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Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder characterized by chronic respiratory symptoms resulting from airway and/or alveolar abnormalities that lead to progressive airflow limitation. It is a major global health concern associated with significant mortality and socioeconomic burden¹ Acute exacerbations of COPD (AE-COPD) contribute substantially to COPD-related deaths, underscoring the need to identify factors that influence these events.

In Korea, a recent study from the Korea COPD Subgroup Study (KOCOSS) cohort reported a mean of 1.1 moderate or severe AE-COPD events per patient year—substantially higher than rates observed in Western populations—indicating a high exacerbation burden. The study also highlighted environmental exposures such as tobacco smoking, air pollution, and biomass fuel as important contributors to increased exacerbation risk and disease progression.² While smoking remains a major cause of COPD, recent research increasingly emphasizes the role of environmental³ and occupational exposures, including fine particulate matter, biomass smoke, and dust – as drivers of both COPD incidence and exacerbations.^4–6

Urban green space, a proxy for natural vegetation within residential areas, has received growing attention as a modifiable environmental factor associated with improved respiratory health. A mechanism underlying this association is the potential of urban green spaces to improve air quality by reducing air pollution (ie, PM2.5).^7,8 Several previous studies have revealed that urban green spaces, compared to rural areas, have more distinctly defined vegetation zones and can improve air quality more efficiently, even at small scales of urban districts.^9–11 Although some studies suggest that exposure to green space may reduce the risk of cardiovascular disease, mental health disorders, and obesity, our focus is on its relevance to respiratory outcomes, particularly COPD. Prior research has linked green space to improved air quality, physical activity, and microbial diversity, all of which may influence respiratory health.¹² Recent epidemiologic evidence from the United States,¹³ United Kingdom,¹⁴ Belgium,¹⁵ and other has reported inverse associations between green space exposure and all-cause mortality, including among individuals with COPD. In South Korea, studies have linked green space exposure to reduced mortality from cardiovascular,¹⁴ allergic,^16,17 and renal disease.¹⁸

However, research in Asia has primarily focused on the relationship between green space and COPD incidence rather than acute exacerbations. For example, residential green space in China has been associated with lower COPD prevalence,¹⁹ and a recent study in Chongqing suggested regional variation in COPD-related mortality risk.²⁰ Despite AE-COPD being a key driver of morbidity, mortality, and healthcare burden, no study to date has specifically examined its relationship with urban green space in the Asian context, highlighting a critical gap in the literature.

To address this gap, we analyzed data from the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC) from 2006 to 2019 to investigate the association between residential green space exposure and AE-COPD and all-cause mortality in patients with COPD. Green space exposure was assessed using 2017 park area data from the Korean Statistical Information Service (KOSIS), which reflects the proportion of designated park area within each district. We hypothesized that higher exposure to urban green space would be associated with a lower risk of AE-COPD and mortality.

Methods

Data Source

This study utilized data from the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC), covering the period from 2006 to 2019 (NHIS No.: NHIS-2023-2-302). The NHIS-NSC includes 2% of the eligible Korean population in 2006, sampled via stratification based on sex, age, insurance type, premium decile, and region.²¹ It provides comprehensive, longitudinal data on healthcare utilization and demographic characteristics. Residential addresses are updated annually at the district (Gu) level.²² To protect personal information, all data were de-identified and sensitive variables were masked or grouped.

Study Population

We identified patients with COPD aged ≥40 years who had both a diagnosis of COPD (ICD-10: J43, excluding J43.0 [MacLeod syndrome], or J44) and a prescription for COPD-related medications between January 1, 2006, and December 31, 2015. To ensure chronicity, patients were required to have at least one additional COPD diagnosis and related prescription within the following year (Figure 1). COPD-related medications included long-acting muscarinic antagonists (LAMAs), long-acting beta-2 agonists (LABAs), inhaled corticosteroids (ICSs), ICS/LABA combinations, short-acting bronchodilators (SAMAs/SABAs), methylxanthines, oral corticosteroids, and systemic beta-2 agonists (Supplementary Table 1).²³

The date of the first qualifying diagnosis was set as the index date. To reduce immortal time bias and allow sufficient follow-up, only patients diagnosed through 2015 were included. The interval between first and second prescriptions was examined, and sensitivity analyses were performed excluding individuals with more than 180 days between them. The analysis was restricted to residents of the seven largest metropolitan cities in Korea (Seoul, Busan, Daegu, Incheon, Gwangju, Daejeon, Ulsan), which allow stratification based on urban green space levels and ensure consistent exposure classification.

