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Abstract 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.

Aims and Objectives: To explore the process by which people with hypersensitivity pneumonitis implement continuous antigen avoidance, alongside the situations that influence this process. Background: Antigen avoidance is the primary treatment for people with hypersensitivity pneumonitis. However, the best method to support antigen avoidance has not yet been established. Design: The present qualitative study used a constructivist grounded theory approach. Methods: The participants were inpatients or outpatients with hypersensitivity pneumonitis diagnosed at a Japanese urban university hospital. In parallel with semi‐structured interviews and a medical record survey from 2016 to 2021, we conducted coding, categorising, writing memos, theoretical sampling and continuous comparisons of experiences from finding physical abnormalities to implementing antigen avoidance. The COREQ checklist was followed for reporting. Results: Interpreting the experiences leading to the implementation of continuous antigen avoidance by 28 participants provided a process consisting of a core category: trying to maintain one's desired life under uncertain situations, and four phases: (1) searching for a convincing cause of the illness, (2) gradually understanding the disease, (3) realising the need for behaviour change and (4) seeking a good balance between behaviour change and one's desired life. The situations that influenced the process were also revealed. Conclusions: Being convinced of the cause of one's illness and realising its severity led to the participants' realisation of the need for a behavioural change to avoid antigens. The uncertainty of the cause of illness and measures taken, a lack of clear advice from healthcare providers and one's desired life influenced participants' implementation of continuous antigen avoidance. Relevance to clinical practice: This study provides important insights regarding how healthcare providers should better understand and support people with hypersensitivity pneumonitis in avoiding antigens. [ABSTRACT FROM AUTHOR]

We herein report a rare case of hypersensitivity pneumonitis (HP) that was initially demonstrated as solitary pure ground-glass opacity (GGO) on chest computed tomography (CT). A 51-year-old woman with a history of breast cancer underwent follow-up CT, which revealed solitary pure GGO. The patient developed exertional dyspnea after two years, and CT revealed diffuse centrilobular nodules in addition to GGO, which had increased in size. An antigen avoidance test was performed to diagnose HP, leading to the resolution of CT abnormalities, including the GGO. Our findings suggested that nonfibrotic HP can present as solitary pure GGO.

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied.

• Suspected causative antigens were mainly fungi, bacteria, or avian proteins. • Both desirable and insufficient antigen avoidance behaviour were reported. • Continuous and desirable antigen avoidance tended to improve or maintain conditions. Antigen avoidance (AA) is essential for people with hypersensitivity pneumonitis (HP). An intervention programme to promote continuous AA in people with HP will be the focus of future research. We systematically analysed the AA behaviour of people with HP, interventions of health-care providers to promote AA behaviour, clinical outcomes after AA, and evaluation methods after AA. We conducted a scoping review using six online databases and manual searches. Papers written in English or Japanese that reported cases on AA were selected. The extracted data were classified qualitatively. In total 205 cases included in 109 eligible papers were examined. This review clarified the fundamental evidence of AA in people with HP. These people required the continuous support of health-care providers to continue appropriate AA. This review highlighted four aspects that require further research to design interventions for promoting effective and continuous AA in people with HP. [ABSTRACT FROM AUTHOR]

Abstract Background In chronic hypersensitivity pneumonitis (chronic HP), antigen avoidance is critical for disease management; however, complete avoidance is difficult because of unrecognized exposure to antigens. Recently, we revealed that the amount of avian antigen (AAA) in household dust at the time of diagnosis predicted the progression of chronic bird‐related HP. The purpose of this study is to evaluate the relationship between the prognosis of chronic bird‐related HP and the AAA that remained in the environment during antigen avoidance. Methods First, we measured the AAA in household dust of 28 consecutive patients (22 with chronic bird‐related HP and 6 with acute bird‐related HP) and 12 healthy volunteers. Second, we measured the AAA and collected questionnaires on the environmental conditions of the homes of 53 patients with various lung diseases, including bird‐related HP, to investigate the environmental parameters related to a higher AAA. Finally, we prospectively recruited 14 consecutive patients with chronic bird‐related HP, measured the AAA periodically, and collected clinical data. Results The AAA was higher in patients with chronic bird‐related HP at the time of diagnosis compared to healthy volunteers and was highest in patients with acute bird‐related HP. Logistic regression analysis showed that birds frequenting a residence was the only significant factor for a higher AAA (odds ratio, 5.686; 95%CI, 1.263–25.59; P = 0.024). There was a correlation between the mean AAA and decline of vital capacity for 1 year (r = −0.55; 95%CI −0.84 to −0.01; P = 0.043). Conclusion Measurements of the AAA after diagnosis predict the progression of chronic bird‐related HP. Avian antigen can exist in the indoor environment regardless of antigen avoidance. The presence of avian antigen in the indoor environment can be attributed to wild birds found outdoors.

