[Lifelong Mask Mandate].

INTRODUCTION: A 31-year-old farmer is being treated for suspected pneumonia. As the symptoms persist despite antibiotic treatment, the suspicion of hypersensitivity pneumonitis type Farmer´s lung arises after taking into account the patients occupational history. Information from various examination modalities and the clinical course confirm the suspected diagnosis. Thanks to the rapid diagnosis and the measures taken as a result, it was possible for the patient to remain in his profession.

Hypersensitivity Pneumonitis in Farmers: Improving Etiologic Diagnosis to Optimize Counselling.

In a farmer, a diagnosis of hypersensitivity pneumonitis (HP) might cause drastic changes in life, and guidance concerning future prospects within farming requires a best possible etiological diagnosis. We aimed to assess (1) if immunological analyses based on material samples from the work environment could be used to improve the etiologic diagnosis in a farmer suffering from HP, and (2) if combining a longitudinal immunological investigation of workplace material with a realistic work place inhalation challenge could be used to optimize counselling with respect to further employment within farming. A realistic workplace inhalation challenge was performed to explore potential associations between exposure, symptoms and immune responses. Material samples were collected from various places on the farm, and enzyme-linked immunosorbent assay (ELISA) was performed to identify possible IgE and IgG antibodies in patient serum towards these material samples. Electrophoresis (SDS-PAGE) and immunoblot were used to detect the specific proteins in the material samples that were recognized by ELISA. The patient's symptoms were reproduced by the workplace challenge, and more severe symptoms were associated with increased serum levels of specific IgG antibodies towards material samples from the workplace. The immunoblot detected IgG binding proteins in agreement with known allergens of the fungi Alternaria and Pullularia. Combining realistic workplace challenge with immunological analyses of workplace material may improve the basis for counselling farmers with farmer´s lung concerning future work within farming.

[A case of farmer's lung associated with allergic bronchopulmonary aspergillosis]. / L'association inhabituelle de deux maladies pulmonaires immunoallergiques : un cas de pneumopathie d'hypersensibilité associée à une aspergillose bronchopulmonaire allergique.

Hypersensitivity pneumonitis and allergic bronchopulmonary aspergillosis are two forms of lung disease with presumed distinct immunoallergic mechanisms. We report the observation of a 38-year-old French farmer who, for one month, had fever and dyspnoea resistant to antibiotic therapy. A diagnosis of farmer's lung, and allergic bronchopulmonary aspergillosis was made on clinical, biological, functional and radiological evidence and according to the criteria established. The evolution was favorable with antigenic eviction and corticosteroid therapy. This observation is to our knowledge the 5th case that describes the association of hypersensitivity pneumonitis and allergic bronchopulmonary aspergillosis. It suggests the existence of risk factors and immunoallergic mechanisms common to both diseases and discusses the hypothesis that the same antigen(s) is (are) responsible for them.

Farmer's lung disease: Analysis of 75 cases. / Enfermedad del pulmón del granjero: análisis de 75 casos.

INTRODUCTION: Farmer's lung disease (FLD) is a common form of hypersensitivity pneumonitis possibly underdiagnosed in our midst. The aim of this study was to describe clinical characteristics, evolution and factors that influence the prognosis of patients with FLD. PATIENTS AND METHODS: A retrospective study that included all patients diagnosed with FLD presenting an environmental exposure risk, a clinic, lung function and a compatible radiology, in which antigen sensitisation was demonstrated and/or a concordant pathology. RESULTS: We selected 75 patients with FLD, 50 with acute or subacute form (ASF) and 25 with chronic form (CF). Forty-four percent of patients (n=33) were diagnosed during the months of March and April, especially those with ASF compared to CF (52 vs. 28%; P=.0018). In the ASF group, DLco showed an improvement during follow-up (P=.047). The determination of specific IgG antibodies was positive in 39 patients (78%) with ASF (44% of them against Aspergillus) and CF 12 (48%). The realisation of antigenic avoidance (OR 9.26, 95% CI 1.3-66.7, P=.026) and the administration of immunosuppressive therapy (OR 16.13, 95% CI 1.26-200, P=.033) were predictors of better disease progression. CONCLUSIONS: FLD is predominantly seasonal in our environment. CF usually has a negative specific IgG antibodies unlike ASF, where antibodies against Aspergillus are the most common. The realisation of antigenic avoidance and immunosuppressive treatment are possible predictors of better disease progression.

