Similarities and differences between asthma and asthma masqueraders

Similarities and Differences of Asthma and Asthma Masqueraders

BYDr.Sahar Farghaly

Assuit University

Assistant Lecturer of Chest Diseases

Not all who wheeze have Asthma

Educational aims:•Not all people who report respiratory symptoms have

asthma.•COUGH, WHEEZING (AND other respiratory noises), and dyspnea are

common respiratory symptoms that potentially have an extensive differential diagnosis.

•The diagnosis of asthma should be documented by variable lung function, airway hyperresponsiveness and inflammation

Outline Hallmarks of asthma Overview of differential diagnosis Distinguishing asthma from COPD Distinguishing asthma from VCD Distinguishing asthma from cardiac asthma Less common and uncommon

masqueraders

.A chronic inflammatory disorder of the airways

.Many cells and cellular elements play a role

.Chronic inflammation is associated with airway hyper responsiveness that leads to recurrent episodes of

• wheezing• breathlessness• chest tightness• and coughing particularly at night or in the early morning• Widespread, variable, and often reversible airflow obstruction

GINA 2012

Hallmarks of Asthma

WHEN IS IT NOT ASTHMA?The distinguishing characteristic of asthma:

•is the response to bronchodilator orcorticosteroids when the patient is symptomatic.

•For patients who are old enough to perform a pulmonary function test, substantial improvement of airway obstruction from an aerosol bronchodilator or a short course of reasonably high-dose systemic corticosteroid, 2mg/kg twice daily to a maximum of 40 mg twice daily

WEINBERGER, ABU-HASAN :Pesudo-asthma: W hen Cough, Wheezing, andDyspnea Are Not Asthma .PEDIATRICS Volume120, Number 4, October 2007

So, Failure to observe substantial improvement in:

•symptoms within 5 to 7 days of optimal medication and•Pulmonary function after a maximum of 10 days

Argues against asthma as the etiology,Provided that the patient has taken the medication.


MISDIAGNOSIS OF NON-ASTHMATIC CONDITIONS AS UNCONTROLLED ASTHMA HAS BEEN REPORTED TO BE AS HIGH AS 12–30%

So, the evaluation should start with:• Careful history with emphasis on asthma symptoms

including dyspnoea (and relation to exercise), cough,wheezing, chest tightness and nocturnal awakenings.

• In addition, information should be obtained onexacerbating triggers, environmental or occupational factors

and comorbidities that may be contributing.

• Children and adults should be evaluated for other conditions that may mimic or be associated with asthma

•1 )Rhinosinusitis/(adults) nasal polyps•2 )Psychological factors: personality trait, symptom perception,

anxiety, depression•3 )Vocal cord dysfunction

•4 )Obesity•5 )Smoking/smoking related disease

•6 )Obstructive sleep apnoea•7 )Hyperventilation syndrome

•8 )Hormonal influences: premenstrual, menarche, menopause, thyroid disorders

•9 )Gastro-oesophageal reflux disease (symptomatic)•10 )Drugs: aspirin, non-steroidal anti-inflammatory drugs (NSAIDs),b-

adrenergic blockers, angiotensinconverting enzyme inhibitors

Comorbidities and contributory factors OF sever asthma

ERS/ATS GUIDELINES ON SEVERE ASTHMA | K.F. CHUNG ET AL, 2014

Children1. Bronchiolitis2. Recurrent (micro)aspiration, reflux, swallowing

dysfunction3. Prematurity and related lung disease4. Cystic fibrosis5. Congenital or acquired immune deficiency6. Primary ciliary dyskinesia7. Tracheobronchomalacia

8. ERS/ATS GUIDELINES ON SEVERE ASTHMA | K.F. CHUNG ET AL, 2014

Diseases which can masquerade as severe asthma

9.Carcinoid or other tumour10.Mediastinal mass/enlarged lymph node11.Congenital heart disease12.Interstitial lung disease13.Connective tissue disease14.Central airways obstruction/compression15.Foreign body16.Congenital malformations including vascular ring17.habit-cough syndrome18.Exercise-induced supraventricular tachycardia19.Exercise-induced laryngomalacia


