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Effect of the Buteyko Method on Resting Ventilation
and Asthma Control in Asthma Patients
Monique van Oosten
Ritgerð til meistaragráðu Háskóli Íslands
Læknadeild Námsbraut í Lýðheilsuvísindum
Heilbrigðisvísindasvið
Áhrif Buteyko aðferðinnar á hvíldaröndun og stjórnun astmasjúkdómsins hjá astmasjúklingum
Monique van Oosten
Ritgerð til meistaragráðu í Lýðheilsuvísindum
Leiðbeinandi: Marta Guðjónsdóttir
Meistaranámsnefnd: Marta Guðjónsdóttir, Auðna Ágústsdóttir og Björn Magnússon
Læknadeild
Námsbraut í Lýðheilsuvísindum
Heilbrigðisvísindasvið Háskóla Íslands
Mars 2017
Effect of the Buteyko Method on Resting Ventilation and Asthma Control in Asthma Patients
Monique van Oosten
Thesis for the degree of Master of Science
Supervisor: Marta Guðjónsdóttir
Masters committee: Marta Guðjónsdóttir, Auðna Ágústsdóttir and Björn Magnússon
Faculty of Medicine
Department of Public Health
School of Health Sciences
March 2017
Ritgerð þessi er til meistaragráðu í lýðheilsufræði og er óheimilt að afrita ritgerðina á
nokkurn hátt nema með leyfi rétthafa.
© Monique van Oosten 2017
Prentun: Háskólaprent
Reykjavík, Ísland 2017
3
Ágrip
Bakgrunnur. Buteyko meðferðin (BM) virðist breyta öndun, bæta lífsgæði og astma stjórnun hjá astma
sjúklingum. Rannsóknir hafa fram að þessu ekki skilgreint nægilega vel lífeðlisfræðileg áhrif
meðferðarinnar.
Markmið þessarar rannsóknar er að skoða lífeðlisfræðileg áhrif BM á hvíldaröndun og stjórnun astma í
hóp astmasjúklinga.
Aðferð. Í þessari framskyggnu, íhlutandi rannsókn með samanburðarhópi voru astmasjúklingar mældir
þrisvar sinnum í algjörri hvíld, með 6 mánaða millibili. Þeir voru paraðir miðað við aldur, kyn og
líkamsþyngdarstuðul (BMI) við heilbrigðan samanburðahóp. BM var kennd eftir fyrstu 6 mánuðina. Síðan
var hópnum fylgt eftir og mældur að nýju 6 mánuðum síðar. Hvíldaröndun (öndunartíðni og andrýmd
(VT)), næmni öndunarstöðva metin út frá viljastýrðu öndunarstoppi, efnaskipti, og astma control
spurningalisti (ACT) voru skoðuð. Hlutfall milli heildaröndunar (V´E) og koltvísýringsútskilnaðar
(V´E/V´CO2) var reiknað út. Fráblástursgeta á einni sekúndu (FEV1) var mæld og reiknuð sem hlutfall af
hámarksandrýmd (FEV1/FVC).
Niðurstöður: 22 (61%) af þeim 36 astmasjúklingum sem hófu rannsóknina og 20 þátttakendur í
samanburðarhópi luku þátttöku. Í byrjum rannsóknarinnar voru hóparnir eins varðandi aldur, kyn og BMI,
en FEV1/FVC hlutfallið var lægra og viljastýrða öndunarstoppið styttra hjá astmahópnum (p<0.05). Eftir
BM hjá astmahópnum hafði hlutþrýstingur koltvísýrings við lok útöndunar (PETCO2), V´E/V´CO2, og stig
fyrir ACT aukist (p<0.05) og viljastýrða öndunarstoppið hafði lengst (p<0.001). Eins hafði hlutþrýstingur
súrefnis við lok útöndunar (PETO2), V´E, VT og efnaskipti minnkað en BMI hafði hækkað (p<0.05).
FEV1/FVC var óbreytt.
Umræða: Í upphafi var hvíldaröndun svipuð hjá hópunum en næmni öndunarstöðva var meiri hjá
astmahópnum. BM virðist minnka næmni öndunarstöðva þar sem viljastýrða öndunarstoppið verður
lengra. Hærra PETCO2 og lægra PETO2 bendir til að hlutfall milli alveolar öndunar (V´A) og V´CO2 (V´A/
V´CO2) hafi minnkað, þrátt fyrir hærra V´E/V´CO2. Því má álykta að lægra VT hafi aukið öndun í
dauðarýminu. BM bætir stjórnun á astma án þess að hafa breytt FEV1/FVC.
4
5
Abstract
Background: The Buteyko method (BM) seems to change breathing patterns, increase quality of life
and asthma control in asthmatics. Until now, studies have not been able to identify sufficiently the
physiological mechanism behind the BM.
The aim of this study is to evaluate the physiological effect of BM on resting ventilation and asthma
control in an asthma group.
Methods: In this prospective, intervention study, asthmatics were measured 3 times at complete rest,
at a 6-month interval. They were matched by age, gender, and body mass index (BMI) to control
subjects. The first 6-month interval was the control period. The BM was taught to the asthmatics after
the control period. Asthmatics were followed up and measured again after 6 months. Resting ventilation
(respiratory rate and tidal volume (VT)), respiratory chemosensitivity evaluated by breath holding time
(BHT) and metabolism were assessed, and the asthma control test questionnaire (ACT) was applied.
The equivalent of pulmonary ventilation (V´E) for carbon dioxide output (V´E/V´CO2) was calculated. The
forced expiratory volume in one second (FEV1) was measured and calculated as a percentage of the
forced vital capacity (FEV1/FVC).
Results: 22 (61%) of 36 asthmatics and 20 control subjects finished the study. At baseline, groups were
comparable regarding age, gender and BMI. In the asthma group, FEV1/FVC was lower and BHT was
shorter (p<0.05). After BM in the asthma group, partial pressure of end-tidal carbon dioxide (PETCO2),
V´E/V´CO2, BMI and scores for the ACT had increased (p<0.05) and BHT had become longer (p<0.001).
Partial pressure of end-tidal oxygen (PETO2), V´E, VT and metabolism had decreased (p<0.05). FEV1/FVC
remained the same.
Discussion: At baseline, resting ventilation was alike between the groups, but respiratory
chemosensitivity was higher in the asthma group as seen in shorter BHT. BM effected resting ventilation
by decreasing respiratory chemosensitivity for CO2 as evaluated by longer BHT. It could be concluded
that the equivalent of alveolar ventilation (V´A) for V´CO2 (V´A/V´CO2) had decreased, evidenced by
higher levels of PETCO2 and lower levels of PETO2. However, V´E/V´CO2 had increased, implying greater
dead space ventilation as a result of decreased VT. BM improved asthma control without altering
FEV1/FVC.
6
7
Acknowledgements
First of all, I would like to express my deepest gratitude to my supervisor, Marta Guðjónsdóttir for carrying
out this research project with me, and for all her guidance, support, encouragement, patience, and, most
of all, her excellent teaching.
I am very grateful to my master’s committee, Auðna Ágústsdóttir and Björn Magnússon, for
supporting me in this work and for sharing their expertise.
I am grateful to Reykjalundur for giving us the opportunity to perform our research in their laboratory.
Finally, I would like to thank all my family and friends for their mental support, and last, but not least,
my beloved daughter Katrín Möller, for her invaluable help.
This project was financially supported by the Asthma and Allergy Foundation, the Icelandic
Physiotherapy Society and the Oddur Ólafsson Foundation.
8
Table of contents
Ágrip ........................................................................................................................................................ 3
Abstract .................................................................................................................................................... 5
Acknowledgements.................................................................................................................................. 7
Table of contents ..................................................................................................................................... 8
List of Figures ........................................................................................................................................ 10
List of tables ........................................................................................................................................... 11
List of abbreviations ............................................................................................................................... 12
1 Introduction .................................................................................................................................... 14
1.1 What is asthma? .................................................................................................................... 14
Diagnosis ................................................................................................................... 14
Risk factors and allergies ........................................................................................... 15
1.2 Asthma control ....................................................................................................................... 15
Control-based asthma management ......................................................................... 16
Psychological factors. ................................................................................................ 17
Posture and physical condition .................................................................................. 17
1.3 Ventilation at rest ................................................................................................................... 18
The Respiratory system ............................................................................................. 18
Pulmonary ventilation ................................................................................................ 22
Alveolar ventilation ..................................................................................................... 22
Dead space ventilation .............................................................................................. 23
The bicarbonate buffer system .................................................................................. 24
Spirometry.................................................................................................................. 25
Ventilation musculature ............................................................................................. 25
Breathing control ........................................................................................................ 26
Chemosensors ........................................................................................................... 28
Physiological efficient and functional ventilation........................................................ 29
Metabolism................................................................................................................. 30
1.4 Asthma and resting ventilation .............................................................................................. 30
Asthma and breathing therapy................................................................................... 31
1.5 The Buteyko method .............................................................................................................. 32
Research on BM ........................................................................................................ 33
Breath holding and the Buteyko method ................................................................... 34
2 Aims and Objectives ...................................................................................................................... 36
3 Methods ......................................................................................................................................... 37
3.1 Participants ............................................................................................................................ 37
9
3.2 Protocol .................................................................................................................................. 38
Measures ................................................................................................................... 39
3.3 Procedure .............................................................................................................................. 40
3.4 Statistical analysis ................................................................................................................. 41
4 Results ........................................................................................................................................... 43
4.1 Ventilation .............................................................................................................................. 43
4.2 Asthma control ....................................................................................................................... 45
4.3 Metabolism ............................................................................................................................ 46
4.4 Breath holding time ................................................................................................................ 46
5 Discussion ..................................................................................................................................... 47
5.1 Pre-intervention ..................................................................................................................... 47
5.2 Post-intervention .................................................................................................................... 49
5.3 Strength and limitations ......................................................................................................... 51
5.4 Future studies ........................................................................................................................ 53
6 Conclusion ..................................................................................................................................... 53
References ............................................................................................................................................ 55
Appendix A ............................................................................................................................................ 63
Appendix B ............................................................................................................................................ 64
Appendix C ............................................................................................................................................ 66
Appendix D ............................................................................................................................................ 70
Appendix E ............................................................................................................................................ 72
Appendix F ............................................................................................................................................. 73
10
List of Figures
Figure 1. The respiratory system. ..................................................................................................... 19
Figure 2. Airway branching in the lower respiratory tract. ................................................................ 20
Figure 3. Normal bronchial tube at left side and narrowing of the bronchial tube in asthma ........... 21
Figure 4. The hemoglobine saturation curve for partial pressures of oxygen. ................................. 22
Figure 5. Hypo- and hyperventilation ............................................................................................... 23
Figure 6. The anatomic dead space. ................................................................................................ 24
Figure 7. Spirometry, a volume-time graph. ..................................................................................... 25
Figure 8. Muscles of breathing. ........................................................................................................ 26
Figure 9. A control system has three interconnecting components. ................................................ 27
Figure 10. Central (left-side of picture) and peripheral chemosensors (right-side) .......................... 28
Figure 11. Flowchart of procedure and participants ......................................................................... 40
Figure 12. Measurements performed for both groups at M1, M2 and M3 ....................................... 41
Figure 13. Partial pressures of end-tidal carbon dioxide (PETCO2) and oxygen (PETCO2) ............... 44
Figure 14. Results from the ACT. ..................................................................................................... 45
Figure 15. SABA usage before and after the Buteyko method. ....................................................... 45
Figure 16. Breath holding time measures ........................................................................................ 46
Figure 17.∆ BHT Line Fit Plot without extreme case ........................................................................ 47
11
List of tables
Table 1. Potential risk factors for asthma15 ...................................................................................... 15
Table 2. Randomized control trials involving BM ............................................................................. 33
Table 3. Asthma history and medication usage at M1 ..................................................................... 38
Table 4. Measures of age, gender and BMI for all participants at M1 ............................................. 43
Table 5. Ventilation measurements at M1 ........................................................................................ 43
Table 6. Body mass index, lung function and ventilation parameters. ............................................. 44
12
List of abbreviations
ANS Autonomic nerve system
APC Antigen-presenting immune cell
BHT Breath holding time
BM Buteyko Method
BTS/ACPRC guideline Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient
C3 Cervical vertebra number 3
Cl- Chloride ion
CO2 Carbon dioxide
COPD Chronic obstructive pulmonary disease
CPG Central pattern generator
CSF Cerebral spinal fluid
DALYs Disability-adjusted life years
DB Dysfunctional breathing
DRG Doral respiratory generator
ECF Extracellular fluid
ECRHS The European Community Respiratory Health Survey I and II
EMG Electromyography
f Frequency of breathing
FEV1 Forced expiratory volume in one second
FVC Forced vital capacity
GERD Gastroesophageal reflux disease
GINA15 Global Initiative for Asthma 2015
GOLD Global Initiative for Chronic Obstructive Lung Disease
H2CO3 Carbonic acid
H2O Water
Hb Hemoglobin
HbO2 Oxyhemoglobin
HCO3- Bicarbonate
HHb Deoxyhemoglobin
HV Hyperventilation
ICS Inhaled corticosteroids
IgE Immunoglobulin E
ISAAC The International Study on Asthma and Allergies in Childhood
13
L Liters
LABA Long-acting beta2-agonist
Log Logarithm
Min Minutes
Ml Milliliter
mmHg Millimeter of Mercury
Mmol Millimole
NAEPP National Asthma Education and Prevention Program
NTS Nucleus tractus solitaries
O2 Oxygen
PaCO2 Arterial pressure of carbon dioxide
PaHCO3- Arterial pressure of bicarbonate
PaO2 Arterial partial pressure of oxygen
PCO2 Partial pressure of carbon dioxide
PEF Peak expiratory flow
pH -log[H+]; measure of hydrogen ion activity
pK logarithm of dissociation constant, K
PO2 Partial pressure of oxygen
PRG Pontine respiratory generator
RR Respiratory rate
SABA Short-acting beta2-agonist
SHR Sensory hyperactivity
SIGN British guidelines on management of asthma
U-BIOPRED Unbiased BIOmarkers for the PREDiction of Respiratory Disease Outcome.
V’A Alveolar ventilation
V’E Pulmonary ventilation
V´D Dead space ventilation
VRG Ventral respiratory generator
VT Tidal volume
WHO World Health Organization
14
1 Introduction
Over 2000 years ago, the Greek Hippocrates (460-377 BC) recognized symptoms of abnormal breathing
and named these symptoms as a disease asthma.1 Asthma is nowadays a highly prevalent chronic
illness, affecting approximately 300 million individuals worldwide, and the incidences are increasing.
Global prevalence of asthma ranges from 1 16 %. In Iceland, prevalence of asthma is about 10% in
children2 and 5-7% in adults.3 Almost 14 million disability-adjusted life years (DALYs) are lost annually
worldwide, due to asthma. This represents 1.8% of the total global disease burden4 and is similar to
diabetes.5 Both morbidity and mortality from asthma are significant, and it is estimated that 346.000
individuals die worldwide every year because of asthma.4 The World Health Organisation (WHO)
estimates that asthma deaths will increase over the next ten years if urgent action is not taken.6
Asthma is ineffectively treated despite a better understanding of pathophysiology and new
pharmacological strategies.4 According to WHO, access to cost-effective strategies and asthma
medication should be improved to prevent asthma attacks and asthma-related death.6 Non-
pharmacological therapies such as breathing therapies have shown to increase asthma control and
quality of life. One of them, the Buteyko method (BM) has garnered interest in the asthmatic population
worldwide.7, 8 BM is a technique that uses breath control to treat asthma and is believed to be connected
to low levels of carbon dioxide (CO2) in the body.9, 10 There is little scientific evidence that supports the
CO2 theory of BM. In this study, physiological mechanisms behind the theory such as resting ventilation
and chemosensitivity for CO2 are examined.
