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Background: Hypersensitivity pneumonitis (HP) is a complex and heterogenous interstitial lung disease (ILD) that occurs in susceptible individuals due to certain inhaled antigens. Fibrotic-HP is a major underlying disease of progressive pulmonary fibrosis. Therefore, in addition to the radiological features of HP, quantitatively measuring fibrosis is important to evaluate disease severity and progression. The present study aimed to compare three-dimensional computed tomography (3D-CT)-derived lung volumes (LVs) of patients with HP and determine its association with mortality risk. Methods: In this retrospective and multicenter cohort study, 126 patients diagnosed with HP (fibrotic, n = 72 and non-fibrotic, n = 54) with a confidence level higher than moderate were enrolled. Each lobe LV was measured using 3D-CT at the time of diagnosis and standardized using predicted forced vital capacity. The 3D-CT LV was compared with those of 42 controls and 140 patients with idiopathic pulmonary fibrosis (IPF). Results: Compared to patients with fibrotic-HP, the standardized total LV was significantly higher in controls and patients with non-fibrotic-HP and was similar in patients with IPF. Longitudinal analyses demonstrated that approximately half of the patients with fibrotic-HP had an annual decrease in total LV. Decreased total and lower-lobe LVs were associated with shorter survival, and were independently associated with mortality together with ongoing exposure to inciting antigens. A composite model consisting of ongoing exposure to inciting antigens and total or lower-lobe LV successfully classified mortality risk into three groups. Conclusions: Quantitatively measuring standardized LV can help determine disease severity, progression, and mortality risk in patients with fibrotic-HP.

The reversed halo sign was initially reported as a representative computed tomography scan finding of cryptogenic organizing pneumonia. Since then, however, it has been reported in various diseases and is now considered a nonspecific finding. However, there are no cases of humidifier lung with the reversed halo sign. An 82-year-old Japanese male patient presented with moving difficulties 48 days after starting darolutamide treatment for prostate cancer. He was admitted to the hospital due to acute pneumonia, which presented as bilateral extensive nonsegmental ground-glass opacities in the peripheral regions and extensive areas of ground-glass opacity with a circumferential halo of consolidation, with the reversed halo sign on computed tomography scan. After darolutamide discontinuation with the concomitant administration of antibiotics, the patient's pneumonia improved, and he was discharged from the hospital. However, within a few days, he was again admitted to the hospital due to pneumonia. He was found to have been using an ultrasonic humidifier at home and was then diagnosed with humidifier lung based on the bronchoscopy and provocative testing findings. Hence, ultrasonic humidifier lung should be considered as a differential diagnosis in patients presenting with the reversed halo sign, and a detailed medical history must be taken.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

A 29-year-old man presented to Emergency Department with nonspecific symptoms. Through a series of radiological and invasive diagnostic studies we finally reach an unexpected diagnosis of hypersentivity pneumonitis; this is a complex and heterogeneous disease which diagnosis can be challenging as its clinical, radiologic and histopathologic features overlap with those of other interstitial lung diseases (ILDs). Diagnosing an ILD is a dynamic process, and that is the reason why complex cases discussed in a multidisciplinary team may need to be reconsidered in light of evolution of the disease and the results of the performed exams with a flexible approach.

We report a 60-year-old man with humidifier lung showing diffusely distributed centrilobular micronodules and branching opacities on chest computed tomography (CT). Fever and dyspnea occurred 2 months after using an ultrasonic humidifier. KL-6 and SP-D were within normal ranges. Bronchoalveolar lavage showed elevated lymphocytes (53 %) and histological findings of transbronchial lung biopsy demonstrated organizing pneumonia. His condition improved after cessation of the humidifier. A provocation test exhibited a positive response to the humidifier. Humidifier lung should be considered as a differential diagnosis in patients with these CT findings. Detailed clinical, pathological and microbiological examinations are needed to exclude other diseases.

