Skip to main content
OpenTrials
Completed

NCT Number: NCT01620099

Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital Grosshansdorf, Großhansdorf, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • nonsmokers: patients who never smoked
  • 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).

Treatment and study plan

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

Primary outcomes

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

    Time frame: At baseline

    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

Secondary outcomes

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

    Time frame: At baseline

    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.

  2. Respiratory Resistance by oscillometry technique

    Time frame: At baseline

    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.

  3. Lung volumes

    Time frame: At baseline

    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.

  4. Asthma control

    Time frame: At baseline

    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.

  5. Correlations between small airway functional parameters and asthma control scores

    Time frame: At baseline

    To evaluate at baseline correlations between parameters related to asthma control (questionnaire scores, symptoms and use of rescue medications) and functional measurements

  6. Changes after extrafine intervention

    Time frame: Change at 3 months vs baseline

    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.

Sponsors and collaborators

Lead sponsor

Università degli Studi di Ferrara

Other

Collaborators

  • Chiesi Farmaceutici S.p.A.

Registry information

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
Jun 15, 2012
Registry last updated
May 6, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.