Adults1. Dysfunctional breathlessness/vocal cord

dysfunction(VCD)2. Chronic obstructive pulmonary disease(COPD)3. Hyperventilation with panic attacks4. Bronchiolitis obliterans5. Congestive heart failure6. Adverse drug reaction (e.g. angiotensin-converting

enzyme inhibitors)7. Bronchiectasis/cystic fibrosis8. Hypersensitivity pneumonitis


9.Hypereosinophilic syndromes10.Pulmonary embolus11.Herpetic tracheobronchitis12.Endobronchial lesion/foreign body (e.g. amyloid, carcinoid, tracheal

stricture)13.Allergic bronchopulmonary aspergillosis14.Acquired tracheobronchomalacia15.Churg–Strauss syndrome16. Pulmonary migraine(Pulmonary migraine consists of combined

recurrent asthma; cough with thick mucoid sputum; lower back pain radiating to the shoulder; subtotal or total atelectasis of a segment or lobe; focal headache, occasionally, nausea with vomiting)due to Spastic narrowing of the bronchi is postulated—along with retained mucous secretions, smooth muscle hypertrophy, and thickened bronchial walls . Cerebral and abdominal vascular migraine episodes are believed to accompany pulmonary migraine.{Tucker GF Jr. Pulmonary migraine. Ann Otol Rhinol Laryngol. Sep-Oct 1977;86(5 Pt 1):671-6}

17.Reactive airways dysfunction syndrome

VOCAL CORD DYSFUNCTION• Vocal cord dysfunction (VCD) is the intermittent, abnormal adduction

of the vocal cords during respirationresulting in variable upper airway obstruction. The variable airway

obstruction classically affects the inspiratory phase of respiration but the expiratory phase can be affected as well.

• VCD frequently co-exists with asthma and complicates effective care and management when not recognized as a separate entity(refractory asthma).

• The cord function is reversed in that the vocal folds Adduct on inspiration versus Abduct

• Leads to tightness or spasm in the larynx• Inspiratory wheeze evident

Normal Larynx

Two phenotypes of vocal cord dysfunction syndromehave been described:

• One type occurs spontaneously,with the patient experiencing dyspnea and inspiratorystridor (often described as “wheezing”) at various andoften unpredictable times. Whether this is a panic- oranxiety-induced reaction is speculative. • The other phenotype is a reaction that occurs only with

exercise,which is commonly seen in adolescent athletes duringcompetitive aerobic activities. Typically transient andrelieved spontaneously with a period of rest,

• FIGURE 5 Flow-volume loops obtained before and when symptomatic for 2 patterns of vocal corddysfunction syndrome. A, Preexercise flow-volume loop with the midinspiratory andmidexpiratory flows approximately equal and the postexercise loop exhibiting the typicalflattening of the inspiratory portion of the flow-volume loop in a 15-year-old girl withexercise-induced inspiratory stridor that had been described as “wheezing” by previousPhysicians.This indicates reversible upper airway obstruction that was thenconfirmed by visualizing adduction of the vocal cords on inspiration with flexible laryngoscopy. B, Flow-

volume loops from a 15-year-old girl with a history of repeated episodes of sudden-onset severe dyspnea. She had spontaneous onset of severe dyspnea

during our initial evaluation with marked compromise of both inspiration and expirationillustrated by the spirometric tracing. Flexible laryngoscopy demonstrated the vocalcords and false vocal cords to be severely adducted, leaving only an2-mm opening forair movement except when talking.

• The gold standard for the diagnosis of VCD is by directobservation of the vocal cords with videolaryngostroboscopy (VLS). The

variable nature of VCD can limit the diagnostic value of VLS and other direct observational approaches if symptoms are not present at the time of the study.

