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Am J Respir Crit Care Med. 2009 Mar 1;179(5):369-74. doi: 10.1164/rccm.200807-1067OC. Epub 2008 Dec 12.

Temporal clustering of exacerbations in chronic obstructive pulmonary disease.

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  • 1Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, London, United Kingdom.

Abstract

RATIONALE:

Exacerbations are important events in chronic obstructive pulmonary disease. Preventing exacerbations is a key treatment goal. Observational data suggest that after a first exacerbation, patients may be at increased risk of a second exacerbation, but this has not been specifically studied. We hypothesized that exacerbations may cluster together in time, a finding that would have important implications for targeting preventative interventions and the analysis of clinical trial data.

OBJECTIVES:

To assess whether exacerbations are random events, or cluster in time.

METHODS:

A total of 297 patients in the London chronic obstructive pulmonary disease cohort recorded daily symptoms and were assessed for a total of 904 patient-years. The observed timing of second exacerbations after an initial exacerbation was compared with that expected should exacerbations occur randomly.

MEASUREMENTS AND MAIN RESULTS:

The observed timing distribution of second exacerbations differed significantly (P < 0.001) from the expected exponential function (shape parameter of the fitted Weibull function, 0.966 [95% confidence interval, 0.948-0.985]), suggesting that more second exacerbations occurred sooner than later and that exacerbations cluster together in time. Twenty-seven percent of first exacerbations were followed by a second recurrent event within 8 weeks. Approximately one third of exacerbations were recurrent exacerbations. Although initial exacerbations were milder than isolated events, they were not less likely to receive treatment, and under-treatment of initial events is not a plausible explanation for exacerbation recurrence. Recurrent exacerbations contribute significantly to overall exacerbation frequency (rho = 0.81; P < 0.0001).

CONCLUSIONS:

Exacerbations are not random events but cluster together in time such that there is a high-risk period for recurrent exacerbation in the 8-week period after an initial excerbation.

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PMID:
19074596
[PubMed - indexed for MEDLINE]
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