Identification of Antigenic Proteins from Lichtheimia corymbifera for Farmer's Lung Disease Diagnosis.

The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.

Farmer's Lung Disease. A Review. / Revisión de la enfermedad del pulmón de granjero.

Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality.

Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

Combined pulmonary fibrosis and emphysema is a distinct syndrome reported in patients who smoke. A 72-year-old, never-smoking female dairy farmer was referred for progressive dyspnoea on exertion, basal crackles on auscultation, normal spirometry and normal lung volumes but decreased diffusing capacity of the lung for carbon monoxide, centrilobular emphysema in the upper zones of the lungs and diffuse infiltrative lung disease in the lower zones on high-resolution CT scan. Bronchoalveolar lavage differential cell count showed 35% lymphocytosis, and precipitating antibodies for Wallemia sebi, Trichoderma species and Cladosporium sphaerospermum were identified. The diagnosis of farmer's lung disease with combined pulmonary fibrosis and emphysema was retained. This case highlights for the first time that hypersensitivity pneumonitis should be suspected in the setting of combined pulmonary fibrosis and emphysema in non-smoking patients.

[Chronic Farmer's lung disease with emphysema]. / Forme emphysémateuse de la maladie du poumon de fermier.

INTRODUCTION: Farmer's lung (FL) is the most common type of hypersensitivity pneumonitis (HP), with an estimated prevalence of between 0.5 and 1.5% in dairy farmers. In chronic FL, fibrotic sequelae are widely described in the literature although our experience and occasional epidemiological studies emphasize an increased risk of developing emphysema in these patients. CASE REPORT: We report a case of FL in a 37-year-old patient with typical clinical features (exertional dyspnoea, lymphocytic alveolitis and computed tomography appearances) together with proven allergen exposure. This patient developed early pulmonary emphysema probably due to intermittent massive exposure to antigens and to bacterial and fungal micro-organisms. CONCLUSION: The current classification of HP differentiates acute, subacute and chronic forms but does not take account of the role of the mode of exposure and the evolution of the disease. The prognosis and evolution of HP seem to be dependent on the type and pattern of exposure. A new classification with two clusters has been suggested: in type 1, massive and intermittent exposure, as in FL, may lead to emphysema with chronic airflow obstruction and, in type 2, chronic exposure to a low level, as in bird fanciers, may lead to fibrosis with a restrictive pattern.

Western blotting as a tool for the serodiagnosis of farmer's lung disease: validation with Lichtheimia corymbifera protein extracts.

Electrosyneresis and double diffusion are immunoprecipitation techniques commonly used in the serological diagnosis of Farmer's lung disease (FLD). These techniques are reliable but lack standardization. The aim of this study was to evaluate Western blotting for the serodiagnosis of FLD. We carried out Western blotting with an antigenic extract of Lichtheimia corymbifera, an important aetiological agent of the disease. The membranes were probed with sera from 21 patients with FLD and 21 healthy exposed controls to examine the IgG antibody responses against purified somatic antigens. Given the low prevalence of the disease, 21 patients could be considered as a relevant series. Four bands were significantly more frequently represented in membranes probed with FLD sera (bands at 27.7, 40.5, 44.0 and 50.5 kDa) than those probed with control sera. We assessed the diagnostic value of different criteria alone or in combination. The diagnostic accuracy of the test was highest with the inclusion of at least two of the following criteria: at least five bands on the strip and the presence of one band at 40.5 or 44.0 kDa. Sensitivity, specificity and positive and negative predictive values were all 81%, and the odds ratio was 18.06. Inclusion of bands of high intensity diminished rather than improved the diagnostic value of the test. We concluded that Western blotting is a valuable technique for the serodiagnosis of FLD. The industrial production of ready-to-use membranes would enable the routine use of this technique in laboratories, and provide reliable and standardized diagnostic results within a few hours.

