Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis.

Results: Eighteen randomized controlled trials (n=16 996) with 24 to 156 weeks of follow-up were included after a detailed screening of 97 articles. Inhaled corticosteroids were associated with a significantly increased risk of any pneumonia (relative risk [RR], 1.60; 95% confidence interval [CI], 1.33-1.92 [P.001]; I 2 =16%) and serious pneumonia (1.71; 1.46-1.99 [P.001]; I 2 =0%) but without a significantly increased risk of pneumonia-related mortality (1.27; 0.80-2.03 [P=.31]; I 2 =0%) or overall mortality (0.96; 0.86-1.08 [P=.51]; I 2 =0%). Inhaled corticosteroids were associated with a significantly increased risk of serious pneumonia when compared with placebo (RR, 1.81; 95% CI, 1.44-2.29 [P.001]) or when the combination of inhaled corticosteroids and long-acting -agonists was compared with long-acting -agonists (1.68; 1.20-2.34 [P=.002]). Conclusion: Among patients with COPD, inhaled corticosteroid use for at least 24 weeks is associated with a significantly increased risk of serious pneumonia, without a significantly increased risk of death.

[1]  S. Hurd,et al.  Global Strategy for the Diagnosis, Management and Prevention of COPD: 2003 update , 2003, European Respiratory Journal.

[2]  D. Postma,et al.  Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease , 2005, Thorax.

[3]  C. Jenkins,et al.  Salmeterol/Fluticasone propionate and survival in chronic obstructive pulmonary disease:the TORCH trail. , 2007 .

[4]  C. Strange,et al.  Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis. , 2003, Annals of internal medicine.

[5]  J. Bourbeau,et al.  Tiotropium in Combination with Placebo, Salmeterol, or FluticasoneSalmeterol for Treatment of Chronic Obstructive Pulmonary Disease , 2007, Annals of Internal Medicine.

[6]  S. Suissa,et al.  METHODOLOGICAL ISSUES IN THERAPEUTIC TRIALS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE , 2008 .

[7]  I. Bolíbar,et al.  Risk factors for community-acquired pneumonia in adults: a population-based case-control study. , 1999, The European respiratory journal.

[8]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[9]  D. Postma,et al.  Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial , 2005, Thorax.

[10]  P. Barnes.  Inhaled corticosteroids are not beneficial in chronic obstructive pulmonary disease. , 2000, American journal of respiratory and critical care medicine.

[11]  Frederick Wolfe,et al.  Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. , 2006, Arthritis and rheumatism.

[12]  A. Anzueto,et al.  Effect of fluticasone propionate/salmeterol (250/50 g) or salmeterol (50 g) on COPD exacerbations , 2008 .

[13]  T. Lasserson,et al.  Combined corticosteroid and long-acting beta-agonist in one inhaler versus long-acting beta-agonists for chronic obstructive pulmonary disease. , 2007, The Cochrane database of systematic reviews.

[14]  A. Gillissen,et al.  Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study , 2003, Thorax.

[15]  S. Suissa,et al.  Low-dose inhaled and nasal corticosteroid use and the risk of cataracts , 2006, European Respiratory Journal.

[16]  N. Hanania,et al.  The Efficacy and Safety of Fluticasone Propionate (250 μg)/Salmeterol (50 μg) Combined in the Diskus Inhaler for the Treatment of COPD , 2003 .

[17]  A. LaCroix,et al.  Prospective study of pneumonia hospitalizations and mortality of U.S. older people: the role of chronic conditions, health behaviors, and nutritional status. , 1989, Public health reports.

[18]  J. Yates,et al.  Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease. , 2002, American journal of respiratory and critical care medicine.

[19]  S. Suissa,et al.  Inhaled and nasal corticosteroid use and the risk of fracture. , 2004, American journal of respiratory and critical care medicine.

[20]  C. Vogelmeier,et al.  Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[21]  A. Anzueto,et al.  COPD is associated with increased mortality in patients with community-acquired pneumonia , 2006, European Respiratory Journal.

[22]  K. Lohr,et al.  Efficacy and Safety of Inhaled Corticosteroids in Patients With COPD: A Systematic Review and Meta-Analysis of Health Outcomes , 2006, The Annals of Family Medicine.

[23]  P. Paggiaro,et al.  Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease , 1998, The Lancet.

[24]  T. Seemungal,et al.  The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. , 2008, American journal of respiratory and critical care medicine.

[25]  J. van der Palen,et al.  Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. , 2002, American journal of respiratory and critical care medicine.

[26]  T. Wilt,et al.  Management of Stable Chronic Obstructive Pulmonary Disease: A Systematic Review for a Clinical Practice Guideline , 2007, Annals of Internal Medicine.

[27]  P. Calverley,et al.  Maintenance therapy with budesonide and formoterol in chronicobstructive pulmonary disease , 2003, European Respiratory Journal.

[28]  A. Anzueto,et al.  Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. , 2008, Respiratory medicine.

[29]  S. Suissa,et al.  Methodological issues in therapeutic trials of COPD , 2008, European Respiratory Journal.

[30]  C L Bartlett,et al.  Risk factors for community-acquired pneumonia diagnosed upon hospital admission. British Thoracic Society Pneumonia Study Group. , 2000, Respiratory medicine.

[31]  P. Lange,et al.  Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial , 1999, The Lancet.

[32]  Bartolome Celli,et al.  Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. , 2007, The New England journal of medicine.

[33]  A. Gonzalez,et al.  Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. , 2007, American journal of respiratory and critical care medicine.

[34]  P. Barnes.  Reduced histone deacetylase in COPD: clinical implications. , 2006, Chest.

[35]  M. Rosenberg,et al.  THE FILE‐DRAWER PROBLEM REVISITED: A GENERAL WEIGHTED METHOD FOR CALCULATING FAIL‐SAFE NUMBERS IN META‐ANALYSIS , 2005, Evolution; international journal of organic evolution.

[36]  D. Postma,et al.  A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo. , 2007, Chest.

[37]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[38]  I. Adcock,et al.  Decreased histone deacetylase activity in chronic obstructive pulmonary disease. , 2005, The New England journal of medicine.