Exposure Assessment: Urban Green Space

Urban green space was assessed using park area data from the Korean Statistical Information Service (KOSIS), based on a 2017 nationwide survey conducted by the Ministry of Land, Infrastructure, and Transport (MOLIT). This dataset includes multiple park types: urban natural parks (including national urban parks), neighborhood parks, children’s parks, historic and cultural parks, waterside parks, cemetery parks, sports parks, agricultural parks, and other public parks designated by local ordinances.²⁴

For each district, we calculated the total park area (m²) and derived a park-area-based greenness index, defined as the ratio of total park area to total district area.²⁵ Although the park data represent a single year (2017), we applied the same static measure across the entire study period (2006–2019), based on the assumption that relative green space rankings among districts remained generally stable Potential limitations due to urban development and changes in green space availability over time are acknowledged. The resulting index was categorized into quartiles: quartile 1 (Q1; lowest greenness), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4; high greenness) (Figure 2).

Figure 2 Regional distribution of green space exposure across selected districts in South Korea. Notes: The main map displays the national administrative boundaries, with selected regions indicated by colored boxes corresponding to subpanels a–g. (a) Incheon Metropolitan City, (b) Seoul Special Metropolitan City, (c) Daejeon Metropolitan City, (d) Gwangju Metropolitan City, (e) Daegu Metropolitan City, (f) Ulsan Metropolitan City, (g) Busan Metropolitan City. Districts are classified by quartiles based on the average urban park area per capita derived from the Korean Statistical Information Service (KOSIS) database: Q1 (lowest greenness) to Q4 (highest greenness).

Outcomes

The primary outcome was the first occurrence of acute exacerbation of COPD (AE-COPD), defined as a prescription for systemic corticosteroids and/or antibiotics within 7 days of a healthcare visit (outpatient, emergency department, or hospitalization) with a COPD diagnosis.²³ This operational definition may not fully distinguish mild from severe events and could include some prophylactic treatments; this is discussed as a limitation. The secondary outcome was all-cause mortality, determined through NHIS eligibility records. Follow-up continued from the index date until the occurrence of an outcome, death, or end of the study period.

Statistical Analysis

Baseline characteristics were presented as frequencies and proportions for categorical variables and as means with standard deviations (SDs) for continuous variables. Cox proportional hazards regression analysis was employed to estimate adjusted hazard ratios (aHRs) and their corresponding 95% confidence intervals (CIs), accounting for time-to-event data through the hazard function.²⁶ The proportional hazards assumption was assessed using Schoenfeld residuals. The models were adjusted for variables with a p-value ≤ 0.2 in the baseline characteristics analysis or those considered clinically important, including sex, age, income (insurance premium quartiles), disability status (normal, mild, severe), and the Charlson Comorbidity Index (CCI).²⁷ The CCI, calculated from diagnoses within one year before the index date, included a range of chronic conditions excluding COPD (eg, cardiovascular disease, diabetes, liver disease, cancer, HIV).²⁸

The green space index was modeled in quartiles, with Q1 as the reference. Trend tests were conducted by treating quartiles as continuous variables to assess linear exposure-response relationships.²⁹ This approach was supported by preliminary visual inspections of exposure-response plots. Subgroup analyses were conducted by sex, age group, income level, and CCI score. For the health screening subgroup, analyses were further stratified by body mass index (BMI, ≤25 or >25 kg/m²), smoking status (never, former, current), and physical activity (≥3 times/week, 1–2 times/week, none). To account for the risk of false-positive findings due to multiple comparisons, subgroup results were interpreted as exploratory, and interaction terms were tested when appropriate. All statistical analyses were performed using SAS Enterprise Guide (version 8.3; SAS Institute Inc., Cary, NC, USA), with significance defined as a two-sided p-value <0.05.

