Risk of pneumonia with inhaled corticosteroid/long-acting β2 agonist therapy in chronic obstructive pulmonary disease: a cluster analysis

Int J Chron Obstruct Pulmon Dis. 2014 May 7;9:457-68. doi: 10.2147/COPD.S60498. eCollection 2014.


Background: Pneumonia poses a significant risk in patients with moderate to severe chronic obstructive pulmonary disease but data are limited on the disease phenotypes most susceptible to pneumonia.

Methods: Cluster analysis using a data-driven recursive partitioning algorithm was employed using baseline data from two pooled one-year randomized exacerbation trials (n=3,255) of fluticasone furoate/vilanterol or vilanterol alone to identify distinct patient groups at greatest risk of pneumonia or serious (hospitalization or death) pneumonia.

Results: Five clusters were identified. Patients at greater risk of first pneumonia had more severe obstruction (forced expiratory volume in one second/forced vital capacity <46%) and either a body mass index <19 kg/m(2) (hazard ratio 7.8, 95% confidence interval 4.7-13.0; n=144) or a pneumonia history and greater comorbidities (hazard ratio 4.8, 95% confidence interval 3.0-7.7; n=374) relative to the cluster with the lowest pneumonia risk (reference; n=1310). Multiple comorbidities and use of psychoanaleptics also contributed to an increased risk of pneumonia in more obstructed patients. Independent of cluster, use of inhaled corticosteroids was associated with pneumonia (hazard ratio 1.89, 95% confidence interval 1.25-2.84) and serious pneumonia (hazard ratio 2.92, 95% confidence interval 1.40-6.01).

Conclusion: Cluster analysis can identify patient populations at risk for serious safety outcomes and inform risk management strategies to optimize patient management. The greatest risk for pneumonia was in subjects with multiple pneumonia risk factors.

Keywords: chronic obstructive pulmonary disease; cluster analysis; inhaled corticosteroids; long-acting β2-agonists; pneumonia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / adverse effects*
  • Aged
  • Androstadienes / administration & dosage
  • Androstadienes / adverse effects*
  • Benzyl Alcohols / administration & dosage
  • Benzyl Alcohols / adverse effects*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Chlorobenzenes / administration & dosage
  • Chlorobenzenes / adverse effects*
  • Cluster Analysis
  • Comorbidity
  • Disease Progression
  • Female
  • Hospitalization
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pneumonia / chemically induced*
  • Pneumonia / diagnosis
  • Pneumonia / mortality
  • Pneumonia / therapy
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors


  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Androstadienes
  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • vilanterol
  • fluticasone furoate