Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2017 Jun 15;12(6):e0178112.
doi: 10.1371/journal.pone.0178112. eCollection 2017.

Risk of pneumonia in obstructive lung disease: A real-life study comparing extra-fine and fine-particle inhaled corticosteroids

Samatha Sonnappa  1   2 , Richard Martin  3 , Elliot Israel  4 , Dirkje Postma  5 , Wim van Aalderen  6 , Annie Burden  1 , Omar S Usmani  7 , David B Price  1   8 ; Respiratory Effectiveness Group, Small Airways Study Group
Affiliations
Comparative Study

Risk of pneumonia in obstructive lung disease: A real-life study comparing extra-fine and fine-particle inhaled corticosteroids

Samatha Sonnappa et al. PLoS One. .

Abstract

Background: Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD. The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used.

Methods: Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS. The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose. To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used.

Results: 14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS. On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS. Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size.

Conclusions: These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: Samatha Sonnappa is an employee of Observational and Pragmatic Research Institute Pte Ltd, which conducted this study and has conducted paid research in respiratory disease on behalf of the following other organizations in the past 5 years: Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva. Richard J. Martin reports grants from MedImmune, NHLBI, and Chiesi Farmaceutici SpA; consultancy fees from Teva Pharmaceuticals and PMD Healthcare; support for travel to meetings from Respiratory Effectiveness Group; royalties from UpToDate; and sits on an advisory board for AstraZeneca. In the past 36 months, Elliot Israel reports receiving consulting fees from AstraZeneca, Bird Rock Bio, Novartis, Nuvelution Pharmaceuticals, Philips Respironics, Regeneron Pharmaceuticals, TEVA Specialty Pharmaceuticals and Vitaeris, Inc; travel grant support from Research in Real Life (RiRL) and TEVA Specialty Pharmaceuticals; Deputy Editor fees from the American Thoracic Society, and having grant support paid to his institution from Genentech, Sanofi, and the NIH. The University of Groningen has received money for Dirkje Postma regarding a grant for research from Astra Zeneca, Chiesi, Genentec, GSK and Roche. Fees for consultancies were given to the University of Groningen by Astra Zeneca, Boehringer Ingelheim, Chiesi, GSK, Takeda and TEVA. Wim van Aalderen is a member of the Medical advisory board of Astra Zeneca. Anne Burden was an employee of Observational and Pragmatic Research Institute Pte Ltd at the time of the study. Observational and Pragmatic Research Institute Pte Ltd conducted this study and has conducted paid research in respiratory disease on behalf of the following other organizations in the past 5 years: Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva. David B. Price has board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda, and Teva Pharmaceuticals; payment for manuscript preparation from Mundipharma and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; funding for patient enrollment or completion of research from Chiesi, Novartis, Teva Pharmaceuticals, and Zentiva; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd, UK and 74% of Observational and Pragmatic Research Institute Pte Ltd, Singapore; and is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, Health Technology Assessment, and Medical Research Council. Omar S. Usmani reports grants from AstraZeneca, personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, personal fees from Aerocrine, grants from GlaxoSmithKline, personal fees from Napp, personal fees from Mundipharma, personal fees from Sandoz, grants from Prosonix, personal fees from Takeda, personal fees from Zentiva, grants from Edmond Pharma. He is a recipient of a UK National Institute for Health Research (NIHR) Career Development Fellowship and supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Probability (95% CI) of pneumonia in outcome period by treatment group.
Fig 2
Fig 2. Probability (95% CI) of pneumonia in outcome period by average daily consumed ICS dose during outcome period.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Global Initiative for Asthma (GINA) (2016) Global Strategy for Asthma Management and Prevention.
    1. Global initiative for chronic obstructive lung disease (GOLD) (2016) Global Strategy for the Diagnosis, management and prevention of COPD. - PubMed
    1. Greening AP, Ind PW, Northfield M, Shaw G. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group. Lancet. 1994;344:219–224. - PubMed
    1. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997;337:1405–1411. doi: 10.1056/NEJM199711133372001 - DOI - PubMed
    1. Usmani OS, Ito K, Maneechotesuwan K, Ito M, Johnson M, Barnes PJ, et al. Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med. 2005;172:704–712. 200408-1041OC [pii]; doi: 10.1164/rccm.200408-1041OC - DOI - PubMed

Publication types

MeSH terms

Substances