Acute Hypersensitivity Pneumonitis Research Articles

Гіперсенситивний пневмоніт. Клінічний випадок

Abstract. Hypersensitivity pneumonitis (HP), or exogenous allergic alveolitis, is a complex and heterogeneous immune-mediated inflammatory and/or fibrotic disease of the lung parenchyma, small airways and interstitium that occurs in people with congenital or acquired hypersensitivity/ susceptibility to certain inhaled antigens. The disease can occur in acute/inflammatory form (duration of the disease is less than 6 months) or chronic form (duration of the disease is more than 6 months). According to the latter classification, HP is divided into fibrotic and non-fibrotic forms: non-fibrotic HP is a mild form of HP compared to fibrotic HP. However, non-fibrotic HP often progresses to fibrosis, i.e. it can be recurrent. The article describes a clinical case of acute HP induced by poultry antigens in the occupational environment. The clinical case study shows that the anamnesis data, namely the identification of a direct link between the occupational environment and the onset of symptoms of dyspnoea, cough, weakness, and headache, made it possible to suspect poultry antigen-induced HP. The characteristic picture of HP observed on computed tomography images, as well as auscultation and radiological findings, made it possible to confirm the diagnosis. The results of the respiratory function assessment showed the presence of pulmonary insufficiency, and the laboratory examination data showed the presence of inflammation, immunological imbalance, acid-base (alkaline) disorders and hypoxia.

Hypersensitivity pneumonitis against the background of the use of organic substances, probably mustard powder (clinical case)

We describe a clinical case of hypersensitivity pneumonitis against the background of the use of organic substances, probably mustard powder.Patient K. is 18 years old and lives in the city. The disease began on 01.11.2022, with complaints of cough with difficult secretion of thick sputum, shortness of breath with slight physical exertion, an increase in body temperature to 37.5 °C, a feeling of palpitations. Complaints were observed for about three weeks and increased in dynamics. Consulted a pulmonologist at a private medical center, where a diagnosis of allergic bronchitis was made and treatment was prescribed, which did not have a positive effect. On 21.11.2022, the family doctor referred him for an X-ray examination, where pathological changes in the lungs were detected. The patient was referred to a pulmonologist for consultation, and a computed tomography (CT) of the chest was also performed. Changes characteristic of hypersensitivity pneumonitis were detected, hospitalized in the pulmonology department of the Ternopil Regional Phthisiopulmonological Medical Center. It is known from the anamnesis that for about three months he worked in the production of food products where mustard powder was used, he did not use respiratory protection means.Additional examination methods were carried out. Bronchoscopy, conclusion — Catarrhal laryngitis, diffuse bilateral catarrhal tracheobronchitis. Computed tomography of the chest organs dated 22.11.2022, the conclusion is that the picture of the dissemination syndrome in the lungs is more characteristic of acute hypersensitivity pneumonitis. The patient was consulted by a cardiologist. The clinical diagnosis «Hyper­sensitive pneumonitis against the background of the use of organic substances, probably mustard powder, subacute form, diagnosed for the first time. Pulmonary insufficiency of the 2nd degree. Idiopathic mitral valve prolapse. Metabolic cardiomyopathy. Heart failure of the 0th stage». Treatment is prescribed. 09.12.2022 discharged for outpatient treatment with improvement. According to the data of the control examination (CT dated 09.01.2023) dynamics of partial resorption of hypersensitivity pneumonitis.

Ceftriaxone-Induced Acute Hypersensitivity Section Pneumonitis: A Rare Case Report

Hypersensitivity Pneumonitis (HP), also known as extrinsic allergic alveolitis, is a pulmonary disorder characterised by an inflammatory response of the alveoli and small airways due to exposure to a variety of antigens. HP can manifest as acute, subacute, or chronic, depending on the mode of onset and its duration. A broad spectrum of antigens, derived from fungi, bacteria, mycobacteria, birds, chemical sources, and certain drugs such as cyclophosphamide and sulfonamides, has been associated with the development of HP. However, HP developed by Ceftriaxone is an extremely rare occurrence. Here, the authors presented a case of a 26-year-old male who experienced the onset of HP immediately following the administration of injectable Ceftriaxone. He developed a sudden onset of breathlessness and cough, necessitating Mechanical Ventilation (MV) and steroid support. Radiological imaging indicated pneumonitis, and the symptoms gradually resolved after discontinuing Ceftriaxone. Ceftriaxone-induced acute HP represents an unusual clinical presentation. In the present case report, the authors highlighted the possibility of Ceftriaxone as a potential cause of HP, given its capacity for rapid reversal upon its timely removal.

