Impact of exercise maintenance on mortality in interstitial lung disease: a population-based retrospective cohort study

Abstract

Background:

Previous studies have proposed exercise capacity as a mortality predictor in individuals with interstitial lung disease (ILD). However, limited information is available regarding whether maintaining exercise is associated with improved survival in individuals with ILD.

Objectives:

We aimed to evaluate the association between exercise maintenance and mortality in individuals with ILD using a longitudinal, large population-based database.

Design:

This retrospective cohort study used the Korean National Health Insurance claims-based database.

Methods:

We analyzed a total of 3850 individuals with ILD who underwent two consecutive health screening examinations. The study exposure was the change in exercise habits between the two examinations, with individuals classified as exercisers (exercise maintainers and exercise non-maintainers) or non-exercisers. The primary outcome was mortality. We adjusted for age, sex, body mass index (BMI), smoking status, alcohol status, economic status, residential area, and comorbidities.

Results:

During a median follow-up of 7.2 (interquartile range, 5.6–9.2) years, the incidence rate of death for exercisers was lower than that of non-exercisers (341.28 per 10,000 person-years (PY) vs 401.81 per 10,000 PY). Multivariable Cox regression analysis showed that the risk of mortality was substantially lower in exercisers compared to non-exercisers (adjusted hazard ratio (aHR): 0.82, 95% confidence interval (CI): 0.72–0.94). The risk of reduction for death was correlated with exercise adherence, with the lowest risk among exercise maintainers (aHR: 0.78 (0.66–0.92)) followed by exercise non-maintainers (aHR: 0.85 (0.73–0.99)), compared to non-exercisers. In subgroup analyses, BMI and economic status had a significant interaction in the association between exercise and mortality. The risk of death was lower in individuals with a lower BMI and higher economic status compared to their counterparts.

Conclusion:

Among individuals with ILD, the risk of death was inversely correlated with the level of exercise adherence, cautiously suggesting the importance of exercise maintenance in individuals with ILD.

Plain language summary

Exercise and survival in interstitial lung disease

Exercise is often limited in people living with interstitial lung disease (ILD). However, little is known about whether maintaining physical activity could influence how long they live. This study followed 3850 individuals in Korea with ILD who completed two health check-ups—one before and one after ILD diagnosis. Based on self-reported physical activity, participants were categorized as “exercisers” or “non-exercisers,” and were then followed for an average of 7 years to track mortality outcomes. The findings revealed that exercisers had a lower risk of death compared to non-exercisers. The greatest benefit was seen in those who consistently exercised, though even those who started or stopped exercising during the study period had better outcomes than those who remained inactive.

Keywords

epidemiology exercise interstitial lung disease mortality

Introduction

Interstitial lung disease (ILD) is a heterogeneous group of chronic respiratory diseases characterized by inflammation and progressive pulmonary fibrosis.^1,2 ILDs are classified according to their etiology and encompass idiopathic interstitial pneumonias, connective tissue disease (CTD)-related ILD, hypersensitivity pneumonitis, and other forms, such as drug-induced and postinfectious ILD. Among these, idiopathic pulmonary fibrosis (IPF) is the most prevalent, accounting for over 30% of ILD cases. Although each type of ILD has distinct pathophysiological features, clinical presentations, and prognoses, all forms can ultimately lead to irreversible pulmonary fibrosis.³

In terms of symptoms and presentations, ILD is typically characterized by progressive dyspnea and limited physical activity,^1,2 which have also been suggested to be associated with high levels of premature mortality. In ILD, lung function is the most commonly used predictor of mortality and the prognosis after diagnosis. Moreover, measures of exercise capacity and physical activity have also been proposed as predictors of mortality.⁴ For example, previous studies demonstrated that reduced physical activity,⁵ lower exercise capacity indicated by the six-minute walk test (6MWT),^6,7 and decreased peak oxygen uptake (VO₂ peak)^8,9 are associated with a higher mortality risk in individuals with IPF or other ILDs.¹⁰ However, the sample size was relatively small, and the follow-up duration was insufficient. In addition, these studies did not consider changes in exercise capacity and primarily evaluated patients with IPF. Furthermore, covariate adjustments were insufficient; while some studies adjusted for age, sex, baseline lung function, or smoking history,^6,7 others did not account for clinical variables that could affect the outcomes.

