Usefulness of Transbronchial Lung Cryobiopsy When Starting Antifibrotic Treatment and Predicting Progressive Fibrosing Interstitial Lung Disease: Descriptive Research.

BACKGROUND: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. METHODS: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. RESULTS: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. CONCLUSIONS: TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.

Hypersensitivity Pneumonitis on Thin-Section Chest CT Scans: Diagnostic Performance of the ATS/JRS/ALAT versus ACCP Imaging Guidelines.

Purpose To compare the diagnostic performance of the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) versus the American College of Chest Physicians (ACCP) imaging classifications for hypersensitivity pneumonitis (HP). Materials and Methods Patients in the institutional review board-approved Interstitial Lung Disease (ILD) registry referred for multidisciplinary discussion (MDD) at the authors' institution (January 1, 2006-April 1, 2021) were included in this retrospective study when ILD was diagnosed at MDD. MDD diagnoses included HP, connective tissue disease-ILD, and idiopathic pulmonary fibrosis. Retrospective review of thin-section CT images was performed in consensus by two cardiothoracic radiologists blinded to the diagnosis. Diagnostic patterns were determined for thin-section CT images using both classifications. Discordance rates were determined. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were assessed using MDD diagnosis as the reference standard. Results A total of 297 patients were included in the study: 200 (67%) with HP, 49 (16%) with connective tissue disease-ILD, and 48 (16%) with idiopathic pulmonary fibrosis at MDD. The discordance rate between the two classifications was 21%. Assuming low HP prevalence (10%), ATS/JRS/ALAT classification outperformed ACCP classification, with greater accuracy (92.3% vs 87.6%) and greater positive predictive value (60.7% vs 42.9%). Assuming high prevalence (50%), accuracy and negative predictive value were superior using ACCP classification (81.7% vs 79.7% and 77.7% vs 72.6%, respectively), and positive predictive value was superior using ATS/JRS/ALAT classification (93.3% vs 87.1%). Conclusion Accuracy of the ATS/JRS/ALAT and ACCP HP classifications was greater in settings with low and high HP prevalence, respectively. Diagnostic performance of both classifications was discordant in a minority of cases. Keywords: CT, Thorax, Hypersensitivity Pneumonitis, Interstitial Lung Disease Supplemental material is available for this article. © RSNA, 2024.

Hypersensitivity pneumonitis associated with inhalation of Lycoperdon spores (lycoperdonosis) in a 3-month-old English setter dog in Quebec.

A 3-month-old female English setter dog was presented to the Faculty of Veterinary Medicine of the Université de Montréal (Quebec) with acute respiratory distress. The dog had moderately increased C-reactive protein concentrations, and thoracic radiographs revealed a moderate, caudodorsal, nodular-to-miliary alveolo-interstitial pulmonary pattern that was worse in the perihilar region. Initial differential diagnoses included a fungal pneumonia (e.g., blastomycosis or histoplasmosis). Cytology of the bronchoalveolar lavage revealed several round, green structures ~2 µm in diameter, consistent with fungal spores. The dog was hospitalized, but within 24 h the respiratory condition deteriorated and euthanasia was elected. Post-mortem panfungal PCR and sequencing tests identified the spores as Lycoperdon sp. Retrospectively, the owners recalled that the dog had played in a wood pile with mushrooms and had sneezed in a cloud of spores, implying inhalation of Lycoperdon spores. This is the first report of a confirmed case of canine lycoperdonosis in eastern Canada (Quebec), and the radiographic features in this case differed slightly from previous reports. Diagnosis before bronchoalveolar lavage analysis was challenging, as spore inhalation was not initially reported. Although the disease is infrequently reported in dogs, this case report reminds veterinarians to consider lycoperdonosis as a differential diagnosis when addressing animals presented with acute dyspnea with similar radiographic lesions, and highlights the importance of history and cytology in diagnosing this condition. Key clinical message: Hypersensitivity pneumonitis secondary to inhalation of Lycoperdon spores must be included in differential diagnoses for a dog with acute onset of respiratory signs and a nodular-to-miliary interstitial pulmonary pattern coalescing in patchy perihilar alveolar pulmonary lesions, and should prompt clinicians to question owners regarding inhalation of mushroom spores.Although cytological examination of a bronchoalveolar lavage reveals the presence of fungal spores, panfungal PCR and sequencing tests are needed to pinpoint the species involved.