E-CIGARETTE OR VAPING USE-ASSOCIATED LUNG INJURY (EVALI): EFFECTS OF VAPING OR COVID-19?

E-CIGARETTE OR VAPING USE-ASSOCIATED LUNG INJURY (EVALI): EFFECTS OF VAPING OR COVID-19?

How much do we know about genetic predisposition of hypersensitivity pneumonitis?

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by iterative inhalation of various environmental agents. The clinical presentation is variable, acute HP commonly presents an inflammatory response, whereas the development and clinical consequences in chronic HP may be similar to IPF (idiopathic pulmonary fibrosis). The aim of the study is to present the latest discoveries regarding the genetic predisposition of HP. The appropriate scientific literature was reviewed and analyzed. Studies have discovered relevant gene polymorphisms in HP, including polymorphisms in the major histocompatibility complex in the metalloproteinases genes. The length of the peripheral blood leukocyte telomere has been investigated and discovered to be important. Recently, the need to study miRNAs in ILD (interstitial lung disease) has been highlighted. Exposed HP developed only in some people and a genetic susceptibility significantly increases the risk. Further more current studies on large groups of patients are needed to learn more about the genetic predisposition and risk factors of HP.

Contribution of Protein Kinase D1 on Acute Pulmonary Inflammation and Hypersensitivity Pneumonitis Induced by Saccharopolyspora rectivirgula.

Protein kinase D1 (PKD1), a ubiquitously expressed serine/threonine kinase, regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, vesicle trafficking, Ag receptor signaling, and pattern recognition receptor signaling. We found previously that exposure to hypersensitivity pneumonitis (HP) inciting Ag Saccharopolyspora rectivirgula leads to the activation of PKD1 in a MyD88-dependent manner in various types of murine cells in vitro and in the mouse lung in vivo. However, it is currently unknown whether PKD1 plays a role in the S. rectivirgula-induced HP. In this study, we investigated contributions of PKD1 on the S. rectivirgula-induced HP using conditional PKD1-insufficient mice. Compared to control PKD1-sufficient mice, PKD1-insufficient mice showed substantially suppressed activation of MAPKs and NF-κB, expression of cytokines and chemokines, and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula The significantly reduced levels of alveolitis, MHC class II surface expression on neutrophils and macrophages, and IL-17A and CXCL9 expression in lung tissue were observed in the PKD1-insufficient mice repeatedly exposed to S. rectivirgula for 5 wk. PKD1-insuficient mice exposed to S. rectivirgula for 5 wk also showed reduced granuloma formation. Our results demonstrate that PKD1 plays an essential role in the initial proinflammatory responses and neutrophil influx in the lung after exposure to S. rectivirgula and substantially contribute to the development of HP caused by repeated exposure to S. rectivirgula Our findings suggest that PKD1 can be an attractive new molecular target for therapy of S. rectivirgula-induced HP.

Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide

BackgroundInhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger).MethodsC57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.ResultsIn comparison to mice challenged only with A. niger, addition of LPS (1 μg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.ConclusionsIn contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.

