Relative incidence of interstitial lung diseases in Brazil.

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

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

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

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study.

OBJECTIVE: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. METHODS: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. RESULTS: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. CONCLUSIONS: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

Clinical characteristics and outcomes of hypersensitivity pneumonitis in South Korea.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood. OBJECTIVES: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea. DESIGN: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea. METHODS: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines. RESULTS: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort. CONCLUSION: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

Masks of hypersensitivity pneumonitis in children.

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is the most common interstitial lung disease in children, but remains rarely recognized in the pediatric population. Early recognition of triggering factors and a high index of suspicion of HP could lead to timely diagnosis and individualized treatment. This study aimed to present four clinical cases of HP reported between 2012 and 2022 in Lithuania to improve the suspicion of the disease in children.

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.

Evaluation of cases with hypersensitivity pneumonia: 10 year analysis.

INTRODUCTION: The aim of this study was to examine the clinical features of hypersensitivity pneumonia (HP) cases, diagnostic methods, and related conditions in our hospital, which is a reference clinic in Turkey for chest disease. METHODS: The population of this retrospective cross-sectional study consists of all hypersensitivity pneumonia patients followed in a tertiary hospital between 2010 and 2019. The data of 78 patients were included in the analysis. Data were grouped by source of exposure (occupational, environmental, and cryptogenic) by examining the files of the patients. RESULTS: Occupational risk factors were detected in 29 (37.2%) of the cases, environmental risk factors were found in 24 (30.8%) cases, neither occupational nor environmental risk factors were detected in 25 (32%) cases, and they were evaluated as cryptogenic. The time from the onset of symptoms to diagnosis was 15.8 ± 26.6 months. The time from the onset of symptoms to diagnosis was found to be longer in the group with occupational risk factors compared with the other groups and was statistically significant (0.044). CONCLUSION: HP is a immune-mediated interstitial lung disease induced by repeated exposure to environmental and occupational antigens. Etiological agent can be detected in HP patients by detailed questioning of occupational and environmental exposure that may be associated with the onset of symptoms in cases with suspected HP.

Clusters of comorbidities in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting to irreversible and progressive pulmonary fibrosis. Comorbidities are common in HP and may have an impact on prognosis. Due to the heterogeneity of HP presentation and progression, the identification of specific phenotypes in relationship to disease course and outcome is essential. The aim of this study was to identify clusters of comorbidities which could represent phenotypes in fibrotic HP and examine their impact on prognosis. METHODS: Patients diagnosed with fibrotic HP at a tertiary referral center for ILD were included. Comorbidities were systematically registered and clusters of comorbidities were identified using cluster analyses. Disease progression and survival was estimated for each cluster. RESULTS: The cohort comprised 211 patients with 53.6% males, mean age 63.0, baseline FVC 72.7%, DLCO 44.1%. Median follow-up time was 1.8 years (IQR 0.7-3.9). Three clusters with distinct comorbidity profiles and clinical characteristics were identified. One cluster dominated by elder male patients with predominantly cardiovascular diseases was associated with more respiratory hospitalizations and a worse prognosis. Differences in pulmonary function or exercise capacity trajectories between clusters were not observed. CONCLUSIONS: Three clusters with distinct comorbidities were identified and could represent phenotypes in fibrotic HP not previously recognized. The worst prognosis was observed in a cluster dominated by elder males with cardiovascular diseases. Increased focus on prevention and treatment of comorbidities could potentially improve the prognosis of patients with fibrotic HP.

Impact of climate change on wood and woodworkers-Cryptostroma corticale (sooty bark disease): A risk factor for trees and exposed employees.