Pulmonary rehabilitation, including exercise training, in individuals with ILD is strongly recommended since it is related to improved exercise performance and quality of life.^11,12 Beyond these beneficial effects, exercise may be associated with a reduction in overall mortality in individuals with ILD. However, limited information is available regarding whether maintaining exercise is associated with improved survival in individuals with ILD. Therefore, we aimed to evaluate the impact of exercise maintenance on mortality in individuals with ILD using a longitudinal, large population-based database.

Methods

Data source

This retrospective cohort study utilized the Korean National Health Insurance claims-based database, administered by the National Health Insurance Service (NHIS). The NHIS functions as a government-managed universal insurance provider, extending coverage to approximately 97% of the Korean population, encompassing around 50 million individuals.^13,14 The NHIS provides health screening exams and reports on sociodemographic data, a self-questionnaire survey, basic clinical laboratory findings, inpatient and outpatient usage, prescription records, and recorded diagnoses based on International Classification of Diseases 10th Revision (ICD-10) codes. Mortality information was also acquired from the NHIS database, supplied by Statistics Korea under the auspices of the Ministry of Strategy and Finance of Korea.^15,16 This extensive NHIS database has been widely employed in diverse epidemiological studies aimed at identifying risk factors and prognoses in pulmonary diseases.^17,18

Study population

Among 8050 individuals who were newly diagnosed with ILD between January 2010 and December 2016, we included 4042 who underwent two consecutive health examinations within 2 years before and after the ILD diagnosis to measure changes in their exercise habits between the two time points. Among them, those with a follow-up duration of less than 1 year were excluded to ensure enough prognostic observation. In addition, we excluded individuals aged <20 years and those with missing variables on health screening examinations (n = 116). The final ILD cohort comprised 3850 individuals (Figure 1).

Figure 1.

Flow chart of the study population.

ILD was defined as claims with any of the ICD-10 diagnosis codes J84. ILD subtypes were categorized as IPF (J84.1 or J84.18) or non-IPF ILD (CTD-related ILD, J84 codes with CTD codes (M05, M06, M30, M31, M32, M33, M34, M35, M36, M45), hypersensitivity pneumonitis (D67), sarcoidosis (D86), and other ILDs that do not classify into the previous subtypes).^17,19,20

Study exposure: Exercise

The exposure in our study was the change in exercise habits. The intensity and frequency of regular physical activity were assessed using a self-reported questionnaire during two consecutive health screening examinations. This questionnaire has been used in several high-quality studies and includes the frequency of light, moderate, or vigorous weekly physical activity of varying intensity.^21–23

Regular exercise was defined as a moderate-intensity exercise for more than 5 days per week or vigorous-intensity exercise for more than 3 days per week.²⁴ To evaluate the impact of changes in exercise habits on the risk of mortality, the study population was subdivided into three groups according to changes in exercise performance: non-exercisers were individuals who never performed exercise in either examination, while exercise non-maintainers were those who were non-exercisers in the first examination but exercisers in the second examination or exercisers in the first examination but non-exercisers in the second examination. Exercise maintainers were individuals who exercised in both examinations.

Study outcome: Mortality

The primary outcome was a comparison of the incidence and risk of all-cause mortality. Death-related information was available through December 31, 2022. Thus, for the mortality analysis, we tracked individuals until the date of death or December 31, 2022, whichever came first. We had a 1-year lagging period to evaluate the impact of exercise on the long-term prognosis of ILD.

