Epidemiological burden and mortality of idiopathic pulmonary fibrosis in Brazil: historical trends and future outlook

Introduction

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic, and progressive fibrosing interstitial lung disease of unknown etiology, characterized by irreversible decline in lung function and poor prognosis. In the European Union, a rare disease is defined as affecting fewer than 5 individuals per 10,000 population (1), and IPF consistently meets this threshold worldwide.

Despite advances in antifibrotic therapy, IPF remains associated with high mortality. Median survival is estimated at 3 to 3.5 years post-diagnosis, with 5-year survival rates below 50% in most cohorts (2,3). Large population-based studies report significantly elevated all-cause mortality among individuals with IPF, with standardized mortality ratios approaching 4.7 and age-standardized mortality rates ranging from 3.1 to 6.3 per 100,000 person-years, especially among older adults and men (4-6). Even modest declines in pulmonary function are linked to substantially worse outcomes; a ≥5% absolute reduction in forced vital capacity (FVC) doubles the risk of death or lung transplantation, while a ≥10% decline increases the hazard ratio to 2.7. Reductions exceeding 15% are associated with a sixfold increase in mortality risk (6).

Globally, IPF mortality trends exhibit notable geographic variation. In Europe, age-adjusted mortality increased by 1.7% annually between 2013 and 2018, with significant inter-country heterogeneity (7). In contrast, the United States (U.S.) showed a modest decline in IPF mortality from 2004 to 2017, particularly among women and individuals under age 85 years (8). In Australia, IPF-related deaths increased steadily over the past two decades, though the trend may be stabilizing (9). Occupational exposures are increasingly recognized as important contributors; in the U.S., approximately 21% of IPF deaths are attributable to workplace-related factors, with elevated risk among certain industries (10).

Antifibrotic agents such as pirfenidone and nintedanib can extend survival by 1 to 2.5 years by slowing FVC decline, though most patients continue to experience disease progression (2). In this context, understanding national mortality trends remains essential for early diagnosis, care planning, and informed health policy.

However, population-level data on IPF remain limited in low- and middle-income countries (LMICs), including Brazil. IPF is not a notifiable condition, and reliance on International Classification of Diseases (ICD-10) code J84.1—used to classify various fibrosing interstitial lung diseases—may lead to underestimation. To address this gap, we analyzed national mortality data in Brazil from 1996 to 2023 to evaluate long-term trends in the frequency, relative risk, and odds of IPF-related death. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1493/rc).

Methods

We conducted a retrospective, population-based time-trend (ecological) study to assess trends in IPF mortality in Brazil over a 28-year period, from January 1, 1996 to December 31, 2023. Mortality data were obtained from the official national mortality information system [Sistema de Informações sobre Mortalidade (SIM)], available through the DATASUS platform managed by the Brazilian Ministry of Health (11). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This investigation was designed as an observational, cross-sectional, population-based study using retrospective national mortality data.

Annual records were retrieved using the ICD-10 code J84.1, which includes IPF and related fibrosing interstitial lung diseases, consistent with international epidemiological practices (12). It is important to note that ICD-10 code J84.1, used in this study to identify deaths related to IPF, also includes other fibrosing interstitial lung diseases, such as chronic hypersensitivity pneumonitis and connective tissue diseases-associated interstitial lung disease (CTD-ILD). Although this code is widely used in international epidemiological studies due to its relative specificity, it may lead to either overestimation or underestimation of the true IPF mortality burden, depending on local diagnostic and coding practices. This limitation reflects the lack of more granular classification codes in the current system and underscores the need to establish national clinical registries for IPF, based on standardized diagnostic criteria and, whenever possible, radiologic or histopathologic confirmation.

Population estimates, including stratification by age and sex for each calendar year, were obtained from census projections published by the Brazilian Institute of Geography and Statistics (IBGE) (13).

Statistical analysis

We described the absolute number of IPF-related deaths per year and calculated annual mortality rates per 10,000 inhabitants. The proportion of IPF deaths relative to total annual deaths was used to estimate relative risk. Odds ratios (ORs) were calculated to compare each study year to the baseline year [1996], both overall and stratified by sex, in order to identify potential gender-based differences.

To explore potential demographic disparities in IPF-related mortality, we also performed stratified descriptive analyses and comparative statistical tests to assess associations between mortality and sex, ethnicity, and age. Chi-squared tests were applied to evaluate the statistical significance of observed differences in mortality distribution across demographic groups. These analyses aimed to provide a more granular understanding of the demographic profile of IPF mortality in Brazil and to identify subpopulations that may be disproportionately affected. Descriptive statistics and mortality rate calculations were performed using Microsoft Excel^® (Microsoft Corporation, Redmond, WA, USA). Statistical analyses, including OR estimations and confidence intervals, were conducted using R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria). Rate standardizations accounted for population growth over the study period.

