Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

NCT01620099 | Completed Phase 4

• 1 other identifier: SAISA01
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Asthma

Keywords

Asthma; Cigarette smoke; Small airways; Lung function; Asthma control

Outcome Measures

Primary Outcomes (1)

• slope of phase III (dN2) by nitrogen single breath test

  The primary outcome will measure and compare at baseline slope of phase III (dN2) by nitrogen single breath test (NSBT) between asthmatic who smoke and asthmatic who do not smoke matched for age, gender and % predicted FEV1

  At baseline

Secondary Outcomes (6)

• Closing volume and closing capacity by nitrogen single breath test (NSBT)

  At baseline

• Respiratory Resistance by oscillometry technique

  At baseline

• Lung volumes

  At baseline

• Asthma control

  At baseline

• Correlations between small airway functional parameters and asthma control scores

  At baseline

Study Arms (2)

Asthmatic nonsmokers

EXPERIMENTAL

Asthmatic patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines, on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations, will be enrolled. This group includes patients who never smoked. Following the initial evaluation (cross-sectional - primary outcome) patients will be switched to an extrafine equipotent dose of the same compound (BDP-HFA if the patient was on ICS) or combination (BDP-HFA/F if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control

Drug: Extrafine treatment (Clenilexx(R) or Foster(R))

Asthmatic smokers

ACTIVE COMPARATOR

Asthmatic patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines, on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations, will be enrolled. This group includes patients who smoked with a smoking habit ranging from 10 to 20 pack/years. Following the initial evaluation (cross-sectional - primary outcome) patients will be switched to an extrafine equipotent dose of the same compound (BDP-HFA if the patient was on ICS) or combination (BDP-HFA/F if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control

Drug: Extrafine treatment (Clenilexx(R) or Foster(R))

Interventions

Extrafine treatment (Clenilexx(R) or Foster(R)) DRUG

Following the initial evaluation (cross-sectional) patients will be switched to an extrafine equipotent dose of the same compound (extrafine beclomethasone dipropionate - Clenilexx(R) - if the patient was on ICS) or combination (extrafine beclomethasone dipropionate/formoterol - Foster(R) - if the patient was on ICS/LABA combination). After 3-months patients will be reassessed for lung function and asthma control

Asthmatic nonsmokers; Asthmatic smokers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• patients aged 18-50 years old, at stage 2-3 according to GINA international guidelines
• patients must be free from an exacerbation from at least 2 months
• patients must be on inhaled treatment (ICS alone or combination ICS/LABA) other than extrafine formulations from at least 3 months.
• according to smoking habit, patients will be divided in two groups:
• nonsmokers: patients who never smoked
• smokers: patients with a smoking habit ranging from 10 to 20 pack/years.

You may not qualify if:

• aged \> 50 years
• heavy-smoker patients (pack/years \> 20)
• patients with a not fully reversible airflow obstruction (i.e. post-bronchodilator FEV1/FVC \< 70%)
• patients with an impaired diffusion capacity (DLCO \< 80%v predicted).

Sponsors & Collaborators

• Università degli Studi di Ferrara: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (2)

Hospital Grosshansdorf

Großhansdorf, 22927, Germany

Location

Research Centre on Asthma and COPD, University of Ferrara

Ferrara, 44121, Italy

Location

Related Publications (12)

• 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.

  PMID: 15256389 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.

  PMID: 19909298 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.

  PMID: 10983616 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.

  PMID: 17894539 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.

  PMID: 12171824 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.

  PMID: 19077704 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.

  PMID: 11867826 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.

  PMID: 15790982 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.

  PMID: 17935765 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.

  PMID: 17959642 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.

  PMID: 16787166 BACKGROUND

• 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.

  PMID: 26869674 DERIVED

MeSH Terms

Conditions

Asthma; Cigarette Smoking

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Study Officials

• Alberto Papi, MD

  Università degli Studi di Ferrara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 9, 2012
• First Posted: June 15, 2012
• Study Start: November 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 6, 2014

Record last verified: 2014-05

Locations

DE (1); IT (1)