It appears that chronic obstructive pulmonary disease with frequent exacerbations constitutes a distinct phenotype of the disease that can occur at mild, moderate, or severe levels of illness, according to results from a data analysis reported in the Sept. 16 issue of the New England Journal of Medicine.
The frequency of COPD exacerbations appears to be relatively stable over time, and a distinct subgroup of patients appears to be prone to frequent (two or more times per year) exacerbations year after year, said Dr. John R. Hurst of University College London Medical School and his associates.
“Despite the importance of exacerbations, we know relatively little about their incidence, their determinants, and their effects in patients with COPD at various levels of severity,” the investigators noted. They used data from a large observational study – the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) – to examine exacerbation frequency.
The international ECLIPSE study included 2,138 patients aged 40-75 years with a history of 10 or more pack-years of smoking, a forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value, and an FEV1-to-forced vital capacity ratio of 0.7 or less after use of a bronchodilator. The subjects had a wide range of COPD severity, and were evaluated at baseline, 3 months, and 6 months, and at 6-month intervals thereafter for 3 years.
Although exacerbations tended to increase with increasing disease severity, patients also tended to fall into and remain in one of two groups: those with infrequent exacerbations (0 or 1 per year) or those with more frequent exacerbations.
For example, 1,187 patients had infrequent exacerbations in the first year of the study, and 987 (83%) of them also had infrequent exacerbations in the second year. Another 492 patients had frequent exacerbations in year 1, and 296 of them (60%) had frequent exacerbations in year 2 as well. “Thus, exacerbation frequency in the first year had a sensitivity of 60% and a specificity of 83%” for predicting the frequency in the second year, Dr. Hurst and his colleagues said (N. Engl. J. Med. 2010;363:1128-38).
Similarly, 994 (84%) of the 1,187 patients with infrequent exacerbations also had infrequent exacerbations during the third study year, while 276 (56%) of the 496 with frequent exacerbations also had frequent exacerbations during the third study year.
And 210 (71%) of those with frequent exacerbations during years 1 and 2 went on to have frequent exacerbations in year 3, while 388 (74%) of those who had no exacerbations during years 1 and 2 also had no exacerbations in year 3.
The easiest and most accurate way of predicting a patient’s susceptibility to exacerbations was simply to ask that patient how many exacerbations they had had the preceding year, the researchers said.
A full 22% of the patients with moderate COPD were found to have frequent exacerbations, which is “an important observation, considering that such patients, who have relatively mild disease according to FEV1 criteria, may not at present be identified for interventions to reduce exacerbations,” they noted.
Conversely, 29% of the subjects who had very severe COPD appeared to have some resistance to exacerbations, since they experienced none or very few exacerbations during the study.
The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.