As this study used publicly available, anonymized secondary data, no ethical approval or informed consent was required, in accordance with national research regulations.

Results

Between 1996 and 2023, a total of 61,518 deaths were attributed to IPF in Brazil. The annual number of deaths ranged from 979 in 1997 to a peak of 3,778 in 2023, showing year-to-year variability but a clear long-term upward trend (11) (Table 1 and Figure 1). Projections derived from linear extrapolation of observed age-specific mortality rates indicate that the annual deaths of IPF-related deaths in Brazil will continue to rise beyond 2023. Using a linear regression model fitted to observed age-specific mortality rates, projections indicate that the annual number of IPF-related deaths in Brazil will continue to rise beyond 2023. The total is expected to increase from approximately 3,600 deaths in 2024 to over 4,000 deaths by 2028, representing a growth of about 12% compared to 2023. These projections highlight a sustained upward trajectory in IPF mortality and reinforce its growing contribution to the national burden of respiratory disease (Figure 1, Table S1).

Figure 1 Temporal trend of IPF-related mortality in Brazil from 1996 to 2023. Crude mortality rates are expressed as deaths per 10,000 inhabitants. The graph demonstrates a consistent upward trend over the study period, with notable acceleration after 2010. Observed crude mortality rates are shown as a solid black line with markers. Segmented regression analysis demonstrates a steeper increase from 1996–2011 (black dashed line) and a more gradual rise from 2012–2023 (black dotted line). A linear projection model suggests a continued increase from 2024 to 2028 (black dash-dot line). Statistical method: linear regression models stratified by period (1996–2011, 2012–2023) and extrapolated for 2024–2028. Source: DATASUS/SIM (11). IPF, idiopathic pulmonary fibrosis.

When adjusted for population size, the mortality-based prevalence of IPF increased from 0.63 deaths per 10,000 inhabitants in 1996 to 0.74 in 2023. Although the trend was not strictly linear, with periods of decline in the late 1990s and mid-2000s, a more consistent rise has been observed over the past decade. From 1996 to 2023, IPF mortality grew at an average annual rate of 5.03%, surpassing the growth observed for all respiratory deaths (2.54%) and all-cause mortality (1.87%) over the same period (11,12).

In relative terms, IPF accounted for approximately 0.063% of all deaths in 1996, increasing to 0.075% in 2023. Similarly, the share of IPF among all respiratory-related deaths rose by 1.07 percentage points over the study period {Figure 2, relative risk of dying from IPF vs. total mortality [1996–2023]}.

Figure 2 Relative risk of dying from IPF compared to all-cause mortality in Brazil, 1996–2023. The figure shows the proportion of IPF-related deaths relative to total annual deaths. The steady increase highlights IPF’s growing contribution to overall mortality, despite its classification as a rare disease. Source: DATASUS/SIM (11); IBGE (13). IPF, idiopathic pulmonary fibrosis.

Stratified analyses revealed demographic patterns. By sex, the distribution of IPF-related deaths was nearly balanced: 50.3% occurred among females and 49.7% among males. After age adjustment using the 2023 Brazilian life table as the standard population, the overall IPF mortality rate was 3,906 per 100,000 inhabitants. Stratified by sex, the age-adjusted mortality was 1,965 per 100,000 in males and 1,941 per 100,000 in females. Over the 28-year period, a total of 30,593 IPF-related deaths occurred among males and 31,481 among females, reflecting a nearly equal distribution. The Chi-squared test showed no statistically significant difference between sexes (χ²=1.78; P=0.18). Ethnicity-based analysis revealed a disproportionate distribution of IPF-related deaths: 67.4% occurred among White individuals, 23.7% among Afro-Brazilians (combining Black and Brown categories), 1.3% among Asians, 0.1% among Indigenous individuals, and 7.5% were classified as unknown or unreported. The Chi-squared test showed a highly significant difference across ethnic groups (χ²=123.165; P≤0.001).

When accounting for the ethnic composition of the Brazilian population (IBGE, 2022), we observed a disproportionate distribution of IPF-related deaths. In 2023, White individuals represented 67.0% of IPF deaths but only 50.3% of the population, corresponding to a 33% relative excess. Asian individuals also showed an overrepresentation (1.5% of deaths vs. 0.6% of the population; ~2.5-fold higher than expected). In contrast, Afro-Brazilian groups (Black and Brown) accounted for 29.9% of IPF deaths despite representing 47.1% of the population, while Indigenous individuals were markedly underrepresented (0.1% of deaths vs. 0.4% of the population). The Chi-squared test confirmed that the observed distribution of IPF mortality significantly deviated from population expectations (χ²=508.5; P<0.001), supporting the presence of true ethnic disparities (Table S1, all data).