Pneumopathie d'hypersensibilité associée à l'inhalation de spores de Lycoperdon (lycoperdonose) chez un chien setter anglais de 3 mois au Québec. Une chienne setter anglais âgée de 3 mois a été présentée à la Faculté de médecine vétérinaire de l'Université de Montréal (Québec) avec une détresse respiratoire aiguë. Le chien présentait des concentrations de protéine C-réactive modérément augmentées et les radiographies thoraciques ont révélé un schéma pulmonaire alvéolo-interstitiel modéré, caudodorsal, nodulaire à miliaire, pire dans la région périhilaire. Les diagnostics différentiels initiaux incluaient une pneumonie fongique (par exemple, blastomycose ou histoplasmose). La cytologie du lavage broncho-alvéolaire a révélé plusieurs structures rondes et vertes d'environ 2 µm de diamètre, compatibles avec des spores fongiques. Le chien a été hospitalisé, mais en 24 heures, l'état respiratoire s'est détérioré et l'euthanasie a été décidée. Les tests panfongiques PCR et de séquençage post-mortem ont identifié les spores comme étant Lycoperdon sp. Rétrospectivement, les propriétaires ont mentionné que le chien avait joué dans un tas de bois avec des champignons et avait éternué dans un nuage de spores, ce qui implique une inhalation de spores de Lycoperdon. Il s'agit du premier rapport d'un cas confirmé de lycoperdonose canine dans l'est du Canada (Québec), et les caractéristiques radiographiques de ce cas différaient légèrement des rapports précédents. Le diagnostic avant l'analyse du lavage broncho-alvéolaire était difficile, car l'inhalation de spores n'avait pas été initialement signalée. Bien que la maladie soit rarement rapportée chez les chiens, ce rapport de cas rappelle aux vétérinaires de considérer la lycoperdonose comme un diagnostic différentiel lorsqu'ils traitent des animaux présentant une dyspnée aiguë avec des lésions radiographiques similaires, et souligne l'importance de l'anamnèse et de la cytologie dans le diagnostic de cette affection.Message clinique clé : La pneumopathie d'hypersensibilité secondaire à l'inhalation de spores de Lycoperdon doit être incluse dans les diagnostics différentiels chez un chien présentant un début aigu de signes respiratoires et un schéma pulmonaire interstitiel nodulaire à miliaire fusionnant dans des lésions pulmonaires alvéolaires périhilaires inégales, et devrait inciter les cliniciens à interroger les propriétaires concernant l'inhalation de spores de champignons.Bien que l'examen cytologique d'un lavage broncho-alvéolaire révèle la présence de spores fongiques, des tests panfongiques PCR et de séquençage sont nécessaires pour identifier les espèces impliquées.(Traduit par Dr Serge Messier).

The heterogeneity of lung involvement in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome: a case of hypersensitivity pneumonitis-like pattern.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which cause dysregulation of ubiquitin-mediated processes. This case describes a 71-year-old male patient with VEXAS syndrome who presented with refractory lung inflammation with a pattern similar to computed tomography hypersensitivity pneumonitis, a novel finding in VEXAS syndrome. The presented clinical case highlights the protean involvement of the lung in VEXAS syndrome and emphasizes the importance of considering interstitial lung disease in the differential diagnosis.

[Morphology of hypersensitivity pneumonitis]. / Morfologiya giperchuvstvitel'nogo pnevmonita.

