Disease burden of interstitial lung disease and pulmonary sarcoidosis from 1992 to 2021 and prediction of future disease burden trend in China

Introduction

Interstitial lung disease (ILD) refers to a wide array of approximately 200 conditions marked by diffuse inflammation and fibrosis, impacting various parts of the respiratory system. In severe cases, ILD can lead to respiratory failure, with symptoms such as dyspnea, chest tightness, and persistent cough leading to significant ventilatory impairment (1). Patients often experience high mortality rates and a reduced quality of life, creating significant challenges for both individuals and society. While therapeutic interventions, such as immunomodulation and lung transplantation, are available, they remain limited by efficacy and potential adverse effects (2). A comprehensive understanding of the disease burden is thus critical for informing health economic models and shaping effective prevention strategies, underscoring the far-reaching impact of ILD (3). The burden of ILD varies significantly across countries and regions. According to the 2019 Global Burden of Disease (GBD) report, the age-standardized mortality rate (ASMR) for ILD was 20.66 per 100,000 in the United States and 8.29 per 100,000 in the United Kingdom (4). However, ASMRs have been increasing in nearly all global regions. ILD ranks second worldwide in incidence and mortality among chronic respiratory diseases, following asthma (4). Among the various forms of ILD, pulmonary sarcoidosis (PS) is notably common, yet no comprehensive assessment nor predictive analysis of the disease burden of ILD and PS has been undertaken in China.

The age-period-cohort (APC) model is a valuable tool for examining variations in disease trends over time. This model allows for the analysis of multiple factors—age, period, and cohort—simultaneously, providing insights into the epidemiological patterns of ILD (5). Furthermore, the APC model’s capacity to integrate these factors within a unified analytical framework provides a more nuanced understanding of epidemiological patterns than analyses focusing on individual variables alone (6). Prior to applying the APC model, data can be preprocessed using the Joinpoint regression (JPR) model, which identifies key points of change in trends and calculates both annual and average percentage changes in disease incidence and mortality (7). The Bayesian age-period-cohort (BAPC) model further enhances this analysis by using Two-dimensional spatial conditional autoregression (CAR) to account for potential interactions within the age-cohort framework, refining predictions and improving the accuracy of trend projections (8). Unfortunately, there is a scarcity of studies that integrate the JPR model, the APC model, and the BAPC model to predict disease burden. While some researchers have examined the global burden of chronic respiratory diseases and analyzed trends in ILD and PS across various countries and regions, the specific effects of age, period, and cohort on the global burden of ILD & PS remain largely unexplored (4).

Given that approximately one-fifth of the global population resides in China, it is imperative to expand research on the burden of ILD and PS within this region, as it has profound implications for global health (9). This study aims to investigate the effects of age, period, and cohort on the disease burden of ILD and PS in China. Additionally, we aim to inform projections of future trends in the burden of ILD and PS in China, providing an evidence-based foundation for the development of targeted prevention strategies and public health policies. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-651/rc).

Methods

Data sources

This study utilized data on the disease burden of ILD and PS in China from the GBD 2021 public database (https://vizhub.healthdata.org/gbd-results/), covering the years 1992 to 2021. The GBD database aggregates disease burden metrics, including incidence, prevalence, and mortality, for 369 diseases across 204 countries and regions. Uncertainty intervals (UIs) were generated for every metric using the 25th and 95th ordered 1,000 draw values of the posterior distribution (10). The 95% UI is the actual probability distribution around the true parameter value, i.e., 95% of the possible values of the parameter are within the 95% UI (11). Data sources for the GBD include air pollution monitoring, disease notifications, registries, civil registration statistics, household surveys, and demographic censuses (12). In China, data specific to ILD and PS were primarily sourced from the China Disease Surveillance Point, Death Registry, Chronic Disease and Risk Factor Surveillance, Health and Nutrition Survey, and the Hong Kong/Macao Vital Registry, alongside relevant published literature. The reliability and representativeness of this data have been confirmed through methodological studies. The relevant ICD-10 codes for ILD and PS include D86.0–86.2, D86.9, J84.0, J84.1, J84.8, and J84.9. Although PS is classified as a form of ILD, the GBD database distinguishes PS as a separate category alongside ILD. On the other hand, while pneumoconiosis is also categorized as an ILD, they are not included within the scope of this study as per GBD data parameters. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

