;3(9):774– 9. 275 Kisely S, Goldberg D, Simon G. A comparison between somatic symptoms with and without clear organic cause: results of an international study. Psychol Med. 1997;27(5):1011 – 9. 276 Van Boven K, Lucassen P, van Ravesteijn H, olde Hartman T, Bor H, van Weel-Baumgarten E, van Weel C. Do unexplained symptoms predict anxiety or depression? Ten-year data from a practice-based research network. Br J Gen Pract. 2011 Jun;61(587):e316-25. 277 de Waal MW, Arnold IA, Spinhoven P, Eekhof JA, van Hemert AM. The reporting of specific physical symptoms for mental distress in general practice. J Psychosom Res. 2005 Aug;59(2):89-95. 278 Van Boven K, Lucassen P, van Ravesteijn H, olde Hartman T, Bor H, van Weel-Baumgarten E, van Weel C. Do unexplained symptoms predict anxiety or depression? Ten-year data from a practice-based research network. Br J Gen Pract. 2011 Jun;61(587):e316-25. 279 Leivseth L, Nilsen TI, Mai XM, Johnsen R, Langhammer A. Lung function and anxiety in association with dyspnoea: the HUNT study. Respir Med. 2012 Aug;106(8):1148-57. 280 Leivseth L, Nilsen TI, Mai XM, Johnsen R, Langhammer A. Lung function and anxiety in association with dyspnoea: the HUNT study. Respir Med. 2012 Aug;106(8):1148-57. 281 de Waal MW, Arnold IA, Spinhoven P, Eekhof JA, van Hemert AM. The reporting of specific physical symptoms for mental distress in general practice. J Psychosom Res. 2005 Aug;59(2):89-95. 282 Dales RE, Spitzer WO, Schechter MT, Suissa S. The influence of psychological status on respiratory symptom reporting. Am Rev Respir Dis. 1989 Jun;139(6):1459-63. 283 Janson C, Björnsson E, Hetta J, Boman G. Anxiety and depression in relation to respiratory symptoms and asthma. Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):930-4.

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walking on flat ground, 6.5% of women and 4.6% of men with anxiety reported breathlessness when sitting still, and 8.9% of women and 8.5% with anxiety reported to be woken at night by breathlessness.284

In the general population, the number of adults presenting with breathlessness which is caused by anxiety has been estimated in the range of 0 and 16%, depending on the characteristics of the populations studied and the definition of anxiety adopted.

According to the data collected through the BEACH program, a continuous national study of general practice activity in Australia, among the 602,100 encounters recorded from April 1998 to March 2004, there were 5215 at which the patient gave shortness of breath as one of their reasons for encounter (RFE), therefore presenting at a rate of 0.9 per 100 encounters. Of these, 3.4% received a diagnosis of anxiety.285

In his 50 patients newly presenting with breathlessness in his practice, Jolly found a much higher rate. According to his results, 16% of the patients were found with psychological disorders possibly explaining their breathlessness.286

A couple of study realized in specialist clinics reported prevalence rates in the range of 5-10%. In order to test diagnostic approach based on objective confirmation of suspected diagnoses, Pratter et al. prospectively studied 85 patients with a primary complaint of breathlessness seen in a pulmonary subspecialty clinic and found psychogenic breathlessness in 5% of them.287

In Pratter et al. (2011), the study group consisted of 123 patients with a chief complaint of breathlessness of unknown cause present for >8 weeks referred to a university pulmonary practice. Patients underwent an algorithmic approach to breathlessness which was treated at any time that data supported a treatable diagnosis. Whenever possible, accuracy of diagnosis was confirmed with an improvement in breathlessness after therapy. For 10% of the patients enrolled breathlessness did not have a physiologic explanation, being therefore associated with a possible psychogenic cause.288

At the CCG level, a prevalence rate of anxiety of 4.4% for the adult population would correspond to 7,600 patients and of them, 680 to 1,200 patients (average 1,000) would complain of breathlessness. Assuming that 10% [9%-11%] of the CCG population would complain of breathlessness, about 17,200 patients [15,300-19,000], we can estimate that in 8.6% of them, about 1,300 [520-2,500] their breathlessness may be caused by anxiety.