Introduction and Objectives: International guidelines for the diagnosis of Hypersensitivity Pneumonitis (HP) have improved the diagnostic standardization of this heterogeneous interstitial lung disease. Our goal was to determine how the final multidisciplinary discussion confidence level for suspected fibrotic HP (fHP) can be impacted by the application of different guidelines validated in this context., Materials and Methods: Retrospective study including patients submitted to transbronchial lung cryobiopsy (TBLC) with a final multidisciplinary meeting diagnosis of fHP. Both guidelines were applied to all patients in a stepwise fashion and directly compared according to the level of confidence in a fHP diagnosis., Results: A total of 170 patients were diagnosed with fHP after TBLC and subsequent multidisciplinary discussion. Overall, there was a statistically significant change in proportion towards higher confidence diagnostic levels using the CHEST guideline (p < 0.0001). Changes were significant at three different levels: ATS/JRS/ALAT's "fHP not excluded" subgroup significantly upscaled to CHEST's "provisional low-confidence" subgroup (76.2 % increase; p < 0.001) and the proportion of patients in ATS/JRS/ALAT's "low confidence" subgroup significantly upscaled to both CHEST's "provisional high-confidence" (67.4 % increase; p < 0.001) and "definitive fHP" (50 % increase; p < 0.001) subgroups. The alternative application of the CHEST guideline in multidisciplinary discussion would have resulted in 73 less TBLC (42.9 % decrease versus the ATS/JRS/ALAT-oriented decision)., Conclusions: This study suggests a significant increase in definite fHP diagnosis when applying the CHEST versus the ATS/JRS/ALAT guideline, resulting in almost a 43 % decrease in referrals to TBLC when compared with the latter due to a combination of less strict radiological criteria and a more prominent role of BAL., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The radiologic criteria of hypersensitivity pneumonitis (HP) guidelines focus on four HP compatible features (HPCF) in high-resolution computed tomography (HRCT): ground glass opacities, mosaic attenuation, air-trapping, and centrilobular nodules. However, evidence to support these criteria are limited., Methods: Consecutive interstitial lung disease (ILD) patients who underwent HRCT between 2016 and 2021 in three medical centers were included. We assessed the prevalence of HPCF in each ILD and their association with HP diagnosis. We evaluated the impact of HPCF amount for HP diagnosis and the performance of the radiologic criteria by the ATS/JRS/ALAT and CHEST HP guidelines., Results: 436 patients with ILD were included (mean age 66, 48 % females), of them, 56 (13 %) with HP. All four HPCF were more prevalent in HP than in non-HP ILD (p < 0.001 for all). In multivariate analysis, air-trapping was the strongest independent predictor (AOR 4.1, 95 % CI 2-8.4, p < 0.001). Centrilobular nodules were present almost exclusively in HP and smoking-related ILD. The amount of HPCF in HRCT had an excellent predictive ability for HP diagnosis (receiver operating characteristic AUC 0.85, 95 % CI 0.80-0.90). The radiologic criteria of both guidelines had high specificity for "typical HP" and high sensitivity for "compatible with HP", although with low positive predictive values. Our findings remained robust even when including only patients that had a diagnostic biopsy., Conclusion: The presence and amount of HPCF in HRCT predicted HP diagnosis in real-life settings. While current HP radiologic criteria demonstrated good diagnostic performance, our findings highlight areas for future improvement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Avraham Unterman reports a relationship with Boehringer Ingelheim Ltd that includes: funding grants. Avraham Unterman reports a relationship with RemedyCell that includes: consulting or advisory. Avraham Unterman reports a relationship with Augmanity Nano Ltd that includes: consulting or advisory. Avraham Unterman reports a relationship with 1E Therapeutics that includes: consulting or advisory. Yochai Adir reports a relationship with Teva Health that includes: consulting or advisory. Yochai Adir reports a relationship with GSK that includes: consulting or advisory and funding grants. Yochai Adir reports a relationship with AstraZeneca that includes: consulting or advisory and funding grants. Yochai Adir reports a relationship with Sanofi that includes: consulting or advisory. Yochai Adir reports a relationship with BI that includes: consulting or advisory. Yochai Adir reports a relationship with Kamada Ltd that includes: consulting or advisory., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fungal contamination is omnipresent, and inhalation of fungi-contaminated organic dust leads to hypersensitivity pneumonitis (HP), in which neutrophils played a pivotal role. Existing studies have suggested that cell homeostasis is crucial for the pathogenesis of the inflammatory disease. Although HMGB1 has been shown to contribute to suppressing HP, there is a lack of studies on its mechanisms, especially the regulation of neutrophil homeostasis. This study aims to investigate how HMGB1 regulates neutrophil function by affecting neutrophil homeostasis, and then affects lung inflammation induced by β-glucan, the exposure marker of fungi. Our results showed that deficient HMGB1 led to neutrophil death by disrupting the balance between autophagy and pyroptosis after β-glucan treatment. And HMGB1 deficiency exacerbated the β-glucan-induced lung inflammation and neutrophil dysfunction both in vivo and in vitro. Furthermore, HMGB1 contributed to remodeling neutrophil function by restricting autophagy and aggravating pyroptosis β-glucan exposure. Our funding suggested that HMGB1 deficiency could break the balance between autophagy and pyroptosis towards pyroptosis to cause neutrophil dysfunction during the exacerbated inflammatory response, which provides insights into the pathogenesis of HP and the potential biological targets for its treatment. Data Availability: The datasets used during the current study are available from the corresponding author on reasonable request

