Investigating Annual Variation in Exacerbation Frequency in Patients With COPD

March 6, 2019

Analysis of a 2-year study showed that fluctuations in yearly chronic obstructive pulmonary disease (COPD) exacerbation rates may be associated with variations in Haemophilus influenzae colonization.

Fluctuations in annual exacerbation rates in patients with chronic obstructive pulmonary disease (COPD) may be attributed to variations in Haemophilus influenzae (H influenzae) colonization, according to a study in ERJ Open Research.

During exacerbations, patients considered frequent exacerbators (2 or more exacerbations in a year) were found to have greater rates of bacterial infections while patients who were infrequent exacerbators (1 exacerbation) had higher rates of viral infections. This led researchers to believe that bacterial infections may be the strongest indicator of the frequent-exacerbator phenotype.

Acute exacerbations of COPD result in rapid decline in lung function, poor quality of life, and greater risk of hospitalization, and serve as strong predictors of early mortality across all COPD stages.

Researchers analyzed 2-year follow-up data from the prospective observational Acute Exacerbation and Respiratory Infections in COPD, known as AERIS, study of patients with COPD to assess yearly variation in exacerbation rates and their causes. A cohort of 127 patients provided blood and sputum samples monthly and during exacerbations to detect respiratory infections and targeted tissue inflammation. In total, 103 patients continued into the second year of the study and 88 completed both years.

Participants were patients with COPD between 40 and 85 years old whose condition was considered moderate, severe, or very severe and were recruited from June 2011 to June 2012. Patients were monitored for 24 months in the stable state and examined within 72 hours of displaying symptoms of an exacerbation. Exacerbations were tracked with daily electronic diary cards.

The mean exacerbation rate was 3.04 and 2.32 per year for years 1 and 2, respectively. A total of 223 acute exacerbations were recorded during the second year and 60.2% of patients had two or more exacerbations. During the first year of follow-up, 355 acute exacerbations were recorded and 61.4% of patients had two or more exacerbations.

In sputum collected during exacerbations of frequent exacerbators, bacterial infection was detected by culture in 60.0% of patients in the first year and 52.3% in the second, while viral infection was detected in 43.8% in year 1 and 42.2% in year 2. For infrequent exacerbators, bacterial infection was detected by culture in 76.5% in the first year and 50.0% in the second, while viral infection was detected in 60.0% in year 1 and 78.6% in year 2.

Rates of sputum collection throughout the study were high. No antibiotics were administered to patients prior to collection for 98.9% of stable and 91.4% of exacerbation samples during the year 1 and 91.3% of stable and 88.7% of exacerbation samples during year 2. Researchers recognized bacterial colonization by presence of bacteria when patients were at stable states.

The most prevalent bacterial species found during stable and exacerbation periods was H. influenzae. Incidence of cultures that were positive for H influenzae or Moraxella catarrhalis was higher at exacerbation than at stable states.

The percentage of sputum samples positive for at least 1 virus increased from stable to exacerbation states from 11.0% during year 1 to 33.3% during year 2. While the incidence of specific viral pathogens varied from year to year, the most common species detected was human rhinovirus, found in 6.4% of stable and 18.1% of exacerbation samples.

Persistent infection of airways with H influenzae has been shown to contribute to chronic airway inflammation that increases symptoms and accelerates the progression of lung disease. Researchers believe chronic colonization with H influenzae is a significant, possibly modifiable risk factor for exacerbations and suggest future clinical trials should specifically target the specific bacterium.


Wilkinson T, Aris E, Bourne S, et al. Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort [published online February 25, 2019]. ERJ Open Res. doi: 10.1183/23120541.00248-2018.