• Anterior portions of the vocal folds are ADDucted• Only a small area of opening at the Posterior aspect of the vocal folds• Diamond shaped ‘CHINK’• May be evident on both inhalationand exhalation

Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary Medicine2011(17:45–49)

Common symptomsof VCD

• intermittent shortness of breath• wheezing,• stridor, • or cough, which may be interpreted as• worsening asthma control given their nonspecific natureand can lead to unnecessary increases in asthma therapy.• Difficulty with inspiratory phase• Throat tightening > bronchial/ chest• Dysphonia during/following an attack• Abrupt onset and resolution• Little or NO response to medical treatment (inhalers,

bronchodilators)

.

Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary Medicine201117:45–49

The concept of a hyper-responsive larynx, similar to thehyper-responsive airway in asthma, has been the focus ofrecent studies and may help explain the high prevalenceof VCD seen in asthmatics. The larynx is highly innervated with sensory and motor

nerve fibers which are:thought to become hyperexcitable by intrinsic or extrinsic

stimuli resulting in hyperfunctional glottic movement,cough and other laryngeal sensations

Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary Medicine2011 17:45–49

DIAGNOSTIC FEATURES VCD AND ASTHMAVCD ASTHMA

FEV1/FVC

FEV1

Normal

Normal

Low

Low

Flow volume loop Flattening of the inspiratory limb

affection of the expiratory limb

Precipitators (triggers) Exercise, extreme temperatures Exercise, extreme temp. temperatur,.. irritants,,

emotional stressors ,allergens,

Number of triggers Usually one Usually multiple

Breathing obstruction Laryngeal area Chest area location

Timing of breathing Stridor on Wheezing on noises inspiration exhalation

VCD ASTHMA

Pattern of dyspneic event Sudden onset and relatively rapid cessation

More gradual onset , longer recovery period

Nocturnal awakeningwith symptoms

Rarely Almost always

Response to bronchodilators and/or systemiccorticosteroids

No response Good response

VCD managment

• Speech therapy The mainstays of treatment for vocal cord dysfunction (VCD) involve teaching the

patient vocal cord relaxation techniques and breathing exercises. These procedures have been very successful and are used concomitantly with psychological support in difficult cases

• Psychotherapy • The role of the psychiatrist is to implement cognitive behavior psychotherapy or

general psychotherapy based upon evaluation of psychiatric and/or personality disorders.

• Helium-oxygen therapy in the emergent treatment of acute VCD.• Anticholinergic agent

Inhaled ipratropium may be helpful treatment in patients with exercise-induced VCD

Benninger et al ,Vocal cord dysfunction and asthma: Current Opinion in Pulmonary Medicine201117:45–49

Deckert J, Deckert L. Vocal cord dysfunction. Am Fam Physician. Jan 15 2010;81(2):156-9

The similarity between asthma and COPD

• Asthma and chronic obstructive pulmonarydisease (COPD) are both characterized by airway obstruction, which is variable

and reversible in asthma but is progressive and largely irreversible in COPD

• In both diseases,-there is chronic inflammation of the respiratory tract, which is mediated by the

increased expression of multiple inflammatory proteins, including cytokines, chemokines, adhesionmolecules, inflammatory enzymes and receptors• In both diseases there are acute episodesor exacerbations, when the intensity of thisinflammation increases.

P.J. Barnes , Similarities and differences in Inflammatory Mechanisms of Asthma andCOPD :Breathe| March 2011| Volume 7| No 3

The differences between asthma and COPD

Despite the similarity of some clinical features of asthma and COPD,• there are marked differences in the pattern of inflammation that occurs in the

respiratory tract• different mediators produced, distinct consequences of inflammation and differing

responses to therapy. In addition, the inflammation seen in asthma is mainly located in the larger conducting

airways, although smallairways may also be involved in more severedisease

• P.J. Barnes , • Similarities and differences in Inflamatory Mechanisms of Asthma andCOPD :Breathe| March

2011| Volume 7| No 3

By contrast, COPD predominantlyaffects the small airways and lung

parenchyma, although similar inflammatory changes may also be found in larger airways

These differences in disease distribution maypartly reflect the distribution of inhaledinciting agents, such as allergens in asthmaand tobacco smoke in COPD

P.J. Barnes , Similarities and differences in Inflamatory Mechanisms of Asthma andCOPD :Breathe| March 2011| Volume 7| No 3

