[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.

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.

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.

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.

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.

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.

Clinical Decision-Making in Hypersensitivity Pneumonitis: Diagnosis and Management.

This review provides an updated approach to the diagnosis and management of hypersensitivity pneumonitis (HP). The importance of using a multidisciplinary discussion to increase diagnostic and treatment confidence is emphasized. The role of Bayesian reasoning is highlighted throughout, underscoring the importance of hypothesis generation (differential diagnosis) and diagnostic test interpretation based on the probability of HP. Probability estimates of diagnostic certainty (i.e., a confident versus a working diagnosis) and treatment thresholds are carefully examined.Therapeutically, beyond antigen avoidance and newly available antifibrotic therapy for patients with a progressive fibrosing phenotype; the role, timing, and expected response to anti-inflammatory therapy in individual patients are unanswered questions. Since the evidence and validation of testing generally performed during the diagnostic work-up and longitudinal monitoring of HP is feeble at best, the viewpoints discussed are not intended to resolve current controversies but rather to provide a conceptual framework for evaluating discordant information when evaluating and caring for patients with HP.

Fibrotic Hypersensitivity Pneumonitis: Diagnosis and Management.

Fibrotic hypersensitivity pneumonitis is a complex interstitial lung disease that is not entirely understood. In its chronic and fibrotic form, hypersensitivity pneumonitis is one of the main mimickers of idiopathic pulmonary fibrosis (IPF). Distinguishing between these two conditions is challenging but is of particular clinical relevance. Two approved therapies are available for IPF, and a considerable number of clinical trials are now exploring newer pharmacological options. This impressive research effort is a consequence of new pathogenetic understanding, updated diagnostic criteria and a long history of pharmacological trials. Conversely, current knowledge gaps on pathogenesis of chronic hypersensitivity pneumonitis, coupled with lack of validated diagnostic criteria, make the management of this disease an unsolved clinical challenge. This also reflects the paucity of therapeutic clinical trials in this field. In this review, we describe the current evidence and the possible future options to approach this complex disease.

Change in Serum Biomarker CA 15-3 as an Early Predictor of Response to Treatment and Survival in Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a heterogeneous course of disease and treatment response. Cancer antigen 15-3 (CA 15-3), part of mucin 1, is believed to reflect epithelial cell injury and lung permeability and could be a potential biomarker for treatment response in HP. OBJECTIVE: To assess the value of CA 15-3 as a predictive biomarker in non-fibrotic and fibrotic HP during immunosuppressive therapy. DESIGN: Serum levels of CA 15-3 and pulmonary function tests (PFTs) were retrospectively retrieved from 48 HP patients treated with prednisone or cyclophosphamide at initiation of therapy (baseline), after 3 and 6 months. Pearson's correlation coefficient was computed to assess correlations between change in serum levels and PFT. Survival was evaluated using Kaplan-Meier curves. RESULTS: After 6 months of immunosuppressive therapy CA 15-3 levels decreased significantly compared to baseline (p = 0.001). Change in CA 15-3 after 6 months correlated with FVC change (r = - 0.469; p = 0.001). Correlations with FVC change were observed in prednisone-treated HP (r = - 0.514; p = 0.005) and fibrotic HP (r = - 0.417; p = 0.007). Three-month CA 15-3 change correlated with 6-month FVC change (r = - 0.599; p < 0.001). CA 15-3 declines of at least 7.9% after 6 months were associated with increased survival compared to minor CA 15-3 changes (HR 0.34; p = 0.020). CONCLUSION: Serum CA 15-3 correlates with PFT during 6 months of immunosuppressive therapy in HP. Interestingly, early CA 15-3 changes could predict future PFT. Furthermore, a decrease in CA 15-3 is related to longer survival. Therefore, serum CA 15-3 is a promising biomarker for implementation in HP care.

[Extrinsic allergic alveolitis: minimum for clinical practice]. / Exogenní alergické alveolitidy: minimum pro praxi.

Extrinsic allergic alveolitis (EAA) represent a group of diseases, that develop in susceptible individuals after repeated exposure to usually organic inhalation antigen. Patient may be in contact with these agents both in occupational and in home environment, as well as during free time activities and hobbies. The course of the disease is highly variable - EAA may have dramatic symptoms with fever, cough and severe dyspnoea as well as may be presented with slowly increasing dyspnoea and chronic cough. The more inconspicious are the symptoms of chronic EAA, the more problematic its treatment may be. Treatment options must be sought individually and respect potential risks and benefits for the patient. Avoiding further contact with offending antigens as well as optimizing patients nutritional status and starting pulmonary rehabilitation should be emphasized.Key words: corticosteroids - extrinsic allergic alveolitis - environmental exposure.

