Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort study

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Abstract

<div class="section"> <a class="named-anchor" id="bcp13295-sec-0001">  </a> <h5 class="section-title" id="d6594168e235">Aim</h5> <p id="d6594168e237">Studies have linked the use of inhaled corticosteroids (ICSs) to excess pneumonia risk in chronic obstructive pulmonary disease patients. The risk in asthma patients remains unclear. The objective of the present study was to examine the risk of pneumonia with ICSs in asthma patients aged 12–35 years. </p> </div><div class="section"> <a class="named-anchor" id="bcp13295-sec-0002">  </a> <h5 class="section-title" id="d6594168e240">Methods</h5> <p id="d6594168e242">We formed a cohort of asthma patients treated from 1990 to 2007 using Quebec health insurance databases. Subjects were considered currently exposed if they had had an ICS dispensed within the 60 days prior to their pneumonia index event or matched person‐moment. Secondary analyses investigated the risk of pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences (RDs) were both estimated through a quasi‐cohort approach. </p> </div><div class="section"> <a class="named-anchor" id="bcp13295-sec-0003">  </a> <h5 class="section-title" id="d6594168e245">Results</h5> <p id="d6594168e247">The cohort included 152 412 subjects, of whom 1928 had a pneumonia event during follow‐up. There was an increased risk of pneumonia associated with current use of ICSs [RR 1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases per 1000 person‐years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI 1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58, 2.36), specifically relative to no use. When accounting for potential protopathic bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22, 1.78). </p> </div><div class="section"> <a class="named-anchor" id="bcp13295-sec-0004">  </a> <h5 class="section-title" id="d6594168e250">Conclusion</h5> <p id="d6594168e252">ICS use in asthma patients appears to be associated with an increased risk of pneumonia and is present for both budesonide and fluticasone. </p> </div>

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Low-dose inhaled corticosteroids and the prevention of death from asthma.

S Suissa, P. Ernst, S Benayoun … (2000)

Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

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Inhaled corticosteroids and the risks of diabetes onset and progression.

Samy Suissa, A Kezouh, Pierre Ernst (2010)

Systemic corticosteroids are known to increase diabetes risk, but the effects of high-dose inhaled corticosteroids are unknown. We assessed whether the use and dose of inhaled corticosteroids increase the risk of diabetes onset and progression. We formed a new-user cohort of patients treated for respiratory disease during 1990-2005, identified using the Quebec health insurance databases and followed through 2007 or until diabetes onset. The subcohort treated with oral hypoglycemics was followed until diabetes progression. A nested case-control analysis was used to estimate the rate ratios of diabetes onset and progression associated with current inhaled corticosteroid use, adjusted for age, sex, respiratory disease severity, and co-morbidity. The cohort included 388,584 patients, of whom 30,167 had diabetes onset during 5.5 years of follow-up (incidence rate 14.2/1000/year), and 2099 subsequently progressed from oral hypoglycemic treatment to insulin (incidence rate 19.8/1000/year). Current use of inhaled corticosteroids was associated with a 34% increase in the rate of diabetes (rate ratio [RR] 1.34; 95% confidence interval [CI], 1.29-1.39) and in the rate of diabetes progression (RR 1.34; 95% CI, 1.17-1.53). The risk increases were greatest with the highest inhaled corticosteroid doses, equivalent to fluticasone 1000 μg per day or more (RR 1.64; 95% CI, 1.52-1.76 and RR 1.54; 95% CI, 1.18-2.02; respectively). In patients with respiratory disease, inhaled corticosteroid use is associated with modest increases in the risks of diabetes onset and diabetes progression. The risks are more pronounced at the higher doses currently prescribed in the treatment of chronic obstructive pulmonary disease. Copyright © 2010 Elsevier Inc. All rights reserved.

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Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia.

Samy Suissa, Paul Brassard, Pierre Ernst … (2007)

Inhaled corticosteroids are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD). To examine whether these medications might be associated with an excess risk of pneumonia. We conducted a nested case-control study within a cohort of patients with COPD from Quebec, Canada, over the period 1988-2003, identified on the basis of administrative databases linking hospitalization and drug-dispensing information. Each subject hospitalized for pneumonia during follow-up (case subjects) was age and time matched to four control subjects. The effect of the use of inhaled corticosteroids was assessed by conditional logistic regression, after adjusting for comorbidity and COPD severity. The cohort included 175,906 patients with COPD of whom 23,942 were hospitalized for pneumonia during follow-up, for a rate of 1.9 per 100 per year, and matched to 95,768 control subjects. The adjusted rate ratio of hospitalization for pneumonia associated with current use of inhaled corticosteroids was 1.70 (95% confidence interval [CI], 1.63-1.77) and 1.53 (95% CI, 1.30-1.80) for pneumonia hospitalization followed by death within 30 days. The rate ratio of hospitalization for pneumonia was greatest with the highest doses of inhaled corticosteroids, equivalent to fluticasone at 1,000 microg/day or more (rate ratio, 2.25; 95% CI, 2.07-2.44). All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they had received inhaled corticosteroids in the recent past (7.4 and 8.2%, respectively). The use of inhaled corticosteroids is associated with an excess risk of pneumonia hospitalization and of pneumonia hospitalization followed by death within 30 days, among elderly patients with COPD.