284 Leivseth L, Nilsen TI, Mai XM, Johnsen R, Langhammer A. Lung function and anxiety in association with dyspnoea: the HUNT study. Respir Med. 2012 Aug;106(8):1148-57. 285 Charles J, Ng A, Britt H. Presentations of shortness of breath in Australian general practice. Australian family physician. 2005;34(7):520–1. 286 Jolly DT. Dyspnea in Primary Care. Can.Fam.Physician. 1978;24:983–988. 287 Pratter MR. Cause and evaluation of chronic dyspnea in a pulmonary disease clinic. Archives of internal medicine. 1989;149(10):2277. 288 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011;105(7):1014–21.

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Table 9 – Estimate of the burden of disease of breathlessness associated with anxiety at the CCG level

No. patients per CCG Prevalence rates

Population baseline MIN MAX AVG MIN MAX AVG

Median CCG population (adult only) 172,730

Prevalence of anxiety 7,600 4% Breathless patients in the general population 15,373 19,000 17,273 9% 11% 10%

Breathless patients diagnosed with anxiety 523 2,460 1,330 3% 16% 8.65%

Patients with anxiety complaining of breathlessness

678 1,216 1,011 9% 16% 13.31%

Scaling down these data at the level of a single GP, there would be 50 patients diagnosed with anxiety. Of them about 7 [4-8] would complain of breathlessness. Of the 114 patients presenting with breathlessness [range 91-125], in about 10 [3-20] their breathlessness would be caused by anxiety.

Table 10 – Estimate of the burden of disease of breathlessness associated with anxiety at the GP level No. patients per GP Prevalence rates

Population baseline MIN MAX AVG MIN MAX AVG

Average patients list per GP in England (adult only) 1,140

prevalence of anxiety 50 4.4% Breathless patients in the general population 91 125 114 8% 11%

10% Breathless patients diagnosed with anxiety 3 20 10 3% 16% 8.65%

Patients with anxiety complaining of breathlessness

4 8 7 9% 16% 13%

Anaemia Anaemia is defined as a state in which the quality and/or quantity of circulating red blood cells are below normal.289 Blood haemoglobin (Hb) concentration serves as the key indicator for anaemia because it can be measured directly, has an international standard, and is not influenced by differences in technology. According to the WHO, the diagnostic criteria for anaemia are Hb < 12 g/l for women and <130 g/l for men.290

289 National Clinical Guideline Centre. Anaemia management in people with chronic kidney disease (CG114). London: National Clinical Guideline Centre; 2011. Available from: http://guidance.nice.org.uk/CG114. 290 Goddard AF, James, MW, McIntyre, AS, Scott, BB. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60(10):1309-1316.

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Prevalence of anaemia in the general population (men and women 50 years or older) have been estimated at 2-5%. Higher rates are known for pregnant women (16%, 15.2% in the UK) and the elderly (men and women over 65) with data ranging from 3 to 26%.

Anaemia is often present in persons with a high burden of chronic disease without a clearly defined aetiology. Anaemia of Chronic Disease (ACD) occurs in patients with acute or chronic infection or inflammation, such as COPD, and it represents the systemic inflammatory response often occurring in some chronic conditions.

Anaemia has been reported in 23-40% of HF patients. Lower comorbidities have been found for COPD (8.8-23% of COPD patients also have anaemia) and asthma (10% of asthmatic have also anaemia). Almost half (45%) of cancer patients are also anaemic. Anaemia can be pretty common in patients with chronic renal insufficiency (with prevalence rates ranging between 27 and 72%).

According to the Third National Health and Nutrition Examination Survey (NHANES III) possible causes of anaemia are distributed as follows: one third of anaemia appeared related to a nutrient deficiency (within this group, half the anaemia is related to iron deficiency), approximately another third of older anaemic persons have anaemia of chronic and the remaining one third have unexplained anaemia.291

Prevalence rates of anaemia increase with comorbidity in the elderly. The Leiden 85-plus Study showed that anaemia was present in about 35% of patients with one diagnosed condition and in 46% of those with two or more diagnoses.292

When looking for evidence of the association between anaemia and breathlessness, we found very little. To our knowledge no study has been published on the prevalence of breathlessness in anaemic patients, whereas anaemia barely features in studies assessing the possible underlying causes of breathlessness.