Dendritic Cell Trafficking and Function in Rare Lung Diseases.

Dendritic cells (DCs) are highly specialized immune cells that capture antigens and then migrate to lymphoid tissue and present antigen to T cells. This critical function of DCs is well defined, and recent studies further demonstrate that DCs are also key regulators of several innate immune responses. Studies focused on the roles of DCs in the pathogenesis of common lung diseases, such as asthma, infection, and cancer, have traditionally driven our mechanistic understanding of pulmonary DC biology. The emerging development of novel DC reagents, techniques, and genetically modified animal models has provided abundant data revealing distinct populations of DCs in the lung, and allow us to examine mechanisms of DC development, migration, and function in pulmonary disease with unprecedented detail. This enhanced understanding of DCs permits the examination of the potential role of DCs in diseases with known or suspected immunological underpinnings. Recent advances in the study of rare lung diseases, including pulmonary Langerhans cell histiocytosis, sarcoidosis, hypersensitivity pneumonitis, and pulmonary fibrosis, reveal expanding potential pathogenic roles for DCs. Here, we provide a review of DC development, trafficking, and effector functions in the lung, and discuss how alterations in these DC pathways contribute to the pathogenesis of rare lung diseases.

Occupational hypersensitivity pneumonitis: an EAACI position paper.

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.

[Hypersensitivity pneumonitis: Diagnostic criteria, treatment, prognosis and prevention]. / Alergiczne zapalenie pecherzyków plucnych - kryteria rozpoznania, leczenie, rokowanie i zapobieganie.

Hypersensitivity pneumonitis (HP) is caused by inhalation of environmental antigens. Farmers and bird keepers are most frequently affected by this desease. The HP diagnosis is based on clinical symptoms (cough, dyspnea) in a person exposed to environmental antigens, and the presence of characteristic changes in high resolution chest computed tomography (HRCT) (bilateral, mosaic, ground glass opacities in the middle and lower lung zones, ill-defined centrilobular nodules and the sign of air-trapping on expiration). This type of HRCT pattern is most frequently found in the patients with subacute HP. Bronchioloalveolar lavage fluid (BALF) examination is helpful in establishing the HP diagnosis, when the increased total number of cells, with the predominance of T lymphocytes (> 50%), and the increased number of neutrophils (> 3%) and mastocytes (> 1%) are found. The presence of specific serum precipitins increases the likelihood of HP. In case of atypical clinical presentation, lung biopsy is recommended. The diagnostic criterion of HP is the presence of ill-defined non-necrotising granulomas, after excluding other granulomatous lung diseases. The prevention and treatment of HP is based on the elimination of the antigen from the environment. Corticosteroids may contribute to the improvement in the acute and sub-acute form of the disease but their long term effectiveness is uncertain. The prognosis of HP patients is generally perceived as good, especially in those patients in whom antigen avoidance is possible. Nevertheless, in some patients progressive pulmonary fibrosis and development of severe respiratory insufficiency is observed. Med Pr 2016;67(4):517-527.

Hypersensitivity Pneumonitis: A Comprehensive Review.

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex pulmonary syndrome mediated by the immune system and caused by inhalation of a wide variety of antigens to which the individual has been previously sensitized. The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP. Due to the lack of a diagnostic gold standard, the diagnosis of HP is not straightforward and relies on the integration of a number of factors, including history of exposure, precipitating antibodies to the offending antigen, clinical features, bronchoalveolar lavage, and radiological and pathologic features. However, in the appropriate setting, a high index of suspicion is critically important and may obviate the need for more invasive tests. Clinical presentation and natural history vary widely. Acute forms generally resolve without sequelae, while chronic forms, which are caused by persistent low-grade exposures, are associated with poor prognosis. Corticosteroids may be useful in acute episodes for symptomatic relief or in chronic and progressive disease, but their long-term efficacy has never been validated in prospective clinical trials. Ideally, patients with HP should be referred to centers with expertise, as the overlap with other forms of interstitial lung disease may be substantial. Making the correct diagnosis has critical therapeutic and prognostic implications.

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.