Comparison of Asthma and COPDClinical criteria ASTHMA COPD

Age of onset any age elderly smokers

Classic symptoms

Episodic wheezing, cough, dyspnea and chest tightness

dyspnea on exertion

Relation of sx to respiratory Cycle

exhalation > inhalation

exhalation > inhalation

Tilles SA, Nelson HS Current Review of asthma. Current Medicine, 2003

Comparison of Asthma and COPDcriteria ASTHMA COPD

Chest radiology Hyperinflation in acute attack

Hyperinflation and hyperlucency

PFTs reversible Obstruction

Increased volumes,

normal or increased DLCO

irreversible obstruction

Increased volumes ,

,decreased DLCO


Comparison of Asthma and COPDPathological criteria ASTHMA COPD

inflammatorycells

EosinophilsNeutrophils

Mast cellsCD4+ T cells

Th2

NeutrophilsMacrophages

Th2 ,CD8+ T cells

Structural changes

Airway sm muscle +++All airways

No Parenchymal change

Epithelial shedding

Fibrosis + (subepithelial)Mucous secretion +

Airway sm muscle+ Peripheral airways

Parenchymal destruction

Epithelial metaplasiaFibrosis ++

(peribronchiolar)Mucous secretion+++

Tzortzaki EG, et al J Allergy 2011; 2011:843543

Comparison of Asthma and COPDResponse to treatment ASTHMA COPD

Response to Corticosteroids

Response to bronchodilators

good

good modest

Poor

good modest


Figure 1 Inflammatory and immune cells involved in asthma


Figure 2Inflammatory and immune cells involved in chronic obstructive

pulmonarydisease (COPD)


Figure 3Contrasting histopathology of asthma and chronic obstructive pulmonarydisease (COPD). small airway from a patient who died from asthma and a similar sized airway from a patientwith severe COPD are shown. There is an infiltration with inflammatory cells in both diseases.The airway smooth muscle (ASM) layer is thickened in asthma but only to a minimal degree inCOPD. The basement membrane (BM) is thickened in asthma due to collagen deposition(subepithelial fibrosis) but not in COPD, whereas in COPD collagen is deposited mainly aroundthe airway (peribronchiolar fibrosis). The alveolar attachments are intact in asthma, butdisrupted in COPD as a result of emphysema. Images courtesy of J. Hogg (Vancouver, Canada).


Although the inflammatory and immunemechanisms of asthma and COPD describedabove are markedly different, there are severalsituations where they become more similar andthe distinction between asthma and COPDbecomes blurred as in table


Table Comparison between asthma and chronic obstructive pulmonary disease (COPD) inflammation patterns

The Asthma–Chronic Obstructive Pulmonary Disease Overlap

Syndrome• Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a commonly encountered yet loosely defined clinical entity. ACOS accounts for approximately 15–25% of the obstructive airway diseases and patients experience worse outcomes compared with asthma or COPD alone.Patients with ACOS have the • combined risk factors of smoking and atopy, are generally younger than patients with COPD and experience acute exacerbations with higher frequency and greater severity than lone COPDmajor criteria for ACOS: 1.A physician diagnosis of asthma and COPD in the same patient, history or evidence of atopy, for example, hay fever,

elevated total IgE

2.Age 40 years or more, smoking >10 pack-years,

3.postbronchodilator FEV1 <80% predicted and FEV1/FVC <70%. A ≥15% increase in • FEV1 ≥12% and ≥200 ml increase in FEV1 postbronchodilator treatment with albuterol would be a minor criteria.

