Beclomethasone/Formoterol in Extra-Fine Formulation Improves Small Airway Dysfunction in COPD Patients

Overview

Journal Pulm Ther

Publisher Springer

Date 2021 Feb 4

PMID 33538996

Citations 2

Authors

Roberta Pisi

Marina Aiello

Alessio Piraino

Davide Paleari

Annalisa Frizzelli

Giuseppina Bertorelli

Alfredo Chetta

Affiliations

Soon will be listed here.

Abstract

Introduction: In patients with chronic obstructive pulmonary disease (COPD), small airway dysfunction (SAD) is a key element and a functional consequence of the pathology. The exact role of SAD as a specific 'pharmacological target' represents an important research topic. Our objective was to ascertain whether an extra-fine formulation of beclomethasone dipropionate/formoterol fumarate (BDP/FF) NEXThaler 100/6 μg b.i.d. could improve SAD and, consequently, the quality of life of COPD patients.

Methods: We enrolled COPD patients with severe airflow obstruction and at least one moderate exacerbation in the previous year, having started treatment with BDP/FF NEXThaler for no more than 1 week. Patients underwent three visits: at the start of the treatment (V1), 6 weeks (V2), and 12 weeks later (V3). At each visit, we evaluated the fall in resistance from 5 to 20 Hz (R5-R20) and residual volume/total lung capacity (RV/TLC) ratio by impulse oscillometry, spirometry, and plethysmography. The COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also administered to assess the disease's impact on quality of life.

Results: We enrolled 43 COPD patients (mean age 69 years, FEV 43%). R5-R20 significantly changed from baseline [0.23 ± 0.09 kPa/(l/s)] to V2 [0.16 ± 0.09 kPa/(l/s)] and V3 [0.16 ± 0.08 kPa/(l/s)] (p < 0.05). Clinical status was also significantly improved compared to baseline; in fact, CAT score changed from an average baseline value of 13-6 and 4 (V2 and V3, respectively) (p < 0.05). A correlation was found between CAT percentage change values and the corresponding ones of R5-R20 (r = - 0.329, p = 0.045) and RV/TLC (r = 0.354, p = 0.029).

Conclusions: In COPD patients, treatment with BDP/FF extra-fine formulation improved functional parameters related to small airway disease as well as the disease impact on health status.

Trial Registration: ClinicalTrials.gov identifier, NCT04421742.

Citing Articles

Impulse oscillometry in patients with persistent post-COVID-19 symptoms: A retrospective study.

Lu C, Lin S, Chen C Health Sci Rep. 2024; 7(6):e2191.

PMID: 38933420 PMC: 11199183. DOI: 10.1002/hsr2.2191.

Impulse Oscillometry, Small Airways Disease, and Extra-Fine Formulations in Asthma and Chronic Obstructive Pulmonary Disease: Windows for New Opportunities.

Chetta A, Facciolongo N, Franco C, Franzini L, Piraino A, Rossi C Ther Clin Risk Manag. 2022; 18:965-979.

PMID: 36212050 PMC: 9533783. DOI: 10.2147/TCRM.S369876.

References

George J, Kong D, Thoman R, Stewart K . Factors associated with medication nonadherence in patients with COPD. Chest. 2005; 128(5):3198-204. DOI: 10.1378/chest.128.5.3198. View

Hogg J, Chu F, Tan W, Sin D, Patel S, Pare P . Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med. 2007; 176(5):454-9. PMC: 1976540. DOI: 10.1164/rccm.200612-1772OC. View

de Boer A, Gjaltema D, Hagedoorn P, Frijlink H . Can 'extrafine' dry powder aerosols improve lung deposition?. Eur J Pharm Biopharm. 2015; 96:143-51. DOI: 10.1016/j.ejpb.2015.07.016. View

Crisafulli E, Pisi R, Aiello M, Vigna M, Tzani P, Torres A . Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease. Respiration. 2016; 93(1):32-41. DOI: 10.1159/000452479. View

Oppenheimer B, Goldring R, Herberg M, Hofer I, Reyfman P, Liautaud S . Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007; 132(4):1275-82. DOI: 10.1378/chest.07-0913. View

Virchow J, Poli G, Herpich C, Kietzig C, Ehlich H, Braeutigam D . Lung Deposition of the Dry Powder Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Using NEXThaler Device in Healthy Subjects, Asthmatic Patients, and COPD Patients. J Aerosol Med Pulm Drug Deliv. 2018; 31(5):269-280. PMC: 6161336. DOI: 10.1089/jamp.2016.1359. View

Charlson M, Szatrowski T, Peterson J, Gold J . Validation of a combined comorbidity index. J Clin Epidemiol. 1994; 47(11):1245-51. DOI: 10.1016/0895-4356(94)90129-5. View

Kon S, Canavan J, Jones S, M Nolan C, Clark A, Dickson M . Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014; 2(3):195-203. DOI: 10.1016/S2213-2600(14)70001-3. View

Basile M, Baiamonte P, Mazzuca E, Principe S, Pennavaria F, Benfante A . Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction. COPD. 2018; 15(4):350-354. DOI: 10.1080/15412555.2018.1504015. View

10.

Yanai M, Sekizawa K, Ohrui T, Sasaki H, Takishima T . Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol (1985). 1992; 72(3):1016-23. DOI: 10.1152/jappl.1992.72.3.1016. View

11.

De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C . Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010; 23(3):137-48. PMC: 3123836. DOI: 10.1089/jamp.2009.0772. View

12.

Singh D, Nicolini G, Bindi E, Corradi M, Guastalla D, Kampschulte J . Extrafine beclomethasone/formoterol compared to fluticasone/salmeterol combination therapy in COPD. BMC Pulm Med. 2014; 14:43. PMC: 4008134. DOI: 10.1186/1471-2466-14-43. View

13.

Haruna A, Oga T, Muro S, Ohara T, Sato S, Marumo S . Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study. BMC Pulm Med. 2010; 10:10. PMC: 2841100. DOI: 10.1186/1471-2466-10-10. View

14.

Lipworth B, Jabbal S . What can we learn about COPD from impulse oscillometry?. Respir Med. 2018; 139:106-109. DOI: 10.1016/j.rmed.2018.05.004. View

15.

Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K . The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003; 22(6):1026-41. DOI: 10.1183/09031936.03.00089403. View

16.

Pellegrino R, Viegi G, Brusasco V, Crapo R, Burgos F, Casaburi R . Interpretative strategies for lung function tests. Eur Respir J. 2005; 26(5):948-68. DOI: 10.1183/09031936.05.00035205. View

17.

Celli B, MacNee W . Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23(6):932-46. DOI: 10.1183/09031936.04.00014304. View

18.

Voshaar T, Spinola M, Linnane P, Campanini A, Lock D, Lafratta A . Comparing usability of NEXThaler(®) with other inhaled corticosteroid/long-acting β2-agonist fixed combination dry powder inhalers in asthma patients. J Aerosol Med Pulm Drug Deliv. 2013; 27(5):363-70. PMC: 4175427. DOI: 10.1089/jamp.2013.1086. View

19.

Hogg J, Chu F, Utokaparch S, Woods R, Elliott W, Buzatu L . The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350(26):2645-53. DOI: 10.1056/NEJMoa032158. View

20.

Wedzicha J, Singh D, Vestbo J, Paggiaro P, Jones P, Bonnet-Gonod F . Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014; 108(8):1153-62. DOI: 10.1016/j.rmed.2014.05.013. View