Immunoreactive proteins of Saccharopolyspora rectivirgula for farmer's lung serodiagnosis.

PURPOSE: Saccharopolyspora rectivirgula is the principal cause of farmer's lung disease (FLD). Serodiagnosis is based on immunoprecipitation techniques or enzyme immunoassays with homemade crude antigens and is not standardized. We aimed to produce specific recombinant antigens for the development of a standardized ELISA. EXPERIMENTAL DESIGN: We recruited 41 patients and 43 healthy exposed controls from five university hospital pneumology departments in France and Switzerland. S. rectivirgula proteins were extracted, separated by 2D electrophoresis, and subjected to Western blotting, with sera from FLD patients or controls. FLD-specific proteins were identified by MS and were produced as recombinant antigens. The diagnostic performance of ELISA tests using the recombinant antigens was assessed with all the sera from FLD patients and controls. RESULTS: We identified 25 FLD-specific proteins, some of which play important roles in transport, nutrition, or virulence. We produced 17 of these proteins as recombinant antigens and assessed their suitability for inclusion in the ELISA test. A combination of three of these proteins (SR1FA, SR17, and SR22) proved remarkably effective at discriminating between patients and controls, with a sensitivity of 83% and a specificity of 77%. CONCLUSIONS AND CLINICAL RELEVANCE: The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.

[Domestic hypersensitivity pneumonitis]. / Pneumopathies d'hypersensibilité domestiques. Alvéolites allergiques extrinsèques domestiques.

INTRODUCTION: Domestic hypersensitivity pneumonitis (HP) cases are relatively widespread, with an overall annual incidence of approximately 1/100,000 reported in a British study covering several million patients. All-causes mortality is three times higher within HP-affected patients than amongst the general population. STATE OF THE ART: Cases of HP are usually diagnosed as 'farmer's lung' (FL) and 'bird fancier's lung' (BFL) diseases, however we suggest that other domestic causes, such as humidifier lung, hot tub pneumonitis, feather duvet and domestic exposure to moulds may be more frequent than widely suggested. Usually, the diagnosis is established on the basis of characteristic clinical, functional, radiological and broncho-alveolar lavage findings or recurrence of respiratory symptoms after returning home. PERSPECTIVES: In the absence of a common cause (FL or BFL), physicians must have a high index of clinical suspicion and should consider an environmental antigen source. Detailed questioning of HP patients on their living conditions and, where appropriate, a home inspection conducted by an environmental health expert are necessary for identifying causative antigens. CONCLUSION: The cornerstone of therapy is antigen avoidance.

Chronic hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by the inhalation of environmental antigens. Chronic HP may mimic other fibrotic lung diseases, such as idiopathic pulmonary fibrosis. Recognition of the antigen is important for diagnosis; avoidance of further exposure is critical for treatment. Fibrosis on biopsy or high-resolution computed tomography is a predictor of increased mortality. Additional research is needed to understand why the disease develops only in a minority of exposed individuals and why cases of chronic HP may progress without further antigen exposure.

Bronchoalveolar lavage in hypersensitivity pneumonitis: a series of 139 patients.

Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 ± 401.10(3) cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio < 1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis.

Comparison of three antigenic extracts of Eurotium amstelodami in serological diagnosis of farmer's lung disease.

In France and Finland, farmer's lung disease (FLD), a hypersensitivity pneumonitis common in agricultural areas, is mainly caused by Eurotium species. The presence of antibodies in patients' serum is an important criterion for diagnosis. Our study aimed to improve the serological diagnosis of FLD by using common fungal particles that pollute the farm environment as antigens. Fungal particles of the Eurotium species were observed in handled hay. A strain of Eurotium amstelodami was grown in vitro using selected culture media; and antigen extracts from sexual (ascospores), asexual (conidia), and vegetative (hyphae) forms were made. Antigens were tested by enzyme-linked immunosorbent assay (ELISA), which was used to test for immunoglobulin G antibodies from the sera of 17 FLD patients, 40 healthy exposed farmers, and 20 nonexposed controls. The antigens were compared by receiver operating characteristic analysis, and a threshold was then established. The ascospores contained in asci enclosed within cleistothecia were present in 38% of the hay blades observed; conidial heads of aspergillus were less prevalent. The same protocol was followed to make the three antigen extracts. A comparison of the results for FLD patients and exposed controls showed the area under the curve to be 0.850 for the ascospore antigen, 0.731 for the conidia, and 0.690 for the hyphae. The cutoffs that we determined, with the standard deviation for measures being taken into account, showed 67% for sensitivity and 92% for specificity with the ascospore antigen. In conclusion, the serological diagnosis of FLD by ELISA was improved by the adjunction of ascospore antigen.