JPR model

The JPR model, initially developed by Kim et al., is designed to conduct segmented regression based on disease distribution over time (13). This model divides the study period into distinct intervals through connection points, allowing for a detailed examination of temporal trends in disease incidence and mortality. Its core strength lies in its ability to detect statistically significant inflection points—time periods where the trend in prevalence or mortality rate changes direction or magnitude. This is particularly valuable in public health research, as it can highlight the potential impact of health policies, clinical guidelines, environmental exposures, or technological advancements (11). Model measurements are expressed as annual percentage change (APC) and average annual percentage change (AAPC). APC assesses the trend within independent intervals, while AAPC estimates the average trend across the entire study period. The log linear model equation is: E[y|x]=e(β0+β1x+δ1(x−τ1)...+δk(x−τk)+), y is the prevalence or mortality, x is the year, β₁ is the regression coefficient, k is the number of connection points, τ_k is the unknown connection point, a⁺=a when a>0, and 0 otherwise. The APC is calculated as APC=[yx+1−yxyx]×100%, and the AAPC is calculated as follows: AAPC=(e∑iβi∑wi−1)×100%. A downward trend is indicated by APC <0, while an upward trend is indicated by APC >0. If APC equals AAPC, the trend is considered consistent without turning points.

APC model

The APC model is a statistical framework used to analyze the respective impacts of age, time period, and birth cohort on health outcomes (14). This granularity is essential in understanding underlying epidemiological mechanisms and targeting interventions to specific age groups or cohorts. The “age effect” considers variations in risk across different age groups, the “period effect” examines temporal factors that influence all age groups, and the “cohort effect” investigates differences in risk among individuals born in the same time period. The log-linear regression model is expressed as log(Yi)=μ+α*agei+β*periodi+γ*cohorti+ε, where Y_i is the prevalence or mortality of ILD and PS. The α, β and γ represent the age, period, and cohort coefficients, respectively. The µ denotes the intercept of the model, and ε is the residuals of the model. Previous challenges in APC analysis stemmed from inherent collinearities among age, period, and cohort variables. However, the introduction of Yang and Land’s (15) Hierarchical APC-Cross-Classified Random Effects Models (HAPC-CCREM) have addressed these complexities by allowing for a more flexible relationship between the components. In this model, age is treated as a fixed effect, while period and cohort are considered random effects, estimated using the intrinsic estimator (IE).

BAPC analysis

The BAPC model provides a refined analytical approach by employing integrated nested Laplace approximations, which improve upon traditional APC models in terms of coverage and accuracy. It is particularly advantageous for projecting age-standardized rates while accounting for uncertainty in parameter estimation. This Bayesian approach smooths the prior effects of age, period, and cohort through second-order random walks, assuming that adjacent periods exhibit similar impacts. Instead of relying on Markov chain Monte Carlo sampling, the BAPC model approximates the marginal posterior distribution with integrated nested Laplace approximation, alleviating issues related to mixing and convergence (8).

Together, these models offer a complementary suite of insights. The Joinpoint model pinpoints historical trend shifts, the APC model explains those shifts in terms of age, period, and cohort effects, and the BAPC model extends these findings into the future with improved predictive validity.

Statistical analysis

In GBD 2021, ILD and PS mortality was defined as the number of deaths per 100,000 population, while prevalence was calculated as the percentage of patients within the total population. Age-standardized mortality and prevalence rates were computed using the global population as a reference. To account for the multicollinearity inherent in age, period, and cohort variables, the IE method was applied, allowing for the calculation of relative coefficients. These coefficients were then exponentiated to derive the relative risk (RR) of mortality and prevalence for different age, period, and cohort groups. Joinpoint analysis was performed using Joinpoint Regression software version 4.9. APC models were developed using Stata 14.0, while Bayesian analyses were conducted with R version 4.2.1, employing packages such as “ggplot2”, “BAPC”, and “INLA”. Statistical significance was set at a two-tailed P value of <0.05.