BIRD FANCIER'S DISEASE: A CASE OF HYPERSENSITIVITY PNEUMONITIS

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: The immunologic lung disease through inhalation and sensitization of an aerosolized antigen is termed hypersensitivity pneumonitis (HP). Here we describe a case of HP from exposure to avian antigen. CASE PRESENTATION: A 42 y/o F presented with progressively worsening dyspnea at rest & exertion, pleuritic chest pain, dry cough for past 2 months. She denied sick contacts or recent travel. On exam BP: 122/76mmHg, HR 107bpm, RR 30bpm, SpO2 82% on room air. Physical exam, significant for b/l crackles. Labs: WBC 16.33 k/mm3, ABG PaO2 of 45mmHg. CXR showed b/l airspace opacities & CT-thorax showed b/l diffuse GGO. ECHO showed LVEF 55% with normal global systolic function with mildly elevated PASP. Treatment was initiated with hi-flo oxygen and her SpO2 improved to 97%. QuantiFERON Gold, urine legionella, Mycoplasma IgM, and respiratory multiplex viral panel were negative. Cardiac CT revealed patent coronaries. Spirometry revealed severe restrictive ventilatory defect. Further questioning revealed that patient got parakeets a few months prior to onset of symptoms. She was then started on methylprednisolone for possible HP. Bronchoscopy with BAL and transbronchial biopsies showed no bacterial/fungal/viral growth. Cytology was unremarkable and biopsies revealed mild inflammatory changes with lymphocytes and aggregates of intralaveolar foamy macrophages. The CD4:CD8 ratio was 0.89. Patient clinically improved with steroid therapy and gradually weaned from supplemental oxygen. She was discharged on oral prednisone with close follow up where she continued to improve after removal of her parakeets DISCUSSION: HP an immune-mediated response from repeated inhalation, sensitization, & hyperresponsiveness to various organic particles which can be mammalian or avian proteins, fungi, bacterial, or chemicals. Based on duration of exposure & symptoms onset, HP can be divided into acute, subacute, or chronic. Acute HP presents as flu-like illness, subacute HP has insidious onset of symptoms, dyspnea on exertion or reduced exercise capacity. Physical exam reveals inspiratory crackles. Imaging usually demonstrates GGO, mosaic attenuation and centrilobular nodules. BAL reveals lymphocytic predominant cells with CD8 alveolitis. Histopathology usually demonstrates cellular bronchiolitis with predominant lymphocytic or plasmocytic infiltrates. It can also present as interstitial mononuclear infiltrates or loosely-formed granulomas. Treatment for HP is avoidance of antigen exposure. Role of steroids in treating HP is not well known, however general practice is slow tapering steroid regimen for about 3-6 months duration. Prognosis is usually good with complete recovery in most patients; a few may progress to chronic fibrosing HP. CONCLUSIONS: A high level of suspicion should be present in diagnosing HP with a thorough history and prompt management must be initiated to prevent progression of disease. REFERENCE #1: Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Is J Respir Crit Care Med. 2012; 186:314-24. REFERENCE #2: Costabel U, Bonella F, Guzman J. Chronic hypersensitivity pneumonitis. Clin Chest Med. 012; 33:15163. REFERENCE #3: Camarena A, Juárez A, Mejía M, Estrada A, Carrillo G, Falfán R, Zuñiga J, Navarro C, Granados J, Selman M. Major histocompatibility complex and tumor necrosis factor-alpha polymorphisms in pigeon breeder's disease. Am J Respir Crit Care Med. 2001;163:1528-33. DISCLOSURES: no disclosure on file for Jagadish Akella; No relevant relationships by Alex Diaz, source=Web Response no disclosure on file for Iqbal Javed; No relevant relationships by Raghavendra Sanivarapu, source=Web Response

