Effectiveness of pulmonary rehabilitation for patients with asthma: study protocol of a randomized controlled trial (EPRA)

Konrad Schultz, Hildegard Seidl, Danijel Jelusic, Rupert Wagner, Michael Wittmann, Hermann Faller, Dennis Nowak, Michael Schuler, Konrad Schultz, Hildegard Seidl, Danijel Jelusic, Rupert Wagner, Michael Wittmann, Hermann Faller, Dennis Nowak, Michael Schuler

Abstract

Background: Asthma patients are enrolled in multimodal pulmonary rehabilitation (PR) programs. However, available data for the effectiveness of PR in asthma are sparse. Therefore, the primary aim of this randomized control trial (RCT) is to evaluate short-term (end of rehabilitation) and intermediate-term effectiveness (3 months after rehabilitation) of PR for patients with asthma regarding asthma control (primary outcome) and other outcomes. Secondly, moderator effects of gender, age, baseline asthma control, quality of life, and anxiety will be examined. Thirdly, a longitudinal follow-up study will explore the course of the outcomes over one year and the annual costs.

Methods: The EPRA study is a single-center randomized controlled waiting-list trial in the Bad Reichenhall Clinic. Inclusion criteria include a referral diagnosis for uncontrolled asthma, no cognitive impairment and no very severe co-morbidities that indicate significantly greater illness morbidity than asthma alone. In the intervention group (IG), participants will start PR within 4 weeks after randomization; participants of the control group (CG) will start PR 20 weeks after randomization. Data will be assessed at randomization (T0), after 4 weeks (T1; IG: begin of PR), 7 weeks (T2; IG: end of PR), and 20 weeks (T3, CG: begin of PR). The primary outcome is asthma control at T2/T3. Secondary outcomes are health-related quality of life, functional exercise capacity, dyspnea, anxiety, depression, subjective self-management skills, illness perceptions, sick leave and subjective work ability. Outcomes will be analyzed with analysis of covariance, including baseline values of the respective outcomes as covariates. Healthcare costs will be analyzed with a gamma model with a log-link. A longitudinal follow-up study will generate additional data at 3/6/9/12 months after PR for both IG and CG. Latent change models will be used to analyze the course of the primary and secondary outcomes. Annual cost differences before and after rehabilitation will be compared by paired t-test.

Discussion: This RCT will determine the effectiveness of a complex inpatient PR for asthma patients concerning asthma control. Furthermore, important medical and economic information regarding the effectiveness of PR as part of the long-term management of patients with uncontrolled asthma will be generated.

Trial registration: German Clinical Trials Register ( DRKS00007740 , May 15, 2015). Protocol version: 1.0 (December, 23, 2016).

Keywords: ACT; Asthma; Asthma control; Economic evaluation; Inpatient rehabilitation; Longitudinal; Longitudinal study; Pulmonary rehabilitation; RCT; Randomized controlled trial.

Figures

Fig. 1
Fig. 1
Study design and measurement occasions; PR: pulmonary rehabilitation; M: months; W: weeks; not shadowed: data for randomized control trial; grey shadowed: data used only in the longitudinal study