1.1 What is asthma?
Asthma is an umbrella term for a heterogeneous disease and is characterized by variable airflow
limitation, both in time and in intention, due to bronchial contraction, bronchial swelling and mucus
accumulation. These can cause various and variable respiratory symptoms, such as wheezing, shortage
of breath, chest tightness, and coughing. Chronic inflammation and hyper-responsive airways are
common features of asthma.4
Diagnosis
The diagnosis of asthma is made according to family and medical history, physical examination, and
lung function tests, such as spirometry and peak flow tests (PEF). To diagnose inflammation in the
airways, a bronchoprovocation, or challenge, test is done to trigger symptoms and confirm the variable
expiratory airflow limitation.
A thorough diagnosis is necessary for good asthma control and management. Asthma is easily
confused with asthma-related disorders, like vocal cord dysfunction, airway sensory hyperactivity (SHR),
hyperventilation, dysfunctional breathing, non-obstructive dyspnoea, and gastroesophageal reflux
disease (GERD). Asthma medications do not offer relief in these asthma-like disorders.11
15
Risk factors and allergies
Fundamental causes of asthma are difficult to establish. Genetic predisposition12 seems to be a part,
but does not explain the increase in asthma prevalence alone.13 The Unbiased BIOmarkers for the
PREDiction of Respiratory Disease Outcome (U-BIOPRED) project, set up in 2009, aimed to identify
the heterogeneity of asthma in so-called phenotypes, leading to new treatment targets and better
approaches to asthma therapy.14 Certain risk factors can have an influence on the development and
severity of asthma (see Table 1).15 Asthma often involves an inflammatory disorder of the lungs and
inflammation can be found in all airways, including the nose, called rhinitis. For example, 80% of
asthmatics have rhinitis, and 20-50% of those with rhinitis have asthma.4, 16
Table 1. Potential risk factors for asthma15
Host factors
Age
Gender15
Genetic predisposition12
Atopy
Environmental Factors
Early life and social factors
Indoor environment
Outdoor environment
Stress
Lifestyle Factors
Smoking
Diet
Obesity and physical activity17
Gastroesophageal reflux
Occupational Factors
Work exposures
It is difficult to understand how these risk factors in Table 1 contribute to the development of asthma.
However, it is known that some risk factors, also called triggers, have an unyielding influence on asthma.
These can be indoor allergens (house mites, pollution, and pet dander), outdoor allergens (pollen and
mold), and tobacco smoke. It is estimated that 15% of asthma cases among adults of working age are
due to chemical irritants in work places (occupational asthma).4, 18 When one is exposed for a long time
to these risk factors, structural changes in the airways, also called airway modelling, are seen and are
often associated with chronic allergic inflammation.19
1.2 Asthma control
Asthma control is defined as the “effective management of the clinical characteristics of the disease,
including symptoms (such as dyspnea, cough and wheezing), nocturnal awakening, reliever medication
16
use, activity limitation and lung function”, according to the Global Initiative for Asthma (GINA16)4.
GINA16 defines three levels of asthma control, “controlled/well controlled, partially controlled/ not well-
controlled, and uncontrolled/very poorly controlled”.4
To assess levels of asthma control, the Asthma Control TestTM questionnaire (ACT; Quality Metric
Inc., Lincoln, RI, , USA) was concluded to be reliable, valid, and preferred in clinical practice according
to a recent review.20 The ACT is a five question, self-administered health survey used to measure
asthma control in individuals 12 years of age and older. It has a four-week recall period. The ACT has
a cut-off score of 19. Asthma is well-controlled with scores above 19, and not well-controlled with 19 or
below. Diary cards are used in studies together with the ACT to recognize fluctuations by recording
symptoms, medication usage, or other required measurements.21-23
Control-based asthma management
The goal of asthma management is to obtain and maintain control of the disease, with the minimum and
adequate level of therapy and minimum side effects. As the variable character of asthma can make it
difficult for health care professionals, and asthmatics themselves, to control symptoms, guidelines are
focused on levels of asthma control, rather than disease severity.24 Proper diagnosis by trained health
care professionals, a good patient-doctor relationship, patient education, self-management, avoidance
of exposure to triggers and adherence to treatment are recommended to achieve control and reduce
asthma-related deaths, according to WHO.6
Asthma management should prevent exacerbations, decreased lung function, and adverse side
effects of medications by using the lowest possible medication dosage. Supervised medication
management is required based on guidelines. These guidelines mostly provide a stepwise medication
strategy according to levels of control. As for the bronchoconstriction component, asthma is managed
by a combination of short-acting B2-agonist (SABA) and/or long-acting B2-agonist (LABA). For the
inflammatory component, asthma is controlled by inhaled and/or oral corticosteroids as a treatment or
as a preventative measure.4
Demoly et al.25 showed that 6.1% of the adult population in five countries in Europe (about 15 million
people) are diagnosed with asthma. Of these, 57% of asthmatics who were treated for their asthma
were not well-controlled. As asthma control decreased, direct costs (hospital admission and increased
use of medication) and indirect costs (time lost from work and premature death) for asthmatics
increased.5, 25 Papaioannou et al.24 concluded that, world-wide, asthma is controlled only in a small
percentage of patients. Reasons for this are a lack of understanding or misunderstanding of disease
mechanisms, inadequate adherence to treatment, and a lack of good patient-doctor relationships. Also,
continuous exposure to irritants and the presence of comorbidities are suggested to be causes of not
well-controlled asthma. To access effective management and achieve better control, specialized
healthcare and, most importantly, a better understanding of disease mechanisms are required. Severe
asthma is an important problem, which needs to be focused on.24
In a meta-analysis of placebo-controlled trials of asthma medication dosages, Salpeter et al.26
concluded that regular B2-agonist usage over one week resulted in tolerance to its effects and poorer
disease control. In this analysis, some of the investigated research was funded or sponsored by
17
pharmaceutical companies and some was not. Of this, 73% of the funded research concluded that B2-
agonist usage was of benefit for asthmatics. Only 10% of the unfunded research confirmed B2-agonist
usage to be of benefit for asthmatics. In a recent Cochrane overview of reviews27 it is concluded, that
regular B2-agonist medication usage increased the risk of fatal and non-fatal serious adverse events for
adults or adolescents with asthma.
Psychological factors.
Emotional disorders, such as anxiety and depression can have an impact on asthma control.28 These
disorders are more frequent among asthmatics and can make asthma symptoms more prominent,
although asthma is not a psychosomatic disorder. Vice versa, asthma symptoms themselves can
increase anxiety and panic, and worsen psychosomatic disorders. This process might result in, or be
the result of, disproportionate breathing behaviours, or dysfunctional breathing.29, 30 Pbert et al.31,
suggested that relaxation techniques (mindfulness-based stress reduction) improved the asthma-related
quality of life, and this was seen without decline of lung function. Unfortunately, there is no validated
method to evaluate psychological effects on asthma control.29, 32 When emotional stress makes asthma
worse, GINA16 advises the use of relaxation techniques and breathing exercises to achieve better
asthma control.4
Posture and physical condition
Posture and physical condition are important for the functionality of ventilation in rest. They influence
the mechanical interaction of lung, chest wall, and intra-abdominal pressure, and the vulnerable process
of synchronized activation of the diaphragm and inspiratory muscles.33 Breathing becomes dysfunctional
when this biomechanical function is inappropriate and inefficient due to bad posture and bad physical
condition, and this influences asthma control.34
The diaphragm is the main inspiratory muscle. The synchronous transmutation of the diaphragm
from parachute shape to disk form and back is restricted by many factors because of a lack of stability
in this movement. The tension provoked by the push-pull mechanics of organs above and below the
diaphragm is the only stabilization for the diaphragm. This explains the vulnerability of the efficiency of
the diaphragm and mostly depends on posture and the elastic firmness of tissues such as the diaphragm
itself, the respiratory and pelvic floor muscles, the abdomen viscera, and of the rib cage.35, 36
In asthma, the slightest tension and/or mucus accumulation in the bronchi increases deep
inspirations. The auxiliary muscles, as scalenii, the sternocleidomastoids, and the trapezuis, become
more activated and try to decrease the feeling of dyspnea, leading to higher costal and dysfunctional
breathing patterns. Van Dixhoorn et al.36 explained that dysfunctional breathing patterns create a
continuous range of adaptations and adjustments of respiratory muscles and muscular activity in the
whole body, resulting in bad posture. By correcting bad posture habits and training straight posture, the
functionalilty of the biomechanics of breathing improves. Hodges et al.33, 37 demonstrated that the
efficiency of the diaphragm is reduced when the central ventilatory drive is increased. Deep inspirations
resulted in increased tension of the diaphragm, changed posture, and an increased central ventilatory
drive is related to dysfunctional breathing.
18
1.3 Ventilation at rest
Ventilation has multidimensional functions which are interactive. It has both psychological and
physiological components, either of which can become disturbed and result in dysfunctional breathing.38
Thomas et al.39 concluded that 30% of asthmatics are affected by dysfunctional breathing in terms of
breathing in excess of metabolism or hyperventilation. However, the pathophysiology of hyperventilation
is not completely understood yet38, 40-42 and difficult to relate to asthma. One of the main symptoms of
asthma is breathlessness or dyspnea. When in dyspnea, asthmatics feel the need to breathe more43
and studies have shown hyperventilation to be present in asthma attacks44 and in asthmatics.39, 45-47 In
order to explore what is known about ventilation and asthma, the physiology of resting ventilation is
examined and related to asthma. Chemosensitivity to CO2 in breathing control and the relation between
asthma and CO2 are emphasized to assess whether or not asthmatics hyperventilate at rest.
The Respiratory system
Function of the respiratory system
The respiratory system has two primary functions. The first function is respiration, which can be divided
into external and cellular respiration (see Figure 1). External respiration is the gas exchange of oxygen
(O2) and CO2. It occurs together with the circulatory system and between the atmosphere and the body.
External respiration can be separated in four processes, a) the exchange of CO2 and O2 between the
atmosphere and the airways, or ventilation, b) the diffusion of O2 and CO2 between the airways and the
pulmonary capillaries, c) the transport of O2 and CO2 in the blood, and d) the diffusion of these gases
between the blood and the cells.
19
Figure 1. The respiratory system. One main function of the respiratory system is the gas exchange in 4 phases: ventilation, transport, diffusion to cells, and oxidation in cells. The other main function is the maintenance of the acid-base balance (pH).48
Cellular respiration is when oxygen reacts in the cells with nutrients like fatty acids, carbohydrates
(glucose) and amino acids. The reaction provides energy and creates carbon dioxide, water, and waste
products. The purpose of cellular respiration is to obtain energy by burning oxygen in the cells. The
other primary function of the respiratory system is to maintain the acid-base balance (pH) in the blood
stable, together with buffer- and renal system.49
Structure of the respiratory system
The respiratory system is not simply the airways, the lungs and the muscles of respiration. It also
includes the chest wall, important because of the mechanical interaction with the lungs, and the central
nervous system that is concerned with the control of ventilation.
The airways may be divided into two parts: the upper and lower respiratory tracts. Air enters through
the nose and/or mouth. The upper airway: mouth, nasal cavity, pharynx, and larynx, are essential for
conditioning the air before it reaches the lungs and alveoli. Breathing through the mouth is not nearly as
effective as breathing through the nose; the nasal cavity filters out bacteria, viruses and other unwanted
material. It warms outside air to body temperature (37º) and adds water or vapour until the air reaches
100% humidity, so that the inner surface (epithelium) of the lungs do not dry out.49, 50 It matters whether
asthmatics breathe through the nose or mouth. Oral breathing can cause a decrease in lung function in
mild asthmatics at rest. It can initiate asthma symptoms in some, and it may play a role in the
20
pathogenesis of acute asthma exacerbations.51, 52 Nasal breathing is important for asthmatics. It is
shown that impaired nasal function affects the lower airways in asthmatics.16
The lower respiratory tract consists of the trachea and two primary bronchi, each dividing from 10 to
23 times before terminating in a cluster of alveoli in the lungs (see Figure 2). The first 16 bronchioles, or
the conductive zone, contain no alveoli and their walls are too thick for gas exchange with venous blood.
The area from the beginning of the mouth and nose through the conductive zone is called the anatomic
dead space. The structure of the airways varies, dependent on their location in the tracheobronchial
tree. The trachea is a fibromuscular tube, supported by C-shaped cartilage. The cartilage support
diminishes progressively in distal airways. Cartilage support disappears in airways with a diameter of 1
mm, called bronchioles.49
Figure 2. Airway branching in the lower respiratory tract. The conducting system is part of the anatomic dead space where there is no gas exchange. The exchange surface is for diffusion of gases.48
The diameter of these bronchioles is regulated primarily by the autonomic nervous system and
locally, among other factors, by levels of CO2 in air passing through them. If levels of CO2 fall, as in
breathing in excess of metabolism or hyperventilation, the bronchioles constrict. If levels rise, they
dilate.49 Most of the respiratory tract is coated by mucus-covered, ciliated epithelium. When asthma
symptoms are present, the epithelium often produces more mucus and is thickened, diminishing the
radius of the bronchioles and narrowing the respiratory tract (see Figure 3).49
21
Figure 3. Normal bronchial tube at left side and narrowing of the bronchial tube in asthma at right side of picture.53
Diffusion of O2 and CO2 takes place through the alveoli and their associated pulmonary capillaries,
or the alveolar-capillary interface. The ventilation/perfusion ratio (V’/Q’ ratio) in respiratory physiology is
a ratio used to assess the efficiency and adequacy of the matching of two variables: V’, ventilation or
the air that reaches the alveoli and Q’, perfusion or the blood that reaches the capillaries surrounding
the alveoli. The surface area and thickness of the alveolar-capillary membrane is important for
diffusion.49
The transport of oxygen and carbon dioxide.
Less than 2% of O2 is transported dissolved in the blood. About 98% is chemically bound to the protein
hemoglobin (Hb), situated in the red blood cells, or erythrocytes. The amount of Hb present in blood is
important for the capacity and the content of O2 in blood. The percent saturation (% Hb saturation)
expresses the proportion of Hb bound to oxygen. The affinity of Hb for O2 is expressed in the
oxyhemoglobin (HbO2) dissociation curve.
Several mechanisms have an effect on the percentage of Hb saturation and the availability of O2 for
metabolism. It starts to be critical when the partial pressure of oxygen (PO2) falls below 60 mm Hg. At
this state, Hb is 90% saturated (see Figure 4), with a normal partial pressure of CO2 (PCO2) of 40 mm
Hg.49
22
Figure 4. The hemoglobine saturation curve for partial pressures of oxygen. The effect of different partial pressures of CO2 (PCO2) on hemoglobine saturation.48
However, in situations of hyperventilation (PCO2 is 20 mm Hg), the dissociation curve shifts to the left
(see Figure 4). Hyperventilation increases the affinity of Hb for O2 and off-loading of O2 on the tissues
will be reduced.49
The tissues are vascularized by a fine capillary network. There, the exchange of O2 and nutrients
diffuse out of the blood into the cells. About 5-10% of the CO2 is transported in the blood dissolved in
the plasma, 20% bound to Hb and 70% as bicarbonate (HCO3 ), an important buffer for the pH in blood.
