Effects of inhaled corticosteroids on mortality and hospitalisation in elderly asthma and chronic obstructive pulmonary disease patients: appraising the evidence

Schmier JK, Halpern MT, Jones ML.

Publication Details

CRD summary

This review examined the mortality and hospitalisation rates associated with the use of inhaled corticosteroids (ICS) in elderly patients with chronic obstructive pulmonary disease. The authors concluded that lower rates of hospitalisation and mortality were found to be associated with ICS use. However, concerns about potential biases in the review data mean that the findings are unlikely to be robust.

Authors' objectives

To review mortality and hospitalisation rates associated with the use of inhaled corticosteroids (ICS) in elderly patients with chronic obstructive pulmonary disease (COPD). The review also examined the characteristics of ICS users and the rate of adherence to treatment; these data are not included in this abstract.

Searching

PubMed was searched; the search terms were reported but the search dates were not. The searches were limited to publications in the English language and studies carried out in the elderly. Reference lists of identified publications, authors' publication lists, conference proceedings and consensus workshop publications were also searched.

Study selection

Study designs of evaluations included in the review

The authors did not specify which types of study were eligible for inclusion. Prospective and retrospective cohort studies, nested case-control, retrospective chart review, retrospective follow-up and reanalyses of existing data were included in the review.

Specific interventions included in the review

Studies of ICS were eligible for inclusion. Where reported, the included studies assessed ICS (salmeterolalone and/or fluticasone propionate), alone or in combination with long-acting beta-adrenoceptor agonists or short-acting beta-adrenoceptor agonists. Where reported, the comparators were other ICS regimens and no treatment.

Participants included in the review

Studies of elderly patients (at least 50 years of age) with COPD and/or asthma were eligible for inclusion. Where the minimum age of the participants was not reported, studies were included if the participants had a mean age of over 60 years. The severity and duration of disease varied between the studies, as did the eligibility criteria for each study; details were reported in the review. The mean age of the participants included in the review ranged from 65 to 76 years. The proportion of male participants ranged from over 30% to 98%; most studies had between 30 and 75%.

Outcomes assessed in the review

Studies reporting the rate of hospitalisation and/or mortality were eligible for inclusion. All-cause and pulmonary-specific mortality, annual hospitalisation rates, readmission rates and recurrent hospitalisation rates were reported.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not report any formal assessment of the validity of the primary studies. However, some methodological issues were discussed within the text.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

The outcomes were often reported as percentage values. In some cases, where available, relative risks (RRs) or odds ratios were reported with 95% confidence intervals (CIs).

Methods of synthesis

How were the studies combined?

The studies were grouped by the outcome of interest and combined in a narrative.

How were differences between studies investigated?

Some methodological issues were also discussed. Differences between the studies were presented in a table and some were discussed in the text.

Results of the review

Fifteen studies (n at least 44,558) were included in total. However, only 10 studies (n at least 74,559) reported mortality and hospitalisation data; two of these appeared to use the same population of patients. The 10 studies included one controlled trial, two prospective cohort studies, one nested case-control, two retrospective cohort studies, one retrospective longitudinal study, one retrospective follow-up study, one retrospective data analysis and one reanalysis of existing data.

Mortality (8 studies).

Four studies (two prospective cohort studies, one retrospective follow-up study and one reanalysis of data) showed no significant differences in mortality rates between those taking and those not taking ICS.

One retrospective cohort of COPD patients (n=4,263) reported a significant reduction in mortality in a multivariate analysis among patients taking ICS (mortality 17.1%) or ICS plus long-acting beta-adrenoceptor agonist (10.5%) compared with neither (24.3%).

One controlled trial of newly diagnosed COPD patients (n=4,665) reported patients using fluticasone propionate either alone (adjusted hazard ratio 0.48, 95% CI: 0.31, 0.73) or with salmeterol (adjusted hazard ratio 0.62, 95% CI: 0.45, 0.85) had significantly lower mortality than those using neither drug.

One retrospective cohort of asthma patients (n=6,254) reported a 39% reduction in all-cause mortality for patients who received ICS within 90 days of discharge, compared with those not taking ICS.

One retrospective chart analysis of COPD patients (n=6,740) reported that ICS treatment after discharge resulted in a significantly lower mortality rate (RR 0.75, 95% CI: 0.69, 0.86) and pulmonary-specific mortality rate (RR 0.70, 95% CI: 0.53, 0.93) than no ICS; this reduction was greater for those patients taking medium (52% reduction) to high doses (45% reduction) as compared with low doses (23% reduction).

Hospitalisation (6 studies).

Three studies (one nested case-control study, one prospective cohort and one prospective cohort study) reported no significant differences in hospitalisation rates between those patients taking and those not taking ICS.

One retrospective longitudinal study of patients with moderate to severe COPD (n unknown) reported that greater adherence to ICS treatment was associated with a significant 20% decrease in annual hospitalisation rates and a decrease in the length of hospital stay (0.7 days versus 1.76 days for control patients).

One retrospective cohort of asthma patients (n=6,254) reported a 29% reduction in recurrent hospitalisation for patients who received ICS within 90 days of discharge, compared with those not taking ICS.

One retrospective cohort of COPD patients (n=4,263) reported a reduction in re-hospitalisations in an unadjusted analysis for those patients taking ICS as compared with those not taking ICS (no further data).

Authors' conclusions

Lower rates of hospitalisation and mortality were found to be associated with ICS use. However, further investigation is needed to assess the degree of bias associated with these findings. Recommendations for further research were also suggested.

CRD commentary

This review addressed a clear question that was defined in terms of the interventions, participants and outcomes. Criteria for study design were not reported and this resulted in the inclusion of a wide variety of study designs. The authors searched PubMed but did not specify individual databases or search dates. This was supplemented with searches of a range of other sources to find further studies and also unpublished material, but no specific details of these sources were reported. However, relevant studies might have been excluded or missed as the searches were limited to publications in English and studies of elderly populations. It was not possible to assess the potential for errors in reporting and selection bias in the review as the authors failed to state how studies were selected for the review and how the data were extracted. There also appears to have been no formal assessment of study quality which, given the wide range of study designs included, is an important omission.

The use of a narrative synthesis was sensible given the differences between the included studies. However, these differences in populations, study designs, interventions and outcomes make it difficult to synthesise the review findings. The authors also pointed out that some of the studies may have potential methodological biases. Overall, given the concerns about the reliability of the review data and the poor reporting of the review methods, the authors' findings are unlikely to be robust.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further research is required to confirm the findings and address possible sources of bias in the review findings. Such studies should include adequately defined and reported patient populations and analyse data according to important differences in the patient populations (e.g. age, disease severity, disease type). Mortality analyses should be conducted using robust methods in which patients are identified by criteria that already indicate a period of survival. Further research is also needed to address the convergence of various end points in order to evaluate the overall value to the patient of ICS treatment.

Bibliographic details

Schmier J K, Halpern M T, Jones M L. Effects of inhaled corticosteroids on mortality and hospitalisation in elderly asthma and chronic obstructive pulmonary disease patients: appraising the evidence. Drugs and Aging 2005; 22(9): 717-729. [PubMed: 16156676]

Indexing Status

Subject indexing assigned by NLM

MeSH

Administration, Inhalation; Adrenal Cortex Hormones /economics /therapeutic use; Adrenergic beta-Agonists /economics /therapeutic use; Aged; Aged, 80 and over; Asthma /drug therapy /economics /mortality; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Hospitalization /economics; Humans; Male; Patient Compliance; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive /drug therapy /economics /mortality

AccessionNumber

12006003248

Database entry date

28/02/2007

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.