In Pratter et al. (2011), the study group consisted of 123 patients with a chief complaint of breathlessness of unknown cause present for >8 weeks referred to a university pulmonary practice. Patients underwent an algorithmic approach to breathlessness which was treated at any time that data supported a treatable diagnosis. 3% of patients enrolled received a final diagnosis of anaemia (defined as a haemoglobin level below 10gm/dl).293 Severe anaemia was found in an a marginal proportion of patients (1%) also in a group of 284 patients with breathlessness of at least two-weeks duration referred from the GPs to an hospital-based breathlessness clinic.294

Running a model using the prevalence rates of anaemia in different population groups allows estimating that the number of anaemic patients in a CCG would range between 7,100 and 17,800 (average 11,600). We are not able to estimate how many of them would be breathless as we could not find the prevalence of breathlessness in anaemia. According to the data available we can quantify that the number of breathless patients in

291 Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004 Oct 15;104(8):2263-8. 292 den Elzen WP, Willems JM, Westendorp RG, de Craen AJ, Assendelft WJ, Gussekloo J. Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study. CMAJ. 2009 Aug 4;181(3-4):151-7. 293 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respiratory medicine. 2011;105(7):1014–21. 294 Nielsen LS, Svanegaard J, Wiggers P, Egeblad H. The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. J Intern Med. Nov 2001;250(5):422-8.

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whom the underlying cause of their breathlessness is anaemia is between 150 and 200 (average 170).

Table 11 – Estimate of the burden of disease of breathlessness associated with anaemia in a CCG

No. patients per CCG Prevalence rates Population baseline MIN MAX MIN MAX MIN MAX

Median CCG population (adult only) 172,730

Prevalence of anemia in the general population (men and women 50+)

1,733

4,332 3,032 2% 5% 3.5%

Prevalence of anaemia in non pregnant women 15-50

4,306

4,306 4,306 8.8%

Prevalence of anaemia in the elderly (men and women 65+)

1,062

9,207 4,249 3% 26% 12%

Cases of anaemia - total 7,101 17,845 11,588 Breathless patients in the general population

15,373 19,173 17,273 9% 11% 10%

Breathless patients receiving a diagnosis of anaemia

154 192 173 1% 3% 3%

Anaemic patients who complain of breathlessness

nk nk nk nk nk nk

Table 12 – Estimate of the burden of disease of breathlessness associated with anaemia at the GP level

No. patients per GP Prevalence rates Population

baseline MIN MAX AVG MIN MAX AVG Average patients list per GP in England (adult 20+) 1,140

Prevalence of anemia in the general population (men 20-65 and women 50-64)

12 29 20 2% 5% 3.5%

Prevalence of anaemia in women 20-49 27 8.8%

Prevalence of anaemia in the elderly men and women 65+ 7 64 30 3% 26% 12%

Anaemic patients total 46 121 77 Breathless patients in the general population 101 126 114 9% 11% 10%

Breathless patients receiving a diagnosis of anaemia 1 3 3 1% 3% 3%

Anaemic patients breathless nk nk nk nk nk nk

Similarly, we can estimate that a GP with a patient list of about 1,150 adults would have 50 to 120 anaemic patients (average 77): about 30 would be elderly, 27 would be women in their reproductive age and the rest would be men aged 20-65 and women in

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their middle age (50-65 year old). Due to the lack of date we cannot estimate how many of them will report also breathlessness.

According to the data available, of the 10% of the breathless patients in the GP list [101-126, average 114], 1% of them would have their breathlessness caused by anaemia [1-3].

Multimorbidity We have performed a review of the studies which investigated the prevalence of multi and comorbidity in breathlessness-related conditions. A synthetic analysis of the data collected is as difficult as ever because of the usual heterogeneity of methodologies.

Starting with studies on cohorts of HF patients, anxiety has been found to be in 3-45% of the study populations, asthma in 5-15.9%, obesity in 14.4% of men and 16.3% of women, COPD in 14.5-32.9%.

