BACKGROUND: Whether risk of exacerbations of chronic obstructive pulmonary disease (COPD) is influenced by severity of symptoms and maintenance treatment is unclear.

OBJECTIVE: We hypothesized that in addition to history of exacerbations of COPD, the severity of dyspnoea and use of maintenance medications are associated with risk of future exacerbations.

METHODS: We included 96,462 adults from the Copenhagen General Population Study and assessed risk of moderate and severe exacerbations from 2003 to 2013 according to exacerbation history, dyspnoea score (mMRC), and presence/absence of maintenance treatment with inhaled long-acting bronchodilators and/or inhaled corticosteroids.

FINDINGS: Among 13,380 individuals with COPD, we observed 1543 moderate and 348 severe exacerbations. In treatment naïve individuals and in those on maintenance treatment, history of previous exacerbations and to a smaller degree also dyspnoea were associated with a higher risk of future exacerbations; 32% of the treatment naïve individuals with mMRC≥2 and a single moderate exacerbation in the previous year experienced a moderate exacerbation during the following year compared with only 3% in the individuals with similar severity of dyspnoea but no exacerbations in the previous year yielding an adjusted hazard ratio of 6.26 (95% confidence interval, 3.70-10.58).

INTERPRETATION: This observational study of the general population suggests that in addition to exacerbation history also the severity of dyspnoea predicts the risk of future COPD exacerbations. In subjects with severe dyspnoea, a history of a single moderate exacerbation is associated with a high risk of future exacerbations, suggesting that this subgroup needs special attention in order to prevent these events.