Results

Prevalence and mortality of ILD and PS in China

In 2021, approximately 628,383 cases (95% UI: 534,993.12–737,822.25) of ILD and PS were reported in China, along with an estimated 7,674 deaths (95% UI: 4,637.26–10,371.39) attributed to these conditions. The trends in prevalence and mortality from 1992 to 2021 are depicted in Figure 1 and Table S1. Mortality due to ILD and PS increased from 0.26 per 100,000 people in 1992 to 0.54 per 100,000 in 2021. The age-standardized prevalence rose by 8%, while the overall mortality rate also increased, despite a 2.5% decrease in the ASMR. Males consistently exhibited higher death rates than females.

Figure 1 Analysis of prevalence and mortality of ILD and PS in China. (A1) All age prevalence of ILD and PS in China. (A2) Age standardized prevalence of ILD and PS in China. (B1) All age mortality of ILD and PS in China. (B2) Age standardized mortality of ILD and PS in China. ILD, interstitial lung disease; PS, pulmonary sarcoidosis.

Joinpoint analysis of ILD and PS prevalence and mortality

Joinpoint analysis revealed distinct trends in ILD and PS prevalence and mortality (Figure 2A,2B). Since 1992, there have been significant increases in prevalence during two intervals: from 2005 to 2010 and from 2019 to 2021, with APC of 5.56% and 2.31%, respectively. The AAPC for prevalence over the entire period was 2.41% (95% UI: 2.31–2.50%). Mortality trends similarly demonstrated significant increases, particularly during 1999–2006, 2006–2009, and 2009–2012, with APCs of 2.94%, 6.65%, and 3.63%, respectively. The AAPC for mortality across the entire period was 2.56% (95% CI: 2.30–2.82%).

Figure 2 Joinpoint analysis of prevalence (A) and mortality (B) in China’s ILD and PS. ILD, interstitial lung disease; PS, pulmonary sarcoidosis.

APC analysis of ILD and PS incidence and mortality in China

The Age, period and cohort effects of ILD & PS prevalence and mortality rate are depicted in Table S2 and Figures 3,4. Figure 3A presents the APC model for the prevalence of ILD and PS in China. When focusing on the age effect, the prevalence of both diseases gradually increases between ages 45 and 75 years, followed by a decline after age 75 years. The period effect indicates that the prevalence of ILD and PS has increased over time, whereas mortality rates across age groups show relatively minor fluctuations. The cohort effect reveals that individuals born around 1932 exhibit the highest risk of disease, with a progressive decline in prevalence among more recent birth cohorts, suggesting a reduced risk among younger generations. Figure 3B displays the APC model for the mortality of ILD and PS in China. The age effect shows a clear upward trend, with mortality rates increasing steadily with age. The period effect reflects a slow but consistent rise in mortality over time. Meanwhile, the cohort effect demonstrates a gradual decline in mortality risk across successive birth cohorts.

Figure 3 The APC model of prevalence (A) and mortality (B) of China ILD & PS in China. The blue and red area indicates the 95% CI of the predicted value. APC, age-period-cohort; CI, confidence interval; ILD, interstitial lung disease; PS, pulmonary sarcoidosis.

Figure 4 The effect of age, period, and cohort on the prevalence and mortality of ILD and PS in China. (A1) Age-specific prevalence of ILD and PS across different time periods. (A2) Age-specific prevalence of ILD and PS across different cohorts. (A3) Cohort-specific prevalence of ILD and PS across different time periods. (B1) Age-specific mortality of ILD and PS across different time periods. (B2) Age-specific mortality of ILD and PS across different cohorts. (B3) Cohort-specific mortality of ILD and PS across different time periods. ILD, interstitial lung disease; PS, pulmonary sarcoidosis.