Measurement of the levels of serum immunoglobulin A antibody against glycopeptidolipid (GPL) core antigen, a cell surface antigen found in Mycobacterium avium complex (MAC), has been reported to be useful in the diagnosis and management of pulmonary MAC infection. However, evidence on its utility in hypersensitivity pneumonitis (HP) associated with MAC (i.e., “hot-tub lung”) is limited. We herein report a case of HP associated with MAC in which the GPL core antibody levels were serially measured from diagnosis to treatment and thereafter. A 61-year-old man was suspected to have non-fibrotic HP based on the clinical course, laboratory findings, imaging pattern, bronchoalveolar lavage (BAL) lymphocytosis, and histopathological findings. Based on the history of whirlpool bath use, inhalation of aerosolized MAC was suspected as the cause of HP. The GPL core antibody level, measured using an enzyme-linked immunosorbent assay kit, was elevated, suggesting an immunological sensitization to MAC. A provocation test using the patient's whirlpool bath was positive. An identical MAC strain was isolated from the BAL fluid and bathtub. Accordingly, the patient was diagnosed with HP caused by the inhalation of aerosolized MAC from the whirlpool bath. The patient recovered after steroid treatment and discontinuation of the whirlpool bath. The GPL core antibody levels decreased with disease improvement. In conclusion, GPL core antibody levels could be elevated in HP associated with MAC and decrease with disease improvement. Thus, measurement of the GPL core antibody level may be useful for the diagnosis and management of HP associated with MAC.

A 68-year-old man exhibited fever and cough three weeks prior to hospital admission after three months of ultrasonic humidifier usage. Chest computed tomography showed bilateral ground-glass opacities, lymphocyte levels in the bronchoalveolar lavage fluid were elevated (60.8%), and the histological examination of a transbronchial lung biopsy showed lymphocytic alveolitis. He gradually improved without medication after he stopped using the humidifier. Accordingly, humidifier lung was the diagnosis. Humidifier water and vapor collected from the patient's humidifier were investigated. Humidifier vapor was obtained by collecting the condensed moisture. Laboratory examinations exhibited gram-negative rods and a high concentration of endotoxin and (1 → 3)-β-D-glucan in both vapor and water. The serum-precipitating antibodies showed a stronger reaction against humidifier vapor than against humidifier water. 16S rRNA metagenomic analysis revealed a high percentage of sequences of Spirosoma lacussanchae and Sphingomonas spp. in both the humidifier vapor and water. The percentages of sequence reads were lower in humidifier vapor than in water; conversely, sequences of Pseudomonas spp. and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were more concentrated in the humidifier vapor than in humidifier water. Although the reason for the different bacterial ratios between humidifier vapor and water is uncertain, the bacteria that were more concentrated in humidifier vapor than in humidifier water might have been the causative antigen underlying the humidifier lung diagnosis. This is the first report to indicate the presence of causative antigens in humidifier vapor.

We report the case of a 71-year-old male with essential thrombosis who presented with ground-glass lung opacity with a mosaic pattern on computed tomography, which resolved spontaneously with hospitalization. This was confused with a case of hypersensitivity pneumonitis (HP), which later turned out to be a drug-induced lung disease caused by surreptitiously administered minoxidil. This case emphasizes the importance of obtaining a correct medication history to make an accurate diagnosis, and this is the first report of minoxidil causing HP-like pulmonary illness.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare and poorly understood pathology. In this case report we present a 51-year-old male that presented with neurological deficits with recent hypersensitivity pneumonitis. Imaging studies showed multiple punctate enhancing lesions involving the brainstem. After initiation of corticosteroids his symptoms improved, with a decrease in size of his lesions 6-months after his initial presentation. Due to its misdiagnosis, we propose the use of diagnostic criteria, described on this case report, for prompt treatment to avoid neurological sequelae.

Background: Bird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research. Methods: We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients. Results: The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85–91% and 73–80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48–61% and 73–80%, respectively. Conclusions: Measurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Respiratory involvement of COVID-19 infection, with presentations ranging from a mild flu-like illness to potentially lethal acute respiratory distress syndrome, is the main clinical manifestation in adults. Chest imaging shows a pictorial fashion of images due to the severity and stage of the disease, starting from focal nodular or mass-like opacities with air bronchogram to areas of ground glass consolidation or whited out lung. However, during the COVID-19 pandemic, CT findings could yield confounding reporting in the case of cancer patients previously treated with thoracic radiotherapy (tRT) due to atypical radiation pneumonitis occurring outside the radiation ports. Hypersensitivity pneumonitis and radiation-induced bronchiolitis obliterans organizing pneumonitis (RT-BOOP) are accounted for in this report.

Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative allergens. These are socioeconomically important diseases that can lead to work interruptions for patients and potentially job loss. We published the first guideline for managing occupational allergic diseases in Japan. The original document was published in Japanese in 2013, and the following year (2014) it was published in English. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis, occupational anaphylaxis shock, and the legal aspects of these diseases. Providing general doctors with the knowledge to make evidence-based diagnoses and to understand the occupational allergic disease treatment policies, was a breakthrough in allergic disease treatment.Due to the discovery of new occupational allergens and the accumulation of additional evidence, we published a revised version of our original article in 2016, and it was published in English in 2017. In addition to including new knowledge of allergens and evidence, the 2016 revision contains a “Flowchart to Diagnosis” for the convenience of general doctors.We report the essence of the revised guidelines in this paper.

