Nationwide Study of the Epidemiology, Diagnosis, and Treatment of Hypersensitivity Pneumonitis in Korea.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a condition with an uncertain global incidence, and information on its diagnosis and management is limited. This study aimed to address these knowledge gaps. METHODS: This study utilized customized claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea from January 2010, to December 2021. Patients with HP were identified based on the diagnosis code (International Classification of Diseases, 10th Revision, J67) between 2011 and 2020. Incident HP cases were defined as new HP claims, excluding those with claims in the previous year. The study examined various factors such as age, sex, comorbidities, diagnostic methods, and treatment patterns. Additionally, multivariate logistic regression analysis was performed to identify risk factors associated with treatment initiation. RESULTS: A total of 8,678 HP incident cases were confirmed, with age- and sex-adjusted annual incidence rates ranging from 1.14/100,000 in 2020 to 2.16/100,000 in 2012. The mean age of patients with incident HP was 52 years, with a higher incidence observed among males. Additionally, the most common comorbidity was asthma. Bronchoscopy was performed on 16.9% of patients, and 25.4% of patients did not receive treatment within 1 year of diagnosis. Among those who received treatment, prednisone was the most used systemic steroid, and azathioprine was the most commonly used second-line immunosuppressant. Factors associated with treatment initiation included the female sex, having asthma or gastroesophageal reflux disease (GERD), and undergoing bronchoscopy. CONCLUSION: This study provides valuable insights into the incidence, diagnosis, and treatment patterns of HP in South Korea using nationwide medical claims data.

Relative incidence of interstitial lung diseases in Brazil.

OBJECTIVE: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. METHODS: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. RESULTS: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). CONCLUSIONS: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis.

BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.

GDF15 as a potential biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis.

Hypersensitivity Pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) characterized by fibrotic HP (fHP) or non-fibrotic HP (non-fHP). Fibrosis is associated with poor prognosis, emphasizing the need for biomarkers to distinguish fHP from non-fHP. This study aimed to determine the plasma levels of GDF15 in HP patients and assess its association with lung function and phenotype classification. GDF15 levels were quantified by ELISA in HP (n = 64), idiopathic pulmonary fibrosis (n = 54), and healthy control (n = 128) groups. Clinical, demographic, and functional data were obtained from medical records. High-resolution chest CT scans were used to classify HP patients into fHP and non-fHP groups. In addition, receiver operating characteristic analysis was performed to determine the cut-off point, sensitivity, and specificity. Our results revealed significantly elevated GDF15 levels in fHP compared to non-fHP (2539 ± 821 pg/ml versus 1783 ± 801 pg/ml; p = 0.009). The estimated cut-off point for plasma GDF15 levels to distinguish fHP from non-fHP was 2193.4 pg/ml (AUC 0.75). These findings suggest that GDF15 may serve as a valuable biomarker for differentiating between fHP and non-fHP, potentially indicating its involvement in lung fibrosis development in HP.

Vasoreactive pulmonary artery hypertension in non-fibrotic hypersensitive pneumonitis.

Group III pulmonary hypertension (PH) is common in patients with hypersensitivity pneumonitis (HSP). Group I PH and vasoreactivity in HSP have not been reported. We describe a case of an elderly veterinarian woman who presented with progressive shortness of breath and desaturation on exertion. The patient was diagnosed with non-fibrotic HSP after consistent findings on chest CT, transbronchial biopsy and a positive HSP serological panel. The patient relocated her birds, and prednisone was started. Due to persistent symptoms, she underwent a right heart catheterisation, which showed PH with vasoreactivity; subsequently, nifedipine was started. Over a 9-month follow-up, there was an improvement in symptoms and a complete resolution of PH and CT scan changes. Our case highlights the rare possibility of group I PH in HSP. It illustrates the importance of confirming the aetiology of PH and initiating treatment early to resolve symptoms.

Hypersensitivity Pneumonitis: Challenges of a Complex Disease.

Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease caused by chronic inhalation of a wide variety of antigens in susceptible and sensitized individuals, commonly associated with an occupational exposure. An impressive number of inciting antigens causing hypersensitivity pneumonitis have been found to cover a wide range of occupations. As working practices have changed over time, especially in industrialized countries, new names for occupational HP have emerged. This review emphasizes the main diagnostic issues arising from the high variability of clinical presentation and the broad spectrum of causal antigens. Furthermore, it provides an overview of current methods to unveil possible causes of hypersensitivity pneumonitis, highlights HP's current diagnostic and treatment challenges and the remaining areas of uncertainty, and presents prevention strategies.

ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases.

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Japanese clinical practice guide 2022 for hypersensitivity pneumonitis.

Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs.

Effect of warm and humid days on the positivity rate of anti-Trichosporon asahii antibody test for the diagnosis of summer-type hypersensitivity pneumonitis.

