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| Name | Class |
|---|---|
| Chiesi Farmaceutici S.p.A. | INDUSTRY |
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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\ [blocked]]. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Alberto Papi, MD | Università degli Studi di Ferrara | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Grosshansdorf | Großhansdorf | 22927 | Germany | |||
| Research Centre on Asthma and COPD, University of Ferrara |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15256389 | Background | 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. | |
| 19909298 | Background |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D000073865 | Cigarette Smoking |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Ferrara |
| 44121 |
| Italy |
| 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. |
| 10983616 | 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. |
| 17894539 | 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. |
| 12171824 | 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. |
| 19077704 | 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. |
| 11867826 | 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. |
| 15790982 | 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. |
| 17935765 | 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. |
| 17959642 | 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. |
| 16787166 | 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. |
| 26869674 | Derived | 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. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000073869 | Tobacco Smoking |
| D012907 | Smoking |
| D001519 | Behavior |
| D064424 | Tobacco Use |