ACUTE PULMONARY HISTOPLASMOSIS: A DIAGNOSTIC DILEMMA DURING COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute histoplasmosis is usually a concern in immunocompromised individuals. In immunocompetent patients, histoplasmosis is generally mild or asymptomatic unless there is inhalation of a large inoculum. Below, we present a case of severe acute pulmonary histoplasmosis in an otherwise healthy, immunocompetent person and discuss the diagnostic challenges it presented during the COVID-19 pandemic. CASE PRESENTATION: A 30-year-old non-smoking Caucasian man with hypertension presented to our hospital with 1 week duration of headache, dyspnea, productive cough and high fever. He was admitted with a provisional diagnosis of COVID-19 pneumonia and started on dexamethasone and empiric antibiotics. He had elevated inflammatory markers. Chest x-ray showed diffuse bilateral interstitial and alveolar opacities. CT chest demonstrated numerous clustered ground glass nodular opacities bilaterally with mediastinal and hilar adenopathy. Subsequently, RT-PCR for SARS-CoV2 returned negative. The patient continued to deteriorate clinically over the next few days. Repeat imaging showed diffuse micronodules with mediastinal adenopathy. Upon further questioning, the patient recalled demolishing a chimney at his parents' house in Michigan 2 weeks prior to admission. The differential diagnosis was broadened to include acute hypersensitivity pneumonitis and fungal infection. BAL, transbronchial biopsies and EBUS-TBNA was performed while escalating steroids. The lung biopsy confirmed Histoplasma. Urine Histoplasma antigen returned positive. The patient was treated with itraconazole with an overlap of steroids for 2 weeks upon discharge. He was readmitted within a week with worsening hypoxia and worsening infiltrates on lung imaging. He was then treated with liposomal amphotericin with gradual clinical improvement. Follow-up 1 month post discharge revealed complete clinical and radiologic resolution. DISCUSSION: Viral pneumonia and acute pulmonary histoplasmosis have overlapping clinical and radiologic features which can make diagnosis challenging. COVID-19 pneumonia typically presents with peripheral ground glass opacities with or without superimposed consolidations. Invasive fungal pneumonia can have a similar appearance on CT usually with additional findings of hilar and mediastinal adenopathy. CONCLUSIONS: This case highlights the challenges involved in diagnosing acute pulmonary histoplasmosis in an immunocompetent individual in the midst of the pandemic. Clinicians should always maintain a wide differential diagnosis to avoid diagnostic delay. REFERENCE #1: Staffolani, S., Buonfrate, D., Angheben, A., Gobbi, F., Giorli, G., Guerriero, M., Barchiesi, F. (2018). Acute histoplasmosis in immunocompetent travelers: A systematic review of literature. BMC Infectious Diseases, 18(1). doi:10.1186/s12879-018-3476-z REFERENCE #2: Duzgun, S. A., Durhan, G., Demirkazik, F. B., Akpinar, M. G., & Ariyurek, O. M. (2020). COVID-19 pneumonia: the great radiological mimicker. Insights into imaging, 11(1), 118. https://doi.org/10.1186/s13244-020-00933-z REFERENCE #3: Klein, M., Khan, M., Salinas, J. L., & Sanchez, R. (2019). Disseminated pulmonary histoplasmosis in immunocompetent patients: A common epidemiological exposure. BMJ Case Reports, 12(3). doi:10.1136/bcr-2018-227994 DISCLOSURES: No relevant relationships by Joseph Arguinchona, source=Web Response No relevant relationships by Michael Kaster, source=Web Response No relevant relationships by Muazzam Mirza, source=Web Response No relevant relationships by Anusha Pinjala, source=Web Response no disclosure on file for Venketraman Sahasranaman;

AMIKACIN-INDUCED HYPERSENSITIVITY PNEUMONITIS IN A PATIENT WITH PULMONARY MYCOBACTERIUM AVIUM COMPLEX INFECTION

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Inhaled amikacin is FDA approved in the treatment of pulmonary Mycobacterium avium complex (MAC). Here we present a case of acute hypersensitivity pneumonitis after initiating therapy with inhaled amikacin. CASE PRESENTATION: An 82 year old male with a history of pulmonary MAC infection and chronic hypoxemia on 2L oxygen presented with progressive non-productive cough and dyspnea. He had been diagnosed with pulmonary MAC three years prior to presentation and had been treated with azithromycin, rifampin, and ethambutol. CT chest imaging demonstrated multifocal bronchiectasis, tree in bud nodules, and cavitary lesions. Respiratory AFB cultures were positive for MAC. He was prescribed oral rifampin and azithromycin. Intravenous amikacin was considered given cavitary disease but deferred in light of age and comorbidities. Inhaled amikacin was prescribed but unable to be started as an outpatient. One week later, he was admitted with new fevers, progressive dry cough, dyspnea, and increased oxygen requirement. CT chest was negative for pulmonary embolism and showed new multifocal ground glass opacities (Image #1). He was admitted for suspected superimposed bacterial or viral pneumonia. COVID-19 and respiratory viral testing were negative. Sputum culture was unable to be obtained due to non-productive cough. Rifampin and azithromycin were continued and nebulized amikacin was initiated. Broad spectrum antibiotics were started to cover for bacterial pneumonia. He initially defervesced but on hospital day #5, his dyspnea and hypoxemia worsened. He required up to 15 liters 100% oxygen via non-rebreather mask. He was empirically diuresed and antibiotic coverage was broadened without improvement. Echocardiogram showed unchanged cardiac function. CT chest imaging on hospital day #7 demonstrated progressive multifocal ground glass opacities with intralobular and interlobular septal thickening (Image #2). Clinical picture was concerning for drug induced pneumonitis. Amikacin was discontinued and oral prednisone was started. His respiratory symptoms improved and he was weaned to 2L via nasal cannula prior to discharge. Nebulized amikacin was not restarted. DISCUSSION: In this patient, initiation of inhaled amikacin was temporally related to the development of an acute hypersensitivity pneumonitis associated with significant hypoxemia which improved promptly with the discontinuation of inhaled amikacin and initiation of corticosteroids. Trial data investigating inhaled liposomal amikacin in pulmonary MAC has reported a 3% incidence of hypersensitivity pneumonitis. CONCLUSIONS: Inhaled amikacin is a useful adjunctive therapy in the treatment of refractory pulmonary MAC infection. The development of hypersensitivity pneumonitis should prompt immediate discontinuation of the drug and consideration for corticosteroid therapy in severe cases. REFERENCE #1: Griffith DE, Eagle G, Thomson R, et al. CONVERT Study Group Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT): A prospective, open-label, randomized study. Am J Respir Crit Care Med 2018; 198:1559–69. REFERENCE #2: Swenson, C, Lapinel NC, and Ali J. Clinical Management of Respiratory Adverse Events Associated With Amikacin Liposome Inhalation Suspension: Results From a Patient Survey. Open Forum Infect Dis. 2020 Apr; 7(4): ofaa079 DISCLOSURES: No relevant relationships by Casey Graziani, source=Web Response No relevant relationships by Ali Jiwani, source=Web Response