Climate changes have promoted an increased fungal infection of maple trees with Cryptostroma corticale, the causative agent of sooty bark disease. The hosts of C. corticale are maples, and since the early 2000s the fungus has been appearing more frequently in European forests, due to the droughts and hot summers of recent years. Infestation by C. corticale discolors the wood and makes it unusable for further processing, which leads to considerable economic damage in the timber industry. Therefore, the occurrence and spread of sooty bark disease raise serious problems. In addition to forestry and economic problems, the conidiospores of C. corticale can also cause health problems in exposed wood workers and they can trigger hypersensitivity pneumonitis (HP). Since the spores, which are deposited over the entire area under the bark of infected trees, can spread during processing, exposed workers must take special precautions to protect themselves against exposure. If an occupational disease is nevertheless suspected following exposure to C. corticale, valid diagnostics are required to confirm possible HP and derive appropriate therapies and exposure reduction or avoidance. Diagnosis of HP is based on several criteria, one of them is the detection of specific IgG in patient's serum against the potentially triggering antigens, in this case C. corticale antigens. To produce a diagnostic tool to measure C. corticale specific IgG, which is not commercially available so far, spores and mycelial material from ITS-sequenced strains of C. corticale was prepared and analyzed. These biochemically characterized extracts of spore and mycelial antigens were biotinylated and coupled to Streptavidin-ImmunoCAPs. To validate these diagnostic test tools the first step is to measure the concentration of C. corticale specific IgG in sera of healthy non-exposed and healthy exposed subjects to establish cut-off values. Suitable participants were recruited and the individual exposure to C. corticale and symptoms experienced during or after working with infected maple trees were recorded using questionnaires. Finally, diagnostic tools for serological testing in suspected cases of HP by C. corticale were created and evaluated. The following article provides recommendations for the treatment and disposal of infected damaged wood and for occupational health protection procedures. Secondly, the diagnosis of HP induced by exposure to C. corticale as an occupational disease is described including the verification of newly developed serological test tools for antigens of C. corticale.

Work-related interstitial lung disease: what is the true burden?

Interstitial lung diseases (ILDs) include a large variety of fibrotic lung conditions caused by genetic and environmental factors. Occupational exposures might also play a significant role, but the real health burden is currently unknown. Here, we aim to evaluate the role of work-related exposures in ILDs, focussing on idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP). We performed a focused review of the literature on work-related HP and IPF over the past 5 years. Using a meta-analytic approach, we quantified the occupational burden of IPF and HP, and estimated that occupational exposures to metal, silica and environmental tobacco smoke increased IPF risk with a pooled odds ratio of 1.7 (95% CI 1.42-2.03). The proportion of HP cases related to workplace exposure was 17% (95% CI 7-28). Our review supports the hypothesis that occupational exposures are a significant risk factor in the aetiopathogenesis of IPF and HP. We recommend that further research be performed to identify the underlying occupational factors and the maximum permitted exposure to reduce the associated IPF and HP burden.

Hypersensitivity Pneumonitis With and Without Autoimmune Features: A Clinical Comparative Analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established. In this study, we examined patients diagnosed with HP and compare them to patients with concomitant HP and autoimmunity. METHODS: Patients were retrospectively screened from a single-center ILD registry. Patients > 18 years with an established multidisciplinary diagnosis of HP were included in the study. Patients with HP without autoimmune features and patients with HP with autoimmune features (HPAF) were assessed. We compared the demographics, clinical characteristics, treatment, and outcomes between the two groups. We used a Cox proportional hazards model to compare lung transplant-free survival outcomes of patients with HPAF to those with non-HPAF HP patients. RESULTS: Of 73 patients with HP, 43 were diagnosed with HPAF. Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to non-HPAF HP patients [48.8 vs 23.3%, p = 0.028, Crude odds ratio (cOR) = 3.14]. Symptomatically, those with HPAF reported a higher prevalence of arthritis as compared to non-HPAF HP (20.9 vs 3.3%, p = 0.040, cOR = 7.68). No significant differences between pulmonary function tests, oxygen requirements, mortality, and lung transplantation rates were found between the two groups. There was no statistically significant difference in transplant-free survival (p = 0.836). CONCLUSION: Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to patients with non-HPAF HP. The clinical characteristics and outcomes did not differ between the two groups and concomitant autoimmunity among the HP group did not portend a poorer prognosis.

The Association between Exposures and Disease Characteristics in Familial Pulmonary Fibrosis.

