New research shows that individual exacerbations in chronic obstructive pulmonary disease (COPD) increase the likelihood of repeat exacerbations, even after 5 days of full, asymptomatic recovery.

"This concept that exacerbations are not random has important implication for the analysis of clinical trial data and identifies a specific high-risk period for recurrent exacerbation during which preventative interventions might be targeted," wrote lead author John Hurst, MD, of the Royal Free and University College Medical School, London.

Prior to this research, exacerbations were assumed to be isolated events unrelated to one another despite observational data that suggested a dependency. In patients with COPD, exacerbations are generally defined as an acute worsening of symptoms, which can decrease lung function, ultimately driving the progression of the disease. Many patients never recover their baseline level of lung function after exacerbations.

To test the validity of this assumption, Hurst and colleagues analyzed daily symptom diaries that were kept for at least 1year by 297 patients with COPD, describing nearly 2,000 distinct exacerbation events. Two or more new or worsening symptoms, one of which must be "major" (dyspnea, more sputum, or a change in color of sputum) constituted an exacerbation, and after 5 days of symptoms reverting to baseline severity, the exacerbation was considered to be over. A second exacerbation occurring within an 8-week period was considered to be a recurrent exacerbation. The researchers further analyzed seasonality of exacerbations, comparing their winter (November to January) frequency with their summer (June through August) frequency.

The researchers identified an 8-week period of time during which monitoring and follow-up are crucial to prevent or minimize further exacerbations in  COPD patients. "Our finding of a high-risk period for recurrent exacerbation may be important in guiding patient follow-up," wrote Hurst.

The researchers also found that exacerbations were significantly more common in the winter than the summer. They also noted that "isolated" exacerbations tended on average to be about 25% more severe than the first of serial exacerbations.

"The mechanisms of exacerbation recurrence remain unexplored, and it is unknown whether recurrence is due to persistence of an existing organism or to acquisition of a new one," said Hurst. "The failure to eradicate bacteria with exacerbation therapy has been associated with an incomplete recovery in inflammatory markers and we have recently reported a relationship between elevated C-reactive protein during the recovery period of an initial exacerbation and shorter time to the next."

Results of the study appear in the first issue for March of the American Journal of Respiratory and Critical Care Medicine.