Louie et al Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) Expert Rev Clin Pharmacol. 2013;6(2):197-219

Cardiac asthma as a common masquerader of asthma

• Congestive heart failure causes engorged pulmonary vessels and interstitial pulmonary edema, which reduce lung compliance and contribute to the sensation of dyspnea and wheezing. Cardiac asthma is characterized by wheezing secondary to bronchospasm in congestive heart failure, and it is related to paroxysmal nocturnal dyspnea and nocturnal coughing

Characterstic features:Dysnea on exertion,PNDRalesEarly night symptomsGallop rhythm and S3CXR and Echocardiography are diagnostic

Asthma Differential Diagnoses -emedicine.medscape.com/article/296301- differential

http://www.google.com.eg/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0CC0QFjAA&url=http://emedicine.medscape.com/article/296301-differential&ei=G6I1U6LeKoHUtQaz1IHADw&usg=AFQjCNGntOdRP3itXd25kiyMkEVQtODmBg&sig2=2a_rntXuNoXjJKeykblqVQ&bvm=bv.63808443,d.Yms

Less Common Asthma Masqueraders

• Tracheal and bronchial lesions (central airway obstruction)A variety of airway tumors are reported to manifest with symptoms similar

to those of asthma. These tumors include endobronchial carcinoid and mucoepidermoid tumors when causing partial airway obstruction

• Foreign bodies Foreign body aspiration may cause not only localized wheezing but also

generalized wheezing. Wheezing occurs in toddlers as well as in adults. As described in one patient, foreign body aspiration may necessitate bronchoscopic retrieval before the patient even recalls the inciting event, and as many as 25% of patients may never recall the event.




• Sinus disease Sinus disease and post nasal drip , especially in children,

is associated with bronchial asthma and wheezing.

• Gastroesophageal reflux Cough, recurrent bronchitis, pneumonia, wheezing, and

asthma are associated with gastroesophageal reflux (GER).The incidence of GER in patients with asthma ranges from 38% in patients with only asthma symptoms to 48% in patients with recurrent pneumonia Asthma Differential Diagnoses -

emedicine.medscape.com/article/296301- differential



• Other conditions and factors Other extrinsic conditions, such as lymphadenopathy

from Hodgkin lymphoma of the upper mediastinum, can contribute to asthma. In addition, aspirin or NSAID hypersensitivity and reactive airways dysfunction syndrome may be mistaken for asthma. Misdiagnoses as refractory bronchial asthma has resulted in inappropriate long-term treatment with corticosteroids.


http://emedicine.medscape.com/article/201886-overview


Less Common Asthma MasqueradersHabit-Cough Syndrome

Habit-cough syndrome is common in children It is a troublesome disorder thatcommonly is treated as asthma that often results in agreat deal of morbidity and ineffective treatment and yetis readily curable rapidly with suggestion therapy with a simple behavioral technique.

The classical presentation of habit-cough syndrome1. is that of a harsh, barking, repetitive cough that occurs several times per minute for

hours2. the complete absence of cough once the patientis asleep.3. a high incidence of abdominalpain and irritable bowel syndrome in many of the children with habit-cough syndrome,

In considering treatment and discussing the issue with the family, it is important not to refer to this as a psychogenic cough



Tracheomalacia• Malacia = “softness”Normal intrathoracic trachea dilates somewhat with inspiration and narrows with expiration

• Inadequate rigidity of the tracheal or main-stem bronchial cartilage results in tracheal collapse, which causes cough by at least 2 mechanisms

1. Collapse of the trachea or main-stembronchi during increased intrathoracic pressure as invigorous exhalation or coughing can cause the anteriorand posterior walls to come into contact, which results inan irritable focus that stimulates further cough. 2.In addition, when secretions are present in the airway, theairway collapse prevents normal airway clearance ofsecretions. The secretions then act as a continued stimulus for a nonproductive cough.

• Types:• Tracheomalacia - trachea• Bronchomalacia - one or both of the main-stem bronchi• Tracheobronchomalacia - both


Causes of tracheomalacia• Congenital disease: (also called primary): consequence of the

inadequate maturity of tracheobronchial cartilage – Polychondritis– Chondromalacia– Mucopolysaccharidoses: Hunter syndrome and Hurler syndrome– Idiopathic “giant trachea” or Mounier- Kuhn syndrome