Studies investigating the occurrence of comorbidity in patients diagnosed with COPD reported prevalence rates in the following ranges: mental health problems in 8.6-28%, overweight in 6-33% and obesity in 4.3-54%, HF in 7-32% and anaemia in 5-10% of the study samples. In a particular study of the elderly, breathlessness was found in all the patients diagnosed with both COPD and HF.295 Only one study assessed the severity of breathlessness in COPD patients who were also overweight or obese. Among the overweight, 21.4% had mild, 55.1% moderate and 23.4% severe breathlessness. The obese patients showed greater prevalence of moderate and severe breathlessness: in fact only 9% reported a mild problem, whereas 57 and 34% were found with moderate and severe breathlessness respectively.296

Anxiety has been found in ranges between 16.8-56% in obese people. More agreement has been found in studies assessing the concomitant presence of obesity or overweight and asthma. Asthma has been found in 32-36.7% of the patients overweight and in 24-33% of the obese.

Studies looking at physical comorbidity in patients diagnosed with anxiety are more rare. Asthma has been found in 13% of patients with anxiety (but the reverse, namely anxiety in patients who already received a diagnosis of asthma was found in 5-45% of them), anaemia in in 4.4% of men and 22.5% of women, obesity in 17.3%. Great variability have been reported both for COPD (8.3-62%) and HF (2.6-70%) in patients with anxiety.

We conclude with studies assessing multiple causes of breathlessness. Unsurprisingly comparability across these studies is difficult, therefore we do not try to combine the data available but we only present them.

In the community-based study by Jolly on 50 patients over age 14 newly presenting with breathlessness, combined respiratory and cardiovascular disorders were found in 10% of the study sample, 11% of men and 9.4% of women.297

Another study testing a diagnostic algorithm for evaluating breathlessness in 152 elderly patients recruited from general practice investigated also the overlap between heart 295 Rutten FH, Cramer MJ, Grobbee DE, Sachs AP, Kirkels JH, Lammers JW, Hoes AW. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J. 2005 Sep;26(18):1887-94. 296 Cecere LM, Littman AJ, Slatore CG, Udris EM, Bryson CL, Boyko EJ, Pierson DJ, Au DH. Obesity and COPD: associated symptoms, health-related quality of life, and medication use. COPD. 2011 Aug;8(4):275-84. 297 Jolly DT. Dyspnea In Primary Care. Can Fam Physician. 1978 October; 24:983-984.

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disease, lung disease and obesity as possible causes of breathlessness. Seven patients (5%) were found to have both heart and lung disease, 9 of them (7%) had lung disease and were obese, 4 (3%) had obesity and concomitant heart disease. The simultaneous combination of obesity, lung disease and heart disease was not found in any patient included in the study population.298

The objective of the study by Pratter and colleagues was to prospectively evaluate an algorithmic approach to the cause(s) of chronic breathlessness in a group of 123 patients with a chief complaint of breathlessness of unknown cause present for >8 weeks. In this sample about 80% of the patients received a single diagnosis for their breathlessness and the rest had two diagnoses. Almost half the diagnoses were non–respiratory (31% non-cardiorespiratory diagnoses and 16% cardiovascular and circulatory diagnoses).299

To conclude The review we conducted allows trying to describe how the population of breathless patients may look like, both at the CCG and the GP level.

Table 13 – Estimate of the burden of breathlessness in a CCG

No. patients per CCG

MIN MAX AVG Total patients diagnosed with a breathlessness related conditions 84,336 74,878 67,235

Total patients diagnosed with a breathlessness related conditions and complaining of breathlessness 14,773 52,775 33,230

Of whom Anxiety diagnosed 5% 2% 3%

HF diagnosed 13% 9% 10% Obesity diagnosed 53% 65% 64% COPD diagnosed 30% 23% 24%

Anaemia diagnosed na na na Breathless patients in the general population 15,373 19,000 17,273 Total breathless patients 6,944 11,917 9,039

Of whom breathlessness caused by Anxiety 8% 21% 15%

HF 40% 29% 35% Obesity 2% 21% 12% COPD 48% 28% 37%

Anaemia 2% 2% 2% According to the data we collected, at the CCG level we would expect in total about 67,000 patients [84,300-74,900] diagnosed with a condition such as COPD; HF, anaemia or anxiety. Of them, about 33,000 [14,800-52,800] would complain of some 298 Pedersen F, Mehlsen J, Raymond I, Atar D, Skjoldborg US, Hildebrandt PR. Evaluation of dyspnoea in a sample of elderly subjects recruited from general practice. International journal of clinical practice. 2007;61(9):1481-91. 299 Pratter MR, Abouzgheib W, Akers S, Kass J, Bartter T. An algorithmic approach to chronic dyspnea. Respir Med. 2011 Jul;105(7):1014-21.