Venous blood returning from body tissues containing a high concentration of CO2 and a low
concentration of O2 is pumped from the right ventricle of the heart into the lungs, where CO2 is exhaled
and O2 is inhaled.49, 54
Pulmonary ventilation
In physiology, the exchange of gas between the lungs and the atmosphere is called the pulmonary
ventilation (V’E), measured as litres per minute (L/min). Pulmonary ventilation is a combination of gas
that exchanges with pulmonary blood, or alveolar ventilation, plus gas that does not exchange with
pulmonary blood, or dead space ventilation. Ventilation is dependent on the tidal volume, or the amount
of air inhaled within each breath, (VT, L) and the frequency of breathing (f, breaths /minute), described
with the formula V´E = VT x f. Pulmonary ventilation at rest ranges much or from 4-7 L/min.49 It is important
to relate resting ventilation to metabolism, as big men have to breathe more air than small women.49
Some studies55-57 have examined resting ventilation in asthmatics, but they have not related these
measures to metabolism. Such results are difficult to evaluate.
Alveolar ventilation
Alveolar ventilation (V’A) is the airflow that enters the alveoli, measured as litres per minute (L/min). It
represents inspired air with 20-21% of O2 and 0.03% of CO2, and in a similar volume of expired air, with
16-17% of O2 and 3-4 % of CO2 leaving the functioning alveoli at rest. When V’A is high
(hyperventilation), PO2 increases and PCO2 decreases in the alveoli. When V´A is low (hypoventilation),
23
the PO2 decreases and PCO2 increases (see Figure 5). Functionally, V´A should be examined relative
to what is required by metabolic demands. In rest, hyperventilation is when V’A is more than metabolic
demands, as for example in stressful and emotional situations.49
Figure 5. Hypo- and hyperventilation. In hyperventilation, alveolar partial pressure of oxygen is higher and of carbon dioxide is lower than in normal ventilation. And vice versa in hypoventilation.48
Dead space ventilation
Gas that does not exchange with pulmonary blood, or dead space ventilation is not included in alveolar
ventilation. Alveolar ventilation is pulmonary ventilation without dead space ventilation. The dead space
is composed of two parts: anatomic and alveolar dead space. Anatomic dead space is the area from the
beginning of the mouth or nose through the conductive zone (see Figure 2). After each inspiration, an
amount of air stays in the conductive zone i.e. dead space volume (VD) and this fresh air has the same
composition as the outside air. After each expiration, an amount of air does not leave the lungs and that
air has the same composition as the alveolar air (see Figure 6). Studies have tried to estimate this space
with non-invasive methods.54, 58 In asthma, this space can alter as the tension in the bronchi changes.
Additionally, traction or compression (as sitting straight or bending) increases and decreases anatomic
dead space respectively. The smaller the tidal volume, the greater the percentage lost to anatomic dead
space ventilation for each breath.59
The alveolar dead space refers to ventilated but non-perfused alveoli in the lungs. Alveolar dead
space is most often more in asthmatics although it varies considerably, because of the variable
ventilation-perfusion (V’A/Q’) mismatch in the alveolar-capillary unit caused by bronchoconstriction.58, 60
The V’A/Q´mismatch is an important factor when interpreting values of resting partial pressure of end-
tidal CO2 (PETCO2) in asthmatics. Measures of PETCO2 are used to estimate measures of partial
pressures of arterial CO2 (PaCO2) for normal subjects.41, 54, 60 Measures of PETCO2 are taken at the end
of quiet exhalations, providing the best conditions to resemble PaCO2. For asthmatic subjects, the
24
relation between PETCO2 and PaCO2 has differed because of the ventilation and perfusion mismatch
(V´A/Q’) in the alveoli. Depending on the severity of this mismatch, differences can be seen in lower
values of PETCO2 than real values of PaCO2. To make precise measures in asthmatics, a blood gas
sample is needed to get exact measures of PaCO2.58
Physiologic dead space is the sum of alveolar and anatomic dead space. Inspired air from these
areas will leave the body as it entered, contributing no CO2 to exhaled air. Thus, the greater the
physiologic dead space, the less the CO2 in exhaled air.49 Dead space ventilation has no physiologic
advantage and, if increased, more energy must be wasted to move additional gas so that alveolar
ventilation can be maintained. This conforms to breathing ineffectively and dysfunctional.
Figure 6. The anatomic dead space. After each inspiration, an amount of air stays in the conductive zone. During expiration, the air in these conductive zones has the same composition as the inspired air. After each expiration, an amount of air does not leave the lungs.48
The bicarbonate buffer system
The bicarbonate buffer system helps, together with the respiratory and renal system, to maintain a
constant internal environment in the cells and the body (homeostasis) by keeping a balance between
acids and bases.
A buffer system is a mixture of an acid and a base that resists changes in its pH. The bicarbonate
buffer system is closely linked to pH through the bicarbonate buffer formula, CO2 + H2O ↔ H2CO3 ↔ H+
+ HCO3 . Weak carbonic acid (H2CO3) and an HCO3 base are a buffer pair. The buffer value is expressed
by the Henderson-Hasselbach equation: pH = pK + log [HCO3 ] / [CO2 + H2CO3] where K is the
dissociation constant and [HCO3 ] is the plasma bicarbonate concentration. Because it is a weak acid,
25
the H2CO3 concentration is negligible. The ability of this buffer system depends on V’E, as V’E controls
the levels of CO2 in the body.49 Higher pH values are seen in acute hyperventilation, but with chronic
hyperventilation pH values are stable and approach normal values.61, 62
Spirometry
Spirometry testing is done to assess lung function (see figure 7). Spirometry values are compared to
predicted values according to the gender, age, height, mass, and ethnicity of the participant. The most
common spirometry values are the forced vital capacity (FVC) and the forced expiratory volume in one
second (FEV1). FVC measures the amount of air from the start of a maximal inspiration until the end of
a maximal forced expiration. The volume of air expired in the first second is a good index of expiration
airways resistance, especially when expressed as ratio with FVC.
Figure 7. Spirometry, a volume-time graph. The proportion of the amount of air, starting after a maximal inspiration, of forced expiration in one second to forced vital capacity (FEV1/FVC).48 FET= forced expiratory time.
In asthma, values lower than 0.7 of the ratio FEV1/FVC indicate obstruction of the expiratory airflow.4
Measures of FEV1 compared to predicted values lower than 80%, indicate the severity of the
obstruction.63 Meuret et al.61 showed that deep and fast breathing, as in spirometry, can lead to airway
obstruction and increase asthma symptoms in asthmatics, while deep inhalations provoke
bronchodilation in healthy airways.64
Fenger et al.65 demonstrated, that changes in weight had an impact on lung function testing.
Increasing adiposity resulted in a decline of FEV1 and FVC, but not FEV1/FVC. The opposite was also
true, decreasing adiposity increased FEV1 and FVC but not FEV1/FVC.
Ventilation musculature
The respiratory muscles are skeletal muscles (see Figure 8). The group of inspiratory muscles includes
the diaphragm, the external intercostal, parasternal, sternocleidomastoid, and scalene muscles. The
group of expiratory muscles includes the internal intercostal muscles, the rectus abdominis, the external
and internal oblique muscles, and the transverse abdominal muscles. During ventilation at rest, only the
inspiratory muscles are active. During increased breathing efforts, the expiratory muscles become active
as well. At this time, respiration is coordinated by a combination of diaphragm and transverse abdominal
26
muscle activitiy.33 The respiratory muscles themselves use 5% of total oxygen uptake, can get tired, and
can be trained.66, 67
The main work of breathing by respiratory muscles, is to overcome the elastic recoil of the lungs and
chest wall, but also the resistance to air flow. Airway resistance is about 35% to 50% in the upper
airways. Airway resistance is higher while breathing through the nose than through the mouth. In normal
conditions, the radius of the bronchi decides the resistance of the airways. In asthma, the bronchi with
the smallest radius causes the highest resistance (see Figure 3).49
Figure 8. Muscles of breathing. Muscles of the thorax, neck, and abdomen create the pressure difference to move air during ventilation.48
Breathing control
Control of breathing is of vital importance to keep the internal environment of our cells constant, one of
the most important physiologic functions of the body. Failure is not an option. Normally, the human body
cannot be without ventilation for more than three minutes. In comparison, we can be without food for
about three weeks and without water for about three days.49
Ventilation is spontaneously triggered in the central nervous system. It is controlled by a fine-tuned
system, aiming at an efficient utilization of blood gases such as CO2 and O2 to keep the pH constant.
The goal of this system is an effective, functional breathing mechanism with a minimum of work and a
minimum of metabolic cost of each breath.
27
Figure 9. A control system has three interconnecting components. Central respiratory centers in medulla oblongata change ventilation by controlling respiratory muscles, according to inputs from chemosensors, the lungs, and other receptors.49
The respiratory control system has three, interconnecting components (see Figure 9). The first
component (central controller) are the respiration centers, which are distributed in the reticular formation
of the medulla oblongata. A complicated synaptic interaction between several neurons in these
medullary respiratory control centers effectively change and adapt ventilation. Pacemaker-like neurons
in the pre-Bötzinger complex, called the central pattern generator (CPG), are situated in the ventral
respiratory groups of the medulla. They generate the timing and the amplitude of respiratory muscles
with a highly regulated lability, modulated by pontine and other inputs.68, 69 The CPG is automatically
modified while talking, singing, or blowing. Dysfunctions of the CPG can result in diseases.48, 68
Secondly, sensory inputs (sensors) from higher brain centers and from central and peripheral
chemosensors consistently influence these respiratory control centers in the brain. Other contributors
are sensory inputs from the lungs, the cardiovascular system, the skeletal muscles, and tendons of
respiratory muscles. The third component (effectors) is the synchronized distribution of motor output to
the respiratory musculature controlling ventilation. The respiratory control system needs further
exploration in order to be able to evaluate how breath control and chemosensitivity for CO2 are related.70
The underlying mechanisms of neural control of ventilation are still not completely understood.49, 68
The spontaneous central pattern generation of respiration can be overwhelmed by centers from the
cortex and human will. They may have a direct influence on the muscles of breathing (diaphragm and
auxiliary muscles), as with breath holding. Other cortex centers, where experiences of stress and
emotions as depression, anxiety, and happiness arise, can initiate widespread ventilatory responses
throughout the body. Emotions and respiration are closely linked in a complex feedback system through
the autonomic nerve system (ANS). Severe and persistent emotional states can cause chronic
hyperventilation, resulting in a sympathetic dominance of the ANS. During meditation and breathing
practices, there is a shift from sympathetic to parasympathetic dominance in the ANS. This results in
decreased respiratory activity and reduced negative emotions.71-74
28
Chemosensors
According to physiology, a respiratory chemosensor is a receptor that detects alterations of its direct
chemical environment and adjusts respiratory activity through the central nervous system.49 Control of
breathing by chemosensors can be seen as a feedback control system.75 V´E controls levels of PaCO2
and PaO2, and respiratory chemosensor reflexes control V´E, apart from influences of higher brain
centers. The respiratory chemosensor reflexes are responsible for controlling PaCO2 and keeping
hydrogen ion concentrations (H+) within certain values. There are two types of chemosensors, the
central chemosensors, located distributed in the medulla, and the peripheral chemosensors, located in
the carotid and aortic bodies.
Figure 10. Central (left-side of picture) and peripheral chemosensors (right-side). CO2 flows into the cerebrospinal fluid through the blood barrier, a highly selective permeable membrane, separating arterial blood from cerebrospinal fluid, keeping the brain safe. This increases ventilation through the reduced pH, sensed by the central chemoreceptors, activating the respiratory control center. Increased PaCO2 also stimulates peripheral chemoreceptors, activating respiratory control centers. Through a negative feedback system of higher amount of O2, and lower amount of CO2, the respiratory control center is inactivated.48
Central respiratory chemosensors lie in brain extracellular fluid (ECF) and are surrounded by
cerebrospinal fluid (CSF). They are effected by local metabolism (see Figure 10). The blood-brain barrier
separates respiratory chemosensors from arterial blood and is highly permeable for PaCO2. It is difficult
for HCO3- and H+ to cross this barrier. Hence, the respiratory chemosensors are not sensitive to CO2,
but to H+ concentrations. When V’E changes, PaCO2 and pH change in the blood, resulting in changes
29
in levels of CO2 in the CSF. In CSF pH changes also, according to the bicarbonate buffer system formula
↕CO2 H2O ↔ H2CO3 ↔ ↕H+ + HCO3 . In response to changes in pH, the central chemosensors
stimulate/inhibit the respiratory centers, controlling respiratory activity through this feedback system.49
It is very important to maintain pH, or H+, levels within certain limits in the CSF. Maintaining pH is done
by keeping the ratio of CO2 to HCO3- constant, as expressed by the Henderson-Hasselbach equation
H+ = CO2/ HCO3 or pH = pK + log (HCO3 /CO2). Regulation of pH in the CSF is made more rapidly than
blood pH (because of a lack of hemoglobin in the CSF).
Under resting conditions ventilation is mostly regulated by CSF pH, directly reflexing PaCO276, and
pH disturbances in CSF are resisted by modulating V’E. In other words, ventilation is a mechanism for
regulating the acidity of the blood and of the CSF through the controlled release of CO2. Furthermore,
the ventilatory drive is dependent on the threshold values of CO2, which stimulates or inhibits breathing
at the central level. With breath holding, levels of PaCO2 increase until the threshold value of CO2 has
been reached, expressing the chemosensitivity of the ventilatory drive. Because V´E controls PaCO2,
persistent changes in V´E can alter the ventilatory recruitment threshold of PaCO2. Where habitually or
chronic hyperventilation develops, the central respiratory control centers become more sensitive for CO2
as a state of chemo hypersensitivity. They trigger breathing at lower levels of PaCO2, maintaining a
hypocapnic state (low PaCO2).75 Laffey et al.62 related asthma to hyperventilation and to causes of
hypocapnia. This state can be intermittent or persistent as asthma symptoms fluctuate widely.
Kassabian et al.77 showed a raised respiratory control sensitivity in asthma and Hide et al.78
demonstrated that the central respiratory control centers have a key role in determining the severity of
asthma.
The peripheral chemoreceptors, located in the carotid and aortic bodies, lie at the fork of the common
carotid arteries that supply the brain with blood. They are sensitive to low PaO2, low pH, and high PaCO2.
They are maximally stimulated when PaO2 decreases below 50-60 mmHg, as can be the case with
severe asthma attacks. The reflex of the peripheral chemoreceptors increase ventilation and constrict
the bronchi but dilate upper airways.76 The peripheral chemoreceptors sensitize the central pattern
generator through both ventilation and sympathetic nerve activity, even for a prolonged time after
cessation of input. The ventilator control system is highly flexible in response to this chemoreceptor
stimuli, even during exercise and sleep.68
A large number of other sensors located in the lungs, the muscles, tendons, and skin have an
influence on the respiratory control centers. Pulmonary stretch receptors decrease respiration through
the central nervous system. Receptors in the nose, mouth, and upper airways (irritant receptors) keep
the airways open when pressure falls in the upper airways (with cough and sneezing reflexes).