– Acquired Tracheomalacia:• Posttraumatic

– Post-intubation– Post-tracheostomy

• Emphysema• Chronic infection/bronchitis• Chronic inflammation

– Relapsing polychondritis• Chronic external compression of the trachea

– Malignancy– Benign tumors– Cysts– Abscesses– Aortic aneurysm

• Vascular rings, previously undiagnosed in childhood



Unexplained extubation failure should prompt evaluation for tracheomalacia

Direct visualization by bronchoscopy is the gold standard to document a narrowing of at least 50% in the sagittal diameter in expiration– Mild : obstruction during expiration is to

one half of the lumen– Moderate : obstruction reaches three

quarters of the lumen– Severe : the posterior wall touches the

anterior wall

Nuutinen J. Acquired tracheobronchomalacia: a clinical study with bronchological correlations. Ann Clin Res 1977;9:350–355



FIGUREBronchomalacia of the right upper lobe (A) and the right main stem (B). Depending onthe degree of obstruction caused by the malacia, either cough or expiratory monophonicwheezing may be heard. Obstruction occurs on expiration with positive intrathoracicpressure during expiration while negative intrathoracic pressure during inspirationopens the airway. Complete airway obstruction during expiration can result in lobaremphysema from persistent hyperinflation of the lobe distal to the malacia. Decreasedclearing of secretions distal to the malacia may be associated with purulent bacterialbronchitis.

Other Rare Causes of Chronic Cough which masquerades asthma

There are some particularly unusual causes ofchronic cough that were misdiagnosed as asthma. Although unlikely to be encountered

frequently, awareness of these entities can encourage additional investigation when the pattern of symptoms and response to

treatment is not consistent with asthma. A uvula thatwas in contact with the epiglottis was cause of along standing .

FIGURETonsils (the lateral masses in the image) impinging on the epiglottis in a 3-year-old girlcaused chronic cough that initially was treated unsuccessfully as asthma. A tonsillectomycured her cough




• Reactive Airways Dysfunction Syndrome or RADS is a term proposed by Stuart M. Brooks M.D. and colleagues in 198. To describe an asthma-like syndrome developing after a single exposure to high levels of an irritating vapor, fume, or smoke. It involves coughing, wheezing, and dysnea.

• It can also manifest in adults with exposure to high levels of chlorine, ammonia, acetic acid or sulphur dioxide, creating symptoms like asthma.[6] The severity of these symptoms can be mild to fatal, and can even create long-term airway damage depending on the amount of exposure and the concentration of chlorine. Some experts classify RADS as occupational asthma. Those with exposure to highly irritating substances should receive treatment to mitigate harmful effects

Aslan et al 2008 . "The Effect of Nebulized NaHCO3 Treatment on 'RADS' Due to Chlorine Gas Inhalation" . Inhalation Toxicology: Vol. 18, Number 11

http://en.wikipedia.org/wiki/Stuart_M._Brooks_M.D.

http://en.wikipedia.org/wiki/Chlorine

http://en.wikipedia.org/wiki/Ammonia

http://en.wikipedia.org/wiki/Acetic_acid

http://en.wikipedia.org/wiki/Sulphur_dioxide

http://en.wikipedia.org/wiki/Sulphur_dioxide

http://en.wikipedia.org/wiki/Reactive_airway_disease

http://web.ebscohost.com/




Often, the term "reactive airway disease" is used when asthma is suspected, but not yet confirmed.

Reactive airway disease in children is a general term that doesn't indicate a specific diagnosis. It may be used to describe a history of coughing, wheezing or shortness of breath triggered by infection. These signs and symptoms may or may not be caused by asthma.

HOME MESSAGE• Not all people who report respiratory symptoms have asthma

• COUGH, WHEEZING (AND other respiratory noises), and dyspnea are common respiratory symptoms that potentially have an extensive

differential diagnosis.• The distinguishing characteristic of asthma : - is the response to bronchodilator orcorticosteroids when the patient is

symptomatic -Improvement of airway obstruction from an aerosol bronchodilator or a short course of systemic corticosteroid which is documented by PFTs.• Failure of response or substantial improvement Argues against asthma as the

etiology, Provided that the patient has taken the medication .

Leadership & Management

Similarities and differences between asthma and asthma masqueraders