Tx54767 1.7

Double blind randomised controlled trial of two different breathing techniques in the management of asthmaC A Slader, H K Reddel, L M Spencer, E G Belousova, C L Armour, S Z Bosnic-Anticevich,F C K Thien, C R Jenkins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thorax 2006;000:1–7. doi: 10.1136/thx.2005.054767 Background: Previous studies have shown that breathing techniques reduce short acting b agonist use andimprove quality of life (QoL) in asthma. The primary aim of this double blind study was to compare theeffects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper bodyexercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS)dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing Methods: After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques . . . . . . . . . . . . . . . . . . . . . . .
learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12.
Results: Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p,0.0001) and ICS dose was reduced by 50% (p,0.0001;p.0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes.
Conclusion: Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over . . . . . . . . . . . . . . . . . . . . . . .
Breathing techniques are among the most popular asthma were identified from a database of volunteers and complementary medicine modalities used by people from advertising in the lay press. All subjects gave informed with asthma.1–4 A Cochrane review concluded that written consent and the institutional ethics committees of breathing exercises for asthma, such as Buteyko, yoga and Royal Prince Alfred Hospital, Camperdown and The Alfred diaphragmatic breathing, led to decreased use of short acting Hospital, Melbourne approved the study. Inclusion criteria b agonists and a trend towards improvement in quality of were: age 15–80 years, as-needed reliever use >4 occasions/ life, but no consistent evidence of improved disease control week, use of ICS (>200 mg/day for >3 months with no dose such as reduced requirement for anti-inflammatory medica- change during the previous 4 weeks), current non-smoker, tion, reduced airway hyperresponsiveness, or improved lung forced expiratory volume in 1second (FEV1) >50% and ,90% function.5 Some proponents of breathing techniques have predicted or FEV1/forced vital capacity (FVC) ratio ,70%, suggested that the failure to demonstrate improvement in reversibility >200 ml to bronchodilator within previous lung function measures such as ambulatory peak expiratory 6 months, and daily access to television/video player.
flow (PEF) was due to the deep inspirations and forced Exclusion criteria included current smoking or .10 pack- expirations required with such monitoring.6 Additionally, the year smoking history, recently unstable asthma, and prior Cochrane review5 highlighted the need for further studies to tuition in Buteyko (for full details see online supplement at evaluate the impact of breathing techniques on symptom free http://www.thoraxjnl.com/supplemental).
days, physiological measurements, and airway inflammation.
This study was designed to test the hypothesis that breathing techniques aimed at reducing tidal volume and The study was a double blind, randomised, controlled, rate of breathing and encouraging the nasal route of multicentre comparison of two breathing techniques—one breathing would result in greater improvement in asthma (group A) aimed at reducing tidal volume, reducing symptoms and measures of disease control, and allow a hyperventilation and encouraging nasal route of breathing, greater reduction of inhaled corticosteroid (ICS) use than and the other (group B) involving non-specific upper body non-specific upper body exercises. A secondary hypothesis mobility exercises. After a 2 week run in period on pre- was that twice daily peak flow monitoring has no detrimental existing treatment, subjects were randomised (fig 1) using effect on asthma outcomes during treatment with either form computer generated permuted blocks (block size of four).
Subjects learned and practised their exercises by videoinstruction (see details under Interventions section and intable 1). They were asked to practise their routine exercises Abbreviations: ACQ, Asthma Control Questionnaire; AQLQ, Asthma The study was conducted at a respiratory research institute in Quality of Life Questionnaire; FEV1, forced expiratory volume in Sydney and a tertiary referral hospital in Melbourne, 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; PEF, Australia. Subjects with stable suboptimally controlled twice daily (approximately 26 minutes). For symptoms normally requiring reliever, subjects in both groups wereadvised to use a shorter set of their allocated breathing exercises (3–5 minutes) first and to take reliever if symptoms persisted. Dose reductions in ICS of 50% were attempted at weeks 16 and 22 for eligible subjects (see online supplement).
curls, arm raises withcontrolled inspiratory-expiratory cycles In the videos the duration, format, and style of presentation were matched for both groups. All subjects were provided with a detailed ‘‘Instruction’’ video for initial teaching and a ‘‘Daily Exercises’’ video. They were instructed to practise their exercises twice daily, watching the video at least once daily.