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.)

Abstract: Background: In chronic hypersensitivity pneumonitis (chronic HP), antigen avoidance is critical for disease management; however, complete avoidance is difficult because of unrecognized exposure to antigens. Recently, we revealed that the amount of avian antigen (AAA) in household dust at the time of diagnosis predicted the progression of chronic bird‐related HP. The purpose of this study is to evaluate the relationship between the prognosis of chronic bird‐related HP and the AAA that remained in the environment during antigen avoidance. Methods: First, we measured the AAA in household dust of 28 consecutive patients (22 with chronic bird‐related HP and 6 with acute bird‐related HP) and 12 healthy volunteers. Second, we measured the AAA and collected questionnaires on the environmental conditions of the homes of 53 patients with various lung diseases, including bird‐related HP, to investigate the environmental parameters related to a higher AAA. Finally, we prospectively recruited 14 consecutive patients with chronic bird‐related HP, measured the AAA periodically, and collected clinical data. Results: The AAA was higher in patients with chronic bird‐related HP at the time of diagnosis compared to healthy volunteers and was highest in patients with acute bird‐related HP. Logistic regression analysis showed that birds frequenting a residence was the only significant factor for a higher AAA (odds ratio, 5.686; 95%CI, 1.263–25.59; P = 0.024). There was a correlation between the mean AAA and decline of vital capacity for 1 year (r = −0.55; 95%CI −0.84 to −0.01; P = 0.043). Conclusion: Measurements of the AAA after diagnosis predict the progression of chronic bird‐related HP. Avian antigen can exist in the indoor environment regardless of antigen avoidance. The presence of avian antigen in the indoor environment can be attributed to wild birds found outdoors. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity pneumonitis (HP) is an immunologically induced lung disease that develops after inhalation of certain environmental antigens only in subjects with susceptibility to antigens. Therefore, both environmental and host immunological factors play important roles in the aetiology and pathogenesis of HP. Areas covered: Determination of an inciting antigen is crucial for diagnosis, treatment and monitoring. For treatment, modification of the environment and of the host immune response are important. The former includes reduction of antigenic burden (i.e. disinfectant, cleaning), protective devices (i.e. filter, respiratory protection mask, ventilation) and avoidance of inciting antigens. The latter includes corticosteroids, lung transplantation and smoking cessation. For monitoring, measurement of serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D concentrations can be used to screen for HP and to detect HP activity. Expert commentary: Measurement of an inciting antigen may be useful to predict the progression and prognosis of the disease. Treatment and monitoring are challenging in chronic HP with fibrosis. [ABSTRACT FROM PUBLISHER]

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied. • Clinical features of fibrotic HP and IPF are often indistinguishable. • Antigen avoidance is crucial in the diagnosis and management of fibrotic HP. • Environmental inhalation challenge is useful when applied properly. • The seasonal change of clinical parameters helps suspecting fibrotic HP. [ABSTRACT FROM AUTHOR]

Background: In the management of hypersensitivity pneumonitis (HP), antigen avoidance is crucial to prevent the progression of disease. Indirect and unrecognized exposure to the antigen may continue for a long time if persistence of the causative antigen is not recognized. To make a correct assessment of the patients' environment, we tried to establish the methods to detect indoor and outdoor avian antigens. Methods: Sixteen patients with bird-related HP, 4 asymptomatic breeders, and 6 healthy controls were examined. We prepared anti-pigeon dropping extracts (PDE) polyclonal antibody from rabbits. Air samples and house dust samples were analyzed by an antigen-capture ELISA with signal amplification using catalyzed reporter deposition. Results: In air samples, avian antigen could be detected in patients with HP (0.73 ± 0.53 ng/m3) and asymptomatic breeders (0.63 ± 0.23 ng/m3). In house dust samples, the amount of avian antigen was higher in patients with HP (2.4 ± 1.8 µg/g) and asymptomatic breeders (4.1 ± 2.3 µg/g) than in the controls (0.1 ± 0.2 µg/g). Conclusions: Detection of indoor and outdoor avian antigen might contribute to the correct diagnosis and appropriate managements of bird-related HP. [ABSTRACT FROM AUTHOR]