Age distribution showed a concentration of deaths among older adults. Among individuals aged ≥50 years, 10.1% of deaths occurred in the 50–59 group, 20.8% in 60–69, 32.4% in 70–79, and 36.6% among those aged 80 years and above, confirming the known age-related pattern of IPF mortality (2,4,6).

The OR for dying from IPF, compared to the baseline year [1996], increased steadily throughout the study period. From 1996 to 2001, the OR remained near 1.0. By 2005, it had reached approximately 1.3, and by 2012 it exceeded 2.0. In 2023, individuals in Brazil were nearly three times more likely to die from IPF than in 1996 (OR =2.97) (Figure 3). A small fluctuation around 2020 may be attributed to competing mortality causes, including the coronavirus disease 2019 (COVID-19) pandemic (11).

Figure 3 OR of IPF-related mortality in Brazil from 1996 to 2023, using 1996 as the baseline reference year. The OR increased progressively throughout the period, indicating a nearly threefold rise in the likelihood of dying from IPF by 2023 compared to 1996. The red dashed line (OR =1.0) represents the baseline reference. IPF, idiopathic pulmonary fibrosis; OR, odds ratio.

When comparing two time periods, 1996–2011 and 2012–2023, the number of IPF-related deaths increased by 133.3% in the first and by 53.7% in the second.

Estimated prevalence, modeled under survival assumptions (3, 5, 8, and 10 years), also increased over time. In 2023, estimated prevalence ranged from 2.1 to 4.2 per 10,000 inhabitants. Under the 5-year survival model, aligned with international survival averages, approximately 16,707 people were estimated to be living with IPF in Brazil. Incidence remained relatively stable across all scenarios, ranging from 3,095 to 3,341 new cases annually (11,12) (Figure 4). Estimated incidence was 2,923 cases in 2015, 3,742 in 2022, and 3,778 in 2023, indicating relative stability over time. In contrast, prevalence increased steadily, rising from 12,499 cases in 2014 to 17,179 in 2023 under the 5-year survival model, reflecting the accumulation of incident cases over longer survival durations.

Figure 4 Prevalence was estimated using annual mortality data and four different assumptions of average survival time following diagnosis: 3, 5, 8, and 10 years. Longer survival durations yielded proportionally higher prevalence values. In 2023, under the 5-year survival model, aligned with global median survival, IPF prevalence was approximately 0.8 per 10,000 inhabitants. The consistent upward trend across all models reflects both increased disease recognition and population aging. IPF, idiopathic pulmonary fibrosis.

Together, these findings demonstrate a sustained increase in both IPF-related mortality and estimated prevalence in Brazil. The growing burden disproportionately affects older adults and ethnically marginalized groups.

Discussion

This study provides the first nationwide, population-based analysis of IPF mortality trends in Brazil over a 28-year period. Our findings reveal a steady and substantial increase in IPF-related deaths, both in absolute numbers and relative to all-cause and respiratory mortality. These patterns suggest that IPF is becoming a more prominent public health concern in Brazil, mirroring - but in some aspects surpassing, global trends observed in higher-income countries.

In contrast to the United States, where age-adjusted IPF mortality declined modestly between 2004 and 2017 (8), Brazil experienced a consistent increase in both crude and age-standardized mortality. Similarly, while European countries reported an average annual increase of 1.7% between 2013 and 2018 (7), Brazil’s average annual growth in IPF-related deaths exceeded 5%, indicating a sharper rise. These differences may reflect disparities in access to antifibrotic therapy, delays in diagnosis, and broader socioeconomic and environmental risk factors.

The upward trend in mortality may also be partially explained by the evolution of diagnostic practices. Prior to 2011, limited clinical consensus and the lack of standardized criteria likely contributed to both underdiagnosis and misclassification. Following the release of international guidelines by ATS/ERS/JRS/ALAT in 2011 (3), diagnostic accuracy likely improved, resulting in more stable, but still rising, mortality patterns. Our segmented analysis supports this interpretation, showing steeper growth before 2011 and a more gradual increase thereafter.