Background: The importance of multidisciplinary discussion (MDD) for diagnosing interstitial lung disease (ILD) is emphasized by several international guidelines. While initial diagnoses are often provisional and require periodic re-evaluation, there is a lack of literature regarding the role of follow-up MDD in clinical practice., Methods: From September 2020 to January 2022, patients underwent an initial MDD (MDD1) based on clinical, radiological, and pathological evaluations. Each diagnosis was assigned a confidence level. One year later, a second MDD (MDD2) was conducted for re-evaluation, based on subsequent clinical and radiological information. Changes in diagnosis and confidence levels between MDD1 and MDD2 were assessed., Results: Among 52 patients enrolled in both MDDs, the diagnosis for 13 (25%) was revised at MDD2. Of these, 10 patients were initially diagnosed with unclassifiable ILD, and 3 received a low confidence diagnosis of either idiopathic pulmonary fibrosis or idiopathic nonspecific interstitial pneumonia. The most common diagnostic revision was due to the deterioration after antigen exposure or improvement after antigen avoidance, which resulted in a revised diagnosis of HP at MDD2., Conclusions: Our findings underscore the importance of periodic reassessment of MDD to improve the accuracy of ILD diagnosis. This study highlights the significance of longitudinal clinical and radiological evaluation for diagnostic revision, even in situations when rebiopsy is not feasible., Competing Interests: Declaration of competing interest Y.Iijima reports grants from Japan Society for the Promotion of Science. H. Furusawa reports grants from Japan Society for the Promotion of Science outside the submitted work. T.Okamoto reports endowment from Nippon Boehringer Ingelheim Co., Ltd. Y. Miyazaki reports grants from Nippon Boehringer Ingelheim Co., Ltd. and Chugai Pharmaceutical Co., Ltd., and personal fees from Nippon Boehringer Ingelheim Co., Ltd. and AstraZeneca K.K., outside the submitted work. The remaining authors have no disclosures., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A 52-year-old woman presented with repeating episodes of pneumonia which spontaneously resolved after hospitalization. Hypersensitivity pneumonitis was suspected, but the causative antigen was not determined whether the parakeets she kept or the humidifier she owned was causative exposure. To identify which exposure is culprit, individual provocation test to a responsible environment was sequentially conducted. First, a home-returning provocation test to the parakeet was negative. Contrarily, the humidifier provocation test to her own humidifier was positive for symptoms, radiological changes, and inflammatory responses in blood test. Finally, she was diagnosed as having humidifier lung. When several antigens are suspected to be the causative agents for hypersensitivity pneumonitis, a step-by-step provocation tests is useful.

A 50-year-old man was diagnosed with hypersensitivity pneumonitis caused by the environment of his bar owing to worsening symptoms, laboratory test results, and computed tomography images after an environmental inhalation challenge test. His hypersensitivity pneumonitis exacerbated despite receiving prednisolone 20 mg/day. The patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor for myelodysplastic syndrome. No exacerbation of hypersensitivity pneumonitis was observed after HSCT. An environmental inhalation challenge test involving exposure to his bar confirmed the remission of hypersensitivity pneumonitis after HSCT. This case demonstrates that hypersensitivity pneumonitis can be remitted by HSCT., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Hypersensitivity pneumonitis has historically been treated with immunosuppression, but recently nintedanib was approved for the treatment of progressive fibrotic HP. One limitation of INBUILD is that the only immunosuppression (IS) permitted at the time of enrollment was glucocorticoids at a dose of less than 20mg per day, so the additive effect of antifibrotic (AF) therapy to IS in HP remains unclear. We present 5 cases of patients with HP for whom AF therapy was added to IS. Trends observed in the cohort include reduced decline in FVC, oxygen requirement, and symptoms in the year after adding AF to IS in 4 of the 5 patients. All 5 patients (100%) in our series demonstrated progression in the year prior to initiation of antifibrotic based on criteria outlined in the INBUILD trial, but only 1 of 5 (20%) progressed in the year after AF. There was a significant decrease in the rate of relative decline in % predicted FVC in the 12 months after initiation of antifibrotic compared to the 12 months prior to antifibrotic (0.4% ±7.6 vs −17.5% ±7.6, p = 0.0495). Compared to the 12 months prior to antifibrotic therapy, fewer patients met criteria for progression in the 12 months after initiating antifibrotic therapy (p = 0.048). Similarly, fewer patients met criteria for progression in the 6 months after initiating antifibrotic therapy compared to the 6 months prior (p = 0.048). A larger study with control groups on IS alone and AF alone is needed to confirm the role of AF therapy in combination with IS in patients with HP.

