LEICESTER, UK—In nonsmokers, chronic obstructive pulmonary disease (COPD) appears to be more common in women. In some cases, it may be associated with organ-specific autoimmune disease.

To better understand the pathophysiological features of COPD in nonsmokers, British researchers recruited 22 nonsmokers with symptoms of chronic airflow obstruction.[1] The patients were questioned about symptoms, occupation, and current and past passive smoking, and they underwent a variety of radiographic and laboratory tests. Further analysis of data revealed many similarities between these 22 patients and other COPD patients—but there were striking differences as well.

One of the most interesting findings was that 19 of the 22 patients were women; average age was 70. Only six patients reported ever smoking, and none had smoked for more than five years. No patient reported current passive smoke exposure, but 14 had been routinely exposed to passive smoke in the past; this rate of exposure was lower than that of the general UK/European population. Patients also had low to medium levels of particle exposure from traffic. Only five patients reported a family history of asthma or bronchitis.

The patients’ radiographic findings and lung function test results were comparable to those from COPD patients who smoked; however, the induced sputum inflammatory cell count suggested two subgroups. Nine patients had sputum eosinophilia. Among the 13 with normal sputum eosinophil counts, 10 had sputum neutrophil counts at or above the upper limit of normal. Six neutrophilic patients had a low peripheral blood lymphocyte count, compared with two eosinophilic patients. Six of the 13 patients without sputum eosinophilia had organ-specific immune dysfunction (usually thyroid disorder). Four patients in this group also had autoantibodies to thyroid. In contrast, only one eosinophilic patient had organ-specific immune dysfunction, and none had autoantibodies.

According to the authors, in the eosinophilic group “the most obvious explanation for the fixed airflow obstruction … is that it is the end result of airway remodeling secondary to long-standing asthma.” However, “our patients had a relatively short history of symptoms, and none gave a history suggesting asthma.” Another possibility is that eosinophilic COPD is an extension of eosinophilic bronchitis, which often causes chronic cough in middle-aged patients.

The authors acknowledged the possibility of a causal association between organ-specific autoimmune disease and airflow obstruction. They theorized that activated inflammatory cells enter the lungs and cause airway wall inflammation, leading to airflow obstruction. An alternative hypothesis is that airflow obstruction is a consequence of an autoimmune bronchitis.

Lead author Surinder Birring, MD, from the Institute for Lung Health at Glenfield Hospital in Leicester, UK, said, “It is likely that factors in addition to smoking are involved in the pathogenesis of COPD in smokers. One reason to study COPD in nonsmokers is that it might illustrate what other factors are important.”

—Gale Jurasek