The Asthma-COPD Overlap Syndrome

Zeki and colleagues defined ACOS as: (1) asthma with partially reversible airflow obstruction, with or without emphysema or reduced carbon monoxide diffusion capacity (DLCO) to < 80% predicted; and (2) COPD with emphysema accompanied by reversible or partially reversible airflow obstruction, with or without environmental allergies or reduced DLCO. ¹⁰ Louie and colleagues proposed the following major criteria for ACOS: a physician diagnosis of asthma and COPD in the same patient, history of evidence of atopy, elevated total IgE, aged ≥ 40 years, smoking > 10 pack-years, postbronchodilator FEV ₁< 80% predicted and FEV ₁/forced vital capacity (FVC) < 70%. ¹¹ Minor criteria consisted of a postbronchodilator increase of FEV ₁ by ≥ 15% or ≥ 12% and ≥ 200 mL following albuterol.

The Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease published a joint consensus document on ACOS, which described a stepwise approach to diagnosis based on defining characteristics. ⁵ To distinguish between the diagnosis of asthma, COPD, and ACOS in an adult patient, the guideline focuses on the features that are felt to be most helpful in distinguishing the syndromes in stepwise fashion. The physician should first assemble the features that favor a diagnosis of asthma or COPD, then compare the number of features in favor of a diagnosis of asthma or COPD, and finally consider the level of certainty around the diagnosis of asthma or COPD or whether there are features of both, suggesting ACOS.

Frequency

In 1995, the American Thoracic Society guidelines defined 11 distinct obstructive lung disease syndromes and identified overlap syndromes in 6 of them. ¹² Soriano and colleagues quantified the subpopulations of these patients by analyzing the U.S. National Health and Nutrition Examination III survey and the U.K. General Practice Research Database and reported an increased frequency of overlapping diagnosis of asthma and COPD with advancing age, with an estimated prevalence for < 10% in patients aged < 50 years and > 50% in patients aged ≥ 80 years. ⁸ A study of patients aged > 50 years by Marsh and colleagues reported a combined syndrome of asthma and COPD to be the most common phenotype as confirmed by spirometry. ¹³ In this study, 62% of subjects with the combined asthma and COPD phenotype were current or former smokers. In a study of 44 adults aged > 55 years with stable asthma or COPD, Gibson and colleague reported that 16% and 21%, respectively, could be categorized as having overlap syndrome. ¹⁴ As in previous studies, those with overlap syndrome and COPD were predominantly ex-smokers.

Braman and colleagues characterized asthma in subjects aged > 70 years. ¹⁵ Compared with those who developed asthma at an advanced age, those with early onset asthma had a significantly greater degree of airflow obstruction on pre- and postbronchodilator testing. This study suggested that long-standing asthma may lead to chronic persistent airflow obstruction and mimic COPD.

A longitudinal study by Vonk and colleagues reported that 16% of patients with asthma had developed incomplete airflow reversibility after 21 to 33 years of followup. ¹⁶ De Marco and colleagues found the prevalence of asthma-COPD overlap to be 1.6%, 2.1%, and 4.5% in the 20 to 44, 45 to 64, and 65 to 84 years age groups, respectively, through a screening questionnaire of the general Italian population in concurrence with previous studies, noting an increased prevalence of ACOS in the elderly. ¹⁷ Lee and colleagues described those with ACOS as older, male asthmatics, who have a higher lifetime smoking history and generally worse lung function. ¹⁸