Major Finding: A COPD patient's frequency of exacerbations remains stable over time, and the subgroup of patients with frequent exacerbations appears to have a particular phenotype of the disease.
Data Source: A secondary analysis of data collected in the multinational, prospective, observational, 3-year ECLIPSE study of 2,138 patients with mild, moderate, or severe COPD.
Disclosures: The ECLIPSE study was funded by GlaxoSmithKline. Dr. Hurst and his associates reported ties to numerous pharmaceutical companies.
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.
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 in the third 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.
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What Is the Mechanism?
The finding of a distinct phenotype of chronic obstructive pulmonary disease implies that some underlying genetic, biologic, or behavioral mechanism determines either susceptibility or resistance to recurrent exacerbations, independent of disease severity, according to Dr. Donald P. Tashkin.
“Such a mechanism could include greater or lesser susceptibility to respiratory tract infection (the principal trigger of exacerbations); microaspiration from gastroesophageal reflux; psychological factors such as perception of dyspnea (the major symptom of exacerbation); and medication adherence.
“Understanding the mechanistic basis for frequent exacerbations might lead to more effective preventive therapy,” he wrote.
It is important for clinicians to identify which patients fit the phenotype, because effective therapies are already available to curb the frequency of exacerbations.
In addition, “a better understanding of the underlying mechanisms that predispose a patient to exacerbations could lead to the development of more targeted preventive strategies,” which in turn would favorably affect the overall course of COPD, he added.