Covariates

Data for baseline characteristics were collected from the study dataset. Body mass index (BMI) was calculated as body weight divided by the square of height (kg/m²) and was classified into four groups, as recommended for Asians: normal (18.5–22.9 kg/m²), low (<18.5 kg/m²), overweight (23.0–24.9 kg/m²), and obese (⩾25 kg/m²).^25,26 Smoking status (never-, ex-, or current smoker) and alcohol status were determined based on a self-reported questionnaire. Income status was divided into the highest 20% (high), the lowest 20% (low), and the rest (middle); individuals supported by the medical aid program were classified as the low-income group. The residential area was classified into metropolitan cities, middle- and small-sized cities, and rural areas. Comorbidities were defined as one or more claims under the following ICD-10 diagnosis codes as major diagnoses within 1 year of the index date^27,28: hypertension (I10–I15), diabetes mellitus (E10–E14), dyslipidemia (E78), chronic kidney disease (N18), and airway disease (chronic obstructive pulmonary diseases (J43, J44, except for J430) and asthma (J45, J46)).

Statistical analysis

Descriptive statistics are presented as numbers (percentages) for categorical variables and as the mean (standard deviation) for continuous variables. Group comparisons were conducted using the chi-square (χ²) test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. The incidence rates of severe exacerbation and death were calculated by dividing the number of incident events by the total follow-up period (per 10,000 person-years (PY)). A cumulative incidence plot was used to compare the incidences of death, and a log-rank test was utilized to evaluate significant differences between the three groups. We used Cox proportional hazards regression analyses to evaluate the risk of death in the non-exercisers versus exercise non-maintainers versus exercise maintainers. The multivariable analysis was adjusted for age, sex, BMI, smoking status, alcohol status, economic status, residential area, and comorbidities (hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and airway disease). We also conducted subgroup analyses based on sex, age, BMI, smoking status, economic status, residential area, and alcohol status. A two-sided p value <0.05 was considered statistically significant. All statistical analyses were carried out using SAS Enterprise Guide software version 7.1 (SAS Institute, Inc., Cary, NC, USA).

The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.²⁹

Results

Baseline characteristics

Of 3850 individuals with ILD, 32% were exercise maintainers (n = 1239), 36% were exercise non-maintainers (n = 1377), and 32% were non-exercisers (n = 1234). As shown in Table 1, exerciser maintainers were more likely to be younger, male, and ever-smokers, and less likely to drink alcohol compared to other groups (all p < 0.001). Exercisers (exercise maintainers and non-maintainers) were more likely to have a high income level (p = 0.027) and to live in metropolitan cities (p < 0.001) compared to non-exercisers. In terms of comorbidities, dyslipidemia was more prevalent in exercisers compared to non-exercisers (p = 0.003).

Table 1.

Baseline characteristics of individuals.

Variables	Exercisers (n = 2616)		Non-exercisers (n = 1234)	p Value
Variables	Exercise maintainers (n = 1239)	Exercise non-maintainers (n = 1377)	Non-exercisers (n = 1234)	p Value
Time interval between two health check-ups, years	1.75 ± 0.68	1.80 ± 0.69	1.76 ± 0.66	0.193
Age, years				<0.001
20–59	409 (33.0)	460 (33.4)	451 (36.5)
60–79	778 (62.8)	837 (60.8)	687 (55.7)
⩾80	52 (4.2)	80 (5.8)	96 (7.8)
Sex, male	863 (69.7)	836 (60.7)	717 (58.1)	<0.001
Body mass index				0.088
Low (<18.5 kg/m²)	27 (2.2)	55 (4.0)	50 (4.1)
Normal (18.5–22.9 kg/m²)	444 (35.8)	518 (37.6)	448 (36.3)
Overweight (23.0–24.9 kg/m²)	338 (27.3)	351 (25.5)	310 (25.1)
Obese (⩾25.0 kg/m²)	430 (34.7)	453 (32.9)	426 (34.5)
Smoking status				<0.001
Never-smoker	598 (48.3)	781 (56.7)	685 (55.5)
Ex-smoker	411 (33.2)	325 (23.6)	262 (21.2)
Current smoker	230 (18.6)	271 (19.7)	287 (23.3)
Alcohol status				<0.001
None	735 (59.3)	923 (67.0)	849 (68.8)
1–2 times/week	333 (26.9)	302 (21.9)	238 (19.3)
3–4 times/week	116 (9.4)	91 (6.6)	85 (6.9)
Almost everyday	55 (4.4)	61 (4.4)	62 (5.0)
Economic status*				0.027
Low	203 (16.4)	239 (17.4)	196 (15.9)
Middle	593 (47.8)	690 (50.1)	664 (53.8)
High	443 (35.8)	448 (32.5)	374 (30.3)
Residential area				<0.001
Middle and small cities	223 (18.0)	289 (21.0)	318 (25.8)
Rural areas	107 (8.6)	183 (13.3)	183 (14.8)
Metropolitan cities	909 (73.4)	905 (65.7)	733 (59.4)
Comorbidities
Hypertension	375 (30.3)	424 (30.8)	373 (30.2)	0.940
Diabetes mellitus	164 (13.2)	219 (15.9)	182 (14.7)	0.156
Dyslipidemia	119 (9.6)	114 (8.3)	73 (5.9)	0.003
Chronic kidney disease	8 (0.6)	14 (1.0)	18 (1.5)	0.136
Airway disease (COPD and asthma)	262 (21.1)	310 (22.5)	294 (23.8)	0.280

