Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

Asthma Clinical Trial

Official title:

Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01620099
• Other study ID #: SAISA01
• Status: Completed
• Phase: Phase 4
• First received: May 9, 2012
• Last updated: May 5, 2014
• Start date: November 2011
• Est. completion date: April 2014

Study information

• Verified date: May 2014
• Source: Università degli Studi di Ferrara
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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:

1. nonsmokers: patients who never smoked

2. smokers: patients with a smoking habit ranging from 10 to 20 pack/years.

Exclusion Criteria:

• to avoid possible overlapping with chronic obstructive pulmonary disease, patients will not be included in the study if any of the following exclusion criteria are present:

• 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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Asthma

Intervention

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

Locations

Country	Name	City	State
Germany	Hospital Grosshansdorf	Grosshansdorf
Italy	Research Centre on Asthma and COPD, University of Ferrara	Ferrara

Sponsors (2)

Lead Sponsor	Collaborator
Università degli Studi di Ferrara	Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

Germany,  Italy, 

References & Publications (11)

Adcock IM, Caramori G, Ito K. New insights into the molecular mechanisms of corticosteroids actions. Curr Drug Targets. 2006 Jun;7(6):649-60. Review. — View Citation

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. Epub 2004 Jul 15. — View Citation

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. — View Citation

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. Epub 2007 Oct 24. — View Citation

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. Review. — View Citation

Hampel F, Lisberg E, Guérin 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. — View Citation

Häussermann 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. — View Citation

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. — View Citation

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. Epub 2007 Nov 1. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Closing volume and closing capacity by nitrogen single breath test (NSBT)	To evaluate and compare at baseline other nitrogen single breath test measures including closing volume and closing capacity in asthmatic who smoke and asthmatic who do not smoke matched for age, gender and % predicted FEV1.	At baseline	No
Secondary	Respiratory Resistance by oscillometry technique	To evaluate differences in mean resistive component of respiratory impedence (Rrs) and resistance at different frequency (Rr0, Rr5, Rr20) by forced oscillometry technique (FOT) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.	At baseline	No
Secondary	Lung volumes	To evaluate differences in forced vital capacity (FVC), slow vital capacity/forced vital capacity ratio (SVC/FVC), residual volume (RV) and total lung capacity (TLC) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.	At baseline	No
Secondary	Asthma control	To evaluate differences in parameters related to asthma control (Asthma Control Test scores, use of rescue medications) at baseline between asthmatics who smoke compared to asthmatics who do not smoke matched for age, gender and % predicted FEV1.	At baseline	No
Secondary	Correlations between small airway functional parameters and asthma control scores	To evaluate at baseline correlations between parameters related to asthma control (questionnaire scores, symptoms and use of rescue medications) and functional measurements	At baseline	No
Secondary	Changes after extrafine intervention	To evaluate changes in functional parameters and parameters related to asthma control in asthmatic patients who smoke compared to asthmatic patients who do not smoke after a 3-months extrafine inhaled treatment.	Change at 3 months vs baseline	No