BACKGROUND: Summer-type hypersensitivity pneumonitis (SHP) has been reported to occur during warm and humid summer seasons in Japan; however, the effect of weather conditions on SHP remains unknown. Anti-Trichosporon asahii antibody (TaAb) test is highly specific and useful for the diagnosing SHP. Therefore, we aimed to investigate the impact of weather conditions on SHP by examining the relationship between the positivity rate of TaAb and warm and humid days. METHODS: TaAb test data from June 2013 to June 2020 were obtained from major commercial laboratories to determine the number of samples and positivity rate of TaAb by prefecture. Using the Japan Meteorological Agency database, we counted the warm and humid days (maximum temperature ≥25 °C and average humidity ≥80 %) for each prefecture. Negative binomial regression was employed to examine the relationship between the positivity rate of TaAb and the number of warm and humid days per month. RESULTS: A total of 79,211 samples and 7626 positive samples (9.6 %) were identified. We found that the number of warm and humid days, 1 or 2 months prior to testing for TaAb, was associated with the positivity rate of the test. An increase in the positivity rate by 1.6 % and 2.9 % was observed with every 1-day increase in warm and humid days 1 month and 2 months before the test, respectively. CONCLUSIONS: Our TaAb analysis revealed a significant increase in TaAb positivity 1 or 2 months after periods of warm and humid days.

Concurrent features of sarcoidosis and hypersensitivity pneumonitis in two patients exposed to fungal antigens.

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are two distinct clinical entities that share granulomatous inflammation, although each of them has specific clinical, radiologic and pathologic profiles. Coexistence of the two diseases have been described, suggesting, at least in some cases, a common biologic background. CASE PRESENTATION: We describe two patients showing the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis. Case 1: a 51-year old never smoker man had a history of occupational exposure, episodes of acute exacerbations and positive serum precipitins to Penicillium spp suggestive of HP, while the positivity of serum angiotensin converting enzyme (ACE) favored sarcoidosis. Case 2: a 42-year old non-smoker woman with occasional finding of enlarged mediastinal lymph nodes had a history of domestic exposure to molds and positive serum precipitins to Aspergillus spp suggestive of HP. In both cases high resolution computed tomography (HRCT) together with broncoscopy findings allowed to maintain both the diagnoses: HRCT showed both enlarged hilar/mediastinal limph nodes and intersitial lung involvement typical of HP; bronchoalveolar lavage presented marked lymphocytosis and granulomatous nodal lesions were observed at transbronchial needle aspiration. CONCLUSIONS: Sarcoidosis and HP share some clinical findings and the differential diagnosis may be difficult. Our cases suggest that a common trait may be responsible for the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis in the same patient.

Clinical characteristics and outcomes of hypersensitivity pneumonitis in South Korea.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood. OBJECTIVES: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea. DESIGN: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea. METHODS: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines. RESULTS: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort. CONCLUSION: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

Masks of hypersensitivity pneumonitis in children.

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is the most common interstitial lung disease in children, but remains rarely recognized in the pediatric population. Early recognition of triggering factors and a high index of suspicion of HP could lead to timely diagnosis and individualized treatment. This study aimed to present four clinical cases of HP reported between 2012 and 2022 in Lithuania to improve the suspicion of the disease in children.

Moldy Hazelnut Husk and Shell Related Hypersensitivity Pneumonitis: A Possible Novel Occupational Causative Agent.

Hypersensitivity pneumonitis (HP) is a complex immune-mediated interstitial lung disease (ILD) triggered by inhalation exposure to environmental or occupational antigens in genetically susceptible individuals. Novel exposure sources and antigens are frequently identified. However, the causative agent remains unidentified in nearly half of HP cases. Early diagnosis for nonfibrotic-HP and quitting the exposure may prevent the disease progression to fibrotic forms and related complications. Here, we present two cases of HP associated with mold exposure in hazelnut husks, leaves, and shells in hazelnut agriculture.

Serum Specific Antibodies Do Not Seem to Have an Additional Role in the Diagnosis of Hypersensitivity Pneumonitis.

BACKGROUND: We aimed to investigate the contribution of serum IgG testing to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis. METHODS: A single-center, retrospective, cross-sectional study including 63 patients pathologically diagnosed with fibrotic hypersensitivity pneumonitis in line with the guidelines of the American Thoracic Society. Descriptive statistics were presented and Kappa statistic was performed to evaluate the compatibility between panel and the history of exposure. RESULTS: The median age was 63 (22-81) years and 34 (54%) were male. Forty-six patients (73%) had a positive history of exposure. Thirty-nine patients (61.9%) had a positive HP/Avian panel. The most common exposure agent was mold (34.9%), followed by parakeet (31.7%). The antibody detected the most was penicillium chrysogenum lgG (36.5%), followed by aspergillus fumigatus (31.8%). There was no compatibility between HP/Avian panel and history of exposure (kappa coefficient= 0.18, p= 0.14). When the exposure was only assessed based on the history, 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 11 (17.46%) with high confidence and 42 (66.67%) with definite confidence; whereas 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 9 (14.29%) patients with high confidence and 44 (69.84%) patients with definite confidence if exposure was evaluated with history and/or panel. CONCLUSIONS: Serum specific precipitating antibody panel does not seem to provide additional value to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis.