Cluster of presumed organic dust toxic syndrome cases among urban landscape workers-Colorado, 2007.

BACKGROUND: Organic dust toxic syndrome (ODTS) is an influenza-like illness typically affecting agricultural workers exposed to organic dusts. In July 2007, Tri-County Health Department investigated a cluster of acute respiratory illnesses among urban landscape workers with known mulch exposure. METHODS: An epidemiologic study of landscape workers was conducted. Employees were interviewed regarding illness and occupational exposures. Medical records were reviewed. Mulch samples were tested for fungi and endotoxins. RESULTS: Five (12%) of 43 employees experienced respiratory illness compatible with ODTS. Illness was associated with prolonged mulch exposure (>or=6 vs. <6 hr/day; relative risk = 24.7; 95% confidence interval = 3.3-184.9). Mulch samples contained high levels of Aspergillus spores and endotoxin. CONCLUSIONS: Contaminated mulch was implicated as the source of presumed ODTS among landscape workers, highlighting that ODTS is not limited to rural agricultural settings. Education of employers, safety officers, and clinicians is necessary to improve recognition and prevention of ODTS within urban occupational groups.

Educational intervention decreases exhaled nitric oxide in farmers with occupational asthma.

Allergic occupational asthma is frequent in farming populations. As educational interventions can improve disease management, the short-term effect of an educational intervention in asthmatic farmers was evaluated on the basis of spirometric indices and exhaled nitric oxide fraction (F(eNO)). Farmers with occupational asthma (n = 81), mostly sensitised against cow dander and storage mites, participated in a 1-day educational programme. Outcome measures were assessed at baseline and after 4-6 weeks, using F(eNO), lung function and a questionnaire. Results were compared with those of a control group without intervention (n = 24). In the educational group, the proportion of subjects reporting work-related symptoms was reduced after the intervention. The F(eNO) decreased from a geometric mean of 28.2 to 25.7 ppb, and, in subjects with an elevated (>35 ppb) baseline F(eNO) (n = 32), from 59.7 to 49.2 ppb. The corresponding changes in the control group were 25.6 versus 27.7 ppb and 49.5 versus 48.1 ppb. Spirometric results were unaltered in the two groups. Thus exhaled nitric oxide fraction, a marker of allergic airway inflammation, indicated a beneficial effect of a short-term educational intervention in farmers with occupational asthma. This suggests a potential for exhaled nitric oxide fraction in assessing the efficacy of preventive measures within a short time with higher sensitivity than spirometry.

Assessment of four serological techniques in the immunological diagnosis of farmers' lung disease.

Farmers' lung disease (FLD) is a pulmonary disease that results from repeated inhalation of antigens from mouldy hay or straw. The objective of this prospective study was to assess the reliability of four serological techniques in FLD diagnosis. Sera from 15 consecutive patients with FLD, 15 healthy control farmers and 30 urban controls were analysed using four serological techniques [electrosyneresis (ES), Ouchterlony double diffusion (DD), ELISA and Western blot (WB)] with four antigens (Absidia corymbifera, Eurotium amstelodami, Wallemia sebi and Saccharopolyspora rectivirgula). In the authors' region, ES on cellulose acetate with A. corymbifera antigen was the most relevant diagnostic tool for discriminating FLD patients from healthy exposed farmers (sensitivity 87 %, specificity 100 %). DD tests were in accordance with ES, but their discriminatory power was lower. No threshold indicating both good sensitivity and specificity could be established with ELISA. WB analysis failed to identify specific bands for FLD. This study demonstrates the efficacy of determining precipitin levels with an appropriate technique, using a panel of antigens consistent with the specific exposure of a given area.