Clinical trial NCT01620099: Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study
Official title: Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Cigarette smoke
Small airways
Lung function
Asthma control
Lead sponsor: Università degli Studi di Ferrara
Sponsor class: OTHER
Collaborators: name: Chiesi Farmaceutici S.p.A.
First posted: 2012-06-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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).

Primary outcomes:
measure: slope of phase III (dN2) by nitrogen single breath test
timeFrame: At baseline
Secondary outcomes:
measure: Closing volume and closing capacity by nitrogen single breath test (NSBT)
timeFrame: At baseline
measure: Respiratory Resistance by oscillometry technique
timeFrame: At baseline
measure: Lung volumes
timeFrame: At baseline
measure: Asthma control
timeFrame: At baseline
measure: Correlations between small airway functional parameters and asthma control scores
timeFrame: At baseline
measure: Changes after extrafine intervention
timeFrame: Change at 3 months vs baseline
Other outcomes:
Locations:
city: Grosshansdorf
country: Germany
facility: Hospital Grosshansdorf
city: Ferrara
country: Italy
facility: Research Centre on Asthma and COPD, University of Ferrara
Study officials:
affiliation: Università degli Studi di Ferrara
name: Alberto Papi, MD
role: PRINCIPAL_INVESTIGATOR
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