Data are presented as number (percentages) or means (standard deviations).

Income status was divided into the highest 20% (high), the lowest 20% (low), and the rest (middle); individuals supported by the medical aid program were classified as the low-income group.

COPD, chronic obstructive pulmonary disease.

Impact of exercise habits on mortality

During a median follow-up of 7.2 (interquartile range, 5.6–9.2) years, the incidence rate of death was lower in exercisers (341.28 per 10,000 PY) compared to non-exercisers (401.81 per 10,000 PY), yielding an adjusted hazard ratio (aHR) of 0.82 (95% confidence interval (CI): 0.72–0.94; Table 2). In the cumulative incidence plot for death, exercisers have a better survival rate than non-exercisers (Figure 2(a), log-rank p = 0.013).

Table 2.

Impact of exercise on risk of mortality in ILD.

Groups	Number at risk	Incident cases (n)	Incidence per 10,000 PY	Unadjusted HR (95% CI)	Adjusted HR* (95% CI)
All patients
Non-exercisers	1234	350	401.81	Reference	Reference
Exercisers	2616	645	341.28	0.85 (0.74–0.97)	0.82 (0.72–0.94)
Exercise non-maintainers	1377	362	360.44	0.89 (0.77–1.04)	0.85 (0.73–0.99)
Exercise maintainers	1239	283	319.56	0.80 (0.68–0.93)	0.78 (0.66–0.92)
ILD subtypes
IPF
Non-exercisers	291	108	541.36	Reference	Reference
Exercisers	667	239	517.20	NA^$	NA^$
Exercise non-maintainers	356	131	527.55	NA^$	NA^$
Exercise maintainers	311	108	505.18	NA^$	NA^$
Non-IPF ILD
Non-exercisers	943	242	360.36	Reference	Reference
Exercisers	1949	406	284.353	0.79 (0.67–0.92)	0.80 (0.68–0.94)
Exercise non-maintainers	1021	231	305.55	0.84 (0.70–1.01)	0.85 (0.71–1.02)
Exercise maintainers	928	175	260.49	0.72 (0.59–0.88)	0.73 (0.60–0.90)

Adjusted for age, sex, BMI, smoking status, alcohol status, economic status, residential area, and comorbidities (hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and airway disease).

Cox regression analyses could not be performed because the proportional hazards assumption was not satisfied.

BMI, body mass index; CI, confidence interval; HR, hazard ratio; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; PY, person-years.

Figure 2.

Cumulative incidence of death in the ILD cohort, stratified by (a) exercise status and (b) exercise maintenance status.

The incidence rate of death was inversely correlated with the level of exercise adherence (319.56 per 10,000 PY for exercise maintainers vs 360.44 per 10,000 PY for exercise non-maintainers vs 401.81 per 10,000 PY for non-exercisers). The risk of death was lowest among exercise maintainers (aHR: 0.78, 95% CI: 0.66–0.92), followed by exercise non-maintainers (aHR: 0.85, 95% CI: 0.73–0.99), compared to non-exercisers (Table 2). The cumulative incidence plot for death showed similar results (Figure 2(b), log-rank p = 0.017).