Pilot Study Using Recombinant Antigens r-PROE and r-IGLL1 for the Serodiagnosis of Feather Duvet Lung

BackgroundFeather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL). MethodsSpecific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15). ResultsThe sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. ConclusionsThe new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows

IntroductionExposure to feather bedding may be an unnoticed cause of hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF). Thus, an in-depth clinical study of the diagnosis of patients with suspected HP and IPF is required in order to determine their etiologies. The objective of the present study is to raise awareness of HP and pulmonary fibrosis due to exposure to feather bedding, and to study the prevalence and describe long-term outcomes. MethodsWe describe a series of 33 patients diagnosed with HP and pulmonary fibrosis due to feather bedding exposure and followed over a 10-year period. The patients were from a subgroup of 127 individuals with HP undergoing in-depth evaluation using a diagnostic protocol at a regional referral center. ResultsEleven (33%) patients were clinically diagnosed with acute HP and 22 (67%) with chronic HP. Ten (45%) chronic HP patients showed a high resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) with suspected IPF. The prevalence of HP was 6.2/100 000 feather bedding users (compared with 54.6 per 100 000 bird-breeders). The survival rates of patients over the 10-year period was 100% for acute HP and 64% for chronic HP. ConclusionsIn a series of HP patients, the diagnosis was attributed to feather bedding exposure in 26%. UIP pattern on HRCT was present in nearly half of the chronic cases. The survival of patients with chronic HP at ten years was 64%, despite avoiding further exposure.

Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related hypersensitivity pneumonitis

BackgroundThe number of reports on sarcoidosis complicated by hypersensitivity pneumonitis (HP) is limited, and most describe cases complicated by chronic bird-related HP. Here, we present for the first time a case with Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related HP.Case presentationA 62-year-old man with a past medical history of sarcoidosis was admitted to our department, and chest computed tomography showed diffuse ground-glass opacities, which appeared as he rapidly increased the number of pigeons he kept for a competition. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas, which contained positively stained substances on immunohistochemistry using the PAB antibody, a specific monoclonal antibody against P. acnes lipoteichoic acid. Poorly formed non-caseating granulomas without positively stained substances were also detected.ConclusionWe describe the successful identification of this exceptionally rare case of sarcoidosis complicated by acute bird-related HP in which two morphologically and immunohistologically different types of granulomas were present in the same lung.

Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®

BackgroundBird 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. MethodsWe 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. ResultsThe 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. ConclusionsMeasurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.

BackgroundApolipoprotein A‐I (apoA‐I) has an antifibrotic effect in idiopathic pulmonary fibrosis. Although pulmonary fibrosis is associated with poor prognosis of patients with hypersensitivity pneumonitis (HP), little is known regarding the role of apoA‐I in the pathogenesis of HP.MethodsTwo‐dimensional electrophoresis, immunoblotting, and enzyme‐linked immunosorbent assays were performed for the identification and quantification of apoA‐I in bronchoalveolar lavage fluid (BALF) from patients with acute and chronic HP. To investigate the degradation of apoA‐I, apoA‐I was incubated with BALF. Moreover, the role of apoA‐I in TGF‐β1‐induced epithelial–mesenchymal transition of A549 cells was examined.ResultsThe concentration of apoA‐I in the BALF was significantly lower in chronic HP (n = 56) compared with acute HP (n = 31). The expression level of apoA‐I was also low in the lung tissues of chronic HP. ApoA‐I was degraded by BALF from HP patients. The number of chymase‐positive mast cells in the alveolar parenchyma was inversely correlated with apoA‐I levels in the BALF of chronic HP patients. In vitro experiment using A549 cells, untreated apoA‐I inhibited TGF‐β1‐induced epithelial–mesenchymal transition, although this trend was not observed in the chymase‐treated apoA‐I.ConclusionsA decrease of apoA‐I was associated with the pathogenesis of chronic HP in terms of pulmonary fibrosis and mast cell chymase attenuated the protective effect of apoA‐I against pulmonary fibrosis. Furthermore, apoA‐I could be a crucial molecule associated with lung fibrogenesis of HP.