Novel therapies have recently emerged for various diseases, and the management of drug-related pneumonitis (DRP) has become increasingly important. In particular, the hypersensitivity pneumonitis (HP) pattern of DRP has been increasingly recognized due to development of new therapeutic strategies, such as immunotherapy. However, literature describing detailed clinical cases is still lacking.Herein, we report three cases of DRP with typical HP radiographic pattern. These patients were treated with different drugs, namely nano albumin-bound (nab)-paclitaxel, everolimus, or nivolumab, but had common clinical features, including a good prognosis.

Abstract For years occupational allergies have been among the most frequently recorded occupational diseases, and both the skin as well as the respiratory tract may be affected. An estimated 9 to 15% of adult asthma is (partially) caused by work-related exposure. Gender-specific differences in exposure cause different risks in the workplace which affect the health of employees. This also applies to exposure and working conditions when handling sensitizing working substances. The presented gender-specific analysis of the German documentation of confirmed occupational respiratory allergic diseases and occupational skin diseases reveals clear differences between men and women in the number of diseases and also in exposure conditions and working areas.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

A 46-year-old man visited our hospital with a fever and cough. The symptoms had started two months after continued use of an ultrasonic humidifier. He had hypoxemia on admission and late inspiratory crackles in both lungs on physical examination. The laboratory findings showed an increased white blood cell count and a C-reactive protein level, and his serum KL-6 level was slightly elevated, at 674 U/mL. Chest computed tomography showed diffuse ground-glass opacities, and histological examination of a transbronchial lung biopsy showed alveolitis without granulomas. The humidifier inhalation challenge test result was positive. Therefore, we diagnosed the patient with humidifier lung. His symptoms gradually improved after avoiding the humidifier without taking medication. The humidifier water was contaminated by various bacteria and fungi, as well as Mycobacterium gordonae and a high concentration of endotoxin. Unlike in those with typical hypersensitivity pneumonitis, the elevation of serum KL-6 levels in humidifier lung patients is mild, and granulomas are not apparent on histological examination, similar to our case. Furthermore, the endotoxin identified from the humidifier is one of the known pathogens of humidifier lung. Thus, humidifier lung seems to have different characteristics compared to other hypersensitivity pneumonitis phenotypes. The mechanism driven by the high concentration of endotoxin could be one of the main causes of humidifier lung.

Bird Fancier's Lung is a type of hypersensitivity pneumonitis, an immunologically mediated lung disease due to repetitive exposure of air-borne avian antigen. This was first described in 1965 and is known as one of the most common causes of hypersensitivity pneumonitis. This case highlights this underdiagnosed etiology of dyspnea, disease presentation and exposure variability, and methods of diagnosis.

While hypersensitivity pneumonitis (HP) and asthma are usually recognized as different disease entities based on their different allergic mechanisms, they may have some connections. A previously healthy 54-year-old Japanese man with no history of allergic diseases was hospitalized due to fever and breathlessness. He had lived in an old musty wooden house. He was diagnosed with acute summer-type HP induced by Trichosporon asahii based on bilateral ground-glass opacities on chest computed tomography (CT), a high titer of serum anti-T. asahii antibody, an increased number of lymphocytes and a decreased CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) and lung pathology suggestive of HP. However, untypical increased eosinophils in BALF (25.2%) and infiltrative eosinophils around bronchial walls were observed. After systemic corticosteroid treatment was started, he recovered, and was discharged with oral prednisone. However, two weeks after returning to his former house, he had fever and severe cough, and was re-hospitalized. While chest CT showed no abnormal shadows indicating a worsening of HP, pulmonary function test revealed a typical obstructive defect and eosinophilic inflammation in his sputum. He spontaneously recovered after re-hospitalization without increasing any treatments. During this second hospitalization, he was diagnosed with asthma, although it remains to be determined whether both HP and asthma were caused by T. asahii. Clinicians should not miss the possible overlapping presentations between HP and asthma, caused by environmental antigens.