Results

Among the total NHIS-NSC cohort of one million individuals (2006–2015), 34,301 patients were diagnosed with COPD and received at least one prescription for COPD-related medication. Of these, 17,430 received a re-prescription within one year, and a final study population of 5,171 patients aged ≥40 years with at least two prescriptions within a one-year period was identified (Figure 1).

The mean age was 67.5 years (SD, 11.2), with 75.8% aged ≥60 years and 60.7% being male. Income distribution and disability status were relatively even across quartiles, and no significant differences were observed in baseline characteristics (Table 1).

Table 1 Descriptive Characteristics of Study Population

In the multivariable analysis adjusted for all covariates, a significant inverse association was observed between urban green space coverage and the risk of AE-COPD (p for trend = 0.016). Specifically, patients residing in areas with the highest green space coverage (fourth quartile) had a significantly lower risk of AE-COPD (HR, 0.75; 95% CI, 0.58–0.96) compared to those in the lowest quartile. The incidence rate of AE-COPD progressively decreased across quartiles, from 35.37 per 1,000 person-years (95% CI, 32.97–37.86) in the first quartile to 31.33 (95% CI, 29.48–33.25) in the fourth quartile. However, increased green space coverage was not associated with a statistically significant reduction in all-cause mortality (p for trend = 0.738). The incidence rates of all-cause death remained relatively consistent across quartiles (Table 2).

Table 2 Association of Urban Green Space Coverage with the Risk of AE-COPD and Death of COPD Patients

Stratified analyses suggested possible variation in the association between green space and AE-COPD risk across subgroups. In particular, lower risks in the highest green space quartile were observed among individuals aged 40–49 years (aHR, 0.12; 95% CI, 0.02–0.65; p for trend = 0.048), men (aHR, 0.70; 95% CI, 0.52–0.95; p for trend = 0.053), and those in the upper half of income distribution (aHR, 0.53; 95% CI, 0.37–0.76; p for trend = 0.007). A protective pattern was also observed in patients with comorbidities (CCI ≥1; aHR, 0.72; 95% CI, 0.56–0.93; p for trend = 0.014). Nonetheless, none of the interaction terms reached statistical significance (all p for interaction > 0.05), and these subgroup-specific findings should be interpreted as exploratory rather than confirmatory (Table 3).

Table 3 Stratified Analysis on the Association of Urban Green Space Coverage with Risk of AE-COPD (n=5171)

In supplementary analyses restricted to 3,318 individuals who underwent standardized health screening examinations, baseline characteristics remained balanced across green space exposure quartiles. Most participants were aged ≥60 years (75.9%), and 61.1% were male. Comorbidity burden was substantial, with 67.5% having a Charlson Comorbidity Index (CCI) score ≥2. Distributions of income, disability status, smoking behavior, and physical activity levels did not significantly differ across quartiles (Supplementary Table 2).

Within this subgroup, the inverse association between green space and AE-COPD was generally consistent. Reduced AE-COPD risks in the highest green space quartile were observed among patients aged 40–49 years (aHR, 0.00; 95% CI, 0.00–0.05), ≥60 years (aHR, 0.71; 95% CI, 0.51–0.99), men (aHR, 0.67; 95% CI, 0.46–0.99), high-income individuals (aHR, 0.45; 95% CI, 0.28–0.71), those with CCI ≥1 (aHR, 0.67; 95% CI, 0.49–0.93), BMI ≤25 (aHR, 0.58; 95% CI, 0.39–0.85), and individuals engaging in physical activity ≥3 times per week (p for trend = 0.022) (Table 4). However, tests for statistical interaction remained nonsignificant across all subgroups (all p for interaction > 0.05), and thus these variations should be considered exploratory in nature.

