[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.

Japanese clinical practice guide 2022 for hypersensitivity pneumonitis.

Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs.

Idiopathic pulmonary fibrosis in the United States: time to diagnosis and treatment.

OBJECTIVE: Create a timeline of diagnosis and treatment for IPF in the US. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019). EXPOSURE: To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease. MAIN OUTCOMES AND MEASURES: Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival. RESULTS: A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years. CONCLUSIONS AND RELEVANCE: Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

When to panic about a panic attack: A challenging case of hypersensitivity pneumonitis.

The COVID-19 pandemic has created diagnostic difficulties with the increase in mental health illnesses that often present with nonspecific symptoms, like hypersensitivity pneumonitis. Hypersensitivity pneumonitis is a complex syndrome of varying triggers, onset, severity, and clinical manifestations that can be challenging to diagnose in many cases. Typical symptoms are nonspecific and can be attributed to other entities. There are no pediatric guidelines, which contributes to diagnostic difficulties and delays in treatment. It is particularly important to avoid diagnostic biases, have an index of suspicion for hypersensitivity pneumonitis, and to develop pediatric guidelines as outcomes are excellent when diagnosed and treated promptly. This article discusses hypersensitivity pneumonitis with a focus on the causes, pathogenesis, diagnostic approach, outcomes, and prognosis while using a case to illustrate the diagnostic difficulties worsened by the COVID-19 pandemic.

Hypersensitivity Pneumonitis: Updates in Evaluation, Management, and Ongoing Dilemmas.

Hypersensitivity pneumonitis (HP) is a heterogenous disease entity characterized by an aberrant immune response to inhalational antigens. Disease modification hinges on early antigen remediation with a goal to attenuate immune dysregulation. Disease severity and progression are mediated by an interface between degree, type and chronicity of exposure, genetic predisposition, and biochemical properties of the inducing agent. Guidelines have provided a standardized approach; however, decision-making remains with many clinical dilemmas. The delineation of fibrotic and nonfibrotic HP is crucial to identify the differences in clinical trajectories, and further clinical trials are needed to understand optimal therapeutic strategies.

[Interstitial lung diseases : Classification, differential diagnosis and treatment approaches in a heterogeneous group of chronic lung disorders]. / Interstitielle Lungenerkrankungen : Klassifikation, Differenzialdiagnostik und therapeutische Ansätze bei einer heterogenen Gruppe chronischer Lungenerkrankungen.

Interstitial lung diseases (ILD) comprise a heterogeneous group of chronic lung disorders of different etiologies that can not only affect the interstitium but also the alveolar space and the bronchial system. According to the "Global Burden of Disease Study" there has been an increase in incidence over the last decades and it is expected that the number of ILD-associated deaths will double over the next 20 years. ILD are grouped into those of unknown cause, e.g. idiopathic pulmonary fibrosis (IPF), and ILD of known cause, which include drug-induced and connective tissue disease-associated ILD as well as granulomatous ILD such as sarcoidosis and hypersensitivity pneumonitis. In addition, some ILD present a progressive fibrosing phenotype, which influences therapeutic decisions. Predominantly inflammatory entities are treated with immunosuppressives, whereas predominantly fibrosing ILD are treated with antifibrotic drugs; in some cases, a combination of both is necessary. The spectrum of differential diagnoses in ILD is broad, but definite diagnosis is essential for treatment selection; therefore, the multidisciplinary ILD board plays a pivotal role.

Diagnosis, course and management of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a complex and heterogeneous interstitial lung disease (ILD) that occurs when susceptible individuals develop an exaggerated immune response to an inhaled antigen. In this review, we discuss the latest guidelines for the diagnostic evaluation of patients with suspected HP, the importance of identifying patients with fibrotic and progressive disease, and the evidence supporting the drugs commonly used in the treatment of HP. Differential diagnosis of HP can be challenging and requires a thorough exposure history, multidisciplinary discussion of clinical and radiologic data, and, in some cases, assessment of bronchoalveolar lavage lymphocytosis and histopathologic findings. Patients with HP may be categorised as having non-fibrotic or fibrotic HP. The presence of fibrosis is associated with worse outcomes. A proportion of patients with fibrotic HP develop a progressive phenotype, characterised by worsening fibrosis, decline in lung function and early mortality. There are no established guidelines for the treatment of HP. Antigen avoidance should be implemented wherever possible. Immunosuppressants are commonly used in patients with HP but have not been shown to slow the worsening of fibrotic disease. Nintedanib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for slowing the progression of chronic fibrosing ILDs with a progressive phenotype, including progressive fibrotic HP. Non-pharmacological interventions, such as oxygen therapy, pulmonary rehabilitation and supportive care, may be important components of the overall care of patients with progressive HP.

Inhalational lung diseases.

The term inhalational lung disease comprises a group of entities that develop secondary to the active aspiration of particles. Most are occupational lung diseases. Inhalational lung diseases are classified as occupational diseases (pneumoconiosis, chemical pneumonitis), hypersensitivity pneumonitis, and electronic-cigarette-associated lung diseases. The radiologic findings often consist of nonspecific interstitial patterns that can be difficult to interpret. Therefore, radiologists' experience and multidisciplinary teamwork are key to ensure correct evaluation. The role of the radiologist is fundamental in preventive measures as well as in diagnosis and management, having an important impact on patients' overall health. It is crucial to take into account patients' possible exposure to particles both at work and at home.

Hypersensitivity pneumonitis: Current concepts in pathogenesis, diagnosis, and treatment.

Hypersensitivity pneumonitis is an immune-mediated interstitial lung disease caused by an aberrant response to an inhaled exposure, which results in mostly T cell-mediated inflammation, granuloma formation, and fibrosis in some cases. HP is diagnosed by exposure identification, HRCT findings of ground-glass opacities, centrilobular nodules, and mosaic attenuation, with traction bronchiectasis and honeycombing in fibrotic cases. Additional testing including serum IgG testing for the presence of antigen exposure, bronchoalveolar lavage lymphocytosis, and lung biopsy demonstrating granulomas, inflammation, and fibrosis, increases the diagnostic confidence. Treatment for HP includes avoidance of the implicated exposure, immunosuppression, and anti-fibrotic therapy in select cases. This narrative review presents the recent literature in the understanding of the immunopathological mechanisms, diagnosis, and treatment of HP.

[Hypersensitivity Pneumonitis - an important differential diagnosis of infiltrative lung diseases]. / Exogen allergische Alveolitis ­ Eine wichtige Differenzialdiagnose der infiltrativen Lungenerkrankungen.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease of the lung parenchyma and terminal bronchioles caused by an allergic reaction to inhaled antigens. The immune response following antigen exposure results in lymphocytic inflammation as well as granuloma formation.The typical histologic pattern of HP consists of cellular interstitial pneumonia, cellular bronchiolitis, and epithelioid cell granulomas. The additional presence of fibrosis has a significant impact on the course as well as the prognosis of the disease and represents a therapeutic approach. Therefore, a classification into a non-fibrotic and a fibrotic phenotype is proposed.The diagnosis of HP is made by high-resolution computed tomography (HRCT) of the lung, evaluation of possible antigen exposure, and bronchoscopy with bronchoalveolar lavage and, if necessary, forceps biopsy. If the diagnosis is inconclusive, transbronchial cryobiopsy or surgical lung biopsy may need to follow. A multidisciplinary board is critical in making the diagnosis.

Mold in Foam Pillows and Mattresses: A Novel Cause of Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease affecting the lung parenchyma and small airways. It typically results from an immune-mediated reaction provoked by an overt or occult inhaled antigen in susceptible individuals. The chronic or fibrotic form of HP has a poor prognosis, especially when no inciting antigen is identified, which occurs in up to 60% of cases. We report two cases of HP associated with exposure to mold in foam pillows and a mattress, which has not previously been reported as a risk factor for HP. Given the high prevalence of foam in pillows and mattresses, mold in foam in bedding may explain many HP cases with a previously unrecognized cause. Early identification and avoidance of foam in bedding may prevent HP progression to end-stage pulmonary fibrosis and death.

An update on interstitial lung disease.

Interstitial lung diseases are a complex group of conditions that cause inflammation and scarring of the lung interstitium. This article discusses the diagnosis and management of common interstitial lung diseases including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue disease associated-interstitial lung disease, sarcoidosis and drug-induced interstitial lung disease. A multidisciplinary approach to diagnosis of interstitial lung disease is the gold standard; key history and examination features, blood panel, pulmonary function tests, high resolution computed tomography imaging, and when required bronchoalveolar lavage and lung biopsy results are discussed to reach a multidisciplinary consensus diagnosis. Advances, including the development of the disease-modifying anti-fibrotic medications nintedanib and pirfenidone, continue to shape the future management of interstitial lung disease. A holistic approach to the care of patients with interstitial lung disease is paramount, as they often have a high symptom burden and considerable palliative care needs.

Barriers to antigen detection and avoidance in chronic hypersensitivity pneumonitis in the United States.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease (ILD) caused by long term exposure to an offending antigen. Antigen avoidance is associated with improved outcomes. We are unable to identify the antigen source in approximately half of patients. When an antigen is successfully identified, patients have difficulty with avoidance. METHODS: We conducted three structured group discussions with US based ILD specialists utilizing the nominal group technique (NGT). Participants listed barriers to antigen detection and avoidance in CHP. Each participant ranked what they perceived to be the top three barriers in the list in terms of importance. The master list of barriers was consolidated across the three groups into themes that were prioritized based on receiving the highest rankings by participants. RESULTS: Twenty-five physicians participated; 56% had experience caring for CHP patients for ≥ 16 years. Sixty barriers to antigen detection were categorized into seven themes of which the top three were: 1. unclear significance of identified exposures; 2. gaps in clinical knowledge and testing capabilities; 3. there are many unknown and undiscovered antigens. Twenty-eight barriers to antigen avoidance were categorized into five themes of which the top three were: 1. patient limitations, financial barriers and lack of resources; 2. individual patient beliefs, emotions and attachments to the antigen source; and 3. gaps in clinical knowledge and testing capabilities. CONCLUSIONS: This study uncovered challenges at the individual patient, organizational, and societal levels and ranked them in terms of level of importance. These findings provide information to guide development and validation of multidisciplinary support and interventions geared towards antigen identification and avoidance in CHP.

Management of Fibrotic Hypersensitivity Pneumonitis.

Fibrotic hypersensitivity pneumonitis (fHP) is a chronic, often progressive fibrosing form of interstitial lung disease caused by inhaled antigenic exposures. fHP can lead to impaired respiratory function, reduced disease-related quality of life, and early mortality. Management of fHP should start with exposure remediation where possible, with systemic immunosuppression and antifibrotic therapy considered in patients with symptomatic or progressive disease. Nonpharmacologic and supportive management should be offered and, in cases of treatment-resistant, progressive illness, lung transplant should be considered.

[New developments in the management of hypersensitivity pneumonitis]. / Nouveautés dans la prise en charge des pneumopathies d'hypersensibilité.

INTRODUCTION: Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, characterized by an inflammatory and/or fibrotic reaction to inhaled antigens. BACKGROUND: The heterogeneity of presentation and the lack of international guidelines makes management complex. In addition, the current treatment, based on antigen eviction and immunosuppressive drugs, is less effective in the fibrotic forms of HP. This article summarizes the latest data on HP and the new recommendations of the American Thoracic Society (ATS) on the diagnosis of HP. CONCLUSION: The new ATS recommendations establish a more precise and rigorous diagnostic approach to HP. Multidisciplinary discussion plays a pivotal role both in the diagnosis and the treatment of the disease. Nintedanib has recently been shown to be effective in fibrotic HP. PERSPECTIVES: Questions remain unanswered about the optimal therapeutic strategy in fibrotic HP, which underlines the need to carry out large-scale studies.

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows / Neumonitis por hipersensibilidad y fibrosis pulmonar (idiopática) debidas a los edredones y las almohadas de plumas

INTRODUCTION: Exposure 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. METHODS: We 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. RESULTS: Eleven (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. CONCLUSIONS: In 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

INTRODUCCIÓN: La exposición a la ropa de cama rellena de plumas puede ser una causa que pase inadvertida de neumonitis por hipersensibilidad (NH) y fibrosis pulmonar idiopática (FPI). Por lo tanto, se requiere un estudio clínico en profundidad durante el proceso diagnóstico de pacientes con sospecha de NH e FPI para determinar sus etiologías. El objetivo del presente estudio es crear conciencia sobre la NH y la fibrosis pulmonar debidas a la exposición a la ropa de cama rellena de plumas, y estudiar la prevalencia y describir los resultados a largo plazo. MÉTODOS: Describimos una serie de 33 pacientes diagnosticados con NH y fibrosis pulmonar debido a la exposición a la ropa de cama rellena de plumas y en seguimiento durante un período de 10 años. Los pacientes pertenecían a un subgrupo de 127 individuos con NH a los cuales se les estaba realizando una evaluación en profundidad utilizando un protocolo de diagnóstico en un centro de referencia regional. RESULTADOS: A 11 pacientes (33%) se les diagnosticó de NH aguda y a 22 (67%) de NH crónica. Diez de los pacientes con NH crónica (45%) mostraron un patrón de neumonía intersticial usual (NIU) en la tomografía computarizada de alta resolución (TCAR), con sospecha de FPI. La prevalencia de NH fue de 6,2/100.000 usuarios de ropa de cama rellena de plumas (en comparación con el 54,6 por cada 100.000 criadores de aves). Las tasas de supervivencia de los pacientes durante el período de 10 años fueron del 100% para la NH aguda y del 64% para la NH crónica. CONCLUSIONES: En una serie de pacientes con NH, el diagnóstico se atribuyó a la exposición a la ropa de cama rellena de plumas en un 26%. El patrón NIU en el TCAR estaba presente en casi la mitad de los casos crónicos. La supervivencia de los pacientes con NH crónica a los 10 años fue del 64%, a pesar de evitar posteriores exposiciones

Chest CT Diagnosis and Clinical Management of Drug-Related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper From the Fleischner Society.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others.

Tobacco Worker's Lung: A Neglected Subtype of Hypersensitivity Pneumonitis.

Tobacco worker's lung (TWL) is a type of hypersensitivity pneumonitis (HP) affecting workers exposed to tobacco leaves and molds in the humidified environment of the tobacco production industry. Limited epidemiological data point to a prevalence of TWL that is not negligible and probably underestimated. As in other types of HP, an acute vs. chronic presentation depends on the pattern of the exposure. Therefore, the clinical presentation can vary from an acute influenza-like syndrome, mostly self-limiting with the removal of the exposure, to an insidious onset of cough, exertional dyspnea, fatigue and weight loss in chronic presentations, where fibrotic changes may be observed. The main treatment strategy is the removal of the exposure to tobacco dust and molds, while the main aim of corticosteroid therapy is to reduce morbidity and prevent complications, namely the development of pulmonary fibrosis and permanent lung dysfunction. Despite the fact that TWL is quite well described, preventive measures are not usually adopted in the tobacco production industry. We present here a state of the art review of this neglected, preventable, but still prevalent and occupational-related subtype of HP.