So-called ‘topical immunotherapy’ (TI) is a well-established treatment modality based on the use of potent contact sensitizers, such as squaric acid dibutylester (SADBE), that are not found in the general or occupational environment of man, and do not induce cross-sensitization to other substances. Thus, unlike patients with sensitivity to other more or less commonplace allergens, subjects submitted to this treatment modality might provide useful data for the study of the natural course of contact sensitivity. On the basis of these premises, we have retrospectively reviewed 40 patients who had consecutively received TI with SADBE for severe alopecia areata and viral warts in the period 1993–2001, and returned to visit after a 1–7-year period since the last therapeutic challenge with the sensitizer. The chronological profile of loss of contact sensitization of this case cohort has been evaluated and compared to that of other series available in the literature. Provided more standardized TI application procedures are established, aim-oriented studies of the outcome of this treatment modality may bring useful data to be employed in construction of predictive models of decay of contact sensitization under conditions of antigen avoidance. [ABSTRACT FROM AUTHOR]

Twenty-three Dermatophagoides pteronyssinus (Dpt)-sensitive asthmatic children aged 7-14 years entered a double-blind, placebo-controlled trial of standardized immunotherapy (IT) (Alpare) while resident at high altitude. Dpt sensitivity was evaluated by skin prick tests at different allergen concentrations at the enrollment and after 6 and 12 months of treatment. Bronchial hyperreactivity was evaluated at the same time points, and on each occasion, histamine challenge and, the following day, Dpt bronchial challenge were performed. All patients, irrespective of active treatment, improved clinically and in lung function with increased PC20 and Dpt-PD20. Alpare-treated patients had a significantly decreased sensitivity on Dpt skin testing (P< 0.009) and felt that their asthma had improved (P< 0.001) compared with placebo-treated subjects, but there was no difference between the treatment groups in lung function or bronchial challenge response. IT neither increased nor decreased bronchial histamine sensitivity. Our results indicate that Dpt IT benefits asthmatic children, but improvement by allergen avoidance at high altitude is even greater. [ABSTRACT FROM AUTHOR]

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables. [ABSTRACT FROM AUTHOR]

Background: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed., Methods: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival., Results: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04)., Conclusions: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression., Competing Interests: Conflict of Interest Yasunari Miyazaki received honoraria from Boehringer-Ingelheim. The other authors have no conflicts of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A 53-year-old-woman presented our hospital with 1 month history of exertional dyspnea and mild fever. When examined, temperature was 37.2℃ and her respiratory rate of 22/min with an O2 saturation of 95% (02 4L/min), the rest of her vital signs were normal. The Chest X-ray was significant for ground-grass attenuation, and computed tomography showed diffuse nodular lesions bilaterally. She reported that the floorboard in the living room had been rotten last two months, and her husband was admitted to another hospital with similar symptoms the day before. We suspected that she and her husband have familial hypersensitivity pneumonitis although their children who live in the same house don't have any symptoms. After the admission, her respiratory status improved without treatment. The trans-bronchial lung biopsy specimens showed lymphocytic infiltration in alveolar area, and epithelioid cell granuloma consisted of CD68-positive macrophages. These findings corresponded to subacute hypersensitivity pneumonitis. The bronchoalveolar lavage revealed predominant lymphocytes of 92%, with a low CD4/8 ratio of 0.39. Serum anti-Trichosporon asahii antibodies were positive. With the result of positive environmental challenge test in her house, which showed elicited dyspnea and temperature increase up to 38℃ a few hours after she came back home, the patient was diagnosed as having summer-type hypersensitivity pneumonitis. Her husband was also diagnosed as the same disease, and symptoms improved with antigen avoidance and prednisolone. The patient was discharged to her relative's place for the moment of house repair. The patient's symptoms did not recur after her house was repaired.