Table 4 Stratified Analysis on the Association of Urban Green Space Coverage with Risk of AE-COPD Among COPD Patients Who Underwent Health Screening Examinations (n=3318)

In the overall subgroup, green space coverage remained significantly associated with reduced AE-COPD risk (aHR, 0.68; 95% CI, 0.50–0.94; p for trend = 0.007), although this finding should also be interpreted with caution in light of the model limitations. No significant relationship was found with all-cause mortality (p for trend = 0.629) (Table 5).

Table 5 Association of Urban Green Space Coverage with the Risk of AE-COPD and Death Among People Who Underwent Health Screening Examinations (n=3318)

Discussion

In this nationwide cohort study, we observed a potential association between greater exposure to urban green space and a reduced risk of acute exacerbation of COPD (AE-COPD). A decreasing trend in AE-COPD incidence was observed across quartiles of green space coverage. While the inverse association appeared stronger in certain subgroups—such as younger adults (40–49 years), men, individuals in the upper income brackets, and those with comorbidities—none of the interaction terms reached statistical significance, suggesting that these subgroup findings should be interpreted as exploratory rather than confirmatory.

Although the association was statistically significant, the absolute difference in AE-COPD incidence between the lowest and highest quartiles was modest (35.4 vs 31.3 per 1,000 person-years), highlighting the need to interpret relative risk reductions within the context of public health impact. In contrast, no significant association was found between green space and all-cause mortality. This null finding may reflect insufficient statistical power, exposure misclassification, or the heterogenous nature of causes contributing to mortality in COPD populations.

Our results are broadly consistent with some prior studies suggesting a potential role of green space on respiratory health, although findings across the literature remain mixed. Such variation likely reflects differences in study setting, population characteristics, and exposure measurement methods. In the Korean context, compact and high-density urban environments may offer relatively equitable access to public green spaces, which may differ from more car-dependent cities. We used district-level park area data from the 2017 Korean Statistical Information Service (KOSIS), which may provide better spatial resolution than remote-sensing-based greenness indices.³⁰ However, because this static measure was applied uniformly across 2006–2019 study period, temporal changes in green space availability were not captured. This may have introduced exposure misclassification, potentially diluting observed associations. While these findings are consistent with the hypothesis that green space may influence respiratory health through mechanisms such as air pollution reduction or increased physical activity—both of which are known to support lung function. Although some studies have reported protective effects of green space on mortality,^14,15 results remain inconsistent.³¹

Interestingly, inverse associations between green space and AE-COPD appeared stronger among men and individuals with higher income—groups that may differ in health behaviors, disease severity, or access to green space and healthcare. These patterns align with the higher COPD prevalence observed among Korean men, who may therefore experience more measurable environmental benefit.^32,33 However, this contrasts with some studies reporting stronger protective effects among women.³⁴ One possible explanation is that Korean women with COPD tend to have greater comorbidity burdens and more severe phenotypes,^35,36 which may attenuate their responsiveness to environmental exposures. Similarly, stronger associations among higher-income individuals may reflect differential access to high-quality green space or healthcare services,^14,37 although residual confounding cannot be ruled out. In contrast, no meaningful association was observed among individuals without comorbidities (CCI = 0), suggesting that green space may confer greater respiratory benefits to individuals with underlying health vulnerabilities.

Subgroup analyses in the health screening population generally aligned with the main findings. Stronger inverse associations were observed among individuals with lower BMI, greater physical activity, and mild disabilities—groups potentially more sensitive to environmental influences. However, several estimates were based on small numbers of AE-COPD events, particularly in younger age groups (eg, aHR = 0.00 in 40–49 years), raising concerns about statistical imprecision. These results reinforce the exploratory nature of subgroup analyses and highlight the need for cautious interpretation.