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level of breathlessness: the obese patients represent the biggest proportion of these patients (64%), followed by COPD patients (24%), HF patients (10%) and patients diagnosed with anxiety (3%).

Given the epidemiological evidence available, at the CCG level we would expect about 17,200 breathless adults [15,400-19,000]. Of them, 9,000 would receive a diagnosis of COPD, HF, obesity or anxiety. Patients whose breathlessness would be caused by either COPD or HF would account for about two thirds. Anxiety would be diagnosed in about 15% of the breathless cases. 12% would be breathless because of their obesity. Anaemia would represent only 2% of the breathless cases.

Similar consideration can be replicated for a GP. We would expect in total about 600 patients [560-650] diagnosed with a condition such as COPD; HF, anaemia or anxiety. Of them, about 220 [100-350] would complain of some level of breathlessness: the obese patients represent the biggest proportion of these patients (64%), followed by COPD patients (24%), HF patients (10%) and patients diagnosed with anxiety (3%).

Given the epidemiological evidence available, a GP would expect about 114 breathless adults [91-125]. Of them, 60 would receive a diagnosis of COPD, HF, obesity or anxiety. Patients whose breathlessness would be caused by either COPD or HF would account for about two thirds. Anxiety would be diagnosed in about 16% of the breathless cases. 12% would be breathless because of their obesity. Anaemia would represent 5% of the breathless cases.

Table 14 – Estimate of the burden of breathlessness for a GP No. patients per GP MIN MAX AVG

Total patients diagnosed with a breathlessness related conditions 556 649

596 Total patients diagnosed with a breathlessness related conditions and complaining of breathlessness 97 348 219

Of whom Anxiety diagnosed 5% 2% 3%

HF diagnosed 13% 9% 10% Obesity diagnosed 53% 66% 64% COPD diagnosed 30% 23% 24%

Anaemia diagnosed na na na Breathless patients in the general population 91 125 114 Total breathless patients 43 82 60

Of whom breathlessness caused by Anxiety 7% 25% 16%

HF 43% 28% 34% Obesity 2% 20% 12% COPD 45% 24% 32%

Anaemia 2% 4% 5% IMPRESS Breathlessness Working Party 2 January 2014 For a full list of participants see http://www.impressresp.com

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APPENDIX Relevant NICE Public health guidance as at December 2013i

PH1 Brief interventions and referral for smoking cessation (PH1)

PH2 Four commonly used methods to increase physical activity (PH2) (partially updated by PH41 and PH44)

PH5 Workplace interventions to promote smoking cessation (PH5) PH6 Behaviour change (PH6) PH8 Physical activity and the environment (PH8) PH9 Community engagement (PH9) PH10 Smoking cessation services (PH10) PH13 Promoting physical activity in the workplace (PH13) PH14 Preventing the uptake of smoking by children and young people (PH14) PH15 Identifying and supporting people most at risk of dying prematurely (PH15) PH16 Mental wellbeing and older people (PH16) PH17 Promoting physical activity for children and young people (PH17) PH21 Reducing differences in the uptake of immunisations (PH21) PH23 School-based interventions to prevent smoking (PH23) PH26 Quitting smoking in pregnancy and following childbirth (PH26) PH41 Walking and cycling (PH41) PH42 Obesity - working with local communities (PH42) PH44 Physical activity: brief advice for adults in primary care (PH44) PH45 Tobacco harm reduction (PH45) PH46 BMI and waist circumference - black, Asian and minority ethnic groups (PH46) PH48 Smoking cessation - acute, maternity and mental health services G43

Obesity: the prevention, identification, assessment and management of overweight and obesity in adults and children

i Our cut off was December 2013 but please note there is the useful NICE Public Health guidance PH49 Behaviour change: individual approaches published in January 2014.