Figure 4 illustrates the effects of age, period, and cohort on the prevalence and mortality of ILD and PS in China. In Figure 4A, the age effect emerges as a key determinant of ILD and PS prevalence after adjusting for period and cohort effects (Figure 4, A1). From 2012 to 2021, the prevalence of both ILD and PS increased progressively with age, peaking around the age of 79 years. This trend highlights the elevated risk of these diseases among older populations. Additionally, a clear cohort effect is evident (Figure 4, A3), indicating significant differences in prevalence across birth cohorts. In Figure 4B, a similar pattern is observed for mortality. The age effect plays a dominant role in shaping ILD and PS mortality trends (Figure 4, B2). Across all time periods analyzed, mortality rates steadily increased with age.

Predictive analysis of ILD and PS in China

Before 2021, the age-standardized prevalence curves for ILD and PS indicate a steady upward trend and age-standardized mortality curve fluctuates, as seen in Figure 5. Between 2021 and 2030, the BAPC model forecasts the age-standardized prevalence trend to continue steadily, while the age-standardized mortality curve will display a steady decline. These trends are expected to be consistent for both males and females. By 2030, the model predicts an age-standardized prevalence of 31.78 cases per 100,000 for men and 24.26 cases per 100,000 for women. The predicted ASMRs for men and women are 0.51 and 0.25 cases per 100,000, respectively. Additionally, the forecast also indicates a continued increase in the absolute number of prevalent cases and deaths from 2021 to 2030, with males accounting for a larger share of both cases and fatalities.

Figure 5 Projections of the number of prevalent cases, prevalence rate (A), number of deaths, and mortality rate (B) of ILD and PS in China based on the BAPC model, 1992–2030. ASR, age-standardized rate; BAPC, Bayesian age-period-cohort; ILD, interstitial lung disease; PS, pulmonary sarcoidosis.

Discussion

In 2021, China reported approximately 628,383 cases of ILD and PS and 7,674 deaths attributed to these conditions. The prevalence of ILD and PS rose from 22.17 per 100,000 in 1992 to 44.17 per 100,000 in 2021. Additionally, the mortality rate grew from 0.26 to 0.54 per 100,000 during the same period. The prevalence was higher than the Indian data (48.3/100,000) but lower than the data reported in France (30.2/100,000) (16,17). ILD and PS places a considerable burden on both patients and the healthcare system. It is frequently associated with serious complications such as pulmonary hypertension and secondary pneumothorax. The average medical cost per patient exceeds 3,700 Euros (18). Our findings indicate that both incidence and mortality rates for ILD and PS in China have increased during this period, with growth rates outpacing those observed globally (4).

China’s aging population has contributed significantly to the rising burden of ILD and PS. In 2020, the elderly population (aged 60 years and above) reached 231 million, representing 16.7% of the total population. Notably, the elderly demographic has expanded by 2.4 times since 1992, with projections suggesting continued growth, and could peak in 2025 (19,20). The APC model reveals that the risk of ILD and PS increases significantly among individuals aged 65 to 75 years, peaking at 75 years, which is 5 years earlier than the global average (21). With China’s aging population continuing to grow, both the prevalence and mortality of ILD and PS are expected to rise further, and the elevated age-standardized prevalence was also able to demonstrate this correlation. However, the risk of prevalence appears to decline after age 75 years, potentially due to the high comorbidity rates in this age group, which may reduce survival rates. Improvements in diagnostic capabilities and treatments may also explain lower mortality rates among younger generations. However, the risk of illness and mortality begins to rise after the age of 45 years. This age-related increase underscores the importance of monitoring the health of the population and paying attention to the growing disease burden of ILD and PS in middle-aged and younger groups. Public health strategies should aim to address these concerns through early detection and intervention, particularly as ILD and PS is no longer confined to older demographics. The period analysis revealed significant variations in ILD and PS prevalence, with cohort effects indicating that prevalence peaked at age 79 years based on data from 2012–2021 (Figure 4, A1). Previous study has shown that globally, the ASMR due to ILD and PS has increased by an average of 0.97% annually (20). Among respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pneumoconiosis, ILD and PS is the only condition showing increasing age-standardized mortality (22). Although the ASMR of ILD and PS in China decreased by 2.5%, the actual death numbers increased from 0.26 per 100,000 in 1992 to 0.54 per 100,000 in 2021. We speculate that this discrepancy may be linked to diagnostic challenges in elderly patients with preexisting respiratory conditions.

