This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación ...Latinoamericana del Tórax.
Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.
The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.
The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.
The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the ...diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non‐IgE‐mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.
The ability of specific histopathologic features to predict mortality or lung transplantation in patients with chronic hypersensitivity pneumonitis (HP) is unknown.
Patients with chronic HP diagnosed ...by surgical lung biopsy were identified from an ongoing longitudinal cohort. The surgical lung biopsy slides were evaluated prospectively by an experienced thoracic pathologist using a standardized checklist to differentiate the major pathologic patterns and score the presence of specific histopathologic features. Cox proportional hazard analysis was used to identify independent predictors of transplant-free survival, and Kaplan-Meier analysis was used to visualize outcomes.
One hundred nineteen patients were identified. Patients with a fibrotic nonspecific interstitial pneumonia (f-NSIP) pattern, bronchiolocentric fibrosis (BF) pattern, or usual interstitial pneumonia (UIP) pattern had significantly worse transplant-free survival than did those with a cellular NSIP (c-NSIP) pattern or peribronchiolar inflammation with poorly formed granulomas (PI-PFG) pattern. No survival difference among patients with an f-NSIP pattern, a BF pattern, or a UIP pattern was found. Fibroblastic foci were identified in a subset of biopsy samples from all pathologic patterns. Peribronchiolar fibrosis was noted in all UIP cases. Independent predictors of time to death or transplantation included the presence of fibroblast foci or dense collagen fibrosis.
Histopathologic patterns of c-NSIP and PI-PFG had a better transplant-free survival than did patterns of UIP, f-NSIP, and BF. The presence of fibroblast foci or dense collagen fibrosis correlated with progression to death or lung transplantation. Identification of fibroblast foci on biopsy samples, regardless of the underlying histopathologic pattern, may be a clinically useful predictor of survival in patients with HP.
Background Resident gut microbiota are now recognized as potent modifiers of host immune responses in various scenarios. Recently, we demonstrated that perinatal exposure to vancomycin, but not ...streptomycin, profoundly alters gut microbiota and enhances susceptibility to a TH 2 model of allergic asthma. Objective Here we sought to further clarify the etiology of these changes by determining whether perinatal antibiotic treatment has a similar effect on the TH 1/TH 17-mediated lung disease, hypersensitivity pneumonitis. Methods Hypersensitivity pneumonitis was induced in C57BL/6 wild-type or recombination-activating gene 1–deficient mice treated perinatally with vancomycin or streptomycin by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Disease severity was assessed by measuring lung inflammation, pathology, cytokine responses, and serum antibodies. Microbial community analyses were performed on stool samples via 16S ribosomal RNA pyrosequencing and correlations between disease severity and specific bacterial taxa were identified. Results Surprisingly, in contrast to our findings in an allergic asthma model, we found that the severity of hypersensitivity pneumonitis was unaffected by vancomycin, but increased dramatically after streptomycin treatment. This likely reflects an effect on the adaptive, rather than innate, immune response because the effects of streptomycin were not observed during the early phases of disease and were abrogated in recombination-activating gene 1–deficient mice. Interestingly, Bacteroidetes dominated the intestinal microbiota of streptomycin-treated animals, while vancomycin promoted the expansion of the Firmicutes. Conclusions Perinatal antibiotics exert highly selective effects on resident gut flora, which, in turn, lead to very specific alterations in susceptibility to TH 2- or TH 1/TH 17-driven lung inflammatory disease.
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex pulmonary syndrome mediated by the immune system and caused by inhalation of a wide variety of antigens to ...which the individual has been previously sensitized. The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP. Due to the lack of a diagnostic gold standard, the diagnosis of HP is not straightforward and relies on the integration of a number of factors, including history of exposure, precipitating antibodies to the offending antigen, clinical features, bronchoalveolar lavage, and radiological and pathologic features. However, in the appropriate setting, a high index of suspicion is critically important and may obviate the need for more invasive tests. Clinical presentation and natural history vary widely. Acute forms generally resolve without sequelae, while chronic forms, which are caused by persistent low-grade exposures, are associated with poor prognosis. Corticosteroids may be useful in acute episodes for symptomatic relief or in chronic and progressive disease, but their long-term efficacy has never been validated in prospective clinical trials. Ideally, patients with HP should be referred to centers with expertise, as the overlap with other forms of interstitial lung disease may be substantial. Making the correct diagnosis has critical therapeutic and prognostic implications.
Antigen identification is important for establishing a confident diagnosis of hypersensitivity pneumonitis (HP). There are no systematically curated lists of HP-associated exposures that inform ...clinical relevance or disease phenotype. We sought to systematically identify all reported causes of HP in the literature and evaluate their clinical relevance. A scoping review was performed to identify all publications describing HP cases and their associated exposures (even if unknown) from Jan 1990–June 2020. Frequencies of exposures and meta-analysis of proportions for registry-based studies were determined for specific exposure categories, and associations with fibrotic and non-fibrotic HP were assessed. 24,138 publications were identified, with 967 publications included in the final analysis, representing 62 unique exposures associated with HP. Certain exposures were more frequently reported than others, including birds (comprising 32% of HP cases in registry-based studies) and mould (17% registry study HP cases). Antigen-indeterminate HP comprised 15–24% of registry-based studies. Limited data found contaminated metal-working fluids, isocyanate exposure, and hot tub lung were rarely associated with fibrotic features, whereas antigen-indeterminate HP cases were more frequently associated with fibrosis. There was heterogeneity in HP case definition and how causative exposures were identified. We identified 62 unique exposures associated with HP, with specific exposures associated with clinical phenotypes. These data may inform clinical assessment and the development of questionnaires to identify antigens in the diagnostic evaluation of suspected HP.
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•This scoping review describing exposures associated with hypersensitivity pneumonitis (HP) identified 62 unique exposures.•Birds and mould were the most frequently reported exposures, accounting for 32% and 17% of HP cases in registry-based studies, respectively.•Antigen-indeterminate HP comprised 15-24% of patients in registry-based studies.•Limited data found MWF, isocyanates, and hot tub lung were rarely; and antigen-indeterminate HP more frequently associated with fibrotic HP.•These data may inform clinical assessment and development of questionnaires to identify exposures in the diagnostic evaluation of suspected HP.
Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of subjects with ...CHP have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF).
To determine the common and unique molecular features of CHP and IPF.
Transcriptome analysis of lung samples from CHP (
= 82), IPF (
= 103), and unaffected controls (
= 103) was conducted. Differential gene expression was determined adjusting for sex, race, age, and smoking history and using false discovery rate to control for multiple comparisons.
When compared with controls, we identified 413 upregulated and 317 downregulated genes in CHP and 861 upregulated and 322 downregulated genes in IPF. Concordantly upregulated or downregulated genes in CHP and IPF were related to collagen catabolic processes and epithelial development, whereas genes specific to CHP (differentially expressed in CHP when compared with control and not differentially expressed in IPF) were related to chemokine-mediated signaling and immune responsiveness. Using weighted gene coexpression network analysis, we found that among subjects with CHP, genes involved in adaptive immunity or epithelial cell development were associated with improved or reduced lung function, respectively, and that MUC5B expression was associated with epithelial cell development. MUC5B expression was also associated with lung fibrosis and honeycombing.
Gene expression analysis of CHP and IPF identified signatures common to CHP and IPF, as well as genes uniquely expressed in CHP. Select modules of gene expression are characterized by distinct clinical and pathological features of CHP.
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