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, the manifestations of which are diverse, and the diagnosis is complex and requires a multidisciplinary approach. HP is an immunologically determined disease in response to inhaled antigens. The main feature of the disease is terminal bronchiole's involvement accompanied by interstitial inflammation and/or fibrosis together with the presence of non-necrotizing granulomas in the interalveolar septa and bronchioles. The article presents the histological features of non-fibrous and fibrotic variants of the disease. Well-defined diagnostic criteria were formulated on the basis of published international recommendations and the authors' own experience.

Longitudinal changes in serum immunoglobulin G testing in patients with fibrotic avian hypersensitivity pneumonitis.

BACKGROUND: Evaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied. METHODS: This study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated. RESULTS: In this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = - 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = - 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982). CONCLUSIONS: In patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.

Granulomatous Lung Diseases: A Practical Approach and Review of Common Entities.

Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes.

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

Increased ER Stress and Unfolded Protein Response Activation in Epithelial and Inflammatory Cells in Hypersensitivity Pneumonitis.

Several types of cytotoxic insults disrupt endoplasmic reticulum (ER) homeostasis, cause ER stress, and activate the unfolded protein response (UPR). The role of ER stress and UPR activation in hypersensitivity pneumonitis (HP) has not been described. HP is an immune-mediated interstitial lung disease that develops following repeated inhalation of various antigens in susceptible and sensitized individuals. The aim of this study was to investigate the lung expression and localization of the key effectors of the UPR, BiP/GRP78, CHOP, and sXBP1 in HP patients compared with control subjects. Furthermore, we developed a mouse model of HP to determine whether ER stress and UPR pathway are induced during this pathogenesis. In human control lungs, we observed weak positive staining for BiP in some epithelial cells and macrophages, while sXBP1 and CHOP were negative. Conversely, strong BiP, sXBP1- and CHOP-positive alveolar and bronchial epithelial, and inflammatory cells were identified in HP lungs. We also found apoptosis and autophagy markers colocalization with UPR proteins in HP lungs. Similar results were obtained in lungs from an HP mouse model. Our findings suggest that the UPR pathway is associated with the pathogenesis of HP.

A new definition and treatment options of allergic alveolitis.

In this review, we discuss a new definition and treatment options of allergic alveolitis (AA). AA is an immune-mediated interstitial lung disease triggered by inhaled antigens, it is defined as non-fibrotic (inflammatory) and/or fibrotic, and diagnosis relies on a multidisciplinary approach using clinical, radiological and sometimes histological assessments. Treatment involves early antigen elimination and may include corticosteroids or other immunosuppressants. Prognosis varies from reversible inflammation to irreversible fibrosis. Early detection is crucial for better outcomes.

Drug-related pneumonitis caused by amikacin liposome inhalation suspension: One pathologically proven case and single-center experience.

Amikacin liposome inhalation suspension (ALIS) is known to cause drug-related pneumonitis, which has been described as "hypersensitivity pneumonitis (HP)". However, its clinical and pathological characteristics have never been reported. We retrospectively evaluated 18 patients treated with ALIS. Three (16.7%) patients developed HP-pattern pneumonitis on high-resolution computed tomography. Serum eosinophil counts were elevated up to above 1000/µL in these three patients, which decreased with ALIS discontinuation only. Of note, the specimen obtained by transbronchial lung cryobiopsy in one patient revealed a mild degree of lymphocyte and eosinophil infiltration. Rather, the findings of acute lung injury such as an edematous thickening of the alveolar walls, and an accumulation of foamy degenerative macrophages in the alveolar lumina was prominent. A pulmonary alveolar proteinosis reaction was also observed. HP-pattern pneumonitis due to ALIS may pathologically correspond to acute lung injury and a pulmonary alveolar proteinosis reaction despite increasing serum eosinophil counts.

[Workplace-associated fever]. / Arbeitsplatzassoziiertes Fieber oder wenn es doch das Zebra ist .

