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 For patients with chronic obstructive pulmonary disease (COPD), prior use of inhaled corticosteroids (ICS) is associated with a lower risk for short-term mortality and lower use of mechanical ventilation after hospitalization for pneumonia, according to the results of a retrospective database analysis reported online April 15 in the American Journal of Respiratory and Critical Care Medicine.

Previous evidence suggests that ICS use in patients with COPD reduces exacerbations but increases the rate of pneumonia.

"It was therefore believed that it also increased mortality," said senior author Eric M. Mortensen, MD, MSc, investigator at VERDICT (Veterans Evidence-based Research, Dissemination, and Implementation Center) at the University of Texas Health Science Center in San Antonio, in a news release. "This was the first large rigorous study to examine whether this was in fact the case."

The goal of the study was to assess the effects of prior ICS use on clinical outcomes for patients with COPD who were hospitalized with pneumonia. Using the national administrative databases of the Department of Veterans Affairs, the investigators identified patients who had a preexisting diagnosis of COPD and a discharge diagnosis of pneumonia and who were treated with at least 1 appropriate pulmonary medication before they were hospitalized. Evaluated endpoints included death, use of invasive mechanical ventilation, and use of vasopressor.

Of 15,768 eligible patients with COPD who were hospitalized for pneumonia, 8271 had prior ICS use and 7497 had no ICS use. Compared with patients with no prior ICS use, those with prior ICS use had a lower 90-day mortality rate (17.3% vs 22.8%; P < .001).

"This result is the opposite of what many experts have believed," Dr. Mortensen said. "We do, however, believe that this represents the reality because ours is one [of] the largest studies and employed a rigorous definition of pneumonia that previous studies did not."

Previous treatment with ICS was associated with lower 30-day mortality risk (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.72 - 0.89), lower 90-day mortality risk (OR, 0.78; 95% CI, 0.72 - 0.85), and less use of mechanical ventilation (OR, 0.83; 95% CI, 0.72 - 0.94), based on multilevel regression analyses. Prior treatment with ICS was not significantly associated with vasopressor use (OR, 0.88; 95% CI, 0.74 - 1.04).

"These results have clear implications for current clinical practice, which has been informed in the past by a series of studies that found an increased risk of pneumonia with ICS use," Dr. Mortensen said. "In contrast, our study would suggest that ICS use may confer a survival benefit to these patients and may be employed when there are not contraindications. These results should reassure clinicians that they can give their COPD patients ICS without fearing that the increased risk of pneumonia will translate into higher risk of mortality."

Limitations of this study include retrospective database analysis, precluding causal inference; lack of generalizability to women; and reliance on International Classification of Diseases, Ninth Revision, codes and medication use to define COPD.

"There is currently a large randomized, controlled trial getting started that is looking at using oral versus intravenous steroids for all pneumonia patients," Dr. Mortensen said. "The potential question is if this is successful would it be as useful to start these patients on inhaled (rather than oral or intravenous) steroids."

The National Institute of Nursing Research supported this study. The views expressed in the journal article are those of the study authors and do not necessarily represent the views of the Department of Veterans Affairs.

Am J Respir Crit Care Med. Published online April 15, 2011. 

COPD is a common cause of morbidity and mortality in developed countries. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), one of the current recommendations is the use of ICS for symptomatic patients with a documented bronchodilator response on spirometry or for patients with a forced expiratory volume in 1 second (FEV₁) of less than 50% predicted. This value is indicative of moderate to severe COPD. Several studies have demonstrated that treatment with ICS for patients with COPD has been shown to be associated with an increased incidence of pneumonia. However, it is unclear if this trend is associated with increased mortality risk.

The aim of this study was to examine the effects of prior ICS use on clinical outcomes for patients with COPD hospitalized with pneumonia.

Study Highlights

• A retrospective cohort study using the national administrative databases of the Department of Veterans Affairs was conducted to examine treatments and outcomes for elderly patients hospitalized with pneumonia.
• The databases are the repositories of clinical and administrative data from the more than 150 Veterans Affairs hospitals and 850 clinics.
• Eligible patients had a preexisting diagnosis of COPD and a discharge diagnosis of pneumonia. They received treatment with 1 or more appropriate pulmonary medications before hospitalization.
• The following medications were classified as ICS: inhaled forms of triamcinolone, fluticasone, budesonide, beclomethasone, and flunisolide.
• Patients were excluded if they had a history of asthma and were treated with outpatient oral corticosteroids within 90 days before hospital admission.
• The primary outcomes for this study were 30-day and 90-day mortality. Other outcomes included use of invasive mechanical ventilation and vasopressor use.
• Results demonstrated that 15,768 patients (8271 with ICS use, 7497 with no ICS use) with COPD were hospitalized for pneumonia.
• The most commonly prescribed medications were flunisolide (51.2%), fluticasone (27.8%), and triamcinolone (19.8%).
• Patients with ICS use were less likely to have cancer, less likely to use tobacco currently, more likely to be married, and more likely to receive a long-acting beta-agonist and/or tiotropium therapy.
• There were significant differences in both 30-day mortality rates (10.2% in ICS users vs 13.6% in nonusers; P < .001) and 90-day mortality rates (17.3% in ICS users vs 22.8% in nonusers; P < .001).
• Multilevel regression analyses demonstrated that prior receipt of ICS was associated with decreased mortality risk at 30 days (OR, 0.80; 95% CI, 0.72 - 0.89) and 90 days (OR, 0.78; 95% CI, 0.72 - 0.85), and decreased use of mechanical ventilation (OR, 0.83; 95% CI, 0.72 - 0.94).
• There was no significant association between receipt of ICS and vasopressor use (OR, 0.88; 95% CI, 0.74 - 1.04).
• For the group that received a short-acting beta-agonist and ipratropium plus-or-minus ICS (n = 11,696), ICS use was not significantly associated with worsening of any of the clinical outcomes, and receipt of ICS was associated with a reduced 90-day mortality risk and less need for mechanical ventilation, but not 30-day mortality risk or vasopressor use.
• For those who received a short-acting beta-agonist, ipratropium, and a long-acting beta-agonist plus-or-minus ICS (n = 1851), there were no significant associations with the outcomes of interest.

Clinical Implications

• According to GOLD, one of the current recommendations is the use of ICS for symptomatic patients with a documented bronchodilator response on spirometry or for patients with an FEV₁ of less than 50% predicted.
• For patients with COPD, prior ICS use is independently associated with a decreased risk for short-term mortality and decreased use of mechanical ventilation after hospitalization for pneumonia.