The ‘‘Instruction’’ video could be used again at any time. An unblinded research assistant contacted the subjects at 2 weekly intervals to review the essential elements of the approximately 13 minutes approximately 13 minutes breathing exercises, answer questions, and clarify concerns.
Subjects were also offered face to face tuition.
All measurements were made by trained research assistants who were blinded to the subjects’ treatment allocation.
Baseline data were collected at week 0. At each visit, spirometry was measured and airway resistance was recorded using the forced oscillation technique.7 Route of breathing (primarily nasal, primarily oral, mixed) was established from headset mounted thermistor recordings, and end tidal CO2 measurements from exhaled breath, while subjects weredistracted with questionnaire tasks. Airway responsiveness to *These exercises were designed to avoid impact on upper body musclestrength.
mannitol8 was assessed at all visits except week –2. Patientand Physician Global Assessments of Asthma Control wererecorded on a visual analogue scale at all visits, and the Asthma Control Questionnaire (ACQ)9 and Asthma Quality Analysis was based on intention-to-treat, with all data from of Life Questionnaire-Sydney (AQLQ)10 range 0–4 (best–worst quality of life) were administered at all visits exceptweek 6.
Subjects used electronic diary spirometers (AM2, Erich Jaeger GmbH, Hoechberg, Germany) twice daily to recordsymptom intensity, night waking, use of reliever, Global Assessment of Asthma Control, time spent doing routine study exercises, and number of times exercises were used for symptom relief. FEV1 and PEF were obtained from the three2 week periods of spirometric recordings (fig 1).
Changes in medications, exacerbations, and adverse events were recorded at all visits. Moderate exacerbations were defined as >2 consecutive days of increased reliever use by .2 occasions/day and/or increase in symptoms (>1 episodeof nocturnal asthma/night and/or early waking requiringreliever) over baseline, and/or in the investigator’s opinionthe subject was experiencing an exacerbation. They were treated with double dose ICS for 2 weeks. Severe exacerba- tions were defined by requirement for oral corticosteroids.
both centres combined. Handling of subject withdrawals and missing data are described in the online supplement.
The primary outcome analyses were AQLQ (total) score Figure 1 Schematic of study design. Inhaled corticosteroid (ICS) dose and daily symptom score between groups at week 12 remained constant until week 16, after which two successive dose (completion of ICS maintenance phase), with adjustment reductions of 50% were attempted for subjects who satisfied the eligibility for baseline. All outcome variables were compared between for reduction criteria (weeks 16 and 22). *ICS dose reduction if clinically groups at weeks 12 and 28. Outcome variables were also Breathing techniques in the management of asthma Table 2 Baseline demographic and clinical characteristics of the study population Daytime symptom intensity scoreÀ1 2.00 (1.00–3.00) FEV1, forced expiratory volume in 1 second; AQLQ, Asthma Quality of Life Questionnaire; ACQ, Asthma ControlQuestionnaire.
*Mean (95% CI).
ÀMedian (IQR).
`Range (best–worst): 0–4;ôRange (best–worst): 0–6;1Range (none–severe): 1–5**Atopic was defined as a positive skin prick test using the following criteria: length6width any allergen from astandard panel > length6width saline and > 3*3.
compared within groups at weeks 12 and 28. The impact of no significant differences between the groups at week 12. The PEF monitoring was assessed by comparing outcome vari- proportion of reliever-free days increased in both groups ables before and after PEF monitoring for clinic measure- between baseline and week 12 (group A: median baseline ments (week 12 v week 14, week 28 v week 30), and with and 6.7%, week 12 53.5%, p = 0.001; group B: baseline 8.3%, week without PEF monitoring for diary variables. Outcomes were 12 55.3%, p = 0.0001) with no significant differences between compared using unpaired (two sample) t tests adjusted for groups (p = 0.49 at baseline; p = 0.19 at week 12).
baseline and paired t tests for normally distributed data, andby Mann-Whitney U and Wilcoxon tests for non-parametric data. Because the ACQ includes a question about reliever use, There was no significant difference between ACQ scores at questions 1–6 (ACQ-6: lung function data removed) and week 12 (p = 0.234). However, there was a statistically questions 1–5 (ACQ-5: lung function and reliever data significant improvement in ACQ at week 12 in group B (p = 0.0324) but not in group A (p = 0.49; see online The sample size of 50 subjects was calculated based on supplement). A significant improvement in ACQ was seen detecting a clinically meaningful difference (0.5) in AQLQ for group B even when the components for b score between groups with 80% power (a = 0.05). To detect a lung function were omitted (see online supplement).