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation of a variety of antigens in susceptible and sensitized individuals. These antigens are found in the environment, mostly derived from bird proteins and fungi. The prevalence and incidence of HP vary widely depending on the intensity of exposure, the geographical area and the local climate. Immunopathologically, HP is characterized by an exaggerated humoral and cellular immune response affecting the small airways and lung parenchyma. A complex interplay of genetic, host and environmental factors underlies the development and progression of HP. HP can be classified into acute, chronic non-fibrotic and chronic fibrotic forms. Acute HP results from intermittent, high-level exposure to the inducing antigen, usually within a few hours of exposure, whereas chronic HP mostly originates from long-term, low-level exposure (usually to birds or moulds in the home), is not easy to define in terms of time, and may occur within weeks, months or even years of exposure. Some patients with fibrotic HP may evolve to a progressive phenotype, even with complete exposure avoidance. Diagnosis is based on an accurate exposure history, clinical presentation, characteristic high-resolution CT findings, specific IgG antibodies to the offending antigen, bronchoalveolar lavage and pathological features. Complete antigen avoidance is the mainstay of treatment. The pharmacotherapy of chronic HP consists of immunosuppressive drugs such as corticosteroids, with antifibrotic therapy being a potential therapy for patients with progressive disease.

Comparative safety of flavocoxid vs prescription NSAIDs among osteoarthritis patients

Flavocoxid is a prescription medical food used to manage osteoarthritis (OA) symptoms. Safety concerns based on case reports raised an association with acute liver injury and hypersensitivity pneumonitis. We determined incidence rates (IR) of these safety events in a cohort of new users of flavocoxid and prescription non-steroidal anti-inflammatory drugs (NSAIDs). MarketScan® claims data (2006-2017) was used to identify patients initiating flavocoxid or NSAIDs. Propensity score matching (1:2 ratio) was used to balance patient characteristics. Outcomes included hospitalization for hypersensitivity pneumonitis, liver injury, gastrointestinal bleeding, myocardial infarction, and acute kidney injury. Poisson regression was used to calculate IRs and Cox regression for calculating adjusted hazard ratios (aHR). 3,337 flavocoxid and 6,674 NSAID users met eligibility criteria. Before matching, flavocoxid users were older (mean 57 vs 51 years), had more polypharmacy (68% vs 29% taking ≥11 medications). After matching, characteristics were well balanced. The rate of hypersensitivity pneumonitis was 1.1 (95% CI 0.0-5.9) per 1,000 PY for flavocoxid and 0.0 (95% CI 0.0-2.2) for NSAIDs. For hospitalized liver injury, it was 3.2 (95% CI 0.7-9.3) for flavocoxid and 2.4 (95% CI 0.7-6.1) for NSAIDs, aHR=1.16, 95% CI 0.23-6.01. A lower rate of GI bleed was observed, IR: 5.3 (1.7-12.3) for flavocoxid and 10.2 (5.9-16.3) for NSAIDs, aHR 0.49 (0.18-1.68). There were no significant differences for MI or AKI. The rate of hypersensitivity pneumonitis and liver injury associated with flavocoxid was low and minimally elevated compared to NSAIDs. Flavocoxid users had a significantly lower risk for hospitalized GI bleeding. The risk-benefit profile of flavocoxid may warrant reevaluation in light of these findings.

