Using a Korean population-based cohort with 2,236 randomly selected individuals aged 40–50 years with spirometry and smoking data, the prevalence of young patients with COPD was 4.2% according to the definition by FEV1/FVC less than 0.7. Risk of exacerbation during a 3-year follow up in ever smokers without COPD and young patients with COPD regardless of smoking status tended to be higher compared to that for the non-smoker without COPD group. However, the risk was not significantly higher because the occurrence of an exacerbation event itself was very rare. Moreover, disease-related medical expenses were not significantly different according to smoking or COPD status.
The prevalence of COPD in young individuals aged between 40 and 50 years old in our study was 4.2% (95 of 2,236 participants). In a nationally representative sample cohort of China, age-standardized prevalence of COPD in young individuals was 1.4% for age group of 20–29 years, 3% for age group of 30–39 years, 5.1% for age group of 40–49 years (22). Both general population cohorts in China and Korea showed similar prevalence of spirometry-defined COPD in young participants.
Studies of mild or asymptomatic COPD with mild to moderate airflow limitation are rare, especially in young individuals because such patients generally do not have sufficient respiratory symptoms that would lead to a voluntary hospital visit. Therefore, it has been difficult to find and enroll these patients into trials or observational cohorts. However, we are able to assess those individuals through the KNHANES database which represents the general population in Korea. In our study, EQ-5D scores of COPD in young patients were almost normal. Most patients did not know their COPD status and were not given maintenance inhaler treatment from a clinician. They were found incidentally via spirometry screening. An extremely low prescription rate of inhaler therapy and normal ranged EQ-5D score indicated that these patients truly comprised of asymptomatic, mild COPD patients who had little motivation to visit clinics and follow up regularly.
Respiratory symptoms including chronic bronchitis (such as cough and phlegm) and shortness of breath are associated with increased risk of having airflow obstruction (23). They are also associated with accelerated decline in lung function with − 2.71 ml/yr excess decline in FEV1 and − 2.18 in FVC (p < 0.001 for both) as well as greater odds of incident airflow obstruction (odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.24–2.14) (24). This suggests that respiratory symptoms are among predictors for early identification of individuals who are at risk for developing COPD. There are questionnaires for respiratory symptoms such as cough, sputum, and dyspnea last for more than three months per year. However, there are no available information on respiratory symptom of COPD in young patients. This might be attributable to the fact that most individuals in this study were asymptomatic who had similar QoL status to those without COPD. However, KNHANES database was not originally designed to evaluate respiratory disease. Thus, in-depth interviews for respiratory symptoms and related history taking might have limitations, although trained interviewers administered questionnaires for various health-related information and gathered self-reported symptoms in the KNHANES survey.
It has become more evident that COPD can begin early in life and develop over many years (3, 25–28). Individuals we encounter in the clinic are mainly older patients with a severe disease. Therefore, most researchers on COPD have focused on these patients. Identifying individuals who are likely to develop COPD at an early age could allow us to implement preventive interventions and resultantly delay progression, thereby reducing clinical and social burden. To date, the lack of a standardized definition for these group of COPD patients is regarded as one of main problems that hinder clinicians to focus on these patients. One international group of experts has proposed an operational definition of early COPD (2) and suggested that early COPD should be defined as individuals aged < 50 years with a smoking exposure more than 10 pack-years with one or more of the following: 1) FEV1/FVC less than the lower limit of normal (LLN), 2) abnormalities on chest CT compatible with COPD such as visual emphysema, air trapping, or bronchial wall thickening, and/or 3) accelerated FEV1 decline of more than 60 ml/yr. Early COPD defined as FEV1/FVC less than the LLL in individuals under 50 years of age with more than 10 pack-years was reported in 15% of a general population cohort (29). Another study defined early COPD with the same criteria except for smoking and found that 3% (168 of 5,497 subjects) had early COPD and 12.5% of early COPD developed clinical COPD (FEV1/FVC of < 0.70 and FEV1 < 80% predicted) after 10 years compared to 1.6% of clinical COPD developed from non-early COPD (30). Taking smoking into account, 24% of smokers with ≥ 10 pack-years, 10% of smoker with < 10 pack-years, and 3% of never smokers developed clinical COPD in those with early COPD. We designed the present study based on recently proposed criteria for COPD in young patients (10) and found that the prevalence was 4.2%. However, when we applied LLL based criteria, 50.8% (1,137 of 2,236 individuals aged 40–50 years old) were classified as young patients with COPD. The possibility of over-estimation might be a problem when defining young patients with COPD by the LLL criteria.
This study has merit as it is the first study to report the prevalence and clinical features of COPD in young patients of Korea based on the recently suggested diagnostic criteria. However, it also has some limitations. First, post-bronchodilator spirometry was not used to identify COPD in young patients at the baseline, nor we identified changes in lung function during the follow-up period. We defined COPD in young patients based on pre-bronchodilator spirometry that revealed FEV1/FVC < 0.70 irrespective of smoking status. Thus, some individuals might have a reversible airflow limitation indicating likelihood for asthma and might not have persistent airflow limitation on repeated examination. However, we assessed the risk of COPD related exacerbation and medical costs using a nationwide health service database based on ICD-10 codes for COPD and operational definition of exacerbation. Although we could not evaluate the progression of COPD in young patients into clinical COPD during three years of follow-up, exacerbation might reflect disease progression. In fact, the exacerbation risk increased in ever smoker young patients with COPD compared to non-smoker non-COPD patients. However, the risk was not statistically significant because the event itself was very rare. Second, we assessed young patients with COPD aged 40–50 years because spirometry was allowed only for adults over the age of 40 in KNHANES. Therefore, there is a possibility of under-estimation for the prevalence of COPD in young patients. Third, we could not evaluate radiologic findings suggestive of COPD such as incidental emphysema or airway wall thickness on chest CT expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and the 15th percentile method (Perc15) known to be associated with an increased risk for the development of airflow limitation (31).
In conclusion, we found 4.2% of individuals aged 40–50 years had COPD through the KNHNES survey which provides us a chance to evaluate asymptomatic, mild COPD in young individuals. Considering the high rate of under-diagnosed COPD in Korea (32), our results may also have the possibility of under-estimation. Although we did not find significant differences in exacerbation risk or healthcare cost between non-COPD and COPD groups of young individuals, there were trends of increased exacerbation risk in COPD young patients irrespective of smoking status. Previous studies showed that younger patients could have better outcomes than older COPD patients(11, 12). Thus, active surveillance for early identification of COPD in young individuals and initiate preventive strategies such as smoking cessation and bronchodilator treatment are needed to reduce disease progression and improve outcome.