Rationale: Heterogeneous characteristics are observed in familial pulmonary fibrosis (FPF), suggesting that nongenetic factors contribute to disease manifestations. Objectives: To determine the relationship between environmental exposures and disease characteristics of FPF, including the morphological characteristics on chest computed tomography (CT) scan, and timing of FPF symptom onset, lung transplantation, or death. Methods: Subjects with FPF with an exposure questionnaire and chest CT were selected from a prospective cohort at Vanderbilt. Disease characteristics were defined by lung parenchymal findings on chest CT associated with fibrotic hypersensitivity pneumonitis (fHP) or usual interstitial pneumonia (UIP) and by time from birth to symptom onset or a composite of lung transplantation or death. After assessing the potential for confounding by sex or smoking, adjusted logistic or Cox proportional hazards regression models identified exposures associated with fHP or UIP CT findings. Findings were validated in a cohort of patients with sporadic pulmonary fibrosis enrolled in the LTRC (Lung Tissue Research Consortium) study. Results: Among 159 subjects with FPF, 98 (61.6%) were males and 96 (60.4%) were ever-smokers. Males were less likely to have CT features of fHP, including mosaic attenuation (FPF: adjusted [for sex and smoking] odds ratio [aOR], 0.27; 95% confidence interval [CI], 0.09-0.76; P = 0.01; LTRC: aOR, 0.35; 95% CI, 0.21-0.61; P = 0.0002). Organic exposures, however, were not consistently associated with fHP features in either cohort. Smoking was a risk factor for honeycombing in both cohorts (FPF: aOR, 2.19; 95% CI, 1.12-4.28; P = 0.02; LTRC: aOR, 1.69; 95% CI, 1.22-2.33; P = 0.002). Rock dust exposure may also be associated with honeycombing, although the association was not statistically-significant when accounting for sex and smoking (FPF: aOR, 2.27; 95% CI, 0.997-5.15; P = 0.051; LTRC: aOR, 1.51; 95% CI, 0.97-2.33; P = 0.07). In the FPF cohort, ever-smokers experienced a shorter transplant-free survival (adjusted hazard ratio, 1.64; 95% CI, 1.07-2.52; P = 0.02), whereas sex was not associated with differential survival (male adjusted hazard ratio, 0.75; 95% CI, 0.50-1.14; P = 0.18). Conclusions: In FPF, smoking contributes to shortened transplant-free survival and development of honeycombing, a finding that is also likely applicable to sporadic pulmonary fibrosis. Females are more likely to manifest CT features of fHP (mosaic attenuation), a finding that was incompletely explained by sex differences in exposures. These findings may have implications for pulmonary fibrosis classification and management.

Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry.

BACKGROUND: Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain. METHODS: Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression. RESULTS: Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression. CONCLUSIONS: Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.

Bronchoalveolar lavage lymphocytosis in hypersensitivity pneumonitis: a retrospective cohort analysis with elimination of incorporation bias.

BACKGROUND: Recent studies support the diagnostic role of bronchoalveolar lavage lymphocytosis (BALL) in patients with suspected hypersensitivity pneumonitis (HP). Our study aim was to determine the spectrum of BALL findings with elimination of incorporation bias in non-fibrotic and fibrotic patients and assess correlates of positive BALL cut-off and BALL association with long-term outcomes in those with fibrotic disease (f-HP). METHODS: A single-center retrospective cohort study was pursued of patients undergoing diagnostic bronchoscopy for interstitial lung disease. Strict study enrollment was based on recent ATS/JRS/ALAT diagnostic guidance meeting 'moderate' or higher diagnostic confidence. BALL findings were assessed in both fibrotic and non-fibrotic HP patients with regression and survival analysis pursued for correlates of positive BALL cut-off and long-term outcome. RESULTS: A total of 148 patients (88 fibrotic and 60 non-fibrotic) meeting moderate or higher diagnostic confidence were included. Median BALL in f-HP was 15% compared to 19% in non-fibrotic patients, with only 28% of f-HP meeting diagnostic cut-off (≥ 30%) compared to 41% of non-fibrotic. For f-HP, centrilobular nodules on computed tomography was positively correlated with a diagnostic BALL (OR 4.07; p = 0.018) while honeycombing was negatively correlated (OR 6.9 × e-8; p = 0.001). Higher BALL was also associated with lower all-cause mortality (HR 0.98; p = 0.015). CONCLUSION: With elimination of incorporation bias, most patients with well-described HP did not meet diagnostic BALL thresholds. Higher BALL was associated with better long-term survival in those with fibrosis, but its diagnostic role may be more additive than characteristic or distinguishing.