This study has several strengths, including the use of a large, nationally representative cohort; long-term follow-up; and a validated claims-based definition of AE-COPD. Quartiles of green space were treated as continuous variables in trend analyses following visual confirmation of linearity, which enhanced the interpretability of exposure–response patterns.

Nonetheless, several limitations should be acknowledged. First, district-level park area may not accurately reflect individual-level exposure due to within-district heterogeneity and the use of static 2017 data over a long follow-up period. Second, the absence of air pollution and smoking data in the full cohort raises the possibility of residual confounding. Third, reliance on administrative claims data may have led to misclassification of AE-COPD events, particularly in distinguishing between mild and severe exacerbations. Fourth, although stratified analyses by age, sex, income level, CCI, and disability revealed some variation in trends, none of the interaction terms were statistically significant; subgroup findings should thus be interpreted as exploratory, emphasizing within-group trends rather than between-group comparisons. Fifth, other environmental factors affecting air quality—such as proximity to industrial complexes, prevailing wind directions, and geographic location—were not considered due to data limitations, potentially resulting in incomplete adjustment for spatial variation in air pollution.^{38, 39} Lastly, in the AE-COPD model, although main exposure variable — urban green space —satisfied the proportionality assumption, two covariates, age and disability status, did not. This violation suggests potential time-varying effects of these two covariates, warranting cautious interpretation of the results.

Conclusion

In this nationwide cohort study, we observed a potential association between greater exposure to urban green space and a reduced risk of acute exacerbation in COPD patients. This inverse association appeared more pronounced in certain subgroups—including younger adults, men, individuals with higher income, and those with comorbid conditions or healthier lifestyles—suggesting that the potential health effects of green space may vary across populations. However, the modest absolute risk reduction, lack of association with all-cause mortality, and absence of statistically significant interaction effects across subgroups indicate that these findings should be interpreted with caution. In particular, given that the AE-COPD model violated the proportional hazards assumption for age and disability status, this limitation should be considered when evaluating the robustness of the results. While our findings support the plausibility of environmental influences on respiratory health, they do not establish causality. Future studies incorporating time-varying and individual-level exposure metrics, direct air quality assessments, and prospective or interventional designs are needed to clarify underlying mechanisms and confirm these associations.

Human Ethics Approval and Declaration

The study protocol was approved by the Ethical Committee of Chung-Ang University Hospital (IRB No. 2307-015-19480) and was conducted in accordance with the approved guidelines. The need for informed consent was waived by the IRB because of the retrospective nature of the study. All data used in this study were fully anonymized prior to access and analysis, and the study complied with relevant data protection and privacy regulations, including the Personal Information Protection Act of the Republic of Korea.

Acknowledgments

Hae In Jung and Ju Won Lee have contributed equally to this work and share first authorship. Kang-Mo Gu and Sun-Young Jung have contributed equally to this work and share corresponding authorship.

Funding

This research was supported by the Chung-Ang University Research Grants in 2024.

Disclosure

The authors report no conflicts of interest in this work.

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The government has amended prescribing regulations to allow the antivirals oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GSK) to be prescribed and dispensed outside of the flu season.

On 1 September 2025, the government said the rule change “will allow doctors and pharmacists to better respond to flu outbreaks”.

“These rules are being removed so action can be taken to tackle flu all year round. This will allow patients to receive treatment sooner and ease winter pressures by allowing outbreaks to be contained,” it added.

Previously, GPs and pharmacies had to be commissioned via a patient-specific direction to prescribe the medicines, but the government noted that this could lead to delays in treatment.

Both oseltamivir and zanamivir are recommended for treating high-risk individuals, following a confirmatory test for flu. 

“They are also recommended to prevent disease in specific settings, such as care homes, where confirmed cases of flu have occurred,” the government said.

The removal of restrictions coincides with the launch of the 2025/2026 flu vaccination programme for pregnant women and children.

Health minister Stephen Kinnock commented: “Flu can strike all year round, so it doesn’t make sense to restrict doctors and pharmacists from taking action to protect the most vulnerable in their communities.