References

    1. (o.A.): Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2016. Available from: . Accessed 5 Mar 2017.
    1. British Thoracic S. Scottish Intercollegiate Guidelines N: British guideline on the management of asthma. Thorax. 2014;69(Suppl 1):1–192.
    1. Demoly P, Annunziata K, Gubba E, Adamek L. Repeated cross-sectional survey of patient-reported asthma control in Europe in the past 5 years. Eur Respir Rev. 2012;21(123):66–74. doi: 10.1183/09059180.00008111.
    1. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009. doi: 10.1038/npjpcrm.2014.9.
    1. Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, Hill K, Holland AE, Lareau SC, Man WD, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8):e13–64. doi: 10.1164/rccm.201309-1634ST.
    1. Spruit MA, Pitta F, Garvey C, ZuWallack RL, Roberts CM, Collins EG, Goldstein R, McNamara R, Surpas P, Atsuyoshi K, et al. Differences in content and organisational aspects of pulmonary rehabilitation programmes. Eur Respir J. 2014;43(5):1326–1337. doi: 10.1183/09031936.00145613.
    1. Nathell L. Effects on sick leave of an inpatient rehabilitation programme for asthmatics in a randomized trial. Scand J Public Health. 2005;33(1):57–64. doi: 10.1080/14034940410028343.
    1. Cambach W, Chadwick-Straver RV, Wagenaar RC, van Keimpema AR, Kemper HC. The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial. Eur Respir J. 1997;10(1):104–113. doi: 10.1183/09031936.97.10010104.
    1. Gibson PG, Powell H, Coughlan J, Wilson AJ, Abramson M, Haywood P, Bauman A, Hensley MJ, Walters EH. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev. 2003;1:CD001117.
    1. Powell H, Gibson PG. Options for self-management education for adults with asthma. Cochrane Database Syst Rev. 2003;1:CD004107.
    1. Bott J, Blumenthal S, Buxton M, Ellum S, Falconer C, Garrod R, Harvey A, Hughes T, Lincoln M, Mikelsons C, et al. Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax. 2009;64(Suppl 1):i1–51. doi: 10.1136/thx.2008.110726.
    1. Bruurs ML, van der Giessen LJ, Moed H. The effectiveness of physiotherapy in patients with asthma: a systematic review of the literature. Respir Med. 2013;107(4):483–494. doi: 10.1016/j.rmed.2012.12.017.
    1. Mendes FA, Goncalves RC, Nunes MP, Saraiva-Romanholo BM, Cukier A, Stelmach R, Jacob-Filho W, Martins MA, Carvalho CR. Effects of aerobic training on psychosocial morbidity and symptoms in patients with asthma: a randomized clinical trial. Chest. 2010;138(2):331–337. doi: 10.1378/chest.09-2389.
    1. Turner S, Eastwood P, Cook A, Jenkins S. Improvements in Symptoms and Quality of Life following Exercise Training in Older Adults with Moderate/Severe Persistent Asthma. Respiration. 2011;81(4):302–310. doi: 10.1159/000315142.
    1. Avallone KM, McLeish AC. Asthma and aerobic exercise: a review of the empirical literature. J Asthma. 2013;50(2):109–116. doi: 10.3109/02770903.2012.759963.
    1. Carson KV, Chandratilleke MG, Picot J, Brinn MP, Esterman AJ, Smith BJ. Physical training for asthma. Cochrane Database Syst Rev. 2013;9:CD001116.
    1. Franca-Pinto A, Mendes FA, de Carvalho-Pinto RM, Agondi RC, Cukier A, Stelmach R, Saraiva-Romanholo BM, Kalil J, Martins MA, Giavina-Bianchi P, et al. Aerobic training decreases bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: a randomised controlled trial. Thorax. 2015;70(8):732–739. doi: 10.1136/thoraxjnl-2014-206070.
    1. Eichenberger PA, Diener SN, Kofmehl R, Spengler CM. Effects of exercise training on airway hyperreactivity in asthma: a systematic review and meta-analysis. Sports Med. 2013;43(11):1157–1170. doi: 10.1007/s40279-013-0077-2.
    1. (o.A.): Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale VersorgungsLeitlinie Asthma – Langfassung, 2. Auflage. Version 5. 2009, zuletzt geändert: August 2013. 2009. doi: 10.6101/AZQ/000163.Available from: . cited:15 May 2016.
    1. Emtner M, Finne M, Stalenheim G. A 3-year follow-up of asthmatic patients participating in a 10-week rehabilitation program with emphasis on physical training. Arch Phys Med Rehabil. 1998;79(5):539–544. doi: 10.1016/S0003-9993(98)90070-3.
    1. Emtner M, Herala M, Stalenheim G. High-intensity physical training in adults with asthma. A 10-week rehabilitation program. Chest. 1996;109(2):323–330. doi: 10.1378/chest.109.2.323.