Background: Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied across different types of antigen exposure., Research Question: In patients with fHP, do disease outcomes and response to treatment vary by antigen type?, Study Design and Methods: A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ 2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival., Results: A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P = .20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P = .88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P = .047)., Interpretation: Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. W. W. reports personal fees from Boehringer Ingelheim and Astra Zeneca, outside the submitted work. V. M. reports personal fees from Boehringer Ingelheim Canada, Hoffman-La Roche Ltd, and Astra Zeneca; and reports grants from the University of Saskatchewan, Royal University Hospital Foundation, Boehringer Ingelheim, Astra Zeneca, and Hoffman-La Roche. D.-C. M. reports consultancy and speaking fees from Boehringer Ingelheim. B. Z. reports speaking fees from Boehringer Ingelheim and Abbvie. D. A. is supported by the Fonds de Recherche du Quebec en Santé, reports personal fees and grants from Boehringer Ingelheim, reports personal fees from Hoffmann-La Roche, and reports grants from the Canadian Institute for Health Research. K. A. J. reports grants from Boehringer Ingelheim, Pulmonary Fibrosis Society of Calgary, and University of Calgary School of Medicine; and reports personal fees from Boehringer Ingelheim, Roche, Three Lakes Foundation, Pliant Therapeutics, Theravance, and Blade Therapeutics. M. K. reports grants from the Canadian Institute for Health Research, Roche, Boehringer Ingelheim, Pieris, and Prometic; and reports personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Belerophon, United Therapeutics, Nitto Denko, MitoImmune, Pieris, Abbvie, DevPro Biopharma, Horizon, Algernon, and CSL Behring. H. M. reports grants from Boehringer Ingelheim and Gilead. J. M. reports personal fees from Boehringer Ingelheim and Roche. C. J. R. reports grants from Boehringer Ingelheim; and reports personal fees from Astra Zeneca, Boehringer Ingelheim, Roche, Pliant Therapeutics, Cipla, and Veracyte. None declared (M. L. M., G. F., J. H. F., N. K., B. M., E. F.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflict of Interest Hiromi Tomioka received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Yasunari Miyazaki received research grants from Nippon Boehringer Ingelheim Co., Ltd. and Chugai Pharmaceutical Co., Ltd. and lecture fees from Nippon Boehringer Ingelheim Co., Ltd. and Astra Zeneca Co., Ltd. Yoshikazu Inoue received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Hiroyuki Sano received lecture fees from AstraZeneca Co., Ltd., Glaxo Smith Kline Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd. and Novartis Pharma Co., Ltd.. Takeshi Johkoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Takeshi Hisada received lecture fees from AstraZeneca Co., Ltd. Junya Fukuoka received honoraria from National Institute of Advanced Industrial Science and Technology and Future Corporation. Yuki Iijima received a research grant from Shionogi & Co.,Ltd. Masahiro Ishizuka received a research grant from GlaxoSmithKline Co.,Ltd. Tsukasa Okamoto received endowments from Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Wako Filter Technology Co.,Ltd., and Car Conveni Club Co.,Ltd. Toshiaki Kikuchi received lecture fees from AstraZeneca Co.,Ltd., Chugai Pharmaceutical Co.,Ltd and Nippon Boehringer Ingelheim Co., Ltd and a research grant from Astra Zeneca Co.,Ltd. and endowments from Ono Pharmaceutical Co.,Ltd, Shionogi & Co.,Ltd., Chugai Pharmaceutical Co., Ltd. and Nippon Eli Lilly Co.,Ltd. Noriho Sakamoto a research grant from PPD-SNBL Co., Ltd.. Noboru Hattori received lecture fees from Astra Zeneca Co.,Ltd, Glaxo Smith Kline Co.,Ltd., Shionogi & Co.,Ltd., Chugai Pharmaceutical Co.,Ltd and Nippon Boehringer Ingelheim Co., Ltd. and endowments from Ono Pharmaceutical Co.,Ltd, Taiho Pharmaceutical Co.,Ltd and Nippon Eli Lilly Co.,Ltd.. Hiroshi Mukae received lecture fees from Astellas Pharma Inc., Astra Zeneca Co.,Ltd., MSD Co.,Ltd., Kyorin Pharmaceutical Co.,Ltd., Shionogi & Co.,Ltd., Daiichi Sankyo Co.,Ltd., Taisho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd and Pfizer Co., Ltd. and research grants from Otsuka Pharmaceutical Co., Ltd., Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and endowments from Astellas Pharma Inc., Kyorin Pharmaceutical Co.,Ltd., Shionogi & Co.,Ltd., Daiichi Sankyo Co.,Ltd., Taisho Pharmaceutical Co., Taiho Pharmaceutical Co.,Ltd, Chugai Pharmaceutical Co.,Ltd, FUJIFILM Toyama Chemical Co.,Ltd, and Meiji Seika Pharma Co.,Ltd. Masao Yamaguchi received lecture fees from AstraZeneca Co.,Ltd. Yoshihiro Nishimura received lecture fees from Astra Zeneca Co.,Ltd., Glaxo Smith Kline Co.,Ltd., Novartis Pharma Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd and research grants from Teijinn Pharma Co., Ltd and endowments from Glaxo Smith Kline Co.,Ltd., Taiho Pharmaceutical Co.,Ltd, Chugai Pharmaceutical Co.,Ltd and Nippon Eli Lilly Co.,Ltd. Masayuki Hanaoka received lecture fees from AstraZeneca Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd and endowments from Bayer Pharma Co., Ltd.. Masashi Bando received lecture fees from AstraZeneca Co., Ltd. Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Ryoko Egashira, Tetsuji Kawamura, Tamiko Takemura, Naohiko Inase, Masaru Ejima, Horoshi Ohnishi, Ryo Okuda, Susumu Sakamoto, Tsuyoshi Shirai, Kozo Suhara, Reoto Takei, Tomoya Tateishi, Kentaro Tanaka, Toshiharu Tsutsui, Yoshihisa Nukui, Haruhiko Furusawa, Yasushi Horimasu, Akemi Matsuo, Takashi Yamana, Yasuyuki Yoshizawa and Masahiro Kaneko have no conflicts of interest., (© 2023 Published by Elsevier B.V. on behalf of The Japanese Respiratory Society.)