When analyzed by ILD subtypes, among individuals with non-IPF ILD, exercisers showed a lower rate of death compared to non-exercisers (284.35 vs 360.36 per 10,000 PY, p = 0.021), yielding an aHR of 0.80 (95% CI: 0.68–0.94; Table 2 and Figure 3(a)). In the IPF group, the mortality rate was lower in exercisers compared to non-exercisers (517.55 vs 541.36 per 10,000 PY, p = 0.838); however, Cox regression analyses could not be performed due to non-satisfaction of the proportional hazards assumption. As shown in Figure 3(b), visually, the cumulative incidence rates for death were lower in exercisers than in non-exercisers up to 7 years after follow-up in the IPF group. However, the difference diminished thereafter. The cumulative incidence plot for death according to exercise maintenance in IPF and non-IPF ILDs is shown in Supplemental Figure 1.

Figure 3.

Cumulative incidence of death in individuals with (a) non-IPF ILD and (b) IPF, stratified by exercise status.

Subgroup analyses

Subgroup analyses regarding the risk of mortality according to exercise among individuals with ILD are shown in Table 3. Age, sex, smoking status, economic status, residential area, and alcohol status exhibited no interaction in the association of exercise with the development of deaths (all p for interaction >0.05). BMI had a significant interaction in the association of exercise with mortality. The risk of death was lower in individuals with lower BMI than in their counterparts (p for interaction = 0.043). In addition, economic status had a significant interaction in the association of exercise with mortality, with individuals of high economic status exhibiting a lower risk of death compared to those of low economic status (p for interaction = 0.037).

Table 3.

Subgroup analysis of mortality risk in ILD.

Subgroups	Exercise	Number at risk	Incident cases (n)	Incidence per 10,000 PY	Unadjusted HR (95% CI)	Adjusted HR* (95% CI)
Age, years
20–59	Non-exercisers	451	43	118.77	Reference	Reference
	Exercisers	869	57	81.38	0.69 (0.46–1.02)	0.70 (0.47–1.06)
60–79	Non-exercisers	687	245	531.76	Reference	Reference
	Exercisers	1615	515	461.53	0.87 (0.74–1.01)	0.86 (0.74–1.01)
⩾80	Non-exercisers	96	62	1,284.43	Reference	Reference
	Exercisers	132	73	990.91	0.75 (0.54–1.06)	0.70 (0.48–1.04)
p for interaction					0.476	0.464
Sex
Female	Non-exercisers	517	90	231.55	Reference	Reference
	Exercisers	917	119	170.29	0.74 (0.56–0.97)	0.87 (0.66–1.16)
Male	Non-exercisers	717	260	539.00	Reference	Reference
	Exercisers	1699	526	441.61	0.82 (0.70–0.95)	0.81 (0.69–0.94)
p for interaction					0.508	0.861
Body mass index
Low (<18.5 kg/m²)	Non-exercisers	50	27	970.92	Reference	Reference
	Exercisers	82	22	396.51	0.42 (0.24–0.74)	0.33 (0.17–0.64)
Normal (18.5–22.9 kg/m²)	Non-exercisers	448	134	419.98	Reference	Reference
	Exercisers	962	249	359.52	0.86 (0.69–1.06)	0.78 (0.62–0.96)
Overweight (23.0–24.9 kg/m²)	Non-exercisers	310	77	350.54	Reference	Reference
	Exercisers	689	167	335.26	0.95 (0.73–1.25)	1.05 (0.79–1.40)
Obese (⩾25.0 kg/m²)	Non-exercisers	426	112	367.79	Reference	Reference
	Exercisers	883	207	321.57	0.87 (0.69–1.10)	0.82 (0.65–1.03)
p for interaction					0.055	0.043
Smoking status
Never-smoker	Non-exercisers	685	167	336.07	Reference	Reference
	Exercisers	1379	272	269.20	0.80 (0.66–0.97)	0.83 (0.68–1.01)
Ex-smoker	Non-exercisers	262	103	626.61	Reference	Reference
	Exercisers	736	230	450.23	0.71 (0.57–0.90)	0.77 (0.60–0.98)
Current smoker	Non-exercisers	287	80	381.40	Reference	Reference
	Exercisers	501	143	387.88	1.02 (0.77–1.34)	0.96 (0.72–1.28)
p for interaction					0.144	0.422
Economic status
Non-high	Non-exercisers	860	219	355.73	Reference	Reference
	Exercisers	1725	429	345.77	0.97 (0.83–1.15)	0.94 (0.80–1.11)
High	Non-exercisers	374	131	512.89	Reference	Reference
	Exercisers	891	216	332.71	0.64 (0.52–0.80)	0.66 (0.52–0.82)
p for interaction					0.014	0.037
Residential area
Non-metropolitan area	Non-exercisers	501	175	515.19	Reference	Reference
	Exercisers	802	247	451.31	0.88 (0.72–1.07)	0.84 (0.69–1.03)
Metropolitan cities	Non-exercisers	733	175	329.33	Reference	Reference
	Exercisers	1814	398	296.43	0.90 (0.75–1.07)	0.82 (0.68–0.98)
p for interaction					0.833	0.982
Alcohol status
Non-user	Non-exercisers	849	267	455.89	Reference	Reference
	Exercisers	1658	427	363.81	0.80 (0.68–0.93)	0.78 (0.67–0.92)
Alcohol user	Non-exercisers	385	83	290.83	Reference	Reference
	Exercisers	958	218	304.36	1.05 (0.81–1.35)	0.86 (0.66–1.12)
p for interaction					0.147	0.430