    1. Foglio K, Bianchi L, Bruletti G, Battista L, Pagani M, Ambrosino N. Long-term effectiveness of pulmonary rehabilitation in patients with chronic airway obstruction. Eur Respir J. 1999;13(1):125–132. doi: 10.1183/09031936.99.13112599.
    1. Renolleau-Courtois D, Lamouroux-Delay A, Delpierre S, Badier M, Lagier-Tessonnier F, Palot A, Gouitaa M, Tummino C, Charpin D, Molinari N, et al. Home-based respiratory rehabilitation in adult patients with moderate or severe persistent asthma. J Asthma. 2014;51(5):552–558. doi: 10.3109/02770903.2014.885039.
    1. Trevor JL, Bhatt SP, Wells JM, Kirkpatrick D, Schumann C, Hitchcock J, Dransfield MT. Benefits of completing pulmonary rehabilitation in patients with asthma. J Asthma. 2015;52(9):969–973. doi: 10.3109/02770903.2015.1025410.
    1. Lingner H, Ernst S, Grobetahennig A, Djahangiri N, Scheub D, Wittmann M, Schultz K. Asthma control and health-related quality of life one year after inpatient pulmonary rehabilitation: the ProKAR Study. J Asthma. 2015;52(6):614–621. doi: 10.3109/02770903.2014.996650.
    1. Ochmann U, Kotschy-Lang N, Raab W, Kellberger J, Nowak D, Jorres RA. Long-term efficacy of pulmonary rehabilitation in patients with occupational respiratory diseases. Respiration. 2012;84(5):396–405. doi: 10.1159/000337271.
    1. Farin E, Opitz U, Jäckel W, Gallenmüller K, Schwiersch M, Schultz K. Pneumological Rehabilitation: Long-term Data on Quality of Life and Predictors of Treatment Eff ects. Phys Med Rehab Kuror. 2009;19:75–84. doi: 10.1055/s-0028-1105912.
    1. Schultz K. DGRW-update: relevance and evidence of pulmonary rehabilitation in chronic obstructive respiratory diseases (adults) Rehabilitation (Stuttg) 2014;53(3):146–154.
    1. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, Murray JJ, Pendergraft TB. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113(1):59–65. doi: 10.1016/j.jaci.2003.09.008.
    1. Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, Kosinski M, Pendergraft TB, Jhingran P. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol. 2006;117(3):549–556. doi: 10.1016/j.jaci.2006.01.011.
    1. Bundesarbeitsgemeinschaft für Rehabilitation (BAR). Rahmenempfehlungen zur ambulanten pneumologischen Rehabilitation. 2008. . Accessed 5 Mar 2017.
    1. Deutsche Rentenversicherung [German statutory pension insurance scheme]. Strukturqualität von Reha-Einrichtungen – Anforderungen der Deutschen Rentenversicherung [Quality of structure of rehabilitation centers - requirements of the German statutory pension insurance scheme]. 2. überarbeitete und erweiterte Auflage, Juli 2014. Available: . Accessed 5 Mar 2017.
    1. Schatz M, Mosen DM, Kosinski M, Vollmer WM, Magid DJ, O’Connor E, Zeiger RS. Validity of the Asthma Control Test completed at home. Am J Manag Care. 2007;13(12):661–667.
    1. Schatz M, Kosinski M, Yarlas AS, Hanlon J, Watson ME, Jhingran P. The minimally important difference of the Asthma Control Test. J Allergy Clin Immunol. 2009;124(4):719–723. doi: 10.1016/j.jaci.2009.06.053.
    1. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–1327. doi: 10.1164/ajrccm/145.6.1321.
    1. Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. 1999;115(5):1265–1270. doi: 10.1378/chest.115.5.1265.
    1. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20(10):1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. Oemar M, Janssen B. EQ-5D-5L User Guide2013; (Version 2.0, October 2013). . Accessed 12 Dec 2016.
    1. Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163–170. doi: 10.1179/jmt.2009.17.3.163.
    1. Morris NR, Sabapathy S, Adams L, Kingsley RA, Schneider DA MSS. Verbal numerical scales are as reliable and sensitive as visual analog scales for rating dyspnea in young and older subjects. Respir Physiol Neurobiol. 2007;157(2-3):360–365. doi: 10.1016/j.resp.2007.01.006.
    1. Radbruch L, Sabatowski R, Elsner F, Everts J, Mendoza T, Cleeland C. Validation of the German version of the brief fatigue inventory. J Pain Symptom Manage. 2003;25(5):449–458. doi: 10.1016/S0885-3924(03)00073-3.
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–613. doi: 10.1046/j.1525-1497.2001.016009606.x.
    1. Kroenke K, Spitzer RL, Williams JB, Lowe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345–359. doi: 10.1016/j.genhosppsych.2010.03.006.
