Exacerbations in bronchodilator-responsive asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) were more frequent and severe than in COPD with emphysema, but only a minority of patients were treated to prevent them, in a review of 1,005 patients from the Annals of the American Thoracic Society.

All the subjects were current or former smokers culled from the COPDGene Study , a multicenter observational study looking for the genetic roots of COPD susceptibility; 385 patients met the investigators’ criteria for ACOS with bronchodilator response (ACOS-BDR), which included a history of asthma or hay fever, airway obstruction with significant bronchodilator responsiveness, and less then 15% emphysema on chest CT.

Another 620 subjects met criteria for COPD with emphysema, including airway obstruction without bronchodilator reversibility, and more than 15% emphysema on chest CT ( Ann Am Thorac Soc. 2016 Sep;13(9):1483-9 ).

Although the ACOS patients had better lung function, they had similar severity and frequency of exacerbations, compared with the COPD group. After adjustment for forced expiratory volume in 1 second percent predicted and other factors, the patients with ACOS-BDR were actually more likely to have severe and frequent exacerbations. Possible explanations for this are that they were more likely to smoke and have gastroesophageal reflux disease and obstructive sleep apnea, all of which increase the risk of exacerbations.

Even so, ACOS-BDR patients were less likely to be on a long-acting beta-agonist (6.8% versus 13.9%); a long-acting muscarinic antagonist (20% versus 60.8%); or a combination long-acting beta-agonist/inhaled corticosteroid (29.9% versus 55.6%).

“Only a small percentage of them were being treated … Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations,” said investigators led by James Cosentino, DO, of Temple University School of Medicine, Philadelphia. Patients with ACOS “are a particularly high-risk group.” They deserve “special attention, and practitioners need to be diligent in evaluation of them.”

ACOS is being increasingly recognized as a distinct clinical entity with perhaps a worse prognosis than either asthma or COPD alone. The goal of the study was to better characterize the disease.

To that end, the team found four features that seemed to distinguish ACOS-BDR from COPD with emphysema: ACOS-BDR patients were younger (60.6 versus 65.9 years old); heavier (body mass index 29.6 versus 25.1 kg/m2; more likely to be African American (26.8% versus 14.4%); and more likely to be current smokers (50.9% versus 20.7%).

It’s “likely that current smoking in subjects with ACOS, coupled with the long duration of asthma, leads to inflammation and small airway remodeling with development of symptoms earlier in the disease course than that seen in those with COPD with emphysema,” the investigators said.

“Early and aggressive treatment with combination therapy may help alleviate symptoms and decrease exacerbations. Recognition and treatment of comorbidities and aggressive smoking cessation may also play a key role in preventing exacerbations and alleviating the morbidity associated with ACOS; however, future studies on the treatment of ACOS are needed,” they said.

The majority of subjects with ACOS-BDR met criteria for Global Initiative for Chronic Obstructive Lung Disease grade B, indicating a high degree of symptoms despite less severe airflow obstruction.

The funding source wasn’t reported. Dr. Cosentino had no conflicts. Other authors disclosed personal fees from Concert Pharmaceuticals, CSA Medical, CSL Behring, Gala Therapeutics, and Novartis.