Preventing exacerbations in chronic obstructive pulmonary disease (COPD) is crucial to limit the decline in lung function that can lead to hospitalizations and poor outcomes. Methods to prevent exacerbations, with an emphasis on newer therapies, were the focus of a symposium presented by Nicola A. Hanania, MD, MS, and Mario Cazzola, MD.
Patients with COPD who have exacerbations experience faster declines in lung function and worsening lung inflammation compared with those without exacerbations, said Dr Hanania, Director of the Asthma Clinical Research Center, and Associate Professor of Medicine, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX.
Exacerbations are also associated with poorer quality of life and an increased risk of mortality in the years after a hospitalization. According to Dr Hanania, patients at high risk for exacerbation include those with:
- A more severe airway obstruction
- Chronic bronchial mucous hypersecretion
- A longer duration of COPD
- Productive cough and wheeze
- Bacterial colonization.
A reliable predictor of future exacerbation is a history of exacerbation.
Influenza vaccination is a simple way to prevent exacerbations. In fluenza vaccination has been shown in a randomized clinical trial to reduce exacerbations, “due to a reduction in exacerbations ≥3 weeks after vaccination and due to influenza,” Dr Hanania said.
Nonpharmaceutical strategies include pulmonary rehabilitation, which is underutilized in the United States, and education to self-manage COPD, which has been shown to reduce the incidence of short- and long-term hospitalization and reduce healthcare utilization.
A 12-week, home-based program of pulmonary rehabilitation was effective in improving exercise tolerance, dyspnea, and quality of life in housebound patients with COPD. At 6 months, patients undergoing pulmonary rehabilitation had a significantly shorter average length of stay at readmission to the hospital with exacerbations.
Long-acting bronchodilators decrease the rate of exacerbations, as evidenced by findings from the UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) study, in which the addition of tiotropium to a baseline COPD treatment regimen reduced exacerbations (median delay to first exacerbation of 16.7 months vs 12.5 months for placebo).
Inhaled corticosteroids have also been proved to reduce exacerbation risk. Fluticasone demonstrated clear efficacy in this regard, Dr Hanania said, and in the TORCH (Towards a Revolution in COPD Health) trial, the combination of a long-acting betaagonist and an inhaled corticosteroid decreased the number of exacerbations. In patients with severe COPD, triple therapy with tiotropium, fluticasone, and salmeterol may reduce hospitalization risk, as observed in the Canadian Optimal Therapy of COPD trial.
The data behind mucolytics with respect to exacerbation risk are mixed. In the PEACE study, oral carbocisteine decreased exacerbation risk by about one third compared with placebo, but results from the BRONCUS (Bronchitis Randomized on NAC Cost-Utility Study) showed no beneficial effect of acetylcysteine on exacerbations. The conflicting data may possibly be explained by the different patient populations enrolled in the studies and the different pharmacologic properties of the 2 mucolytics, said Dr Cazzola, Professor of Respiratory Medicine, University of Rome Tor Vergata, Italy.
“The BRONCUS study recruited less severe patients, with a forced expiratory volume in 1 second [FEV1] predicted of 57% in BRONCUS patients compared with 43% in the PEACE study,” Dr Cazzola said.
Furthermore, more patients in BRONCUS than in the PEACE study were being treated with inhaled corticosteroids (70% vs 17%), which might have diluted the findings in BRONCUS. In addition, the PEACE study was conducted in Chinese patients, whereas BRONCUS enrolled white patients, and there may be pharmacogenetic differences between these 2 ethnic groups, Dr Cazzola said.
With respect to the 2 mucolytics studied, the action of carbocisteine is unique and may, in part, depend on inhibition of viral adherence to the airway.
Because bacterial infection is one of the most important risk factors in COPD exacerbations, it has been proposed that antibiotics could reduce risk. Cyclical moxifloxacin (5 days every 8 weeks) was shown to decrease exacerbations compared with placebo.
A polyvalent mechanical bacterial lysate (the first 10 days of 3 consecutive months) added to regular treatment with salmeterol/fluticasone reduced the total number of exacerbations, the rate of exacerbations per patient per year, the number of exacerbations that required treatment with oral corticosteroids, and the total rate of hospitalizations in a study of 63 patients with COPD, Dr Cazzola said.
While waiting for new families of antibiotics to be developed, current antimicrobial strategy may need to be changed, he said. This may include administration of inhaled or nebulized antibiotics, which would require a motivated patient and is expensive. Another option is to use antibiotics with different mechanisms of action in combination to reduce the possible development of resistance, but “this approach will increase costs and possible side effects.”
Emerging therapies with some success at preventing exacerbations are indacaterol, which increased the median time to a first exacerbation over 52 weeks compared with placebo; aclidinium, which improved the time to a first moderate-to-severe exacerbation in 2 clinical studies; and roflumilast, which was effective in reducing exacerbations with 1 year of treatment in patients with severe COPD.