Chronic hypersensitivity pneumonitis is associated with an increased risk of venous thromboembolism: a retrospective cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis share commonalities in pathogenesis shifting haemostasis balance towards the procoagulant and antifibrinolytic activity. Several studies have suggested an increased risk of venous thromboembolism in IPF. The association between venous thromboembolism and chronic hypersensitivity pneumonitis has not been studied yet. METHODS: A retrospective cohort study of IPF and chronic hypersensitivity pneumonitis patients diagnosed in single tertiary referral center between 2005 and 2018 was conducted. The incidence of symptomatic venous thromboembolism was evaluated. Risk factors for venous thromboembolism and survival among those with and without venous thromboembolism were assessed. RESULTS: A total of 411 (259 IPF and 152 chronic hypersensitivity) patients were included (mean age 66.7 ± 8.4 vs 51.0 ± 13.3 years, respectively). There were 12 (4.6%) incident cases of venous thromboembolism in IPF and 5 (3.3%) in chronic hypersensitivity pneumonitis cohort. The relative risk (RR) of venous thromboembolism in chronic hypersensitivity pneumonitis was not significantly different to that found in patients with IPF (7.1 vs 11.8/1000 person-years, RR 1.661 95% CI 0.545-6.019, respectively). The treatment with systemic steroids (OR 5.38; 95% CI 1.65-18.8, p = 0.006) and GAP stage 3 (OR 7.85; 95% CI 1.49-34.9; p = 0.037) were significant risk factors for venous thromboembolism in IPF. Arterial hypertension and pulmonary hypertension significantly increased risk of venous thromboembolism in chronic hypersensitivity pneumonitis. There were no significant differences in survival between patients with and without venous thromboembolism. CONCLUSIONS: The patients with chronic hypersensitivity pneumonitis have a marked increase in the risk of venous thromboembolism, similar to the patients with IPF. Venous thromboembolism does not affect the survival of patients with IPF and chronic hypersensitivity pneumonitis.

A cluster of hypersensitivity pneumonitis associated with exposure to metalworking fluids.

BACKGROUND: Workers exposed to metalworking fluids (MWF) can develop respiratory illnesses including hypersensitivity pneumonitis (HP). These respiratory manifestations are likely due to microbial contamination of aerosolized MWF. This paper reports a cluster of HP and respiratory symptoms at a manufacturing plant where MWF and workplace air were contaminated with bacterial endotoxin despite frequent negative bacterial cultures of MWF. METHODS: A pulmonologist assessed and treated three workers with respiratory symptoms. The Occupational Safety and Health Administration (OSHA) inspected the plant. OSHA's investigation included bacterial culture of MWF, measurement of endotoxin concentrations in MWF and workplace air, review of the employer's fluid management program, and distribution of a cross-sectional symptom questionnaire. RESULTS: Three workers had biopsy-confirmed HP. In addition, 30.8% of questionnaire respondents reported work-related respiratory symptoms. OSHA detected endotoxin levels as high as 92,000 endotoxin units (EU)/ml in MWF and 3200 EU/m3 in air. Endotoxin concentrations and risk of MWF inhalation were highest near an unenclosed multistation computer numerical control machine. A contractor had tested this machine's MWF for bacterial growth weekly during the preceding three years, and most (96.0%) of those tests were negative. CONCLUSIONS: Contaminated MWF can cause severe occupational lung disease even if microorganisms do not grow in fluid cultures. Endotoxin testing can increase the sensitivity of detection of microbial contamination. However, employers should not rely solely upon MWF testing data to protect workers. Medical surveillance and meticulous source control, such as engineering controls to suppress MWF mist and prevent its inhalation, can reduce the likelihood of respiratory disease.

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.

[Hypersensitivity Pneumonitis: An update]. / 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.

Acute exacerbation of fibrotic hypersensitivity pneumonitis: incidence and outcomes.

BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (HP) show variable clinical courses, and some experience rapid deterioration (RD), including acute exacerbation (AE). However, little is known about AE in fibrotic HP. Here, we retrospectively examined the incidence, risk factors, and outcomes of AE in fibrotic HP. METHODS: The incidence rates of AE were calculated in 101 patients with biopsy-proven HP. AE was defined as the worsening of dyspnoea within 30 days, with new bilateral lung infiltration and no evidence of infection or other causes of dyspnoea. RESULTS: During follow-up (median: 30 months), 18 (17.8%) patients experienced AE. The 1, 3, and 5 year incidence rates of AE were 6.0, 13.6, and 22.8%, respectively. Lower diffusing capacity of the lung for carbon monoxide (DLCO) and a radiologic usual interstitial pneumonia (UIP)-like pattern were risk factors for AE. In-hospital mortality after AE was 44.4%. Median survival from diagnosis was significantly shorter in patients with AE (26.0 months) than in those with no-AE RD (55.0 months; p = 0.008) or no RD (not reached; p < 0.001). AE remained a significant predictor of all-cause mortality (hazard ratio, 8.641; 95% confidence interval, 3.388-22.040; p < 0.001) after adjustment for age, body mass index, lung function, lymphocyte levels in bronchoalveolar lavage fluid, and the presence of a UIP-like pattern. CONCLUSIONS: AE was not uncommon among patients with fibrotic HP and significantly affected prognosis. A lower DLCO value and radiologic UIP-like pattern at diagnosis were associated with the development AE in patients with fibrotic HP.

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.