Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications

Background: Asthma and chronic obstructive pulmonary disease (COPD) are the most common airway diseases. Both diseases share clinical features, and each disease shows phenotypic heterogeneity. Even patients with relatively preserved lung function can experience frequent exacerbation linked to poor quality of life. The aim of this study was to identify subtypes in patients with mild to moderate airflow limitation and to evaluate their clinical and socioeconomic implications.

Methods: We analyzed data from the fourth Korean National Health and Nutrition Examination Survey and National Health Insurance claims in 2007-2012. Subjects who were 19 years old and more and had forced expiratory volume in 1 second (FEV₁) ≥ 60% predicted and a ratio of FEV₁ to forced vital capacity (FVC) < 0.7 were included. K-means clustering was performed to explore subtypes. For clustering analysis, six key input variables, age, body mass index (BMI), FEV₁% predicted, the presence or absence of self-reported wheezing, smoking status, and pack-years of smoking were selected.

Results: Among a total of 2,140 subjects, five subgroups identified through k-means clustering include putative “near-normal (n=232)”, “asthmatic (n=392)”, “COPD (n=37)”, “asthma-overlap (n=893)” and “COPD-overlap (n=586)” subtypes. Among five subgropus, near-normal subgroup showed the oldest mean age (72±7 years) and the highest FEV₁ (102±8% predicted), and asthmatic subgroup was the youngest (46±9 years). Asthma-overlap subgroup had the lowest FEV₁ (77±9% predicted). COPD and COPD-overlap subgroups were male-predominant (100% and 98%, respectively) and all current or ex-smokers. When applying the lower limit of normal FEV₁/FVC as a criterion for airway obstruction, asthma group showed the highest prevalence of airway obstruction. While COPD, asthma-overlap and COPD-overlap subgroups showed high prescription rate of respiratory medicine, asthmatic subgroup had the lowest prescription rate despite the highest proportion of self-reported wheezing. Except asthmatic subgroup, comorbidities such as hypertension, diabetes mellitus, hyperlipidemia and coronary artery disease were frequently observed. Although COPD subgroup represents only 2% of total subjects, they showed the highest mean medical cost and health utilization, comprising 5% of the total cost. When calculating a ratio of total medical expense to household income, mean ratio was the highest in COPD subgroup. 

Conclusion: Subjects with mild to moderate airflow limitation exhibited clinical and epidemiological heterogeneity. Each subgroup may have a different level of demand for health resources.