Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

Summary

Asthma is an inflammatory disease affecting the whole respiratory system, from central to peripheral airways. Anti-inflammatory treatment with inhaled corticosteroids (ICS), with or without long-acting β2-adrenoceptor agonists (LABA), is the cornerstone of asthma management \[GINA Guideline - available at www.ginasthma.com\]. Nevertheless, a considerable subset of asthmatic patients neither benefits from ICS nor gain optimal asthma control even with ICS/LABA combinations. The involvement of the distal lung, i.e. the peripheral membranous bronchioles \< 2 mm in diameter (so-called small airways), in the pathogenesis of asthma has been extensively investigated and its significance debated. However, whether specifically targeting distal lung abnormalities can lead to further clinical benefit is still an open question. In this context, interest has been raised by hydrofluoroalkane (HFA) pressurised metered-dose inhalers, which can deliver compounds with a mass median aerodynamic diameter that is significantly smaller than other available devices, leading to increase peripheral airways drug deposition. Up to 30% of asthmatic patients smoke, mirroring the rate found in the general population. Several data document that smoking habit negatively affect corticosteroid efficacy in asthma. In particular, asthmatic patients who smoke experience faster lung function decline, increased frequency of exacerbations and reduced asthma control despite being regularly treated. Several molecular mechanisms have been proposed to address the issue of reduced corticosteroids responsiveness in smoker patients. However it has been never investigated whether reduced corticosteroid responsiveness in asthmatic patients who smoke can be related to more severe small airways involvement leading to impaired distribution or impaired peripheral deposition of inhaled corticosteroids. If this is the case, asthmatic patients who smoke might benefit from a pharmacological approach able to target and to reach small airways.

Timeline

Start

2011-11

Primary completion

2014-04

Completion

2014-04

Publications

• Background Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE; GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004 Oct 15;170(8):836-44. doi: 10.1164/rccm.200401-033OC. Epub 2004 Jul 15.
• Background Contoli M, Bousquet J, Fabbri LM, Magnussen H, Rabe KF, Siafakas NM, Hamid Q, Kraft M. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy. 2010 Feb;65(2):141-51. doi: 10.1111/j.1398-9995.2009.02242.x. Epub 2009 Nov 11.
• Background Hampel F, Lisberg E, Guerin JC. Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group. J Asthma. 2000 Aug;37(5):389-98. doi: 10.3109/02770900009055464.
• Background Haussermann S, Acerbi D, Brand P, Herpich C, Poli G, Sommerer K, Meyer T. Lung deposition of formoterol HFA (Atimos/Forair) in healthy volunteers, asthmatic and COPD patients. J Aerosol Med. 2007 Fall;20(3):331-41. doi: 10.1089/jam.2007.0613.
• Background Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone : a cross-over study in healthy volunteers. Chest. 2002 Aug;122(2):510-6. doi: 10.1378/chest.122.2.510.
• Background Thomson NC, Chaudhuri R. Asthma in smokers: challenges and opportunities. Curr Opin Pulm Med. 2009 Jan;15(1):39-45. doi: 10.1097/MCP.0b013e32831da894.
• Background Chalmers GW, Macleod KJ, Little SA, Thomson LJ, McSharry CP, Thomson NC. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002 Mar;57(3):226-30. doi: 10.1136/thorax.57.3.226.
• Background Tomlinson JE, McMahon AD, Chaudhuri R, Thompson JM, Wood SF, Thomson NC. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax. 2005 Apr;60(4):282-7. doi: 10.1136/thx.2004.033688.
• Background Pedersen SE, Bateman ED, Bousquet J, Busse WW, Yoxall S, Clark TJ; Gaining Optimal Asthma controL Steering Committee and Investigators. Determinants of response to fluticasone propionate and salmeterol/fluticasone propionate combination in the Gaining Optimal Asthma controL study. J Allergy Clin Immunol. 2007 Nov;120(5):1036-42. doi: 10.1016/j.jaci.2007.07.016. Epub 2007 Nov 1.
• Background Chapman KR, Boulet LP, Rea RM, Franssen E. Suboptimal asthma control: prevalence, detection and consequences in general practice. Eur Respir J. 2008 Feb;31(2):320-5. doi: 10.1183/09031936.00039707. Epub 2007 Oct 24.
• Background Adcock IM, Caramori G, Ito K. New insights into the molecular mechanisms of corticosteroids actions. Curr Drug Targets. 2006 Jun;7(6):649-60. doi: 10.2174/138945006777435344.
• Contoli M, Bellini F, Morandi L, Forini G, Bianchi S, Gnesini G, Marku B, Rabe KF, Papi A. Assessing small airway impairment in mild-to-moderate smoking asthmatic patients. Eur Respir J. 2016 Apr;47(4):1264-7. doi: 10.1183/13993003.01708-2015. Epub 2016 Feb 11. No abstract available.

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