    1. Plummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: a systematic review and diagnostic metaanalysis. Gen Hosp Psychiatry. 2016;39:24–31. doi: 10.1016/j.genhosppsych.2015.11.005.
    1. Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006;60(6):631–637. doi: 10.1016/j.jpsychores.2005.10.020.
    1. Osborne RH, Elsworth GR, Whitfield K. The Health Education Impact Questionnaire (heiQ): an outcomes and evaluation measure for patient education and self-management interventions for people with chronic conditions. Patient Educ Couns. 2007;66(2):192–201. doi: 10.1016/j.pec.2006.12.002.
    1. Schuler M, Musekamp G, Faller H, Ehlebracht-Konig I, Gutenbrunner C, Kirchhof R, Bengel J, Nolte S, Osborne RH, Schwarze M. Assessment of proximal outcomes of self-management programs: translation and psychometric evaluation of a German version of the Health Education Impact Questionnaire (heiQ) Qual Life Res. 2013;22(6):1391–1403. doi: 10.1007/s11136-012-0268-6.
    1. Mahler C, Hermann K, Horne R, Ludt S, Haefeli WE, Szecsenyi J, Jank S. Assessing reported adherence to pharmacological treatment recommendations. Translation and evaluation of the Medication Adherence Report Scale (MARS) in Germany. J Eval Clin Pract. 2010;16(3):574–579.
    1. Svarstad BL, Chewning BA, Sleath BL, Claesson C. The Brief Medication Questionnaire: a tool for screening patient adherence and barriers to adherence. Patient Educ Couns. 1999;37(2):113–124. doi: 10.1016/S0738-3991(98)00107-4.
    1. Criee CP, Baur X, Berdel D, Bosch D, Gappa M, Haidl P, Husemann K, Jorres RA, Kabitz HJ, Kardos P, et al. Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine. Pneumologie. 2015;69(3):147–164. doi: 10.1055/s-0034-1391345.
    1. Criee CP, Sorichter S, Smith HJ, Kardos P, Merget R, Heise D, Berdel D, Kohler D, Magnussen H, Marek W, et al. Body plethysmography--its principles and clinical use. Respir Med. 2011;105(7):959–971. doi: 10.1016/j.rmed.2011.02.006.
    1. Seidl H, Bowles D, Bock JO, Brettschneider C, Greiner W, Konig HH, Holle R. FIMA--questionnaire for health-related resource use in an elderly population: development and pilot study. Gesundheitswesen. 2015;77(1):46–52.
    1. Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, McCormack MC, Carlin BW, Sciurba FC, Pitta F, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014;44(6):1428–1446. doi: 10.1183/09031936.00150314.
    1. Ilmarinen J. Work ability--a comprehensive concept for occupational health research and prevention. Scand J Work Environ Health. 2009;35(1):1–5. doi: 10.5271/sjweh.1304.
    1. Mittag O, Raspe H. A brief scale for measuring subjective prognosis of gainful employment: findings of a study of 4279 statutory pension insurees concerning reliability (Guttman scaling) and validity of the scale. Rehabilitation (Stuttg) 2003;42(3):169–174. doi: 10.1055/s-2003-40095.
    1. Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res. 2011;2(3):109–112. doi: 10.4103/2229-3485.83221.
    1. van Buuren S. Flexible imputation of missing data. Boca Raton: CRC Press; 2012.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869. doi: 10.1136/bmj.c869.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG. Consolidated Standards of Reporting Trials G: CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;63(8):e1–37. doi: 10.1016/j.jclinepi.2010.03.004.
    1. Frazier PA, Tix AP, Barron KE. Testing Moderator and Mediation Effects in Counseling Psychology Research. J Couns Psychol. 2004;51(1):115–134. doi: 10.1037/0022-0167.51.1.115.
    1. Bollen KA, Curran PJ. Latent curve models: a structural equation perspective. Hoboken, N.J.: Wiley-Interscience; 2006.
    1. Newsom JT. Longitudinal structural equation modeling. New York: Routledge; 2015.
    1. Bock JO, Brettschneider C, Seidl H, Bowles D, Holle R, Greiner W, Konig HH. Calculation of standardised unit costs from a societal perspective for health economic evaluation. Gesundheitswesen. 2015;77(1):53–61.
    1. Dodd S, Bassi A, Bodger K, Williamson P. A comparison of multivariable regression models to analyse cost data. J Eval Clin Pract. 2006;12(1):76–86. doi: 10.1111/j.1365-2753.2006.00610.x.
    1. IBM Corp. IBM SPSS Statistics for Windows, Version 23.0. Armonk: IBM Corp.; 2014.
    1. R Development Core Team: R . A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2016.
    1. SAS Institute, Inc., Cary, NC, .

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren