Cause Of Hypersensitivity Pneumonitis Research Articles

Hypersensitivity Pneumonitis: Challenges of a Complex Disease.

Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease caused by chronic inhalation of a wide variety of antigens in susceptible and sensitized individuals, commonly associated with an occupational exposure. An impressive number of inciting antigens causing hypersensitivity pneumonitis have been found to cover a wide range of occupations. As working practices have changed over time, especially in industrialized countries, new names for occupational HP have emerged. This review emphasizes the main diagnostic issues arising from the high variability of clinical presentation and the broad spectrum of causal antigens. Furthermore, it provides an overview of current methods to unveil possible causes of hypersensitivity pneumonitis, highlights HP's current diagnostic and treatment challenges and the remaining areas of uncertainty, and presents prevention strategies.

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.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90days after transplantation were free from chronic lung allograft dysfunction after 3years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

M128 HYPERSENSITIVITY PNEUMONITIS: DON’T OVERESTIMATE THE BIRDS

Hypersensitivity pneumonitis (HP) is an exaggerated response to inhaled antigens causing persistent cough, dyspnea and a restrictive lung disease. Several causative agents have been identified including birds, molds, mycobacteria, and chemicals. Avian proteins are the most common cause of HP. We report a gentleman who raised birds and developed chronic hypersensitivity pneumonitis with precipitins positive to Saccharomonospora viridis, a bacteria found in dried grass, to which he has occupational exposure.

Occupational causes of hypersensitivity pneumonitis: a systematic review and compendium.

BackgroundHypersensitivity pneumonitis (HP) is caused by a variety of antigens and low-molecular-weight chemicals, often through occupational exposure. Making a diagnosis of HP and identifying a cause are challenging. Cryptogenic cases are frequently reported, and missing or incomplete exposure histories can cause misclassification.AimsTo provide an evidence-based compendium of sources of exposure and causes of HP for the clinician, through systematic review of medical literature.MethodsArticles related to HP causative agents and occupational exposure were searched from the databases OVID Medline (1946 to October 2020) and EMBASE (1974 to October 2020). s and full texts of articles were screened by two reviewers. Data on causative antigens, occupational source of exposure and any associated eponymous name were extracted and grouped according to source of exposure.ResultsA total of 1790 articles were identified, from which 305 articles met the inclusion criteria. An additional 22 articles were identified from citation lists of the selected review articles. Sources of exposure identified for HP were sorted into 14 categories of work (agricultural, plant matter processing, wood, animal-related, foodstuff, food processing, metal processing, polymers, other manufacturing, chemicals, aerosolized water, service, waste and sewage and wind instruments).ConclusionsThis work is a comprehensive list of occupational causative agents and exposures causing HP. Cases are grouped by source of exposure, allowing an immediately accessible compendium of causes for use during occupational exposure assessment, which could also form the basis for a clinical questionnaire.

Mise au point : pneumopathies d’hypersensibilité

Hypersensitivity Pneumonitis (HP) is a common immune-mediated interstitial lung disease (ILD) induced by repeated exposure to environmental antigens in susceptible individuals. The most commonly known forms are bird fancier's disease and farmer's lung. However, the antigens involved are widely diverse. Therefore, the list of causes of HP is frequently expanding. HP seems to be under-diagnosed owing to its highly heterogeneous presentation in both the non-fibrotic and fibrotic subtypes and could represent up to 15% of all ILDs encountered in clinical practice. However, the recognition of HP cases is essential to ensure appropriate therapy for the patient. Home health care workers’ intervention is sometimes critical in this context. In case of confirmed exposure, the diagnosis could be considered with high confidence if the high-resolution computed tomography (HR-CT) shows a typical HP pattern associated with a lymphocytosis over 30% in the broncho-alveolar lavage (BAL). In all other situations, the patients should undergo further investigations and additional histopathological sampling should be considered and submitted to a multidisciplinary team discussion. After diagnosis, antigenic eviction is the rule whenever possible. Corticosteroid treatment is the first-line medical treatment for severe forms and aims to prevent the development of fibrosis. Anti-fibrotic therapy is now an option for patients with progressive ILD and failure of immunomodulatory/immunosuppressive therapies.

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.

Bagassosis, rare cause of hypersensitivity pneumonitis: A case report

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma specifically the alveoli, terminal bronchioles and alveolar interstitium. HP is caused by delayed allergic reaction to variety of antigens like microbes, animal proteins, and low-molecular-weight chemicals. Bagassosis is one such HP caused by repetitive inhalation of bagasse. Though use of bagasse as cause of HP is known, use of bagasse in brick- kiln factory as fuel and its association with HP has not been well documented. We report a case of HP in a brick-kiln worker where bagasse was used as fuel. A twenty-five years old man, working in a brick kiln for five years, presented with complaints of dry cough, low grade fever and weight loss for one month. He had bilateral lower lobe crackles on auscultation. The history of bagasse, clay and coal dust exposure, clinical presentation and imaging were suggestive of HP. However, being endemic in India, pulmonary tuberculosis was ruled out by negative Mantoux test, sputum for acid fast bacilli and Cartridge Based Nucleic Acid Amplification Test. He was managed with corticosteroids and symptomatic treatment with good response and resolution of clinical signs and radiological changes.

Pantoea agglomerans chronic exposure induces epithelial-mesenchymal transition in human lung epithelial cells and mice lungs.

Pantoea agglomerans is gram-negative bacteria widely distributed in nature. It predominates in inhalable dust from grain, herbs, and flax, and was identified as the most important cause of hypersensitivity pneumonitis (HP) in eastern Poland. To better understand the molecular mechanism of HP development studies focused on the interactions between P. agglomerans and alveolar epithelial cells as well as lung tissue with particular emphasis on the epithelial-mesenchymal transition (EMT). The studies were conducted on human normal lung epithelial NL20cells and mice strain C57BL/6J. Cells and mice underwent chronic exposure to saline extract of P. agglomerans (SE-PA). Morphological changes were evaluated under light microscopy, the concentration of fibrosis markers was examined by the ELISA method, while the expression of genes involved in EMT was evaluated by RealTime PCR. During incubation with SE-PA epithelial cells underwent conversion and assumed fibroblast phenotype characterized by a decrease in epithelial cells markers (CDH1, CLDN1, JUP) and increase in mesenchymal cells markers (FN1, VIM, CDH2). Mice lungs collected after 14 days of SE-PA treatment revealed inflammation with marked lymphocytes infiltration. The intensified inflammatory process accompanied by increased proliferation of fibrous connective tissue was noted in mice lungs after 28 days of SE-PA exposure. Histological changes correlated with an increase of fibrosis markers (hydroxyproline, collagens), downregulation of epithelial markers (Cdh1, Cldn1, Jup, Ocln) and upregulation of myofibroblasts markers (Acta2, Cdh2, Fn1, Vim). Obtained results revealed SE-PA ability to induce EMT in human lung epithelial cells and mice lung tissue, with the scale of changes proportional to the time of treatment.

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.

Unusual cause of hypersensitivity pneumonitis with characteristic head-cheese sign

Unusual cause of hypersensitivity pneumonitis with characteristic head-cheese sign

281. Hypersensitivity Pneumonitis Diagnosed with Broad-Range PCR Testing after Exposure to Battarrea Mushroom Spores

Background Battarrea puffball mushrooms are found extensively worldwide and contain spore-containing sacs. Inhalation of the spores of similar mushrooms, such as Lycoperdon, have been implicated in cases of lycoperdonosis—a syndrome of hypersensitivity pneumonitis. We report a case of hypersensitivity pneumonitis confirmed to be secondary to Battarrea spore exposure diagnosed by broad-range PCR.MethodsA 23-year-old homeless man with a history of methamphetamine use presented to the emergency department with a 2-week history of fevers, chills, productive cough, and malaise. He reported his symptoms began soon after eating a long-stemmed mushroom he found growing next to a building. He reported inhaling particles from the mushroom when he picked it up prior to eating it. He vomited within 1 hour of ingestion, and then had a worsening progression of cough and malaise over the following 2 weeks. In the emergency department, he was noted to have leukocytosis and mild elevation of transaminases. He required supplemental oxygen due to hypoxemia. CT scan of his chest demonstrated extensive bilateral nodular pulmonary infiltrates. He was admitted and started on treatment for community-acquired pneumonia. Over the next several days, he had worsening respiratory failure, and routine work up for infectious etiologies was unrevealing. To further investigate, bronchoscopy and bronchoalveolar lavage (BAL) was performed and routine bacterial, fungal and mycobacterial cultures and cytology with Gomori Methanamine-silver and acid-fast stains were negative. BAL fluid was sent for broad range DNA testing by PCR. Antibiotic therapy was stopped, and he was started on steroids to treat presumed hypersensitivity pneumonitis. He recovered rapidly and was discharged on a course of oral corticosteroids.ResultsAfter the patient was discharged, molecular testing of BAL fluid resulted with detection of Battarrea species DNA using 28s and ITS primer sets. DNA from no other pathogens was detected.ConclusionIdentified through broad range DNA PCR testing, exposure to Battarrea mushroom spores may be a previously unreported cause of hypersensitivity pneumonitis. PCR testing should be considered in the workup of hypersensitivity pneumonitis with known or suspected exposure to mushroom spores. Disclosures All authors: No reported disclosures.

The Myth of Mycotoxins and Mold Injury.

In recent years, mold has been blamed for many symptoms or a constellation of symptoms. These symptoms are usually vague and subjective and difficult or impossible to measure or quantify. Moreover, there is no scientific evidence that mold has anything to do with these symptoms. In particular, the concept of toxic mold syndrome has permeated the public consciousness, and mycotoxins have falsely been associated with autoimmune diseases and a variety of other conditions. In fact, there is no evidence that the presence of mycotoxins in the air is enough to cause any disease known to man. Molds legitimately can cause allergies and can be a trigger for asthma. Certain specific molds such as Aspergillus can be a cause of hypersensitivity pneumonitis. In immunocompromised hosts, both dermatologic and systemic infections can result from various fungi and can be associated with significant morbidity or even mortality. However, the existence of toxic mold syndrome has been disproven, despite the numerous disreputable practices such as testing homes for mold spores, measuring "mycotoxins" in the urine, and testing patients for IgG to mold. In truth, none of these techniques have been validated, nor do they have any relevance to any clinical disease. All that these tests that are being performed by laboratories of disrepute does is to further propagate misinformation and inflict unnecessary and often exorbitant costs on patients desperate for a clinical diagnosis, right or wrong, for their constellation of maladies.

Lentil aspiration leading to likely hypersensitivity pneumonitis.

A variety of inhaled antigens have been implicated to cause hypersensitivity pneumonitis (HP). We observed that children force-fed with lentil-based weaning food had persistent respiratory symptoms and radiology similar to HP. To describe the clinical features of lentil HP. We conducted a retrospective review of records of children with lentil HP attending Pediatric Chest Clinic at a tertiary care hospital in North India from 2008-2018. We included case records with elevated immunoglobulin G (IgG) specific for lentil antigen. Nine children (seven boys) were identified with median (IQR) age of onset of symptoms and diagnosis at 9 (6, 12) and 11 (10, 16) months, respectively. Chronic cough (100%), shortness of breath (89%), fever (78%), vomiting (56%), and wheezing (33%) were common symptoms. Fine crackles were heard in 33% of children, none had clubbing. CT scans showed nodular opacities and consolidation in 78% and 67% children, respectively. Bronchoalveolar lavage showed increased neutrophils and lymphocytes (67% and 33%, respectively). All children showed rapid remission with systemic steroids (prednisolone), starting at a median dose of 1 (1, 1.1) mg kg-1 day-1 . One child had a clinical relapse which was treated with oral steroids again. IgG specific to lentil antigens was elevated in children with lentil HP (21->200 mgA/L) compared with children with other chronic respiratory illnesses (n = 7, <2-11.4 mgA/L). Lentil aspiration is an important cause of HP in infants of weaning age with force-feeding practices. Further studies are needed to identify aspirated antigens which cause HP in aspiration prone children.

Characteristics of hypersensitivity pneumonitis diagnosed by interstitial and occupational lung disease multi-disciplinary team consensus.

The causes of hypersensitivity pneumonitis (HP) in the UK are changing as working practices evolve, and metalworking fluid (MWF) is now a frequently reported causative exposure. We aimed to review and describe all cases of HP from our UK regional service, with respect to the causative exposure and diagnostic characteristics. In a retrospective, cross-sectional study, we collected patient data for all 206 cases of HP diagnosed within our UK-based regional NHS interstitial and occupational lung disease service, 2002-17. This included demographics, environmental and occupational exposures, clinical features, and diagnostic tests (CT imaging, bronchiolo-alveolar cell count, lung function, histology). We grouped the data by cause (occupational, non-occupational and unknown) and by presence or absence of fibrosis on CT, in order to undertake hypothesis testing. Cases were occupational (n = 50), non-occupational (n = 56) or cryptogenic (n = 100) in aetiology. The commonest causes were birds = 37 (18%) and MWF = 36 (17%). Other occupational causes included humidifiers and household or commercial waste, but only one case of farmers' lung. Cryptogenic cases were associated with significantly older age, female gender, lower lung function parameters, fewer alveolar lymphocyte counts >20%, and fibrosis on CT; exposure information was missing in 22-33% of cryptogenic cases. MWF is the commonest occupational cause of HP, where workers usually present with more acute/subacute features and less fibrosis on CT; refuse work is an emerging cause. Cryptogenic HP has a fibrotic phenotype, and a full occupational history should be taken, as historical workplace exposures may be relevant.

Fungal contamination of wind instruments: Immunological and clinical consequences for musicians

IntroductionPlaying a wind instrument is an increasingly reported cause of hypersensitivity pneumonitis. However, current knowledge about contamination of wind instruments by fungi and specific fungal sensitization is scarce. Therefore, we aimed: (i) to assess the current prevalence and type of fungal contamination of wind instruments, (ii) to identify potential risk factors associated with instrument contamination, and (iii) to evaluate the prevalence of sensitization to these fungi among musicians. Material and methodsMusicians from music schools in eastern France and who played a wind instrument were prospectively recruited (NCT01487850). The mouthpiece and the reed of their instrument were sampled to quantify the magnitude and type of fungi. Each subject had a physical examination, a mycological analysis of saliva and a blood sample in search of serum precipitins against the most frequent fungi isolated from instruments. The results were compared with those of 40 healthy non-exposed controls. ResultsForty musicians playing a wind instrument (bassoon, clarinet, oboe, saxophone) were included. (i) 95% of wind instruments were colonized by fungi, mainly with Phoma spp., Penicillium spp. and Rhodotorula mucilaginosa; (ii) absence of systematic drying of the instrument was a main contributing factor; (iii) serum precipitins were significantly more present in the musicians' sera than in control sera and were consistent with the fungi present in their instrument. ConclusionThis study reveals a constant and specific fungal contamination among wind reed instruments with a significant sensitization among musicians, pleading in favour of regular instrument cleaning. Physicians should be aware of this possible source of antigenic exposure.

Occupational and Environmental Lung Diseases Selected Pneumoconiosis

Environmental and occupational lung diseases encompass a diverse group of lung diseases caused by the inhalation of potentially harmful substances. This review provides an in-depth discussion of the pneumoconioses, hypersensitivity pneumonitis, chronic beryllium disease, and other occupational lung diseases that affect the parenchyma. For each disease, the review presents the epidemiology, biologic mechanisms when known, diagnosis, and clinical care. The review includes tables with different pneumoconioses, occupations and industries associated with silicosis and asbestosis, and some selected causes of hypersensitivity pneumonitis, as well as chest radiographs, computed tomographic scans, and/or pathologic slides of some selected diseases. This review contains 9 figures, 4 tables, and 68 references. Key words: asbestosis, asbestos-related pleural plaque, coal worker’s pneumoconiosis, chronic beryllium disease, hard metal pneumoconiosis, hypersensitivity pneumonitis, pneumoconiosis, progressive massive fibrosis, silicosis

Occupational and Environmental Lung Diseases Selected Pneumoconiosis

Environmental and occupational lung diseases encompass a diverse group of lung diseases caused by the inhalation of potentially harmful substances. This review provides an in-depth discussion of the pneumoconioses, hypersensitivity pneumonitis, chronic beryllium disease, and other occupational lung diseases that affect the parenchyma. For each disease, the review presents the epidemiology, biologic mechanisms when known, diagnosis, and clinical care. The review includes tables with different pneumoconioses, occupations and industries associated with silicosis and asbestosis, and some selected causes of hypersensitivity pneumonitis, as well as chest radiographs, computed tomographic scans, and/or pathologic slides of some selected diseases. This review contains 9 figures, 4 tables, and 68 references. Key words: asbestosis, asbestos-related pleural plaque, coal worker’s pneumoconiosis, chronic beryllium disease, hard metal pneumoconiosis, hypersensitivity pneumonitis, pneumoconiosis, progressive massive fibrosis, silicosis

Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping

BackgroundAvian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated.MethodPigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed.ResultsImmunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production.ConclusionsPigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.

Draft Genome Sequences of Six Mycobacterium immunogenum Strains Obtained from a Chloraminated Drinking Water Distribution System Simulator.

We report here the draft genome sequences of six Mycobacterium immunogenum strains isolated from a chloraminated drinking water distribution system simulator subjected to changes in operational parameters. M. immunogenum, a rapidly growing mycobacterium previously reported to be the cause of hypersensitivity pneumonitis from contaminated metalworking fluid aerosols, is becoming a public health concern.