Asthma rehabilitation at high vs. low altitude: randomized parallel-group trial

Stéphanie Saxer, Simon R Schneider, Paula Appenzeller, Patrick R Bader, Mona Lichtblau, Michael Furian, Ulan Sheraliev, Bermet Estebesova, Berik Emilov, Talant Sooronbaev, Konrad E Bloch, Silvia Ulrich, Stéphanie Saxer, Simon R Schneider, Paula Appenzeller, Patrick R Bader, Mona Lichtblau, Michael Furian, Ulan Sheraliev, Bermet Estebesova, Berik Emilov, Talant Sooronbaev, Konrad E Bloch, Silvia Ulrich

Abstract

Background: To investigate the effect of asthma rehabilitation at high altitude (3100 m, HA) compared to low altitude (760 m, LA).

Methods: For this randomized parallel-group trial insufficiently controlled asthmatics (Asthma Control Questionnaire (ACQ) > 0.75) were randomly assigned to 3-week in-hospital rehabilitation comprising education, physical-&breathing-exercises at LA or HA. Co-primary outcomes assessed at 760 m were between group changes in peak expiratory flow (PEF)-variability, and ACQ) from baseline to end-rehabilitation and 3 months thereafter.

Results: 50 asthmatics were randomized [median (quartiles) LA: ACQ 2.7(1.7;3.2), PEF-variability 19%(14;33); HA: ACQ 2.0(1.6;3.0), PEF-variability 17%(12;32)]. The LA-group improved PEF-variability by median(95%CI) -7%(- 14 to 0, p = 0.033), ACQ - 1.4(- 2.2 to - 0.9, p < 0.001), and after 3 months by - 3%(- 18 to 2, p = 0.103) and - 0.9(- 1.3 to - 0.3, p = 0.002). The HA-group improved PEF-variability by - 10%(- 21 to - 3, p = 0.004), ACQ - 1.1(- 1.3 to - 0.7, p < 0.001), and after 3 months by - 9%(- 10 to - 3, p = 0.003) and - 0.2(- 0.9 to 0.4, p = 0.177). The additive effect of HA vs. LA directly after the rehabilitation on PEF-variability was - 6%(- 14 to 2), on ACQ 0.3(- 0.4 to 1.1) and after 3 months - 5%(- 14 to 5) respectively 0.4(- 0.4 to 1.1), all p = NS.

Conclusion: Asthma rehabilitation is highly effective in improving asthma control in terms of PEF-variability and symptoms, both at LA and HA similarly.

Trial registration: Clinicaltrials.gov: NCT02741583, Registered April 18, 2016.

Keywords: Altitude; Asthma; Pulmonary rehabilitation.

Conflict of interest statement

SU reports grants from Zurich Lung League, grants from Swiss National Science Foundation, during the conduct of the study; grants and personal fees from Actelion SA, personal fees from Bayer SA, personal fees from MSD, grants and personal fees from Orpha Swiss, outside the submitted work. KEB reports grants from Zurich Lung League, grants from Swiss National Science Foundation, during the conduct of the study. SS, SRS, PA, PRB, ML, MF, US, BE, BEm and TS have nothing to declare.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
Peak flow variability of both groups, median changes (95%CI) from baseline to end rehabilitation after 3 weeks and 3 months follow up and median differences (95%CI) between groups
Fig. 3
Fig. 3
Asthma control of both groups, median changes (95%CI) from baseline to end rehabilitation after 3 weeks and 3 months follow up and median differences (95%CI) between groups