INTRODUCTION: Febrile conditions often have an infectious etiology. However, there are also fevers associated with occupational exposures. A detailed occupational history can hold the key to the diagnosis. In the case of exposure to organic dusts, the development of hypersensitivity pneumonitis (HP) is possible. Thus, HP should be considered in the presence of interstitial lung disease of unclear etiology. Failure to recognize this can have dramatic consequences and, in extreme cases, lead to lung transplantation. Differentially, organic dust toxic syndrome (ODTS) must be considered. The syndrome of metal fume fever provoked by inhalation of inorganic substances is usually benign and self-limiting. The disease manifests with fever, cough, and flu-like sensations.

A first look at the reliability, validity and responsiveness of L-PF-35 dyspnea domain scores in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Dyspnea impairs quality of life (QOL) in patients with fibrotic hypersensitivity pneumonitis (FHP). The Living with Pulmonary Fibrosis questionnaire (L-PF) assesses symptoms, their impacts and PF-related QOL in patients with any form of PF. Its scores have not undergone validation analyses in an FHP cohort. METHODS: We used data from the Pirfenidone in FHP trial to examine reliability, validity and responsiveness of the L-PF-35 Dyspnea domain score (Dyspnea) and to estimate its meaningful within-patient change (MWPC) threshold for worsening. Lack of suitable anchors precluded conducting analyses for other L-PF-35 scores. RESULTS: At baseline, Dyspnea's internal consistency (Cronbach's coefficient alpha) was 0.85; there were significant correlations with all four anchors (University of California San Diego Shortness of Breath Questionnaire scores r = 0.81, St. George's Activity domain score r = 0.82, percent predicted forced vital capacity r = 0.37, and percent predicted diffusing capacity of the lung for carbon monoxide r = 0.37). Dyspnea was significantly different between anchor subgroups (e.g., lowest percent predicted forced vital capacity (FVC%) vs. highest, 33.5 ± 18.5 vs. 11.1 ± 9.8, p = 0.01). There were significant correlations between changes in Dyspnea and changes in anchor scores at all trial time points. Longitudinal models further confirmed responsiveness. The MWPC threshold estimate for worsening was 6.6 points (range 5-8). CONCLUSION: The L-PF-35 Dyspnea domain appears to possess acceptable psychometric properties for assessing dyspnea in patients with FHP. Because instrument validation is never accomplished with one study, additional research is needed to build on the foundation these analyses provide. TRIAL REGISTRATION: The data for the analyses presented in this manuscript were generated in a trial registered on ClinicalTrials.gov; the identifier was NCT02958917.

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

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

Relative incidence of interstitial lung diseases in Brazil.

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

Differential Immunogenicity and Lung Disease-Inducing Potential of Mycobacterium immunogenum Genotypes and Impact of Co-Exposure with Pseudomonas: Optimizing a Mouse Model of Chronic Hypersensitivity Pneumonitis.

Mycobacterium immunogenum (MI) colonizing metalworking fluids (MWFs) has been associated with chronic hypersensitivity pneumonitis (HP) in machinists. However, it is etiologically unclear why only certain mycobacteria-contaminated fluids induce this interstitial lung disease. We hypothesized that this may be due to differential immunogenicity and the HP-inducing potential of MI strains/genotypes as well as the confounding effect of co-inhaled endotoxin-producers. To test this hypothesis, we optimized a chronic HP mouse model in terms of MI antigen dose, timepoint of sacrifice, and form of antigen (cell lysates vs. live cells) and compared six different field-isolated MI strains. Overall, MJY10 was identified as the most immunogenic and MJY4 (or MJY13) as the least immunogenic genotype based on lung pathoimmunological changes as well as Th1 cellular response (IFN-γ release). Infection with MI live cells induced a more severe phenotype than MI cell lysate. Co-exposure with Pseudomonas fluorescens caused a greater degree of lung innate immune response and granuloma formation but a diminished adaptive (Th1) immune response (IFN-γ) in the lung and spleen. In summary, this study led to the first demonstration of differential immunogenicity and the disease-inducing potential of field strains of MI and an interfering effect of the co-contaminating Pseudomonas. The improved chronic MI-HP mouse model and the identified polar pair of MI strains will facilitate future diagnostic and therapeutic research on this poorly understood environmental lung disease.