Temperature increases respiratory rate, and sudden pain decreases it. Prolonged pain, on the other
hand, increases respiratory rates.49
Physiological efficient and functional ventilation
Efficient ventilation should be assessed in relation to metabolism. There has to be a balance between
metabolism and ventilation or between O2 demand and supply at the tissue level. Ventilation is normal
when a balance between metabolism and ventilation is achieved without compensation mechanisms
30
(such as bronchoconstriction) i.e. when there is a balance between CO2 production and CO2
exhalation.9, 49
Courtney et al.79 examined the functionality of ventilation at rest. Comprehensive evaluation of the
various aspects of ventilation should include physiological measures, breathing symptom questionnaires
and tests of breathing function such as BHT. The function of the biomechanics of ventilation at rest can
be influenced by posture37, physical conditions80, and breathing techniques81. The efficiency of the
biomechanics of ventilation can have an influence on asthma control. Straight posture, ensuring optimal
diaphragmatic breathing and good physical condition are contributory to asthma control.34 Measures
such as V´E and PaCO2, are essential to evaluate the functionality of ventilation at rest, because of their
key role in central respiratory control and the balance between CO2 production and CO2 exhalation.49,
62
Metabolism
To interpret the efficiency of ventilation at rest, it should be corrected to metabolism. Metabolism is al
biochemical processes that occur in the body in order to provide the cells with their needs and to
maintain homeostasis. Metabolic rate is mostly dependent on gender, age, surface of the skin, and
muscle mass. Gas exchange, O2 consumption (V’O2), and CO2 output (V’CO2), are indicators of
metabolism. An important measure of ventilation is the ratio between the volume of gas breathed out
(V’E) in litres per minute to V´CO2 (V’E /V’CO2) in litres per minute. This ratio is called the ventilatory
equivalent of CO2 and is meant to reflect the efficiency of ventilation. Normal values of the ventilatory
equivalent at rest have not yet been established. Habedank et al.82 found lower rates of V’E/V’CO2 at
rest for men than for women (50.5 ± 8.8 versus 57.6 ± 12.6, p < 0.05). Ventilatory efficiency at rest was
depended primarily on age and gender in that study. If ventilation is in excess to our metabolic rate, we
hyperventilate. When hyperventilating, the ventilatory equivalent will increase, PaCO2 will decrease, and
PaO2 will increase. It is presumed that the ratio of V’A /V’CO2, compared to V’E V’CO2 gives an indication
of ventilation in physiologic dead space at rest. The greater the difference between V’A /V’CO2 and V’E
V’CO2, the more energy is wasted in dead space ventilation. This could indicate dysfunctional breathing.
Hence, to obtain precise measures of V´A, blood gas samples are needed.
Meditation and SABA use have an influence on resting metabolism. Wallace et al.83 and Wolkove et
al.74 showed that reducing ventilation regularly, as in meditation, can result in lower metabolic rates.
Agha et al.84 demonstrated a direct positive correlation between metabolic rate at rest, asthma severity,
and impairment of lung function. They showed that B2-agonist medication increased the metabolic rate
of asthmatics, and more studies85, 86 have confirmed metabolic side effects of B2-agonists in asthma.
1.4 Asthma and resting ventilation
How do asthmatics breathe in rest when they are symptomatic? Do asthma symptoms cause
hyperventilation, or does hyperventilation cause asthma symptoms? Normally, when asthma symptoms
occur, ventilation increases because of the feeling of dyspnea caused by bronchoconstriction. Irritant
receptors in the airways, stimulated by increased mucus, also causes increased ventilation, that result
31
in hypocapnia and a disturbance in pH.49 According to this, asthma symptoms cause hyperventilation.
Only very severe asthma attacks cause high values of CO2 (hypercapnia) and low values of O2
(hypoxia). Due to severe bronchospasm and dyspnea, it is difficult for people with severe asthma
symptoms to do the work of breathing. Severe bronchospasm and dyspnea result in a cycle of
progressive hypoxia (stimulating the peripheral chemoreceptors68), hypercapnia, fatigue, and respiratory
failure.62 Hyperinflation can be a consequence of chronic severe asthma.87
Can hyperventilation cause asthma symptoms? Laffey et al.62 explained how hyperventilation is
related to low baseline levels of PaCO2 (hypocapnia). Hypocapnia is expressed by the equation: PaCO2
= CO2 production/ CO2 exhalation + inspired CO2. As the production of CO2 is not the cause of low
PaCO2 levels, and inspired CO2 is negligibly low, the principle physiologic cause of hypocapnia is
related to hyperventilation. Studies40, 88 have shown that levels of PETCO2 in rest can be normal in people
with symptomatic hyperventilation. It seems more likely, that during symptomatic hyperventilation, levels
of PETCO2 fluctuate rather than becoming chronically low.89, 90 Experimental evidence supports the
potential role of hypocapnia in asthma. Van den Elshout et al.91 found a relation between hypocapnia
and respiratory resistance in asthmatics, caused by bronchoconstriction. Decreased PETCO2, 7.5
mmHg, resulted in 13% increased respiratory resistance in asthmatics, but not in non-asthmatic
subjects, demonstrating that hypocapnia is a possible cause of asthma symptoms. When PETCO2 was
increased, respiratory resistance reduced in both healthy and asthmatic subjects. Hypocapnia also shifts
the oxyhemoglobin curve to the left (see Figure 4), restricting offloading of oxygen to the cells, resulting
in less oxygen supply to the cells (Bohr effect), or tissue hypoxia. Hypocapnia may create a more
anaerobic metabolism, causing the accumulation of organic acids. In other words, the more we breathe,
the less oxygen we have for metabolism.41, 62 This evidence suggests that there is a link between
hyperventilation and decreased oxygen supply at the cellular level. Finally, when hyperventilation
becomes chronic, the central respiratory control centers seem to become more sensitive, triggering
breathing at lower levels of CO2.62, 75 As seen before, raised central respiratory control sensitivity has
been related to asthma.62, 77, 78 Other studies have examined the role of CO2 in asthma and shown
asthma to be related to hypocapnia. Hence, evidence of hyperventilation in asthma is not clear and
further studies are needed.7, 47, 60, 62
Asthma and breathing therapy
Non-pharmaceutical therapies for asthma used with or instead of conventional therapies, have garnered
growing interest in a group of the asthmatic population.92 Concerns and dislikes about medications,
particularly of inhaled and oral corticosteroids, have caused poor medication compliance.46, 93 Plus,
severe asthma has shown to be difficult to control. 93, 94 People with uncontrolled asthma are more likely
to use non-pharmaceutical therapies.92
Studies92-95 have shown that breathing therapies are the most used complementary, non-
pharmaceutical therapies for asthma. GINA164 recommends breathing therapies as a complement to
conventional asthma management. Slader et al.81 suggested that features of breathing therapies, such
as relaxation, voluntary reduction of rescue medication, and self-efficacy, were the primary reasons for
32
improvement in asthma control and not the breathing exercises themselves. GINA164 discusses the
need for high quality studies to test the efficacy of breathing therapies.
Several reviews7, 8, 96 showed that breathing therapies may decrease the use of SABA, and that they
may improve symptoms, quality of life, and psychological outcomes, but not physiological outcomes. All
methods provide instructions on nose and diaphragmatic breathing, reduced ventilation, and daily
training. Offering breathing therapies by physicians is effective for asthma management.8 However, it is
still uncertain what the best and most efficient training method is. Inconsistent outcome measurements
at baseline, and after a retraining intervention, make it difficult to point out a single, best therapy,
according to the review of Bruton et al.7 The most frequently mentioned breathing exercise program in
studies is the Buteyko Method.8, 97-102
1.5 The Buteyko method
The Buteyko method (BM) is a structured, health-promoting method for children and adults with asthma9,
10. BM shows no evidence of adverse effects.21 It is acknowledged by the GINA164, the British guidelines
on management of asthma (SIGN 141)103, and by guidelines for the physiotherapy management (joint
BTS/ACPRC guideline).104 The method is complemental to conventional therapy strategies and does
not conflict with medication use.4, 103, 104 Systemic reviews of breathing methods also suggested BM to
be efficient for asthma management.7, 8, 104
The BM is focused on reducing ventilation gradually, tidal volume at first and frequency when
advanced in the trainings. The BM is based on the theory that asthma can be reversed. It claims hidden
hyperventilation leads to excessive losses of CO2, and this is a fundamental cause of asthma. To adjust
the CO2 balance, the asthmatic body develops defensive reactions such as asthma. The aim of BM is
to normalize levels of CO2 systematically by gradually decreasing ventilation, and matching it with
metabolic needs. Progress or lack of progress is evidenced by breath holding time (BHT), a non-effort
demanding measurement that is standardized in this method. BHT is an indicator of the chemosensitivity
of CO270, but also gives valuable feedback for asthmatics about their health level, risk estimations of
symptom recurrence, and exacerbations.9, 10 The BM differs from other breathing techniques, because
of the BHT feedback system.
The overall complex treatment procedure consists of a combination of breathing instructions, with
both mental and physical components. These include awareness, breathing- and relaxation therapies,
together with common, and also individual advice about nutrition, physical activity and general health.
By these direct and indirect techniques, the BM gradually and unconsciously resets breathing patterns.
The essence of the technique of the method is decreasing the depth of breathing. This is done in daily
training sessions by relaxing conscious and unconscious all the muscles that potentiate the breathing
action until a very slight lack of air is felt. The sensation of slight breathlessness is maintained by keeping
the breathing muscles relaxed, particularly around the shoulders and chest, and by a slight tension of
the transverse abdominal muscle. Sitting straight and breathing through the nose while training is
essential to obtain success.
In a formal Buteyko session, training starts and ends with measuring BHT. A session has been
successful when BHT is longer at the end of the session. Formal training session duration is 15 to 30
33
minutes. Training should be done at least twice a day, upon waking and before sleep. Some common
advice to prevent deep breathing in daily life is included. For example, to control and prevent deep
breathing while sleeping, it is advised to wrap a non-elastic tissue tight around the upper chest.
Asthmatics themselves have found it useful while sleeping to close the mouth loosely and carefully with
a light adhesive tape, to avoid breathing through the mouth. Sometimes it is even necessary to
encourage awakening at night to prevent nocturnal asthma symptoms. Coughing and talking techniques
are taught when needed, aimed at reduced breathing. Coughing should be performed calmly and
efficiently and followed by a holding the breath for a very short period without discomfort afterwards.
Talking should be done calmly, with inspirations through the nose. Physical activity is advised according
to BHT measurements. When BHT is below 10 seconds, only very light physical activity is advised as
walking slowly. When BHT is between 10 to 20 seconds, light physical activity is encouraged as walking
and cycling with nose breathing. When BHT has reached over 20 seconds light moderate training is
advised daily, with intervals if necessary in the beginning to keep up nose breathing. When physical
activity leads to dyspnea, exercise intensity should be lowered. In general, until BHT has reached 60
seconds, physical training should always be guided with BHT measuring and should lead to higher BHT
after training. This is important advice for asthmatics in order to be able to increase their BHT over time.
Research on BM
Several studies on BM have been published.21, 34, 55, 105-111 They mainly investigated the clinical
effectiveness of treatment for asthma. Six of them were randomised, controlled trials (Table 2).
Table 2. Randomized control trials involving BM
First author (date) Study participants Study design Significant Results of BM
1) Bowler (1998)55 39 adults in 2 groups 1. BM vs. ↓Medication use
2. Relaxation + breathing exercises
↓MV
2) Opat (2000)109 36 adults in 2 groups 1. BM video vs. ↓Medication use 2. Placebo video ↑QoL 3) Cooper (2003)106 90 adults in 3 groups 1. BM vs. ↓Symptoms 2. Yoga device vs. ↓Medication use 3. Placebo device 4) McHugh (2003)108 38 adults in 2 groups 1. BM vs. ↓Medication, also ICS use 2. Education +relaxation 5) Abramson(2004)105 95 adults in 4 groups 1. BM + placebo video vs. ↑PETCO2 (4 vs. 3)
2. Asthma education + Buteyko video vs.
↓Medication use
3. Asthma education + placebo video vs.
4. BM + Buteyko video 6) Cowie(2008)21 56 adults in 2 groups 1 .BM vs ↓Symptoms 2. Physiotherapy ↓Medication, also ICS use 7) Prem (2012)110 120 adults in 3 groups 1. Buteyko vs. ↓ Qol 2. Pranayama yoga ↓ Symptoms 3. Control group ↓ Medication use
MV=minute ventilation; QoL=quality of life; ICS=inhaled corticosteroid; PETCO2= partial pressure of end-tidal carbon dioxide; vs. =versus
34
They all demonstrated substantially reduced reliever usage (SABA) and most of them showed increased
quality of life, without impairment of lung function (spirometry). Two studies, (4, 6) also showed reduced
inhaled corticosteroid usage. Cooper et al. (3) compared the method with placebo and the Pink City
Lung Exerciser.
In a non-randomised but controlled study Hassan et al.107 showed, that BHT increased and peak
expiratory flow in one second (PEF1) improved significantly after BM. The study of Bowler et al. (1)
examined therapeutic mechanisms behind the method. They measured lower levels of PETCO2 at
baseline as compared to the control group. They showed a decrease in pulmonary ventilation (V´E) after
the method, but without changes in PETCO2. They also found a correlation between decreased SABA
usage and lower levels of V´E (r2 = 0, 51). The study of Abramson et al. (5), published as an abstract,
reported lower levels of PETCO2 and a marginal reduction in the ventilatory response to CO2 after BM.
Courtney et al.34, showed a significant correlation between short BHT and a thoracic-dominant breathing
pattern, but a negative correlation between PETCO2 and BHT. Another research of Cooper et al.111
demonstrated that mouth-taping without BM had no influence on asthma control in symptomatic
asthmatics.
Until now, research on BM has not been able to fully support the CO2 theory. Thomas et al.32, support
the theory somewhat. They surveyed 210 asthmatic adults using the Nijmegen Questionnaire, a
validated questionnaire that differentiates hyperventilation and dysfunctional breathing. They showed
that hyperventilation is more common in women and in almost 30% asthmatic adults. Further exploration
of the control of respiration and other mechanisms behind the method is needed.112
Breath holding and the Buteyko method
Breath holding competence is an essential part of self-management in BM. BHT is not used for
therapeutic purposes. It is not an exercise, but it gives feedback about risk estimations of symptom
recurrence and exacerbation.9,10 It is also relevant to the respiratory chemosensitivity of CO2.70
Additionally, BHT is shown to have a relation with abnormal spirometry34, PACO2 (Karsten-Voets HMM.
unpublished master thesis, 2006), dysfunctional breathing79, and hyperventilation.113 Success in BM is
evidenced by progressively longer BHT, as chemosensitivity for CO2 decreases and levels of CO2 rise.
However, only a limited amount of research has been done with BHT.
Breath holding measurements are performed differently by different researchers and can possibly
have training effects.79 Nishino et al.70 have investigated different methods of BHT and showed different
training effects (that is, improvements after successive tests), on two distinct periods in the process of
voluntary breath-holding. A first period showed no training effect, and a second period when on-going
breath holding indicated a training effect.