0.5 change in symptom score (80% power, a = 0.05), a total There were no significant differences between groups in Patient or Physician Global Assessments at week 12,although Physician Global Assessment improved significantly for group B but not group A compared with baseline Fifty seven subjects were randomised (28 to group A and 29 (p = 0.0467 and p = 0.073, respectively).
to group B). Nine subjects (five from group A and four from There was no significant difference between groups in group B) withdrew before completion of the study (fig 2).
clinic FEV1 at week 12 (p = 0.30), although there was a small Blinding of randomisation allocation was not broken for any reduction in FEV1 (0.084 l) by week 12 in group B subject. Baseline demographic and clinical characteristics are (p = 0.0359). There were no consistent differences between shown in table 2. At baseline, subjects had mild airway the two groups at week 12 for airway responsiveness to obstruction and used on average 3 puffs reliever/day. Asthma mannitol, or for mean airway resistance before and after deep related quality of life was well preserved and was slightly inspiration. The airway responsiveness data need to be better in group B at baseline (p = 0.0417). There were no interpreted with caution due to missing data (see online significant differences in other variables.
During the study there was no significant difference There was no difference between the groups at week 12 in between the groups in the self-reported time spent on volume of deep inspiration and number of breaths per routine daily exercises (group A: median 12 min/day (IQR minute (see online supplement), end tidal CO2, or route of 7–20); group B: 16 min/day (IQR 8–20); p = 0.66). Median breathing, and no significant changes in any of these overall adherence to twice daily electronic monitoring was measures within either group during weeks 0–12. The end tidal CO2 and route of breathing data need to be interpretedwith caution due to missing data (see online supplement).
Primary outcome measuresPrimary outcome measures are shown in table 3. At week 12 Inhaled corticosteroid dose reduction (weeks 13–28) there was no significant difference between the two groups in AQLQ score (p = 0.29). There were small differences favour- At baseline, median daily ICS dose (BDP equivalent) was ing group B in daytime symptom scores (p = 0.0192) and 800 mg (IQR 758–1900, n = 28) and 800 mg (500–2000, night-time symptom scores (p = 0.0636).
n = 29) for groups A and B, respectively (p = 0.92). The finalICS dose was 200 mg (100–275, n = 23) and 187.5 mg (119– Secondary outcome measures (weeks 1–12) 250, n = 25), respectively. The mean reduction in ICS dose for those who remained in the study beyond week 13 was 50% Both groups had a dramatic reduction in reliever use (IQR 50–75, p,0.0001 compared with baseline (both groups commencing from week 1 after randomisation (fig 3), with Table 3 Primary and secondary outcome measures: comparison between groups *Mean (SD).
ÀMedian (IQR).
`Geometric mean (SD).
ôAsthma Quality of Life Questionnaire; range (best–worst) 0–4.
1Complete Asthma Control Questionnaire questions 1–7; range (best–worst) 0–6.
**Differences represent Group A 2 Group B; ratios represent Group A/Group B.
ÀÀMeasured at clinic visit.
``Measured on a visual analogue scale from 0 (worst) to 100 (best).
11Measured on a custom built device (see online supplement).
ôôRecorded using electronic diary spirometers.
***Calculated based on data recorded on electronic diary spirometers.
Clinical outcomes after ICS dose reduction breathing data, more subjects breathed nasally in group A At week 28 there was no significant difference between than in group B. Stability of asthma was maintained in both groups in AQLQ score, daytime or night time symptom treatment groups during reduction in ICS dosage. This was scores, reliever use, symptom-free days, Patient or Physician demonstrated by maintenance of, or improvement in, asthma outcomes at week 28 compared with week 12 (see online resistance before and after deep inspiration, airway respon- siveness to mannitol, or end tidal CO2 adjusted for baseline(table 3). Data for mannitol challenge, route of breathing, and end tidal CO2 were not available for all subjects at week Twelve moderate exacerbations were experienced by 11 28 (see online supplement), and these results therefore need subjects (three in group A and eight in group B, p = 0.11) to be interpreted with caution. Of 31 subjects with route of during the study. There were 259 other adverse events (138 ingroup A and 121 in group B), none of which was consideredto be related to treatment. Eight adverse events (five in group A and three in group B) were attributed to mannitol (seeonline supplement).
