Reported pneumonia in patients with COPD: findings from the INSPIRE study.
BACKGROUND
Pneumonia is an important complication of COPD and is reported more often in patients receiving inhaled corticosteroids (ICSs). Little is known about the clinical course and factors predisposing to pneumonia in patients with COPD. We investigated patient characteristics and symptoms occurring before pneumonia reports in the Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) study.


METHODS
This was a 2-year, double-blind, double-dummy parallel study of 1,323 patients randomized to salmeterol/fluticasone propionate 50/500 μg bid (SFC) or tiotropium 18 μg once daily (Tio). Baseline demographics, including serum C-reactive protein (CRP) levels, were measured, and daily record cards (DRCs) were completed.


RESULTS
We identified 87 pneumonia reports from adverse event records (SFC=62; Tio=25) in 74 patients (SFC=50; Tio=24), compared with 2,255 exacerbations (SFC=1,185; Tio=1,070). Pneumonia was more common in patients with severe dyspnea and in those with a baseline CRP level>10 mg/L. Numbers of de novo pneumonias (events that were not preceded by symptoms of an exacerbation) were similar between treatment groups, but pneumonia was more likely after either a treated or untreated unresolved exacerbation in patients receiving ICSs (SFC=32; Tio=7). Similar results were seen when analysis was confined to radiologically confirmed events.


CONCLUSIONS
Pneumonia is much less frequent than exacerbation in COPD. The excess of events with ICS treatment appears to be associated with protracted symptomatic exacerbations. Earlier identification and treatment of these events to prevent pneumonia merits further investigation.


BACKGROUND
ClinicalTrials.gov; No.: NCT00361959; Study No.: SC040036; URL: clinicaltrials.gov.
Calverley
Peter M A
PMA
University Hospital Aintree, Liverpool, England. Electronic address: pmacal@liverpool.ac.uk.
Stockley
Robert A
RA
University Hospital Birmingham, Birmingham, England.
Seemungal
Terence A R
TAR
University of the West Indies, Mount Hope, Trinidad and Tobago.
Hagan
Gerry
G
GlaxoSmithKline, Stockley Park, Uxbridge, London, England.
Willits
Lisa R
LR
GlaxoSmithKline, Stockley Park, Uxbridge, London, England.
Riley
John H
JH
GlaxoSmithKline, Stockley Park, Uxbridge, London, England.
Wedzicha
Jadwiga A
JA
Royal Free and University College Medical School, London, England.
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000453:epidemiology* / Q000401:mortality; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy*; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069447:Tiotropium Bromide
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D002097:C-Reactive Protein; D000068298:Fluticasone; D000420:Albuterol; D000069447:Tiotropium Bromide