References

    1. Global Initiative for Asthma Scientific C . Global Strategy for Asthma Management and Prevention. 2017.
    1. Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J, et al. Diagnosis and definition of severe refractory asthma: an international consensus statement from the innovative medicine initiative (IMI) Thorax. 2011;66(10):910–917. doi: 10.1136/thx.2010.153643.
    1. Gibson PG, Powell H, Coughlan J, Wilson AJ, Abramson M, Haywood P, et al. 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. 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. Grootendorst DC, Dahlen SE, Van Den Bos JW, Duiverman EJ, Veselic-Charvat M, Vrijlandt EJ, et al. Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids. Clin Exp Allergy. 2001;31(3):400–408. doi: 10.1046/j.1365-2222.2001.01022.x.
    1. Rijssenbeek-Nouwens LH, Fieten KB, Bron AO, Hashimoto S, Bel EH, Weersink EJ. High-altitude treatment in atopic and nonatopic patients with severe asthma. Eur Respir J. 2012;40(6):1374–1380. doi: 10.1183/09031936.00195211.
    1. Rijssenbeek-Nouwens LH, Bel EH. High-altitude treatment: a therapeutic option for patients with severe, refractory asthma? Clin Exp Allergy. 2011;41(6):775–782. doi: 10.1111/j.1365-2222.2011.03733.x.
    1. Spieksma FT, Zuidema P, Leupen MJ. High altitude and house-dust mites. Br Med J. 1971;1(5740):82–84. doi: 10.1136/bmj.1.5740.82.
    1. Platts-Mills TA, Chapman MD. Dust mites: immunology, allergic disease, and environmental control. J Allergy Clin Immunol. 1987;80(6):755–775. doi: 10.1016/S0091-6749(87)80261-0.
    1. Karagiannidis C, Hense G, Rueckert B, Mantel PY, Ichters B, Blaser K, et al. High-altitude climate therapy reduces local airway inflammation and modulates lymphocyte activation. Scand J Immunol. 2006;63(4):304–310. doi: 10.1111/j.1365-3083.2006.01739.x.
    1. Renzetti G, Silvestre G, D'Amario C, Bottini E, Gloria-Bottini F, Bottini N, et al. Less air pollution leads to rapid reduction of airway inflammation and improved airway function in asthmatic children. Pediatrics. 2009;123(3):1051–1058. doi: 10.1542/peds.2008-1153.
    1. Skloot G, Permutt S, Togias A. Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. J Clin Invest. 1995;96(5):2393–2403. doi: 10.1172/JCI118296.
    1. Haczku A, Panettieri RA., Jr Social stress and asthma: the role of corticosteroid insensitivity. J Allergy Clin Immunol. 2010;125(3):550–558. doi: 10.1016/j.jaci.2009.11.005.
    1. Bosley CM, Corden ZM, Cochrane GM. Psychosocial factors and asthma. Respir Med. 1996;90(8):453–457. doi: 10.1016/S0954-6111(96)90170-5.
    1. WHO. Ambient air pollution: a global assessment of exposure and burden of disease. Geneva: Department of Public Health, Environmental and Social Determinants of Health (PHE) World Health Organization; 2016. Available from:
    1. Juniper EF, Bousquet J, Abetz L, Bateman ED, Committee G. Identifying 'well-controlled' and 'not well-controlled' asthma using the asthma control questionnaire. Respir Med. 2006;100(4):616–621. doi: 10.1016/j.rmed.2005.08.012.
    1. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–615. doi: 10.1164/rccm.9120-11ST.
    1. Sampson JB, Cymerman A, Burse RL, Maher JT, Rock PB. Procedures for the measurement of acute mountain sickness. Aviat Space Environ Med. 1983;54(12 Pt 1):1063–1073.
    1. Bateman ED, Esser D, Chirila C, Fernandez M, Fowler A, Moroni-Zentgraf P, et al. Magnitude of effect of asthma treatments on asthma quality of life questionnaire and asthma control questionnaire scores: systematic review and network meta-analysis. J Allergy Clin Immunol. 2015;136(4):914–922. doi: 10.1016/j.jaci.2015.03.023.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103–115. doi: 10.2307/2529712.
    1. Huss-Marp J, Kramer U, Eberlein B, Pfab F, Ring J, Behrendt H, et al. Reduced exhaled nitric oxide values in children with asthma after inpatient rehabilitation at high altitude. J Allergy Clin Immunol. 2007;120(2):471–472. doi: 10.1016/j.jaci.2007.03.039.
    1. Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med. 2006;173(12):1390–1413. doi: 10.1164/rccm.200508-1211ST.
    1. Trevor JL, Bhatt SP, Wells JM, Kirkpatrick d SC, Hitchcock J, et al. Benefits of completing pulmonary rehabilitation in patients with asthma. J Asthma. 2015;52(9):969–973. doi: 10.3109/02770903.2015.1025410.
    1. Renolleau-Courtois D, Lamouroux-Delay A, Delpierre S, Badier M, Lagier-Tessonnier F, Palot A, 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. Carson KV, Chandratilleke MG, Picot J, Brinn MP, Esterman AJ, Smith BJ. Physical training for asthma. Cochrane Database Syst Rev. 2013;9:CD001116.
    1. Boyd A, Yang CT, Estell K, Ms CT, Gerald LB, Dransfield M, et al. Feasibility of exercising adults with asthma: a randomized pilot study. Allergy Asthma Clin Immunol. 2012;8(1):13. doi: 10.1186/1710-1492-8-13.
    1. Constantini K, Wilhite DP, Chapman RF. A clinician guide to altitude training for optimal endurance exercise performance at sea level. High Alt Med Biol. 2017;18(2):93–101. doi: 10.1089/ham.2017.0020.

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