Potential impact of PEF monitoring on other asthmaoutcomes There were no significant differences in any outcomevariables between these periods, with the exception ofAQLQ in group B for week 12 v week 14 (p = 0.024) where the difference favoured the post-PEF period (see online DISCUSSIONThis study found that similar improvements in asthma symptoms, reliever use, and ICS dose were achieved in subjects with mild to moderate asthma using a technique which focused on the nasal route of breathing, hypoventila-tion, and breath holding, and a breathing technique Breathing techniques in the management of asthma Importantly, these changes were achieved without impacting (86% by study end) and was sustained over 8 months. For negatively on underlying disease control, as measured by both groups there were more symptom-free days at baseline lung function and airways responsiveness. Devising a (group A: 23.5%, group B: 22.1%) than reliever-free days credible control for complementary medicine interventions (group A: 6.7%, group B: 8.3%). Similar disparities have been has been acknowledged as a difficult task,12–15 and previous observed in other asthma studies,26 suggesting that patients studies examining breathing exercises for asthma have used may often use their reliever for prevention rather than actual a variety of control arms including asthma education and relief of symptoms. Presumably, any instruction which defers relaxation, but this approach has limited the conclusions or delays the taking of a b2 agonist will minimise its habitual which can be drawn about the efficacy of the breathing and pre-emptory use. Thus, while breathing exercises may technique itself. Instead, we used a second breathing not confer any particular physiological benefit, the process of technique for which there was no previous evidence of using breathing techniques as first line symptom treatment efficacy in a randomly selected asthma population, and in may allow people to substantially reduce their use of b2 which there was no attempt to modulate pattern of breath- agonist. This itself may be beneficial by reducing adrenergic ing. Unlike previous studies,16–23 we also matched all process side effects, by reducing response to allergens, or by reducing elements of the two interventions, including the instruction about symptom relief, so that the only variable was the Another possible explanation for the overall improvements exercises themselves. The similarity of the improvements is that the subjects recruited were a ‘‘special’’ group in terms seen in both groups, despite the widely disparate nature of of their personality or breathing style. No specific tests of the breathing exercises they were using, suggests that the personality, anxiety, or depression were administered. The observed changes were more likely to be attributable to one fact that breathing exercises were mentioned in some or more of the shared process elements—such as the recruitment material may have attracted subjects who were instruction to use the exercises initially in place of reliever more likely to respond to the interventions, enabling both for symptom relief—than to the breathing exercises them- breathing techniques to function as ‘‘very active placebos’’.
However, the baseline clinical characteristics of the subjects Although we found significant improvements in reliever from this study, including symptom and reliever frequency, use, some patient centred outcomes and ICS dose, there were were similar to those from a more conventional clinical trial no significant changes in physiological parameters. With one recently conducted at the same centres.30 While it is possible exception,18 no previous study of breathing techniques has that the relaxation elements of both interventions assisted in found an improvement in lung function5 or airway hyperre- reducing anxiety and hence in reducing the perceived need sponsiveness,19 and there is no evidence that upper body for reliever, the subscores for the mood domains of the AQLQ exercises such as those used for group B would impact on (which includes questions about anxiety) were very low in lung function. Our results confirm no change in end tidal our subjects at baseline, indicating minimal impact of anxiety CO2, as also reported by Bowler et al.16 While data for end and—unlike in previous studies16 17 23—minimal opportunity tidal CO2 and mannitol challenge in the present study should for improvement in asthma related quality of life. These be interpreted with caution due to missing data, these subscores remained largely unchanged throughout the study, findings—together with the measurement of airway resis- suggesting that the large reduction in b2 agonist use was not tance by the forced oscillation technique—strongly suggest primarily due to the relief of anxiety. There has been that the improvements observed with both breathing considerable interest in the concepts of dysfunctional breath- techniques were not measurably related to physiological ing and hyperventilation syndrome,31 but the clinical impor- tance of such conditions in people with asthma has not yet It has also been suggested6 that the failure of previous been established. The Nijmegen questionnaire has been used studies of breathing techniques to demonstrate improve- to assess dysfunctional breathing, but was not included in ments in lung function was due to a bronchoconstricting the present study as there is considerable overlap with the effect of deep breaths during PEF monitoring. However, we symptoms of asthma itself. A previous study of asthmatic failed to find evidence that 2 week periods of PEF monitoring patients with high Nijmegen scores showed improved quality were detrimental, with even small improvements occurring of life with a breathing technique similar to our group B in some measures. Our findings therefore suggest that intervention, but there was no reduction in reliever use or ICS breathing techniques do not mask any benefit or cause dose.23 Although some patients in the present study may have deterioration in other measures of asthma control.