The first period of BHT was hardly influenced by the stress of breath-holding and the activity of the
respiratory muscles. Precise instructions have to be followed to determine a correct BHT. It is measured
while sitting straight, starting after a gentle expiration and lasting until the first desire to breathe again.
This measurement is performed correctly when tidal volume (VT) and frequency (f) are the same before
and after breath holding.9 When breath holding, CO2 accumulates in the blood. The greater the
35
ventilatory response to CO2, the shorter the period of no respiratory sensation during breath holding. A
significant correlation between the first breath-holding period and CO2 chemosensitivity was observed,
and this measure was concluded to be useful in studies for clinical testing causes of dyspnea.70 The BM
uses this BHT protocol and is considered fairly standardized.79 It is mapped in BM and relates to the
extent of ventilation dysfunction.9
The second period of ongoing breath holding after the first period was shown to be influenced by
physiological and non-physiological factors. It improved with successive trials, showing a training effect.
To obtain the ventilatory CO2 response curve, a rebreathing test using a modified Read’s technique 114
was performed for the two periods separately. These tests showed the first “post-expiratory period of no
respiratory sensation” to be below a certain “central threshold of the centrally generated respiratory
motor command signal”.70
Reducing ventilation, as done in BM, is concluded to be a reasonable approach to increase asthma
control.115 Still, there is a need for physiological based explanations of the mechanisms behind the
positive results of BM.4 Studies with detailed ventilation measures at baseline and after a breathing
intervention are proposed.7 Respiratory chemosensitivity for CO2 is recommended as one of the primary
outcome measures of ventilation.7, 115 Research has shown that continually reducing V´E may increase
the ventilatory recruitment threshold of PaCO275, and the protocol of BHT in BM is a significant indicator
for the respiratory chemosensitivity of CO2.70
36
2 Aims and Objectives
The aim of this study is to assess the effects of BM on resting ventilation and asthma control in a group
of asthmatics.
Objectives are to assess the effects of BM on
• Resting ventilation as measured by V’E, PETCO2 and PETO2.
• Perceived asthma control as measured by the ACT and SABA usage.
• Metabolism as measured by V’CO2 and V’O2.
• Respiratory chemosensitivity for CO2 as evidenced by BHT.
37
3 Methods
This was a prospective, controlled, intervention study with 6-month intervention period.
3.1 Participants
We recruited 36 asthmatics from medical centres, the Icelandic Asthma and Allergy Association, general
practitioners, and from pulmonary specialists. All the participants were 18 years or older. To be included,
the asthmatics had to have a physician diagnosis of asthma. They had to have benefited from SABA
use in the four weeks prior to the start of the study. The asthmatics were divided into three groups
according to their SABA use: very mild, when SABA usage was less than or once a month (≤ 1/month);
mild, when SABA usage was less than once a day (<1/day); and moderate, once a day or more (≥
1/day). They also had to be willing to participate in BM. In addition, they gave their oral agreement to be
prepared to do breathing exercises twice a day. Smokers (2 participants) and ex-smokers (1 participant)
were not excluded. Diagnosis of other respiratory diseases, including chronic obstructive pulmonary
disease (COPD) (1 participant) and co-morbidities such as depression, GERD, high cholesterol,
fibromyalgia and obesity were allowed (see Table 3). To evaluate if the groups were comparable, we
paired 20 healthy control participants for gender, age and BMI with 22 asthmatics, who finished the
study. The healthy control participants were obtained by approaching friends, family and employees of
Reykjalundur. They had no history of obstructive airway disorders as asthma nor dyspnea, they did not
use any health related medication and did not know anything about the BM. Smokers were allowed (3
participants). Approval of the National Bioethics’ Committee was obtained before starting this study (see
Appendix A, number VSNb2012010044/03.7). The participants received an introduction letter before
participating to the study (see Appendix C). Participants were provided with written informed consent
forms that they signed in order to participate in this study (see Appendix B).
38
Table 3. Asthma history and medication usage at M1
Gender Age
(years)
Years since
initial
diagnosis
Comorbidity Steroid and
LABA
Steroid
usage SABA
SABA
usage
F 41 Childhood Allergy Pulmicort 1/day Bricanyl* 3/day"
F 45 12 Depression/
GERD Pulmicort 2/day Ventolin 3/day
F 44 Childhood Fibromyalgia/
Rhinitis Flixotide 2/week Ventolin 1/week"
M 21 Childhood N n n Ventolin 3/week"
F 61 21 Allergy Seretide 1/day Ventolin 3/week
F 23 7 n n n Ventolin* 2/day"
F 42 Childhood Obese/
Rhinitis Seretide 2/day Ventolin 3/day
M 71 26 n Flixotide 1/day Bricanyl* 2/day
F 57 28
Fibromyalgia/
Depression/
Rhinitis
Seretide 1/day Ventolin 3/week
F 61 Childhood Adison disease Dexamethasone 0, 5/day Ventolin 2/day"
F 22 Childhood Obese
/Fibromyalgia Symbicort 1/day Ventolin 2/day
M 38 Childhood GERD
/Blood pressure Symbicort 3/week Bricanyl 2/day
F 55 Childhood Mould
/Rhinitis n n Ventolin 2/day
F 64 20 GERD/
Rhinitis n n Ventolin <1/month
M 40 3 Depression/
GERD Seretide 1/day Ventolin 2/day
M 31 25 n Relvar 1/day Bricanyl 2/day
F 33 26 Rhinitis Seretide 1/day Ventolin 3/week"
F 53 Childhood
COPD/
Chrone’s disease/
Diabetes
Seretide 4/day Ventolin* 1/week"
F 21 5 Xolair- injections/
Rhinitis Relvar 2/day Ventolin 3/day
F 56 4 GERD/
Fibromyalgia Flixotide 2/day Ventolin* 3/week"
F 54 Childhood High cholesterol Flixotide n Ventolin 3/week
M 69 62
GERD/
Hypertension/
Rhinitis
Decortin 1/ day Ventolin* 1/week
n = never; F= female; M = male; COPD= chronic obstructive pulmonary disease; GERD= gastroesophageal reflux disease. * = Nocturnal symptoms 1-2 a week “= Limitation of exercises, SABA use not included
3.2 Protocol
Particular emphasis was placed on measuring at complete rest to ensure the least provocation of the
central respiratory centers. Measurements described below were taken at the laboratory in
Reykjalundur, on the weekends, in the early mornings, and before breakfast. While measuring
39
ventilation, all participants sat straight and listened to the same relaxing audio. No food, medication,
alcohol, caffeine, nor physical activity was allowed at least eight hours before measuring. Measurements
were performed in the following order: weight and height, blood pressure and pulse, resting ventilation
and metabolism, BHT, spirometry, and the ACT (see Figure 12). Care was taken to make certain that
all participants were examined with the same protocols and in the order described. Seasonal influences
were taken into account. Measurements of the participants were spread over the year, as asthma
symptoms can be triggered by the changing of seasons.
Measures
To be able to assess our aim and objectives, the following measurements were taken:
Ventilation at rest, metabolism and spirometry
Measurements of resting ventilation (V’E), end-tidal carbon dioxide (PETCO2), end-tidal oxygen (PETO2),
tidal volume (VT), respiratory rate (RR), carbon dioxide output (V’CO2) and oxygen consumption(V’O2),
were sampled. This was done while participants were connected to a metabolic cart device (Vmax
Encore 29, Sensormedics, CA, USA). They were sitting in a straight position and listened to relaxing
audio for 15 minutes while wearing a facemask. The average of the last four minutes of measurements
were used for statistics. The ventilatory equivalent for CO2 output (V’E V’CO2) was calculated. Measures
of lung function variables, including FEV1 and FVC, were made with the same device and were
expressed as percentages predicted for gender, age, height, mass, and ethnicity.49
Asthma control
The ACT was used to measure asthma management.20, 116, 117 (see Appendix D and E). The ACT
involves 5 items assessing asthma symptoms (daytime and nocturnal), the use of rescue medications,
and the effect of asthma on daily functioning. Each item includes 5 response options corresponding to
a 5-point, Likert-type rating scale. Responses for each of the 5 items are summed to yield a score
ranging from 5 (uncontrolled asthma) to 25 (controlled asthma). A score > 19 points indicates well-
controlled asthma.
Symptoms, SABA use and severity.
Asthmatics had to fill out diary cards (see Appendix F). Diary cards supported the asthmatics in
evaluating their asthma and in completing the ACT. They could recognize fluctuations of asthma control
by registering symptoms such as coughing, breathlessness, and chest tightness, and by registering
waking at night, symptom related restrictions in physical activity, missed school/work days, and visits to
their physician or to an emergency department. Symptoms of allergies, medication use, and asthma
exacerbations had to be registered on these cards.
Breath holding time protocol
BHT in BM is the time after a normal exhalation until the very first sensation of shortage of air.
Participants had to sit straight, and, after a gentle expiration, they had to stop breathing by pinching their
nose with mouth closed, until the first desire to breathe again. The measurement was performed
correctly, if VT and f were the same before and after holding their breath. BHT measurements were
40
repeated three times, with one-minute intervals, and the mean was used for statistics. Time
measurements were done with a stopwatch that measures 0.01 of a second.
3.3 Procedure
Data collection was conducted from June 2012 through January 2016. The asthmatics were measured
three times; 6 months before the intervention (M1), just before the beginning of the intervention (M2),
and 6 months later (M3). The first period (M1-M2) was the control period for the asthmatics. The control
group were measured two times, at M1 and M2 (see Figure 11). Fourteen asthmatics, or 39%, did not
finish the study. Five (36%) of them did not attend the BM classes because of personal problems not
related to the study, five (36%) dropped out directly after the classes because of a lack of interest in the
method, and four (28%) of them tried to keep exercising but resigned as they were unable to follow
instructions and do the exercises.
Figure 11. Flowchart of procedure and participants. Measurements were performed for 36 asthmatics. 14 (39%) of them dropped out of the study. The 22 asthmatics left were compared to 20 healthy controls
The asthmatics had to complete the ACT at M1, M2 and M3 and once a month, from M1-M2 (6
times), from M2-M3 (6 times). They also had to fill out diary cards during M1-M2 and M2-M3 (see Figure
12). For examining SABA use at M1, we used their responses to question 4 on the ACT completed at
M1. For examination of SABA usage at M3, we calculated the average use of SABA in the two months
before M3 from their diary cards, when available. When not available, we used the response to question
4 from their ACT.
41
Figure 12. Measurements performed for both groups at M1, M2 and M3
The intervention
The asthmatics were taught BM after M2. According to their registrations, 6 groups of 4-7 participants
were formed. Instructions of the BM were provided in 5, 2-hour sessions over 3 weeks for each group.
The asthmatics were taught the BM by a trained and internationally accredited Buteyko practitioner and
physiotherapist. They were taught techniques designed to reduce their breathing direct and indirect,
according to components of the method. These included awareness, relaxation, nose- and low tidal
volume breathing techniques. Besides other exercises, they received individual management and
guidance on how to avoid deep breathing in daily life.
The participants had to train twice a day; once in the mornings and once in the evenings and register
BHT on diary cards.9, 10 Breath holding measures were taken before and after exercises to evaluate both
the training and progress. To achieve normal ventilation, BHT set-points had to be assessed with an
end goal of 60 seconds. According to BM, physical activity other than walking was not yet advised during
the study. To be able to increase physical activity, BHT had to be over 20 seconds. The asthmatics were
encouraged to stay on their medication regime, as advised by their physician. If they wished to change
their asthma medication, they were advised to discuss this with their physician.
Intervention period
The second period (M2-M3) was the intervention period for the asthmatics. The evaluation day for
assessing progress and training motivation was in the middle of the intervention period. End measures
were taken at the end of the six months intervention period M3, a year after M1 (see Figure 11).
3.4 Statistical analysis
Data was entered into a statistical program (StatView) and was checked for any abnormalities or errors.
Summary statistics were used to analyse the characteristics of the groups. Descriptive statistics were
42
used to identify trends in outcomes, as measures of resting V´E, ACT, spirometry, PETCO2, BMI, and
BHT. We used unpaired students’ t -tests to compare means of measures between groups. Linear
regression was used to find a correlation between changes in BHT and PETCO2. To detect a within
patient change from M1 to M2 to M3 for measures of resting ventilation, ACT, spirometry, PETCO2, BMI
and BHT, ANOVA for repeated test was used with Fisher post hoc analysis, to correct for repeated
comparisons. To detect changes in control group from M1 to M2, paired t-test was used. To test for
differences in changes between the groups from M1-M2 for measured parameters, an unpaired t-test
was used. Responses were expressed as mean ± SD. Statistical significance was set at p < 0.05.
43
4 Results
To evaluate parameters for the 22 asthmatics who finished the study during the control period, their
measurements were compared between M1 and M2. To assess if the asthma group was comparable
to the healthy control group, we compared measurements of the 22 asthmatics to measurements of the
20 healthy control participants at M1 and at M2 and between M1 and M2. To assess the effects of BM,
measurements of the 22 asthmatics performed at M1 and M2 were compared to their measurements at
M3.
Participants
After matching for age, gender, and BMI, there were no significant differences between the asthma and
healthy control groups (see Table 4). A rough examination shows dropouts in the asthma group not to
be different from those who participated in the study.
Table 4. Measures of age, gender and BMI for all participants at M1
M1 Asthmatics (22) Controls (20) p- value
Age (years) 46.1±14.6 45.1±15 NS
Gender(F/M) 16/6 16/4 NS
BMI 27.9±5.3 26.5±5 NS
BMI = body mass index; F = female; M = male; NS= nonsignificant.
Between M1 and M2, there were no significant differences in or between groups in regards to BMI.
Between M1 and M3, the mean of measured BMI had increased in the asthma group (see Table 6).
4.1 Ventilation
Between M1 and M2, no differences were found between the groups for the means of the measured
parameters of ventilation (see Table 5 and 6). Lung function was in the normal range for both groups,
and no significant difference was observed for FEV1 or FVC. However, the FEV1/FVC ratio was
significantly lower in the asthma group, compared to the control group (see Table 5).
Table 5. Ventilation measurements at M1
M1 Asthmatics (22) Controls (20) p- value
V´E 6.7±1.7 6.4±1.3 NS
FEV1(L) 3.06±1.1 3.36±1.0 NS
FEV1(% pred) 96.6±21.2 105.8±14.1 NS
FVC(L) 4.04±1.1 4.20±1.3 NS
FVC (% pred) 108.6±17.1 112.3±17.7 NS
FEV1/FVC 74±1 80±1 0, 04
V´E = pulmonary ventilation; BHT = breath holding time; FEV1 = forced expiratory volume in one second; FVC = forced vital capacity; pred. = predicted; L = litre; NS = non-significant
At M3, in the asthma group, the means of measured FEV1 and FVC decreased, but the ratio of
FEV1/FVC did not change (see Table 6).
44
PETCO2 and PETO2 were measured to examine alveolar ventilation. In the asthma group, significant
changes were seen between the means of measures from M1 to M3 and from M2 to M3, as PETCO2
increased and PETO2 decreased (see Figure 13).
Figure 13. Partial pressures of end-tidal carbon dioxide (PETCO2) and oxygen (PETCO2) of the asthma group (blue) versus the control group (blue) at three different time points. Points represent mean values and standard deviations for the asthma group and the control group. *= p<0.05 in M3 versus previous
In the asthma group, the means of measures of V‘E and VT decreased between M1 and M3, and M2 and
M3, but the mean of RR remained the same (see Table 6).
Table 6. Parameters before (M1), after the control period and before intervention (M2), and after intervention period in the asthmatic group (M3) as compared to their controls.
Asthmatics (n=22) Controls (n=20)
M1 M2 M3 M1 M2
BMI 27.9±5.3 28.3±5.5 28.7±5.9* 26.5±5 26.4±5.1
FEV1 (% pred.) 96.6±21.2 99.05±19.5 93.8±18.2* 105.8±14.08 105.2±14.34
FVC(% pred.) 108.6±17.1 109.9±18, 1 104.5* 112.3±17.67 112.2±19
FEV1/FVC 74±1 75±1 75±1 80±0.7¥ 80±0.7
V‘O2 L/min 0.180±0.07 0.187±0.06 0.146±0.06* 0.191±0.06 0.196±0.05
V‘CO2 L/min 0.148±0.06 0.16±0.06 0.118±0.05* 0.152±0.05 0.153±0.04
V´E L/min 6.65±1.74 6.88±2.00 5.69±1.70* 6.38±1.3 6.43±1.4
VT(L) 0.58±0.21 0.68±0.27 0.49±0.16* 0.67±0.27 0.66±0.18
RR(per minute) 12.2±2.7 11.1±2.9 12.2±3 10.9±3.5 10.7±2.9
V‘E/V‘CO2 48.3±10.5 44.4±7.7 52.2±13.3* 43.9±9.9 43.3±7.8
FEV1 = forced expiratory volume in one second; FVC = forced vital capacity; pred. = predicted; V’O2 = oxygen consumption; V´CO2 = carbon dioxide output; V´E = pulmonary ventilation, VT = tidal volume, RR = respiratory rate, V’E/V’CO2 = ventilatory equivalent for carbon dioxide. * = p<0.05 in M3 versus previous measurements, ¥ = p<0.05 in control versus asthmatics.
45
4.2 Asthma control
To interpret asthma control, scores from the ACT were examined. At M1 and M2, the asthmatics were
not well controlled, with mean scores of 16.7 and 18.6 respectively. At M3, the mean score was 21.3,
indicating well-controlled asthma (see Figure 14).
Figure 14. Results from the ACT. Bars represent mean values of scores with standard deviations. Scoring > 19 points indicates well-controlled asthma. * = p<0.05 in M3 versus previous measures.
The number of asthmatics with SABA usage ≤ 1/month, or very mild, increased from 1 to 14. Participants
from the asthma group with SABA usage < 1/day, or mild, decreased from 9 to 7. The subgroup with
usage ≥ 1/day, or moderate, decreased from 12 to 1 (see Figure 15). This is calculated to an 85% drop
in SABA usage in the 22 asthmatics. Precise measures of combinations of LABA and inhaled and/or
oral corticosteroids were not performed in this study, but an estimation indicated a decrease of 45%.
Figure 15. SABA usage before and after the Buteyko method. Number of participants according to their SABA use before and after BM. Very mild = ≤ 1/month; mild = < 1/day ; moderate = ≥ 1/day.
46
4.3 Metabolism
To be able to evaluate metabolism, measures of V´O2 and V´CO2 were examined. Between M1 and M2,
the means of these measures did not show differences between the groups (see Table 6). At M3, the
means of measured V´O2 and V´CO2 decreased. As these metabolic measures decreased more than
V´E after the intervention (p < 0.05), values of V’E/V’CO2 increased significantly between M2 and M3.
(see Table 6).
4.4 Breath holding time
BHT was measured to evaluate respiratory chemosensitivity for CO2. At M1 and M2, the results showed
that the asthma group had significantly shorter BHT than the control group. At M3, the mean of BHT
measures became longer in the asthmatic group (see Figure 16).
Figure 16. Breath holding time measures for the asthma group (blue) versus the control group (orange), at three different time points. Points represent mean values and standard deviations for the asthma group and the control group. ¥ = p<0.05 in control group versus asthma group; ¤ = p<0.0001 M3 versus previous measure.
The correlation for changes of measured BHT and PETCO2 was evaluated. A significant correlation
was found when one extreme case with highly variable PETCO2 and BHT levels was excluded. This case
was taken out, as the cause of these extreme values could have been a high dosage of oral steroid use
at M2. The coefficient of determination between the changes in BHT and changes in PETCO2 was r2 = 0,
2772, p<0.02 (see Figure 17).
47
Figure 17.∆ BHT Line Fit Plot without extreme case. A significant correlation was found for changes in BHT and PETCO2 when the extreme case was excluded (r 2 = 0.2772, p<0.02).
In summary, the effects of BM were visible in changed means of measures of resting ventilation, higher
levels of PETCO2, lower levels of PETO2, together with increased asthma control and reduced respiratory
chemosensitivity for CO2 in asthmatics.
5 Discussion
The results showed no difference in resting ventilation in asthmatics at baseline as compared to their
healthy controls. However, BHT among the asthmatics was shorter before BM, indicating higher
respiratory chemosensitivity for CO2. Values of BHT were longer after BM, which is in accord with lower
respiratory chemosensitivity for CO2. Higher values of PETCO2 and lower values of PETO2 were measured
after BM, indicating decreased values of V´A/V´CO2. Both V´E and metabolism decreased after the
intervention, the latter more than the former, resulting in increased V´E/V´CO2. Higher values of
V´E/V´CO2 and PETCO2 and lower values of PETO2 implied more dead space ventilation, due to changes
in breathing patterns, i.e., lower VT. Asthma was not-well controlled before, but well controlled after, BM.
Lung function measures such as FEV1 and FVC decreased, but their ratio stayed the same after the
intervention.
5.1 Pre-intervention
Ventilation was examined at utmost rest in our participants, with the least provocation of respiratory
control. In these conditions, no marked increase in ventilation is shown in the asthma group. Increased
ventilation is expected from past studies and from the theory of the BM.39, 45, 60, 118, 119 Thomas et al.32, 39
tried to evaluate hyperventilation in asthmatics using the Nijmegen questionnaire (NQ)120, a validated
screening tool to distinguish people who hyperventilate from people who do not.38 They reported that
one third of asthmatic women and one fifth of asthmatic men had symptoms associated with
hyperventilation or dysfunctional breathing.39 Bowler et al.55 confirmed significantly lower levels of
PETCO2 at rest in asthmatics as compared to a normal group, without evidence of clinically increased
breathing. In a controlled study of 23 mild and stable asthmatics, Osborne et al.60 reported significant
lower levels of PETCO2 and PaCO2 at rest in asthmatics, compared to healthy controls. Still, they could
48
not show clinically significant hyperventilation. It is difficult to understand the exact reasons for these
findings as they did not measure metabolism. Also, as Osborne et al. themselves noticed, measures
were taken with a mouthpiece and nose clip, which could have influenced breathing.121 Furthermore, it
may be argued whether patients were measured at complete rest in the study of Osborne et al. Although
participants were not allowed to use caffeine nor bronchodilators eight hours before measuring, other
features could have influenced their ventilation such as emotional state, recent physical activities, food
intake, and posture.122, 123 In our study, by measuring in protocolled optimal resting circumstances, with
the least physical and psychological challenges, we tried to normalize conditions pertinent to the disease
and reduce variability that could contribute to our findings for both groups. Hormbrey et al.45 examined
breathing patterns in symptomatic asthmatics, in people with symptoms of hyperventilation and in
healthy subjects. At rest, the asthmatics had significantly higher V´E and lower levels of PETCO2 (37
mmHg), compared to people who were supposed to hyperventilate (40 mmHg) and healthy subjects (41
mmHg). However, there were only 6 participants in each group. In this study, hyperventilation was
related to changes in CO2 levels rather than long-term CO2 levels. William N. Gardner41 explained that
voluntary hyperventilation can result in a drastic removal of alveolar CO2 (PACO2), primarily coming from
alveolar gas, then from blood in pulmonary veins, from the left side of the heart, and, finally, from the
first part of systemic circulation. Hence, a few minutes after hyperventilating, partial pressure of PACO2
had returned to normal. A new balance had been achieved between a wash-out from the lungs and the
tissues with same PACO2 levels, corresponding to “a 50% change of CO2 content of the body tissues
with a change of 5 minutes in PACO2”. The reviews of Bruton et al.115 and Meuritz et al.61 have shown
asthmatics to have a tendency of lower levels of PaCO2, compared to healthy subjects. Also, Dr.
Konstantin Buteyko, who developed the BM, claimed that hidden hyperventilation is one of the causes
of asthma. The primary goal of BM is to decrease ventilation, balance it with metabolism, thereby raising
levels of CO2.9 Hence, other factors need to be sought to explain the theory of the BM.
Asthma in the study subjects was not-well controlled at baseline, according to the mean scores from
the ACT. This finding is somewhat similar to the results of the study of Demoly et al.25, where they also
used the ACT to evaluate asthma control. They concluded that asthma was not well controlled in more
than half of the treated asthmatics in 5 countries in Europe. Furthermore, Papaioannou et al.24 explained
that, world-wide, asthma is only controlled in a small percentage of patients. Most of the asthmatics in
our study were asymptomatic during the measurements, but they were symptomatic during the study.
The severity of their symptoms during the M1-M2 period varied widely. As their SABA use varied from
once a month to more often than once a day, they were divided in three subgroups, corresponding with
very mild (≤ 1/month), mild (< 1/day) to moderate (≥1/day) SABA use, according to the study of Osborne
et al.60 At baseline, 4.5% were very mild, 41% were mild, and 54.5% were moderate.
The mean values of FEV1/FVC were lower for the asthmatics in our study, confirming decreased lung
function as compared to the healthy control group. Ventilation per metabolism (V’E/V’CO2) was higher
for the asthmatics in our study, but not significantly so. These differences of V’E/V’CO2 between
asthmatics and the healthy control group may have become clearer with a larger number of participants.
BHT for the asthmatics was shorter (14.1± 8.2 sec, p< 0.05), compared to the healthy controls, (19±
7.1 sec). According to Nishino et al.70, shorter BHT is related to increased dyspnea and greater
49
respiratory chemosensitivity for CO2. The longer the breath can be held, the better the accumulation of
CO2 is tolerated, the lower respiratory chemosensitivity for CO2. This result conforms to the results in
the review of Hida et al.78, where they indicated that the ventilatory drive in asthmatics is affected by
respiratory chemosensitivity for CO2. They also showed in this review, that the ventilatory drive is related
to asthmatics with both a decreased sensation of dyspnea (as in asthmatics who have experienced near
fatal asthmatic periods) and an increased sensation of dyspnea (as in asthmatics who did not have
experienced near fatal asthmatic periods). They concluded that the ventilatory drive has a fundamental
role in determining the severity of asthma. Also, Kassabian et al.77 showed an increased respiratory
chemosensitivity for CO2 in asthma. Still, in their study PETCO2 and PETO2 were similar to the control
group at baseline, showing no evidence of increased V´A at rest. In literature, it is suggested that PETCO2
can be normal in people with symptomatic hyperventilation at rest.40 Han et al.89, did not find changes
of PETCO2 at rest for people suffering from hyperventilation and anxiety, as compared to people who did
not had those issues. They characterized people who hyperventilate as having a respiratory control
system that is more sensitive to provocation and with unstable breathing patterns. Macnutt et al.124
showed chemosensitivity for CO2 to be higher in women than in men.
It is an attractive proposition to hypothesize that the asthmatics with shorter BHT in this study have
an inefficient or dysfunctional way of breathing; the underlying central respiratory rhythm will regenerate
quicker but only when provoked, resulting in more quickly increased ventilation as when symptomatic.
Increased ventilation decreases levels of PaCO2 and triggers dyspnea sooner compared to subjects
with longer BHT.62, 75 Furthermore, the relation between levels of PETCO2 and bronchodilation/-
constriction is well known in physiology49 and this relation is confirmed by experimental studies of O´Cain
et al.125, van den Elshout et al.91 and other studies.47, 61, 91
5.2 Post-intervention
This study evaluated the effect of the BM on resting ventilation and asthma control in asthmatics. Our
findings showed that asthmatics had retrained their breathing patterns without any study-related adverse
effects. At M3, the asthmatics had become more aware of their breathing and had avoided deep
breathing. Some had even experienced changes in their breathing patterns, such as being aware of
greater breath suspension episodes in daily life, indicating slower RR. However, our data showed no
significant change in RR, but a significant change in VT. This is consistent with the study of Wolkove et
al.74, when they investigated the physiology of ventilation during transcendental meditation (TM) as a
relaxation method. Their results showed minute volume (V’E) to decrease due to a decreased tidal
volume (VT). In their study, VT was smaller at same levels of PETCO2 compared to controls, and these
findings were associated with the chemical and neural regulation of ventilation. Our data also showed
increasing levels of PETCO2 together with decreasing levels of PETO2. According to physiology, these
are indicators of lowered values of V´A in relation to V´CO2. Bowler et al.55 showed reduced V´E after BM
(14 ± 6.5 versus 9.6 ± 3.1 L/min), but without measuring metabolism and with unchanged low levels of
PETCO2. Abramson et al.105 were able to show increased PETCO2 levels after BM. Ritz et al.47 showed
higher levels of PETCO2 after a capnometry assisted respiratory training (CART), but not after slow
breathing and awareness training (SLOW). These trainings were not according to the BM, but they were
50
based on the hypothesis that raised levels of CO2 could increase asthma control. Still, subjects in both
studies increased asthma control, implying that the results only partially supported the hypothesis that
CO2 is related to asthma control.
Asthma was well-controlled after the BM, as average scores for the ACT reached above the set-point
of 19. In the BM, asthmatics were not encouraged to diminish their medication usage unless advised by
their physician. They were instructed to use the BM techniques before using rescue medication. Asthma
control increased in all other research that investigated the effectiveness of the method.21, 55, 81, 106, 108,
109, 126 In our study, after BM, SABA usage had decreased for 85% of the participants. Of those, 63.6%
were with very mild, 31.8% were with mild and 4.6% with moderate SABA usage. Bowler et al.55 also
showed a reduction of SABA usage and found a correlation with reduced V´E, r2= 0, 51 p < 0.004.
Although FEV1 and FVC decreased significantly for the asthmatics, the FEV1/FVC ratio remained the
same after BM. These results resembled the results from Fenger et al.65, where they concluded changes
of adiposity altered levels of FEV1 and FVC, but values for the FEV1/FVC ratio stayed the same.
Metabolism in the asthmatics had reduced at M3, as both values of V’O2 (0.180 ± 0.07 vs. 0.146 ± 0.06
L/min; p < 0.05) and V’CO2 (0.148 ± 0.06 vs 0.118 ± 0.05 L/min; p < 0.05) had decreased. The results
also showed that asthmatics gained weight at M3 as compared to M1. It can be assumed that these
findings are correct as metabolism remained the same in M1-M2 for both groups. A possible explanation
for asthmatics gaining weight could be decreased SABA or B2-agonists usage. Studies84-86 have
confirmed metabolic side effects of B2-agonists in asthma and have suggested these to increase the
metabolic rate in asthmatics. Agha et al. concluded that asthmatics have higher basal metabolic rates
than normal subjects.84 Less B2-agonist usage could possibly have caused weight gain, however slight,
in our study. Increased asthma control and decreased SABA usage was accomplished by reduced
breathing according to our results. The study of Wallace et al.83 showed that meditation reduced
metabolic rates. Other studies examining meditation and relaxation therapies have shown a shift from
sympathetic to parasympathetic dominance in the ANS, together with reduced breathing.71-74 In addition
to this, Matsumoto et al.127 concluded that the bronchodilation effect of B2-agonist medication is through
activation of the sympathetic nervous system. For these reasons, it is suspected that the nervous system
has an impact on the weight gaining effect of reduced breathing and reduced B2-agonist usage.
V’E decreased, but when we corrected V’E for metabolism, we found an increase in values of
V’E/V’CO2 (44.4 ± 7.7 vs. 52.2 ± 13.3; p < 0.05) after BM. Although both V´E and metabolism decreased,
V´E decreased less than metabolism. At the same time values of PETCO2 increased and PETO2
decreased, which is considered supportive for lower values of V’A/CO2. Higher values of V’E/V’CO2 and
estimated lower values of V’A/CO2 after BM, indicate that more energy is wasted in dead space
ventilation. An explanation could be that these changes are derived from a decline in VT, without
changes of RR. The percentage of breathing lost in dead space ventilation (V´D) increases when VT
decreases. In this phase of BM, it could be said that the asthmatics (still) breathe ineffectively or
dysfunctionally. They are in the middle of changing their breathing patterns and life style. They still have
a long way to go to reach the 60-second BHT end-goal of BM, and reducing their RR will very likely be
a part of it.
51
In this study, asthmatics reached the BHT set-point of 20 seconds at M3 (25 ± 8.7 sec). These
measures became similar to measurements from the control group (21.5 ± 11.3 sec). They were similar
to measurements from BHT (13.4 ± 5.19 vs. 22.67 ± 7.38, p < 0.0005) after BM in the study of Hassan
et al.107, when they examined BM on patients with bronchial asthma. Our study presented a positive,
significant correlation for the changes in BHT and PETCO2. The coefficient of determination (r2) between
the changes in BHT and the changes in PETCO2 is r2 = 0, 2772, p< 0.02, indicating that almost 30% of
higher levels of PETCO2 were due to less respiratory chemosensitivity for CO2, as evidenced by higher
BHT. According to Ninisho et al.70, this implicated less dyspnea. In the context of these results, it could
be said that breathing less means less breathlessness.
Our results could be considered supportive for the theory of the BM in that they provides evidence
that confirms reduced breathing to increase asthma control. Higher levels of PETCO2, lower levels of
PETO2, together with increased asthma control may be fundamental to the pathophysiology of asthma.
BM, apparently, reduced the chemosensitivity for CO2 and this might have taken away the underlying
causes of asthma. This study also indicated that breathing patterns may be altered and that the steady
state of ventilation can be reset.
There were undoubtedly nonspecific intervention and professional attention effects that could cause
spontaneous improvements of symptomatic asthmatics, as mentioned in Gina16 and other studies.4, 98,
112 Factors such as relaxation, self-efficacy, and voluntary reduce of medication could partially have
caused the results of the intervention. The techniques used in the BM gave the asthmatics a feeling of
control, reducing their anxiety about their symptoms. The BHT in BM gave asthmatics information about
their progress and results, and improvements might have enhanced their self-efficacy.21, 46, 81, 109
5.3 Strength and limitations
Complex interventions like these were methodologically difficult to control. Our design of comparing an
asthmatic group to themselves as their own control group and comparing them to healthy participants
provided a credible control procedure. Therefore, our results can be related to aspects of the
intervention.
We examined asthma control and ventilation at rest in people with asthma who found relief from
medication. Our most important preselection was that the asthmatics had to have benefited from the
use of rescue reliever medication in the last month. We measured in protocolled optimal resting
circumstances, with minimal physical and psychological challenges. We tried to normalize conditions
pertinent for the disease and reduced variability that could contribute to our findings for both groups. We
tried to assess seasonal effects involving different risk factors on asthma by measuring the groups at
different times of the year. Allergies in summertime and cold dry air in wintertime are the most observed
triggers in this study. The BM was unknown in Iceland, and it was possible that asthmatics could have
found information about the method on the internet or elsewhere, as it was mentioned in our
advertisements for participants.
Limitations
Although a sample size of 20 participants in each group was statistically predicted to be sufficient, bigger
sample sizes would have given even more reliable results.
52
Having more asthmatics participate in the study and randomising them for a BM group and an
untreated group would have made the study a randomised trial. Finding asthmatics willing to participate
was difficult, and this would have taken too long time. The BM is a complemental treatment to initial
treatment strategies, according to guidelines of asthma management. Physicians and lung specialists
in Reykjavík were informed about the BM, but it was difficult to encourage them to help us to find the
right participants. Only two of the subjects had been encouraged by their physician to participate in this
study, but most of the participants had seen recruitment material in pharmacies or medical centers. The
Buteyko method is still unknown on Iceland and, one could say, revolutionary. That could be one of the
reasons why it was difficult to find participants in a small society like Iceland. Further on, it would have
been appropriate for the researcher to inform the family physicians of the asthmatics of their participation
in the study to keep the physicians informed.
We have not been able to assess hyperventilation or dysfunctional breathing in our asthmatics with
the Nijmegen Questionnaire, 38 as this questionnaire has not yet been translated into Icelandic and
tested in Iceland. The inclusion criteria of benefitting from SABA use in the last month was subjective. It
would have had more significance if benefitting from SABA was confirmed in lung function testing. Also,
it would have been interesting to examine psychiatric disorders such as depression and anxiety
assessments. Other studies have evaluated psychiatric disorders and suggested a relationship between
anxiety, depression, and asthma control.29, 60 This could have contributed to the examination of who
benefits the most from these breathing methods.
As nasal breathing is emphasized, it is likely to have affected NO levels in our participants. NO is
produced in many cells in the body and also in the endothelium of the paranasal sinuses. NO is involved
in a large number of physiological processes; it has both local effects such as host-defence by keeping
the nasal sinuses sterile, and distal effects such as bronchodilation, vasodilatation, improving
ventilation/perfusion matching, O2 transport, and immune responses.50, 128
A considerable number of participants dropped out of the study, or 14 (39%) of the 36 asthmatics.
This was not unexpected as participation required a long-term commitment of the participants. The
intervention was complex, involving lifestyle changes and most participants were in their forties. These
could be important limitations, as young people might change their lifestyles more easily. The two
youngest people in our study, 19 and 21 years old, demonstrated significant positive results shortly after
the intervention. Further explanations could be that participants did not pay for the Buteyko method, nor
were they rewarded in any way. The method is unknown, revolutionary and not encouraged by
physicians and this could have an influenced their enthusiasm in compliance with exercising.
Actual compliance with the daily exercises and diary cards was not closely monitored. These
trainings require considerable commitment from the individual patients, in terms of time and effort. The
BM is best suited to people who do not want a quick fix, are not content with medication use, and are
prepared to change life habits. The belief in therapy efficacy grew among the asthmatics who completed
the study, in response to experiencing improvements in their condition. All of the 22 participants reached
the 20-second set point of BHT.9, 10 To reach the 60-second end-goal of the BM, longer follow ups are
required. Then, physical exercise would also become part of the instructions.
53
5.4 Future studies
Asthma diagnose involves a variety of phenotypes. Different therapies may be effective for different
people, and it is not known who benefits most from breathing exercise methods. This study has not
approached this knowledge. Further investigations with breathing methods such as BM are needed.
Longer follow ups are preferable, at least until the BM end-goals are reached for each participant. A
measure of commitment for being prepared to train breathing should be one of the criteria included.
Also, measurements evaluating inflammatory biomarkers, bronchial reactivity, and hyperventilation
assessments, with questionnaires such as the Nijmegen questionnaire38, and blood gas tests are
preferable. This is important for correctly diagnosing and targeting who (according to personality and
breathing style) would benefit most. It would be interesting to investigate the method with children. Two
studies with children have been done and have shown excellent results.129, 130 Studies with severe
asthma offer interesting options to examine whether severe asthmatics can obtain better control with
the method. One study131 examined BM and physical exercise and another is on-going in Germany. It
would be important to investigate if, and what type of asthmatic, hyperventilates during physical
exercise, by examining blood gases. All this is crucial in assuring that the method will become a
responsible and cost-effective part of overall asthma management.
6 Conclusion
In summary, this study provided detailed information about the physiology of ventilation at rest and
asthma control in asthmatics, before and after the Buteyko method. This study showed no evidence of
dissimilar ventilation or PETCO2 at baseline, when measured at utmost rest, compared to a healthy
control group. Asthma was well-controlled after the method, as evidenced by scores from the ACT.
Symptoms decreased and medication use reduced: SABA use by 85% and a combination of
LABA/steroid use was reduced by approximately 45%. The study suggested that asthmatics have
greater respiratory chemosensitivity to CO2, as evidenced by shorter BHT. V´E, chemosensitivity and
metabolism at rest decreased after BM, but V´E/CO2 increased. Values of PETCO2 increased and values
of V´E and PETO2 decreased, indicating decreased values of V´A/CO2 after the BM. As the distance
between estimated V´A/CO2 and V´E/CO2 increased after BM, it may be concluded that dead space
ventilation also increased. Increased dead space ventilation is assumed to be a result of decreased tidal
volumes. Measures of lung function as FEV1 and FVC decreased, probably because of lower metabolic
rates, but their ratio (FEV1/ FVC) remained the same.
In this study, we have tried to give information about the plasticity of chemical ventilatory control and
we suggested the BM to have affected the underlying pathophysiology of asthma without disturbing lung
function. These results could be important for evaluating therapies for asthma and influencing public
health regimes for the management of asthma. Still, asthma is often poorly controlled, despite broadly
endorsed management guidelines. It is important for physiotherapists to be able to offer asthmatics a
scientifically based and acknowledged103 breathing exercising method. SABA usage diminished
enormously. Since medication costs for asthmatics are increasing and safety profiles of these
medications have come under scrutiny, adequate usage and reduction of medication implies a
54
pharmacy-economic benefit for asthmatics and Iceland. These results could also encourage clinicians
to offer qualified, physiotherapy support to patients with asthma for better control of their asthma.
Breathing less means less breathlessness.
55
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91. Van den Elshout FJ, Van Herwaarden CL, Folgering HTM. Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. . Thorax 1991;46:28-32.
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95. Ernst E. Complementary therapies for asthma: what patients use. J Asthma 1998;35:667-71.
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105. Abramson M BB DC, Giolando F, Hartley F. A randomised controlled trial of the Buteyko Method for asthma. Int J Immunorehabil 2004.
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107. Hassan ZM, Riad NM, Ahmed FH. Effect of Buteyko breathing technique on patients with bronchial asthma. Egyptian Journal of Chest Diseases and Tuberculosis 2012;61:235-41.
108. McHugh P, Aitcheson F, Duncan B, Houghton F. Buteyko Breathing Technique for asthma: an effective intervention. N Z Med J 2003;116:U710.
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109. Opat AJ CM BM, Abramson MJ. . A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video. J Asthma 2000;37(7):557-64.
110. Prem V, Sahoo RC, Adhikari P. Comparison of the effects of Buteyko and pranayama breathing techniques on quality of life in patients with asthma - a randomized controlled trial. Clinical rehabilitation 2013;27:133-41.
111. Cooper S, Oborne J, Harrison T, Tattersfield A. Effect of mouth taping at night on asthma control--a randomised single-blind crossover study. Respir Med 2009;103:813-9.
112. Courtney R. Strengths, Weaknesses, and Possibilities of the Buteyko Breathing Method. Biofeedback; 2008:59-63.
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114. Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australasian annals of medicine 1967;16:20-32.
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120. van Dixhoorn J, Duivenvoorden HJ. Efficacy of Nijmegen Questionnaire in recognition of the hyperventilation syndrome. J Psychosom Res 1985;29:199-206.
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124. Macnutt MJ, De Souza MJ, Tomczak SE, Homer JL, Sheel AW. Resting and exercise ventilatory chemosensitivity across the menstrual cycle. J Appl Physiol (1985) 2012;112:737-47.
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127. Matsumoto K, Aizawa H, Fukuyama S, et al. Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma. Respiratory investigation 2013;51:158-65.
128. Lundberg JO, Weitzberg E. Nasal nitric oxide in man. Thorax 1999;54:947-52.
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63
Appendix A
64
Appendix B
FYLGISKJAL 3a
Vegna vísindarannsóknarinnar
„Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins?“
Samþykkisyfirlýsing fyrir þátttakendur með astma.
Markmið og tilgangur rannsóknarinnar er að kanna hvort og hvernig Buteyko öndunarmeðferð hafi áhrif á einkenni og stjórnun á astmasjúkdómnum. Meðferðin byggir á því að með öndunaræfingum sé hægt að minnka astmi einkenni og lyfjanotkun. Niðurstöðurnar geta verið gagnlegar fyrir bættan skilning á astmasjúkdómnum.
Þátttaka í rannsókninni felur í sér að taka þátt í öndunarmeðferð í hópi og halda áfram reglubundnum æfingum samkvæmt leiðbeiningum í allt að sex mánuði. Jafnframt að halda dagbók um lyfjanotkun og líðan. Þátttakan felur einnig í sér að mæta alls þrisvar sinnum í mælingar á Reykjalund á árs tímabili, sem taka um hálfa klukkustund í senn.
Ég staðfesti hér með undirskrift minni að ég hef lesið upplýsingarnar um rannsóknina sem mér voru afhentar, hef fengið tækifæri til að spyrja spurninga um rannsóknina og fengið fullnægjandi svör og útskýringar á atriðum sem mér voru óljós. Ég hef af fúsum og frjálsum vilja ákveðið að taka þátt í rannsókninni.
Mér er ljóst að þó ég hafi skrifað undir þessa samstarfsyfirlýsingu, get ég hætt þátttöku hvenær sem er án útskýringa og án áhrifa á þá læknisþjónustu sem ég á rétt á í framtíðinni.
Mér er ljóst að rannsóknargögnum verður eytt að rannsókn lokinni og eigi síðar en eftir 5 ár frá úrvinnslu rannsóknargagna.
____________________
Dagsetning
___________________________________________________
Nafn þátttakanda
Undirritaður, starfsmaður rannsóknarinnar, staðfestir hér með að hafa veitt upplýsingar um eðli og tilgang rannsóknarinnar, í samræmi við lög og reglur um vísindarannsóknir.
Undirskrift:___________________________________ Dagsetning:____________________
65
FYLGISKJAL 3b
Vegna vísindarannsóknarinnar
„Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins?“
Samþykkisyfirlýsing fyrir þátttakendur í samanburðarhópi.
Markmið og tilgangur rannsóknarinnar er að kanna hvort og hvernig Buteyko öndunarmeðferð hafi áhrif á einkenni og stjórnun á astmasjúkdómnum. Niðurstöðurnar geta verið gagnlegar fyrir bætann skilning á astmasjúkdómnum.
Þátttaka í rannsókninni felst í því að mæta í mælingar tvisvar sinnum á Reykjalund með 6 mánaða millibili. Hvor heimsókn tekur hálfa klukkustund og er þátttakanda að kostnaðarlausu.