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Background: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient., Research Question: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines?, Study Design and Methods: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis., Results: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91)., Interpretation: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Hypersensitivity pneumonitis (HP), is an inflammatory disease that represents one possible response of the interstitial and parenchymal tissue to the intensive and repeated inhalation of organic dusts or reactive chemicals substances. In this case report, for the first time in the literature as we know, acute hypersensitivity pneumonitis in a patient who working in broom grass manufacturing were presented. Broom manufacturer employee 35 years old female patient was admitted with dyspnea, fever and cough, beginning the three months before. Physical examination, there were bilateral basal crackles. On Thorax CT bilateral diffuse ground-glass opacity and mosaic perfusion were observed. Patient was hospitalized, IV prednisolone therapy was started. Almost complete clinical improvement was achieved. We would like to emphasize that detailed occupational history should be questioned; because; diagnosis of acute HP, due to the mixing with the viral infection or atypical pneumonia, easily skipped.

A patient presented with chest pain and clinical features of acute right heart failure. Initial work up revealed the presence of severe PAH. Acute pulmonary embolism is the commonest and most life-threatening cause for acute cor pulmonale. Even though the clinical picture suggested pulmonary embolism, a subtle sign was missed from the first chest X-ray taken in the emergency department. However on reanalysis the ‘continuous diaphragm sign’ later guided us towards the diagnosis. Our case represents one of the first reports of a rare etiology for acute cor pulmonale – hypersensitivity pneumonitis. Right ventricular dysfunction was caused by an acute rise in pulmonary artery pressures as well as by the compressive effects of pneumomediastinum. We emphasize the role played by a good quality chest X-ray early in the management of acute chest pain syndromes. However pulmonary embolism should be ruled out conclusively before redirecting attention to less malignant conditions.

A alveolite alérgica extrínseca e a sarcoidose são ambas doenças granulomatosas pulmonares que se caracterizam pela presença de granulomas não necrotizantes. Ambas apresentam alterações típicas no lavado broncoalveolar, com relações CD4/CD8 opostas. No entanto, a sarcoidose não apresenta hoje em dia factores etiológicos bem definidos, como a alveolite alérgica extrínseca. As autoras apresentam dois casos clínicos com curso clínico, imagiológico, funcional e imunológico semelhante, embora com confirmação histopatológica não concordante com as alterações do LBA e com a particularidade de pertencerem a dois elementos da mesma família, convivente, e de terem surgido com poucas semanas de intervalo.Extrinsic allergic alveolitis and sarcoidosis are two granulomatosis of the lung characterized by non-necrotizing granuloma. Both have typical bronchoalveolar lavage immunology, with opposite CD4/CD8 relation. However, sarcoidosis does not have such well defined etiology as extrinsic allergic alveolitis. The authors present two cases with similar clinical course, imagiology, lung function and immunology, although they both had an histology that was not concordant with the bronchoalveolar lavage, and with the peculiarity of being two elements of the same family, co -inhabitants and with a clinical presentation only a few weeks apart.

We report a case of hypersensitivity pneumonitis and asthma attacks caused by environmental fungi in a 75-year-old man. The diagnosis was established by inhalation challenge with Bjerkandera adusta and Aspergillus fumigatus. The patient was admitted for treatment of fever, wheezing, and dyspnea. Chest computed tomography showed small nodular shadows with diffuse, partially patchy, ground-glass opacities. The findings of bronchoalveolar lavage fluid were compatible with hypersensitivity pneumonitis. His symptoms and objective findings, including chest radiographs, worsened after returning home, suggesting the existence of causative antigens in his house. B. adusta and A. fumigatus were isolated from the living room and bedroom. Based on the results of antigen inhalation bronchoprovocation test, he was given a diagnosis of hypersensitivity pneumonitis caused by B. adusta and bronchial asthma attacks caused by B. adusta and A. fumigatus. After cleaning the entire house, the patient has had no recurrence of the symptoms on returning home.