satisfied the criteria for hyperventilation, the randomisation Previous studies of breathing techniques have shown a process should have ensured that they were equally trend towards a reduction in ICS dose. We found a significant distributed between both treatment arms.
and similar reduction in ICS dose in both groups, with no Although there was little change in AQLQ score, improve- negative impact on other outcome measures. It is unlikely ments were seen in other patient centred outcome measures that this was due to improvement in airway inflammation, including Patient Global Assessment of Control and ACQ given the lack of change in indirect airway hyperresponsive- scores. These improvements suggest that the subjects’ self- ness. However, some of our subjects may have been relatively efficacy was enhanced, which may have been due to a overtreated with ICS at entry, as many clinicians rely on reduction in medication facilitated by breathing techniques.
markers such as reliever use to indicate whether a patient’s While the ‘‘ideal’’ study would include a group of control ICS dose is appropriate. Further, other researchers have been subjects who were instructed to withhold reliever without able to reduce ICS doses by approximately 50% in a clinical any substitute, gaining the agreement of subjects and the trial setting in the absence of any other intervention.24 approval of an ethics committee would undoubtedly be Despite the lack of physiological improvement, any strategy difficult. In the present study, subjects in both groups were which facilitates ICS reduction has important clinical provided with a strategy that offered an alternative to reliever implications and useful applications.
use which they appeared to accept as plausible and credible.
There are several possible mechanisms to explain the We suggest that the combination of these factors enabled reliever reduction observed in this study. One possibility is patients to reduce their reliever use in the absence of any that this effect was due to participation in a clinical trial (Hawthorne effect25). However, this would be an over- In summary, this study shows that two completely simplification given that reliever reduction was substantial different types of breathing techniques, taught by video, can lead to a similar level of improvement in asthma outcomes particularly those relating to the use of a short 1 Ernst E. Complementary therapies for asthma: what patients use. J Asthma 2 agonist. These improvements are of a magnitude 2 Ernst E. Use of complementary therapies in childhood asthma. Pediatr Asthma similar to that observed in conventional clinical trials which assess pharmacological interventions to improve asthma 3 Shenfield G, Lim E, Allen H. Survey of the use of complementary medicines control, and are therefore clinically important. The improve- and therapies in children with asthma. J Paediatr Child Health ment observed was substantial and sustained, but was not 4 Partridge MR, Dockrell M, Smith NM. The use of complementary medicines by associated with a measurable effect on physiological para- those with asthma. Respir Med 2003;97:436–8.
meters of airway inflammation. Given the magnitude of the 5 Holloway E, Ram F. Breathing exercises for asthma. Cochrane Database Syst differences in content of the two breathing techniques which were used in the present study, it appears likely that the 6 Kolb P. In: Buteyko guide for doctors, Buteyko Natural Therapy, 2004; 7 Salome C, Thorpe C, Diba C, et al. Airway re-narrowing following deep observed clinical improvements were not due to the use of a inspiration in asthmatic and nonasthmatic subjects. Eur Respir J particular type of exercise but to the process of both routine and as-required exercises that reinforce a message of 8 Brannan J, Koskela H, Anderson S, et al. Responsiveness to mannitol in asthmatic subjects with exercise- and hyperventilation-induced asthma.
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GlaxoSmithKline. HR was funded by the Asthma Foundation of New 30 Jenkins C, Thien FC, Wheatley J, et al. Traditional and patient-centred South Wales. CS was funded by the Australian Government Department outcomes with three classes of asthma medication. Eur Respir J of Education, Science and Training via an Australian Postgraduate 31 Thomas M, McKinley R, Freeman E, et al. Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross sectional Breathing techniques in the management of asthma Authors QueriesJournal: ThoraxPaper: tx54767Title: Double blind randomised controlled trial of two different breathing techniques in the management of asthma Dear AuthorDuring the preparation of your manuscript for publication, the questions listed below have arisen. Please attend to thesematters and return this form with your proof. Many thanks for your assistance Please give title of paper/chapter,page numbers, publishers andplace of publication for reference6.
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