Ég staðfesti hér með undirskrift minni að ég hef lesið upplýsingarnar um rannsóknina sem mér voru afhentar, hef fengið tækifæri til að spyrja spurninga um rannsóknina og fengið fullnægjandi svör og útskýringar á atriðum sem mér voru óljós. Ég hef af fúsum og frjálsum vilja ákveðið að taka þátt í rannsókninni.
Mér er ljóst að þó ég hafi skrifað undir þessa samstarfsyfirlýsingu, get ég stöðvað þátttöku mína hvenær sem er án útskýringa og án áhrifa á þá læknisþjónustu sem ég á rétt á í framtíðinni.
Mér er ljóst að rannsóknargögnum verður eytt að rannsókn lokinni og eigi síðar en eftir 5 ár frá úrvinnslu rannsóknargagna.
____________________
Dagsetning
___________________________________________________
Nafn þátttakanda
Undirritaður, starfsmaður rannsóknarinnar, staðfestir hér með að hafa veitt upplýsingar um eðli og tilgang rannsóknarinnar, í samræmi við lög og reglur um vísindarannsóknir.
Undirskrift:___________________________________
Dagsetning:____________________
66
Appendix C
FYLGISKJAL 2a
Upplýsingar vegna vísindarannsóknar.
„Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins?“
Ábyrgðamaður rannsóknarinnar er : Dr.Marta Guðjónsdóttir, lífeðlisfræðingur, lektor við Læknadeild Háskóla Íslands og rannsóknastjóri á Reykjalundi.
Sími: 8679890 Tölvupóstfang: [email protected]
Aðrir rannsakendur eru: Monique van Oosten, sjúkraþjálfari, Buteykoþjálfari og meistaranemi í lýðheilsuvísindum.
Sími: 8998456. Tölvupóstfang: monique@centrum
Kæri viðtakandi.
Rannsóknin „Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins“ er meistaraverkefni Monique van Oosten sjúkraþjálfara við námsbraut í Lýðheilsuvísindum við Læknadeild Háskóla Íslands. Leiðbeinandi hennar er Dr. Marta Guðjónsdóttir. Þér er boðið að taka þátt í rannsókninni þar sem þú hafðir samband við Monique í framhaldi af auglýsingu.
Tilgangur rannsóknarinnar er að kanna hvort og hvernig öndunarmeðferð (Buteyko) hafi áhrif á einkenni og stjórnun á astmasjúkdómnum. Buteyko öndunarmeðferðin er viðurkennd meðferð, hún hefur sýnt mjög góðan árangur og stangast ekki á við hefðbundnar meðferðir. Meðferðin byggir á því að með öndunarmeðferð sé hægt að minnka astmaeinkenni og lyfjanotkun.
Þér er boðin að taka þátt ef þú ert 18 ára og eldri, hefur greinst með astma sjúkdóminn, hefur haft þörf fyrir stuttverkandi berkjuvíkkandi lyf eins og Ventolin, einu sinni í viku eða oftar undanfarnar fjórar vikur og ert tilbúin að taka þátt í meðferð og stunda öndunaræfingar reglulega. Ekki verður greitt fyrir þátttöku en mælinga og meðferð verður þáttakendum að kostnaðarlausu. Ef þátttakandi óskar þess munu rannsakendur senda lækni viðkomandi niðurstöður mælinganna sem gerðar eru.
67
FYLGISKJAL 2a
Í hverju felst þátttakan? Þátttaka varir í 12 mánuði og gert er ráð fyrir:
� Þremur heimsóknum á Reykjalund, endurhæfingarmiðstöð SÍBS með 6 mánaða millibili. Hver heimsókn tekur um það bil 30 mínútur þar sem mæld verður öndun, blóðþrýstingur, hæð og þyngd. Því til viðbótar eiga þátttakendur að fylla út spurningarlista um astma með fimm spurningum sem tekur um 5-10 mínútur að svara. Lyfjanotkun verður skráð.
� Þátttöku í 8-9 manna hópi sem mætir í 5 skipti í öndunarmeðferð, í 2 klukkustundir í senn á tveggja og hálfs vikna tímabili. Eftirfylgd verður eftir þrjá mánuði til að meta árangurinn. Hugmyndafræði og Buteyko öndunaræfingar verða kenndar og gert er ráð fyrir að þátttakendur stundi æfingar heima í 15 til 30 mínútur daglega.
� Að halda dagbók um líðan og lyfjanotkun.
Monique van Oosten mun veita frekari upplýsingar í síma eða tölvupósti um meðferðina ef þörf krefur allt rannsóknartímabilið.
Áhætta og ávinningur: Áhætta af þátttöku er engin en beinn ávinningur er fyrir þátttakendur þar sem mjög góð reynsla er af öndunarmeðferðinni þar sem vísindarannsóknir benda til að meðferðin minnki verulega þörf astmasjúklinga fyrir lyf og auki lífsgæði þeirra. Auk þess fá þátttakendur mælingar sér að kostnaðarlausu. Niðurstöðurnar af rannsókninni geta verið gagnlegar fyrir bættan skilning á astmasjúkdómnum og meðferð við honum. Rannsókn þessi er gerð með samþykki Vísindasiðanefndar og hún hefur verið tilkynnt Persónuvernd.
Aðgengi að rannsóknargögum: Allar upplýsingar sem þátttakendur veita í rannsókninni, verða meðhöndlaðar samkvæmt ströngustu reglum um trúnað og nafnleynd og farið að íslenskum lögum varðandi persónuvernd, vinnslu og eyðingu frumgagna. Í tölfræðilegum úrvinnsluskrám koma ekki fram nöfn og kennitölur þátttakenda heldur fær hver og einn sitt númer sem ábyrgðamaður heldur einn skrá yfir. Rannsóknargögn verða varðveitt á öruggum stað hjá ábyrgðarmanni á meðan á rannsókn stendur og öllum gögnum verði eytt að rannsókn lokinni.
Þér er ekki skylt að taka þátt í rannsókninni og þú getur hætt við þátttöku hvenær sem er, án frekari útskýringa. Afstaða þín mun ekki hafa áhrif á þá þjónustu heilbrigðiskerfisins sem þú kannt að þurfa í framtíðinni.
Frekari upplýsingar: Ef þú hefur áhuga að taka þátt í rannsókninni eða fá frekari upplýsingar, vinsamlegast hafðu samband við Monique van Oosten, sjúkraþjálfara í síma 8998456
Með von um góða undirtektir,
Dr. Marta Guðjónsdóttir, lektor og ábyrgðarmaður rannsóknarinnar.
Monique van Oosten, sjúkraþjálfari, Buteykoþjálfari og meistaranemi í lýðheilsuvísindum.
________________________________
Ef þú hefur spurningar um rétt þinn sem þátttakandi í vísindarannsókn eða vilt hætta þátttöku í rannsókninni getur þú snúið þér til Vísindasiðanefndar, Hafnarhúsinu, Tryggvagötu 17, 101Reykjavík. Sími: 551-7100, fax: 551-1444, tölvupóstfang: [email protected].
68
FYLGISKJAL 2b
Upplýsingar vegna vísindarannsóknarinnar:
„Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins?“
Ábyrgðamaður rannsóknarinnar er : Dr.Marta Guðjónsdóttir,
lífeðlisfræðingur, lektor við Læknadeild Háskóla Íslands og rannsóknastjóri á Reykjalundi, Sími: 8679890 Tölvupóstfang: [email protected]
Aðrir rannsakendur eru: Monique van Oosten, sjúkraþjálfari, Buteykoþjálfari og meistaranemi í lýðheilsuvísindum.
Sími: 8998456. Tölvupóstfang: monique@centrum
Kæri viðtakandi.
Rannsóknin, Hvernig hefur öndun áhrif á einkenni og stjórnun astma sjúkdómsins“ er meistaraverkefni Monique van Oosten sjúkraþjálfara við námsbraut í Lýðheilsuvísindum við Læknadeild Háskóla Íslands. Leiðbeinandi hennar er Dr. Marta Guðjónsdóttir. Þér er boðið að taka þátt í rannsókninni þar sem þú hafðir samband við Monique í framhaldi af auglýsingu.
Tilgangur rannsóknarinnar er að kanna hvort og hvernig öndunarmeðferð (Buteyko) hefur áhrif á einkenni og stjórnun á astmasjúkdómnum.
Þér er boðin að taka þátt ef þú ert 18 ára og eldri, hefur ekki greinst með astma sjúkdóminn, notar ekki heilsutengd lyf og hefur ekki tekið þátt í öndunarmeðferð eins og Buteyko meðferðinni.
69
FYLGISKJAL 2b
Þátttaka felst í tveim heimsóknum á Reykjalund, endurhæfingarmiðstöð SÍBS, með 6 mánaða millibili, þar sem hver heimsókn tekur um það bil 30 mínútur. Í heimsóknunum verður öndun, blóðþrýstingur, hæð og þyngd mæld. Ekki verður greitt fyrir þátttöku en mælingarnar verður þáttakendum að kostnaðarlausu. Áhætta og ávinningur: Áhætta af þátttöku er engin en ávinningur er að niðurstöður rannsóknarinnar geta verið gagnlegar fyrir bættan skilning á astmasjúkdómnum. Rannsóknin er unnin með samþykki Vísindasiðanefndar og hefur verið tilkynnt til Persónuverndar.
Aðgengi að rannsóknargögnum: Allar upplýsingar sem þátttakendur veita í rannsókninni, verða meðhöndlaðar samkvæmt ströngustu reglum um trúnað og nafnleynd og farið að íslenskum lögum varðandi persónuvernd, vinnslu og eyðingu frumgagna. Í tölfræðilegum úrvinnsluskrám koma ekki fram nöfn og kennitölur þátttakenda heldur fær hver og einn sitt númer sem ábyrgðamaður heldur einn skrá yfir. Rannsóknargögn verða varðveitt á öruggum stað hjá ábyrgðarmanni á meðan á rannsókn stendur og öllum gögnum verði eytt að rannsókn lokinni. Þér er ekki skylt að taka þátt í rannsókninni og þú getur hætt við þátttöku hvenær sem er, án frekari útskýringa. Afstaða þín mun ekki hafa áhrif á þá þjónustu heilbrigðiskerfisins sem þú kannt að þurfa í framtíðinni Frekari upplýsingar: Ef þú hefur áhuga að taka þátt í rannsókninni eða fá frekari upplýsingar, vinsamlegast hafðu samband við Monique van Oosten í síma 8998456 eða með tölvupósti: monique@centrum
Með von um góðar undirtektir,
Marta Guðjónsdóttir, lektor og ábyrgðarmaður rannsóknarinnar.
Monique van Oosten, sjúkraþjálfari, Buteykoþjálfari og meistaranemi í lýðheilsuvísindum.
________________________________________
Ef þú hefur spurningar um rétt þinn sem þátttakandi í vísindarannsókn eða vilt hætta þátttöku í rannsókninni getur þú snúið þér til Vísindasiðanefndar, Hafnarhúsinu, Tryggvagötu 17, 101Reykjavík. Sími: 551-7100, fax: 551-1444, tölvupóstfang: [email protected].
70
Appendix D
Mat á astmastjórn (ACTTM)
Sjúklinganúmer:___________________
Dagsetning:______________________
Eftirfarandi mat getur auðveldað fólki með astma (12 ára og eldra) að meta astmastjórn sína.
Alls eru FIMM spurningar. Dragðu hring um svarið þitt við hverri spurningu. Svaraðu eins
hreinskilningslega og hægt er.
Þú færð heildarniðurstöðu úr mati þínu á astmastjórnun með því að leggja saman stigin þín fyrir
hvert svar.
1. Síðastliðnar 4 vikur, hversu oft kom astminn í veg fyrir að þú kæmir jafn miklu í verk í vinnu, skóla eða heima?
1) alltaf
2) oftast
3) stundum
4) sjaldan
5) aldrei
2. Síðastliðnar 4 vikur, hve oft hefurðu fundið fyrir mæði? 1) Oftar en einu sinni á dag
2) Einu sinni á dag
3) 3 til 6 sinnum í viku
4) Einu sinnu til tvisvar í viku
5) Alls ekki
3. Síðastliðnar 4 vikur, hversu oft vaknaðir þú um nótt eða fyrr en vanalega að morgni vegna einkenna astmans (blásturshljóðs í lungum, hósta, mæði, þrengsla eða verkjar fyrir brjósti)?
1) 4 eða fleiri nætur í viku
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2) 2 til 3 nætur í viku
3) Einu sinni í viku
4) Einu sinni eða tvisvar
5) Alls ekki
4. Síðastliðnar 4 vikur, hversu oft hefurðu notað neyðarúðann þinn eða innúðalyf (eins
og Ventolin®, Bricanyl® eða Salbutamol NM Pharma®)?
1) 3 eða oftar á dag
2) 1 sinni eða 2 á dag
3) 2 sinnum eða 3 í viku
4) Einu sinni í viku eða sjáldnar
5) Alls ekki
5. Hvaða einkunn myndirðu gefa astmastjórn þinni síðastliðnar 4 vikur? 1) Alls engin stjórn
2) Léleg stjórn
3) Nokkur stjórn
4) Góð stjórn
5) Algjör stjórn
Leggðu nú saman stigin þín.
Samtals:__________________stig. Stig: 25 – Til hamingju. Þú hefur haft algera stjórn á astmanum síðastliðnar 4 vikur. Þú hefur engin einkenni haft og
astminn hefur ekkert hamlað þér. Leitaðu til læknis eða hjúkrunarfræðings ef það breytist. Stig: 20-24 – Á réttri leið. Astmanum hefur e.t.v. verið STJÓRNAÐ VEL, síðastliðnar 4 vikur, en ekki STJÓRNAÐ
ALGERLEGA. Læknir eða hjúkrunarfræðingur gæti hjálpað þér að stefna að ALGERRI STJÓRN.
Stig: færri en 20 – Ekki á réttri leið. Astmanum hefur e.t.v. EKKI VERIÐ STJÓRNAÐ síðastliðnar 4 vikur. Læknir eða
hjúkrunarfræðingur getur mælt með aðgerðaráætlun til að takast á við astmann svo þú náir betri stjórn á honum.
Notað með leyfi GSK á Íslandi.
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Appendix E
ASTMA DAGBÓK
Þessi astma dagbók getur hjálpað okkur að halda utan um þína astmastjórnun.
� Skráðu sjúklingsnúmer og mánuð.
� Einkenni: Notaðu dagbókina til að skrá ef breyting er á einkennum þínum; Skráðu alvarleika: 1 = væg; 2 = meðallagi; 3 = alvarleg.
� Ofnæmisvakar: Skráðu og krossaðu við þegar þú hefur komið í snertingu við einn af mögulegum ofnæmisvökum þínum (t.d. gæludýr, reykingar, frjókorn o.s.frv.).
� Lyfjanotkun: Skráðu og krossaðu við þegar þú hefur tekið neyðarlyf. Skráðu og krossaðu einnig við þegar breyting er á lyfjanotkun sem þú tekur að staðaldri.
� Breath holding time: Þessi mæling byrjar þú að skrá þegar þú ert byrjaður/-uð að æfa samkvæmt öndunarmeðerðinni.
� Astma control test. Þetta fyllir þú út á sama tíma einu sinni á mánuði. Hér áttu að skrá tölustafi samkvæmt ACT leiðbeininum.
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Appendix F