BMI, body mass index, CI, confidence interval; HR, hazard ratio; ILD, interstitial lung disease; PY, person-years.

Subgroup analyses regarding the risk of mortality among individuals with ILD according to exercise maintenance are shown in Supplemental Table 1.

Discussion

Utilizing a nationwide representative dataset, we evaluated the risk of death in nearly 4000 individuals with ILD according to their adherence to exercise. During a median follow-up of 7.2 years, exercisers had a significantly lower risk of death compared to non-exercisers by about 20%. The risk of mortality further decreased as the adherence to exercise maintenance increased in a dose-dependent manner, showing the lowest risk in exercise maintainers.

In individuals with ILD, exercise capacity is reduced, and the mechanisms behind this reduction are multifactorial. The basic physiology involved is known to be as follows. Impaired gas exchange occurs due to the destruction of the pulmonary capillary bed, leading to ventilation-perfusion mismatch and oxygen diffusion limitations.³⁰ Circulatory limitations arise from pulmonary capillary destruction and pulmonary vasoconstriction, which can result in pulmonary hypertension and cardiac dysfunction in some patients.³¹ Ventilatory limitations to exercise may also occur, though they are not considered a major contributor in most patients.³² Peripheral muscle dysfunction, often due to physical deconditioning, may limit exercise capacity.³³

Previous studies have examined measures of exercise capacity and physical activity and their relationship to prognosis in ILD. One retrospective, international cohort study including 710 fibrotic patients with ILD found that those who improved physical performance due to pulmonary rehabilitation had better survival compared with those who did not improve.³⁴ In addition, in a single-center study of 169 patients with ILD without pulmonary hypertension, a 6MWT distance of less than 300 m and a 6MWT final oxygen saturation of less than 85% were associated with an increased risk of mortality.³⁵ However, except for the aforementioned studies, many studies on this issue focused exclusively on IPF. In one review article on the relationship between physical activity, exercise capacity, and mortality risk in ILD, including IPF, both physical activity and exercise capacity were associated with mortality risk.³⁶ However, the evidence was weak due to the small sample sizes of the included studies, and the follow-up periods were not long enough to estimate the prognosis of ILD. Overcoming these limitations of previous studies, we comprehensively included individuals with various types of ILDs as a whole, with a large sample size (a total of 3850 ILDs in three exercise groups). The follow-up duration was also longer than in previous studies, with a median of 7.2 years.

With these advantages, our analysis adds robust evidence for the relationship between exercise habits and ILD prognosis; beyond merely showing exercise as a predictor of mortality in individuals with ILD, our study findings emphasize that adherence to exercise could provide more benefits in individuals with ILD over a long-term period of the natural disease course. In our study, the risk reduction for death increased as adherence to exercise increased (compared to non-exercisers, 22% reduction in exercise maintainers and 15% in exercise non-maintainers), suggesting that the importance of monitoring exercise capacity or providing rehabilitation should be considered in the long-term management of ILD.