Impact of antigen identification on transplant free survival in interstitial lung disease.

INTRODUCTION: Antigen identification impacts diagnosis as well as prognosis in patients with hypersensitivity pneumonitis. An antigen may also be present in other etiologies of interstitial lung disease, however it is unknown whether identification impacts survival. METHODS: We evaluated a retrospective cohort in order to determine if antigen identification affects transplant free survival in patients with hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features. Only patients with definite or high probability of hypersensitivity pneumonitis by American Thoracic Society guidelines were included in the analysis. RESULTS: Transplant free survival was improved with antigen identification in patients with hypersensitivity pneumonitis but not in patients with idiopathic pulmonary fibrosis, connective tissue disease interstitial lung disease, and interstitial pneumonia with autoimmune features. CONCLUSION: Our study suggests that removal of identified antigen in interstitial lung diseases other than hypersensitivity pneumonitis may not be impactful. Additionally, it further suggests that definitive diagnosis of hypersensitivity pneumonitis with bronchoalveolar lavage and transbronchial biopsy may be beneficial prior to recommending antigen removal.

Diagnostic Utility of Bronchoalveolar Lavage Lymphocytosis in Patients with Interstitial Lung Diseases.

BACKGROUND: Interstitial lung diseases (ILDs) are extremely challenging in terms of diagnosis. Extreme bronchoalveolar lavage (BAL) lymphocytosis is thought to strongly point towards the diagnosis of hypersensitivity pneumonitis (HP). OBJECTIVES: Explore the range of different ILD that can present with BAL lymphocytosis, including cases of pronounced lymphocytosis and its diagnostic utility. METHODS: Patients with ILD that were subjected to BAL were identified retrospectively from a cohort of consecutive patients. RESULTS: BAL lymphocytosis ≥20% was recorded in 106 patients (27%), while pronounced BAL lymphocytosis ≥40% was recorded in 49 patients (12.5%). The most common diagnoses in patients with BAL lymphocytosis ≥20% and ≥40%, were HP (32.1%), connective tissue disease (CTD)-ILD (26.4%), sarcoidosis (16%), and HP (38.8%), CTD-ILD (24.5%), sarcoidosis (14.3%), respectively. CONCLUSIONS: Neither the presence nor the degree of BAL lymphocytosis can point to a specific diagnosis.

Machine learning-based metabolism-related genes signature, single-cell RNA sequencing, and experimental validation in hypersensitivity pneumonitis.

Metabolism is involved in the pathogenesis of hypersensitivity pneumonitis. To identify diagnostic feature biomarkers based on metabolism-related genes (MRGs) and determine the correlation between MRGs and M2 macrophages in patients with hypersensitivity pneumonitis (HP). We retrieved the gene expression matrix from the Gene Expression Omnibus database. The differentially expressed MRGs (DE-MRGs) between healthy control (HC) and patients with HP were identified using the "DESeq2" R package. The "clusterProfiler" R package was used to perform "Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses" on DE-MRGs. We used machine learning algorithms for screening diagnostic feature biomarkers for HP. The "receiver operating characteristic curve" was used to evaluate diagnostic feature biomarkers' discriminating ability. Next, we used the "Cell-type Identification by Estimating Relative Subsets of RNA Transcripts" algorithm to determine the infiltration status of 22 types of immune cells in the HC and HP groups. Single-cell sequencing and qRT-PCR were used to validate the diagnostic feature biomarkers. Furthermore, the status of macrophage polarization in the peripheral blood of patients with HP was determined using flow cytometry. Finally, the correlation between the proportion of M2 macrophages in peripheral blood and the diagnostic biomarker expression profile in HP patients was determined using Spearman analysis. We identified a total of 311 DE-MRGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that DE-MRGs were primarily enriched in processes like steroid hormone biosynthesis, drug metabolism, retinol metabolism, etc. Finally, we identified NPR3, GPX3, and SULF1 as diagnostic feature biomarkers for HP using machine learning algorithms. The bioinformatic results were validated using the experimental results. The CIERSORT algorithm and flow cytometry showed a significant difference in the proportion of M2 macrophages in the HC and HP groups. The expression of SULF1 was positively correlated with the proportion of M2-type macrophages. In addition, a positive correlation was observed between SULF1 expression and M2 macrophage proportion. Finally, we identified NPR3, GPX3, and SULF1 as diagnostic feature biomarkers for HP. Further, a correlation between SULF1 and M2 macrophages was observed, providing a novel perspective for treating patients with HP and future studies.

Idiopathic pulmonary fibrosis in the United States: time to diagnosis and treatment.

OBJECTIVE: Create a timeline of diagnosis and treatment for IPF in the US. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019). EXPOSURE: To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease. MAIN OUTCOMES AND MEASURES: Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival. RESULTS: A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years. CONCLUSIONS AND RELEVANCE: Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

Progressive fibrotic interstitial lung disease.

Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.