“That’s why, as well as starting the flu vaccination programme today, we are also removing the need for clinicians to have to ask for permission to prescribe what their patients need.”

Jamie Lopez Bernal, consultant epidemiologist for immunisation at the UK Health Security Agency, said: “While the majority of influenza cases and outbreaks occur during the flu season, we do continue to see outbreaks outside the peak period.

“These changes will allow primary care providers and health protection teams to respond more rapidly with effective treatment to reduce the risk of severe disease and the spread of infection at any time of year.”

Claire Anderson, president of the Royal Pharmaceutical Society, added: “This is a welcome change and will help patients at highest risk of serious illness from flu get timely access to treatment all year round. 

“Pharmacists play a vital role in protecting public health, and this flexibility will support quicker responses to outbreaks, reduce pressures on the NHS and protect vulnerable patients.”

In July 2025, NHS England announced that community pharmacies will be able to provide flu vaccines to children aged two to three years, as part of a trial commissioned for the 2025/2026 winter season.

Drug-coated stents and balloons were not associated with reduced risk of amputation or improved quality of life compared with uncoated devices in two trials in peripheral artery disease (PAD), according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.

Explaining the rationale for the trials, Principal Co-Investigator, Professor Joakim Nordanstig from the University of Gothenburg, Sweden, said: “Drug-coated balloons and stents have been shown to reduce restenosis and the need for reinterventions in the endovascular treatment of PAD. However, there are uncertainties regarding whether drug-coated devices improve outcomes that are meaningful to patients, quality of life and reducing amputations, and there are some concerns over safety. We investigated these and other endpoints in two trials in PAD – one in chronic limb-threatening ischaemia and one in intermittent claudication – comparing drug-coated and uncoated devices.“

SWEDEPAD 1 and 2 were pragmatic, participant-blinded, registry-based randomized trials conducted at 22 sites in Sweden.

In SWEDEPAD 1, 2,355 patients with chronic limb-threatening ischemia (Rutherford stage 4-6) undergoing infra-inguinal endovascular treatment were randomised 1:1 to drug-coated or uncoated balloons or stents. In nearly all of the drug-coated devices implanted, the drug delivered was paclitaxel (>99%). There was no significant difference in the primary endpoint of time to ipsilateral above-ankle amputation with drug-coated vs. uncoated devices (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.87 to 1.27) over 5 years of follow-up. Target vessel reinterventions were reduced in the drug-coated group during the first year (HR 0.81; 95% CI 0.66 to 0.98), but this difference disappeared with longer follow-up. There was no difference in all-cause mortality or in quality of life (as assessed using the VascuQoL-6 questionnaire).

In SWEDEPAD 2, 1,155 patients with intermittent claudication (Rutherford stage 1-3) undergoing infra-inguinal endovascular treatment were randomised 1:1 after successful guidewire crossing to receive either drug-coated or uncoated balloons or stents. All drug-coated devices implanted delivered paclitaxel. There was no difference in the primary efficacy endpoint of quality of life between the drug-coated and uncoated groups at 12 months (mean difference in VascuQoL-6 scores: -0.02; 95% CI -0.66 to 0.62). Target vessel reintervention rates were not different at 1 year or over a median follow-up of 6.2 years. All-cause mortality did not differ over 7.1 years (HR 1.18; 95% CI 0.94 to 1.48), although higher 5-year mortality was noted with drug-coated vs. uncoated devices (HR 1.47; 95% CI 1.09 to 1.98).

Summarizing the findings, Principal Co-Investigator, Professor Mårten Falkenberg from Sahlgrenska University Hospital and the University of Gothenburg, Sweden, said: “Paclitaxel-coated devices were not effective in preventing amputation in chronic limb-threatening ischemia or improving quality of life in intermittent claudication. Given the signal of increased mortality with intermittent claudication, clinicians should carefully evaluate the potential risks and benefits when considering these expensive devices. Devices incorporating antiproliferative agents other than paclitaxel warrant further investigation in PAD.”