Interestingly, in subgroup analyses by ILD subtypes, the benefit of exercise in the IPF group showed for up to 7 years after follow-up; however, it disappeared thereafter. The reasons for this observation are not fully explainable. However, we carefully suggest that factors affecting survival other than exercise capacity may be more complex in patients with IPF than in those with non-IPF, considering the worst prognosis of IPF among various ILDs. For example, the risk of lung cancer and acute exacerbation in IPF increases as the duration of IPF increases, which may affect mortality regardless of exercise capacity.^37,38 Future studies evaluating exercise and mortality in IPF with a long-term follow-up duration should consider this.

Our subgroup analysis further revealed a significant interaction between BMI and economic status in the association between exercise and mortality. Individuals with a lower BMI and higher economic status had a reduced risk of mortality compared to their counterparts. Previous studies have demonstrated that adipose tissue releases pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, and leptin, as well as adipokines that contribute to the progression of pulmonary fibrosis.^39,40 This may explain why individuals with a low or normal BMI in our study exhibited a lower risk of mortality compared to those who were overweight or obese. Economic status can influence access to exercise resources, health literacy, comorbidity burden, and healthcare utilization,^41,42 all of which may impact the interaction between exercise and mortality. Our additional subgroup analyses indicated that individuals in a higher economic status had a lower risk of mortality compared to those in a lower economic status.

Our study has several limitations. First, individuals who underwent health screening examinations were included, which might be associated with healthy user bias. In addition, only subjects with two consecutive health examination results were included in our study, leading to the exclusion of half of the total population and potentially introducing bias. Second, the diagnosis of ILD and other comorbidities relied on ICD-10 codes, potentially leading to overestimations or underestimations of diagnoses. However, the ICD-10 codes used in this study have been validated in many previous studies of ILD.^19,20 Third, there was no data on lung function, imaging, treatment, ILD control status, and time since ILD diagnosis. Future studies are needed to determine if the combination of the data types mentioned above can be used to better predict the prognosis of ILD. Fourth, generalizing our findings to other countries or ethnicities may be challenging since our research utilized a dataset from the Korean population. An additional limitation is the absence of a sample size calculation or justification for the selected cohort in the study’s methodology.

Since factors other than exercise may influence clinical outcomes in individuals with ILD, and given the limitations of this study, including the lack of detailed information on ILD severity and treatment, the results should be interpreted with caution.

Conclusion

In conclusion, among individuals with ILD, exercise was associated with reduced risk of mortality, which was particularly beneficial among exercise maintainers. The effect was more pronounced in the non-IPF group than in the IPF group, and individuals with lower BMI and higher economic status had a lower risk of death compared to other groups.

Supplemental Material

sj-docx-1-tar-10.1177_17534666251362380 – Supplemental material for Impact of exercise maintenance on mortality in interstitial lung disease: a population-based retrospective cohort study

Supplemental material, sj-docx-1-tar-10.1177_17534666251362380 for Impact of exercise maintenance on mortality in interstitial lung disease: a population-based retrospective cohort study by Bo-Guen Kim, Min Gu Kang, Sung Jun Chung, Hyung Koo Kang, Jong Seung Kim and Hyun Lee in Therapeutic Advances in Respiratory Disease

Supplemental Material

sj-docx-2-tar-10.1177_17534666251362380 – Supplemental material for Impact of exercise maintenance on mortality in interstitial lung disease: a population-based retrospective cohort study

Supplemental material, sj-docx-2-tar-10.1177_17534666251362380 for Impact of exercise maintenance on mortality in interstitial lung disease: a population-based retrospective cohort study by Bo-Guen Kim, Min Gu Kang, Sung Jun Chung, Hyung Koo Kang, Jong Seung Kim and Hyun Lee in Therapeutic Advances in Respiratory Disease

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Bo-Guen Kim

Hyun Lee

Supplemental material

Supplemental material for this article is available online.

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