The Joinpoint analysis identified significant increases in ILD and PS prevalence and mortality rates in China post-1992, with notable surges between 2005–2010 and 2019–2021. Factors contributing to these trends include tobacco use, environmental influences, occupational hazards, and the aging population (4,23,24). Occupational hazards, particularly in light of rapid industrialization in China, may play a critical role (25). Additionally, updates in diagnostic criteria by health organizations in 2002 and 2013 have likely improved awareness and detection of ILD and PS, contributing to the observed increases in prevalence. Our results indicate an AAPC for ILD and PS prevalence of 2.41% (95% UI: 2.31–2.50%) from 1992 to 2021, a trend consistent with countries of similar socio-demographic index (SDI). Study suggests that SDI is proportional to the population-standardized AAPC prevalence, underscoring the importance of economic development and health education in mitigating the disease burden (21).

The BAPC model forecasts a potential stabilization in ILD and PS prevalence over the next decade. However, the numbers of cases and deaths are expected to continue rising due to population growth and aging. Coronavirus disease 2019 (COVID-19), which emerged as a global pandemic in 2020, primarily presents with respiratory symptoms such as cough, fever, and shortness of breath. In some patients, severe inflammatory responses—particularly cytokine storms—and repeated injury to the alveolar epithelium can lead to the development of ILD. This condition may become chronic, resulting in post-COVID-19 ILD. As a consequence, the burden of ILD and PS may rise in the future, with potential increases in the numbers of cases and deaths (4). Given the high burden of ILD and PS in China, it is essential to prioritize public health initiatives aimed at early detection and treatment (26-37). To address the growing burden of ILD and PS, public health efforts should prioritize screening, particularly for elderly populations, and gradually expand to include younger cohorts.

While this study provides valuable insights, several limitations must be considered, particularly with respect to the underrepresentation of younger populations (under 15 years) and potential regional disparities in disease classification and reporting. The findings may also reflect regional disparities in ILD and PS causes, with different leading factors reported in North America, Europe, and Asia. In addition, this study relies on GBD data, which standardizes historical records to ensure comparability across decades. Nevertheless, changes in diagnostic guidelines and therapies (e.g., antifibrotics) may affect temporal trends. The GBD corrects for under-diagnosis in early years, but residual bias cannot be excluded. Despite this, our models capture the fundamental drivers of ILD burden—age demographics and environmental exposures—which remain relevant for public health planning. Future studies should integrate clinical data to refine subtype-specific burdens, and focus on enhancing epidemiological data on ILD and PS in developing nations, facilitating a better understanding of global disease burden. Collaborative international efforts, including knowledge sharing and joint research initiatives, will be essential to improving diagnostic accuracy and treatment outcomes across diverse healthcare settings.

Conclusions

This study evaluated the disease burden of ILD and PS in China from 1992 to 2021. Over the past three decades, both prevalence and mortality rates have shown a general increase. Although a decline in prevalence is projected for 2021–2030, the absolute number of cases and deaths is expected to rise. Age remains a significant risk factor. It is essential to develop and implement effective strategies for the prevention and control of ILD and PS.

Acknowledgments

Special thanks to all the nurses working in public health centers and thoracic surgery for their dedication and hard work.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-651/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-651/prf

Funding: This work was supported by Guangdong Zhong Nanshan Foundation, Zhong Nanshan Fund Project (No. ZNSXS-20220067).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-651/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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