Small Airways Involvement in Smoker Asthmatic Patients: a Pilot Study
Status:
Completed
Trial end date:
2014-04-01
Target enrollment:
Participant gender:
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.