Demographic analyses revealed patterns consistent with international literature: mortality was highest among older adults, with over two-thirds of deaths occurring in individuals aged 70 years or older (2,4,6). This apparent female predominance may be partially explained by the use of ICD-10 code J84.1, which encompasses not only IPF but also other fibrosing interstitial lung diseases, including CTD-ILDs, conditions more common in women (2,6). However, when adjusted for age, mortality remains higher in males, as also described by Algranti et al. (14). Ethnic disparities were also evident, with a majority of deaths among White individuals, which may reflect both population distribution and inequalities in access to care or diagnostic services.

The rising OR and relative risk of IPF-related death underscore the growing burden of this disease in the context of Brazil’s demographic transition (15). With the proportion of individuals over 60 years expected to exceed 35% by 2070 (13), IPF-related mortality will likely continue to rise unless early diagnosis, public awareness, and equitable access to treatment are improved.

Occupational and environmental exposures may also contribute to the higher-than-expected burden. As shown in the United States, where 21% of IPF deaths were attributed to occupational factors (10), Brazil’s industrial and agricultural sectors may present similar risks, particularly in areas with limited environmental regulation and worker protection (16).

Smoking, a well-established risk factor for IPF, was also considered. In Brazil, smoking prevalence declined sharply from over 30% in the late 1980s to below 10% in 2019 (17), which may have contributed to shaping long-term IPF mortality trends, although its exact influence remains uncertain due to the multifactorial nature of the disease.

Despite the upward trend in mortality, our estimated annual incidence remained relatively stable, between 3,100 and 3,300 new cases per year depending on the survival model. However, prevalence estimates suggest a growing population living with the disease. In 2023, modeled prevalence approached 4.2 per 10,000 under the 10-year survival scenario, nearing the rare disease threshold of 5 per 10,000 (1,18). These findings support the need for improved IPF surveillance, registry development, and resource planning.

Ethnic disparities in IPF mortality observed in this study must be interpreted in light of Brazil’s unique demographic composition. Although most IPF-related deaths occurred among individuals classified as White (67.4%), Brazil is a majority non-White country, with over 55% of the population identifying as Black or Brown according to the 2022 national census (13). This apparent mismatch may reflect inequalities in healthcare access, diagnostic capacity, and disease recognition across racial groups. Moreover, Brazil’s population is one of the most genetically admixed in the world, shaped by centuries of interaction between Indigenous, European, and African ancestries (19,20). Such genetic admixture not only influences disease susceptibility and expression but also complicates the applicability of findings derived from homogenous populations. As shown by recent a study ancestry-specific genetic variants and the uneven geographic distribution of deleterious alleles can impact health outcomes across different Brazilian subgroups (20). These structural and biological factors must be considered when addressing disparities in IPF diagnosis, treatment, and survival. They also underscore the importance of including admixed and underrepresented populations in both clinical and genetic research to ensure more equitable public health interventions.

This study has several limitations. First, the use of ICD-10 code J84.1, while accepted in epidemiological studies, may result in misclassification, as it includes other fibrosing interstitial lung diseases (19). Second, regional disparities in death certification and diagnostic capacity may introduce bias. Third, the absence of individual-level clinical data (e.g., radiologic findings, lung function, comorbidities, or treatment) limits more granular interpretation.

Despite these limitations, the use of official national mortality data over nearly three decades offers strong evidence of a sustained epidemiologic shift. Compared to previous national estimates by Algranti et al. (14) and Baddini-Martinez and Pereira (15), our study adds updated trend data and introduces prevalence modeling, expanding the understanding of disease burden in Brazil.

These findings may likewise be relevant for other LMICs undergoing similar demographic transitions and facing comparable limitations in diagnostic infrastructure and disease surveillance. By highlighting the trajectory of IPF-related mortality in Brazil, this study provides a model for leveraging national health databases to monitor rare diseases in resource-constrained settings. Strengthening data systems, improving coding accuracy, and developing national registries are essential to enable more effective public health planning and equitable access to care in LMICs worldwide.

Conclusions

IPF is an increasingly significant and underrecognized cause of mortality in Brazil. Mortality projections suggest continued growth through 2028, while relatively stable incidence alongside rising prevalence reflects prolonged survival and accumulation of cases. These findings highlight the urgent need for national policies aimed at earlier detection, equitable access to antifibrotic therapies, and the implementation of robust disease surveillance systems. Such measures are essential to mitigate the growing burden of IPF in Brazil and may provide a model for other middle-income countries facing similar demographic and structural challenges.

Acknowledgments

During the preparation of this work, the authors used ChatGPT-assisted technologies solely to enhance the readability and presentation of the English language.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1493/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1493/prf

Funding: This work was supported by the Rio de Janeiro State Research Support Foundation (FAPERJ) (No. E-26/200.311/2023., to R.R. and C.H.d.C.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1493/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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