Temporal clustering of exacerbations in chronic obstructive pulmonary disease.


Hurst, JR; Donaldson, GC; Quint, JK; Goldring, JJ; Baghai-Ravary, R; Wedzicha, JA; (2009) Temporal clustering of exacerbations in chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 179 (5). pp. 369-74. ISSN 1073-449X DOI: https://doi.org/10.1164/rccm.200807-1067OC

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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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 19074596
Web of Science ID: 263767300006
URI: http://researchonline.lshtm.ac.uk/id/eprint/210198

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