Background: Three epidemiological small-scale studies on hypersensitivity pneumonitis (HP) have been performed in Japan to date. Herein, we aimed to clarify the clinical characteristics of various types of HP diseases using a large nationwide database in Japan., Methods: We used the Japanese Diagnostic Procedure Combination database that includes data from 1,031 participant hospitals. Patients with HP from 2011 to 2017 were identified using International Classification of Diseases 10th Revision codes. We analyzed patient characteristics, the yearly transition of the number of HP cases, rate per one million hospitalizations, geographical distribution, seasonality, and risk factors for in-hospital mortality., Results: In total, 3,634 patients with HP were identified, including summer-type HP (SHP) (n = 490), bird fancier's lung (BFL) (n = 199), ventilation pneumonitis (n = 106), farmer's lung (n = 48), and unspecified HP (n = 2761). The length of hospital stay was significantly longer in patients with BFL (19 days) than in patients with SHP (15 days). SHP was more prevalent in the southwestern region of Japan, and hospitalization occurred mainly in summer (37.8%) and fall (37.3%). Ventilation pneumonitis was predominant in winter (28.6%) and spring (38.7%). In-hospital mortality was significantly associated with old age (p < 0.001), low body mass index (p = 0.016), severe dyspnea (p < 0.001), and BFL diagnosis on admission (p = 0.031)., Conclusions: This study revealed the clinical characteristics of SHP and BFL, including the frequency of causative antigens, geographical distribution, seasonality, and risk factors for mortality, which may help in diagnosing HP and identifying causative antigens., Competing Interests: Conflict of Interest This study has received a Grant-in-Aid for Research on Policy Planning and Evaluation from the Ministry of Health, Labour and Welfare, Japan (20AA2005). Tsukasa Okamoto has received grants from Konica Minolta, Boehringer Ingelheim, Chugai, Kuramochi Clinic and Wako Filter Technology. Yasunari Miyazaki has received grants, consulting fees and payment for lectures and expert testimony from Thermo Fisher Scientific Inc. Shohei Yamashita, Tatsuo Kawahara, Tomoya Tateishi, Tatsuhiko Anzai, Kunihiko Takahashi and Kiyohide Fushimi have no conflict of interest to declare., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Interstitial lung diseases (ILDs) are a varied group of disorders that have been clubbed together due to some common attributes. The data is abundant from the developed world. However, the developing countries have gradually amassed the knowledge of these disorders and epidemiological data is still missing. We aimed to profile the ILD patients at our center., Methods: All ILD patients above the age of 14 years were included in the study. A detailed history, examination, exercise capacity assessment, pulmonary function test and relevant serological investigations were done. Tissue was obtained wherever possible. Diagnosis was made after discussion from concerned specialists., Results: Among the total 884 subjects recruited, 54% were females with a mean age of 53 years. Most were residents of rural areas. Reticulations and traction bronchiectasis was seen in most subjects. Hypersensitivity pneumonitis was present in 35.9% and connective-tissue disease related ILD (CTD-ILD) in 30.9%., Conclusion: Most common ILDs at our center are hypersensitivity pneumonitis and CTD-ILD. Reticulations and traction bronchiectasis are the most common findings on HRCT thorax., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Interstitial lung disease (ILD) is a parenchymal lung disease and restrictive disorder that presents as diffuse infiltrative shadows. The initial diagnosis of ILD is important because management strategies depend on the disease pathogenesis. Connective-tissue disease (CTD)-associated ILD including rheumatoid arthritis (RA), systemic sclerosis (SSc) requires a thorough evaluation of chronic respiratory symptoms such as non-productive cough and exertional dyspnea, as well as physical findings. Moreover, myeloperoxidase-positive anti-neutrophilic cytoplasmic antibody (MPO-ANCA)-associated vasculitis with ILD also shows disease progression. In CTD-associated ILD, the first-line treatment is anti-inflammatory drugs such as prednisolone or immunosuppressants. In hypersensitivity pneumonitis (HP), detailed environmental history-taking is crucial. Therefore, systematic standardized questionnaires are needed. However, the causative antigens are often not identified in daily clinical practice. When an antigen is identified or suspected, the first action is avoidance. If antigen avoidance does not contribute to clinical improvement, anti-inflammatory drugs such as prednisolone might be introduced. Regarding sarcoidosis, while most patients do not require treatment for lung involvement, some need anti-inflammatory drugs or immunosuppressants. Additionally, steroid treatment should be considered for the critical status of extrapulmonary sarcoidosis including cardiac, neurogenic and ocular sarcoidosis. Once starting treatment for ILD, multi-dimensional approaches are applied, including symptom tracking, chest imaging, pulmonary function test (PFT), and 6-min walking test. Recently, the concept of progressive-fibrosing interstitial lung disease (PF-ILD) has been proposed as a new disease entity. The definition of PF-ILD includes symptom progression, PFT decline, and extension of chest high-resolution computed tomography (HRCT) findings. This mini-review describes the background, definition, clinical characteristics, management, and challenges of PF-ILD., Competing Interests: Conflict of Interest I have no conflict of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)