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows

IntroductionExposure to feather bedding may be an unnoticed cause of hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF). Thus, an in-depth clinical study of the diagnosis of patients with suspected HP and IPF is required in order to determine their etiologies. The objective of the present study is to raise awareness of HP and pulmonary fibrosis due to exposure to feather bedding, and to study the prevalence and describe long-term outcomes. MethodsWe describe a series of 33 patients diagnosed with HP and pulmonary fibrosis due to feather bedding exposure and followed over a 10-year period. The patients were from a subgroup of 127 individuals with HP undergoing in-depth evaluation using a diagnostic protocol at a regional referral center. ResultsEleven (33%) patients were clinically diagnosed with acute HP and 22 (67%) with chronic HP. Ten (45%) chronic HP patients showed a high resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) with suspected IPF. The prevalence of HP was 6.2/100 000 feather bedding users (compared with 54.6 per 100 000 bird-breeders). The survival rates of patients over the 10-year period was 100% for acute HP and 64% for chronic HP. ConclusionsIn a series of HP patients, the diagnosis was attributed to feather bedding exposure in 26%. UIP pattern on HRCT was present in nearly half of the chronic cases. The survival of patients with chronic HP at ten years was 64%, despite avoiding further exposure.

Acute hypersensitivity pneumonitis in woodworkers caused by inhalation of birch dust contaminated with Pantoea agglomerans and Microbacterium barkeri.

Five workers (2 males and 3 females) employed in a furniture factory located in eastern Poland developed hypersensitivity pneumonitis (HP) after the pine wood used for furniture production was replaced by birch wood. All of them reported onset of respiratory and general symptoms (cough, shortness of breath, general malaise) after inhalation exposure to birch dust, showed crackles at auscultation, ground-glass attenuations in HRCT examination, and lymphocytosis in the BAL examination. The diagnosis of acute HP was set in 4 persons and the diagnosis of subacute HP in one. Samples of birch wood associated with evoking disease symptoms were subjected to microbiological analysis with the conventional and molecular methods. Two bacterial isolates were found to occur in large quantities (of the order 108 CFU/g) in examined samples: Gram-negative bacterium of the species Pantoea agglomerans and a non-filamentous Gram-positive actinobacterium of the species Microbacterium barkeri. In the test for inhibition of leukocyte migration, 4 out of 5 examined patients showed a positive reaction in the presence of P. agglomerans and 2 in the presence of M. barkeri. Only one person showed the presence of precipitins to P. agglomerans and none to M. barkeri. In the inhalation challenge, which is the most relevant allergological test in the HP diagnostics, all patients reacted positively to P. agglomerans and only one to M. barkeri. The results indicate that P. agglomerans developing in birch wood was the main agent causing HP in the workers exposed to the inhalation of dust from this wood, while the etiologic role of M. barkeri is probably secondary. The results demonstrate that apart from fungi and filamentous actinobacteria, regarded until recently as causative agents of HP in woodworkers, Gram-negative bacteria and non-filamentous actinobacteria may also elicit disease symptoms in the workers processing wood infected with large amounts of these microorganisms. The results obtained also seem to indicate that cellular-mediated reactions are more significant for causing disease symptoms compared to those that are precipitin-mediated.

Hypersensitivity pneumonitis: Main features characterization in a Portuguese cohort

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) which varies in prevalence across the world, depending on disease definition, diagnostic methods, exposure type and intensity, geographical environments, agricultural and industrial practices, and host risk factors. This study aimed to deepen knowledge about HP’s clinical characteristics, diagnosis and functional and imaging features in a cohort of HP patients from the North of Portugal. To achieve this goal, a retrospective assessment of the clinical and diagnostic data was carried out, and patients were classified and compared according to disease presentation (acute, sub-acute and chronic HP forms).Of the 209 HP patients included (mean age 58.3 ± 16.0 years), 52.6% were female and 73.7% presented a chronic form. Most patients had prior exposure to birds (76.6%). Dyspnoea and cough were the most frequently experienced symptoms, but no statistically significant differences were found between groups (p = 0.089, p = 0.418, respectively). Fever was most common in acute HP form (p < 0.001). The most common patterns found in Chest CT were ground glass (p = 0.002) in acute/subacute presentation, and reticulation (p < 0.001) in chronic form, while mosaic attenuation, although was also frequently observed, no statistically significant differences were found between groups (p = 0.512). The most common functional pattern was restrictive (38% of patients, 73.7% with chronic HP form). Bronchoalveolar lavage lymphocytes were higher in acute and subacute forms although not reaching statistical significance (p = 0.072), with lowest CD4/CD8 ratio (p = 0.001) in acute forms.Thus, given the significant disease heterogeneity, further studies with different populations and ambient exposures are needed to achieve a better stratification of the exposure risk, to provide proper implementation of avoidance methods and a precise diagnostic and therapeutic approach.