[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.

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.

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.

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.

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.

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.

Relationship among antigen contact, alveolitis, and clinical status in farmer's lung disease.

We studied 41 subjects with a history of farmer's lung disease who had been free of acute episodes for at least one year. Twenty-six were still in daily contact with hay (group 1), and 15 had ceased all antigenic exposure (group 2). While the incidence of dyspnea was similar in both groups, coughing and sputum were more frequent in group 1. Inspiratory crackles were frequent in group 1 subjects (15 of 26) and absent in all group 2 subjects. In both groups, a high percentage of lymphocytes was demonstrated by bronchoalveolar lavage: 52.5% +/- 21.1% (mean +/- SD) and 26.3% +/- 18.7%, respectively. Lymphocytic alveolitis (greater than 22% lymphocytes) was more common in group 1 (23 of 26) than in group 2 (6 of 15). There was no relationship between functional abnormalities and the intensity of the alveolitis. We conclude that lymphocytic alveolitis may persist after an acute episode of farmer's lung disease, but the intensity of the alveolitis is not associated with functional alterations.

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.

[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.

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.

Familial hypersensitivity pneumonitis.

Two families are described in which seven members of a total of 19 were found to have hypersensitivity pneumonitis due to exposure to avian antigens. Diagnosis was made on the basis of characteristic roentgenologic changes together with respiratory function and immunologic studies. The latter included screening for precipitins, macrophage migration inhibition (MMI) to specific antigens in avian serum and droppings, quantitation of immunoglobulin and alpha1 antitrypsin (AAT) levels and assessment of the complement system. Specific precipitins to pigeon and/or budgerigar serum were found in the serum of only four of the seven patients. Six of these seven patients, however, had a positive MMI. Thus, the MMI test, at least in this group of patients appeared to be a more sensitive indicator of active disease. The finding of seven members of two families with disease led to a search for predisposing factors, either genetic or environmental. Evidence for a genetic predisposition came from tissue typing studies. In the first family, both paternal haplotypes were associated with disease; the maternal haplotype HLA3,7 was not inherited by any child with disease. In the second family, the disease developed in three of four members with the haplotype HL-A2,W15, who were significantly exposed to avian antigen. In the light of recent studies showing an association between immune response (Ir) genes, histocompatibility antigens and disease susceptibility, these findings were interpreted as possible evidence for a subtle genetically linked immune defect in hypersensitivity pneumonitis. Evidence for an environmental predisposition was less clear cut, but it is interesting that members of both families used a gamma isomer of hexachlorobenzene (Nickoff) to eradicate mite infestations in their birds which might have damaged the bronchial mucosa or acted as an immunologic adjuvant in a person with underlying susceptibility to disease. The presence of subclinical respiratory disease in two family members is reported, and the importance of performing a range of investigations of respiratory function in order to detect disease and monitor its progress is emphasized.

Childhood hypersensitivity pneumonitis due to dove antigens.

A case of hypersensitivity pneumonitis due to doves is reported and compared with other cases due to dove or pigeon antigens reported in children. The diagnosis is substantiated by the presence of precipitating antibody to dove and pigeon serum, clinical improvement after contact with the doves was broken, and a positive response to inhalation challenge with pigeon serum. The insidious nature of this disease is emphasized as well as the importance of having detailed environmental information in children with unexplained respiratory disease.

Usefulness of skin test in Farmer's lung.

The skin test with hay extract or with Micropolyspora faeni (MF), is not commonly used in the diagnosis of Farmer's lung (FL), as it is not considered specific. In our study, we have applied the intracutaneous test with these antigens in 26 patients affected with FL; 18 of them were still in contact with the antigen and the remaining eight had not been in contact with the hay during the previous year. Twenty-five asymptomatic farmers (AF) served as a control group. In the first group and with hay extract, the immediate reading (I) was positive in 15 of 18 (83.3 percent), the late reaction (L) in 18 of 18 (100 percent), and the delayed one (D) in eight of 18 (44.4 percent). In the 25 AF, the results were as follows: I, seven of 85 (28 percent); L, 17 of 25 (68 percent); and D, one of 25 (4 percent). Consequently, the differences between both groups were significant: I, p less than 0.01; L, p less than 0.05; and D, p less than 0.01. Using MF as an antigen, the test is somewhat less effective: p less than 0.02, p less than 0.02, and p less than 0.2, respectively. These results suggest that the intradermal injection with hay extract is an easy, effective test in the diagnosis of FL, and at the same time, a better means of distinguishing FL patients from AF than the precipitation test.

Increased airways responsiveness in swine farmers.

A respiratory questionnaire, pulmonary function tests, and an examination of airways responsiveness were conducted on 20 swine farmers and 20 control subjects. The swine farmers represented almost the complete work force from 13 Hutterite colonies and had worked in confinement buildings with more than 2,000 swine (3,270 +/- 1,221 swine) for at least four hours (6.6 +/- 1.8 hours) per day for more than two years (10.5 +/- 7.5 years). The control subjects were randomly selected from outdoor city workers from the city of Saskatoon and were matched for gender, age (+/- 2 years), and smoking status. Eleven swine farmers (55 percent) had chronic cough, compared with three (15 percent) of the control subjects (p less than 0.01). Eight (40 percent) of the swine farmers had symptoms of wheezing, compared with three (15 percent) of the control subjects (p less than 0.05). The FEV1 was significantly lower in swine farmers (97.2 +/- 11.5 percent predicted) than in control subjects (106.0 +/- 12.0 percent of predicted) (p less than 0.05). Airways responsiveness was measured by methacholine challenge with doubling concentrations ranging from 0.25 to 256 mg/ml. The provocation concentrations resulting in a reduction of 10 percent (PC10) and 20 percent (PC20) in FEV1 were lower in swine farmers than in control subjects (PC10, 77.2 +/- 78.8 mg/ml vs 180.8 +/- 96.5 mg/ml; p less than 0.01; and PC20, 154.5 +/- 99.9 mg/ml vs 229.6 +/- 66.8 mg/ml; p less than 0.05). Twelve swine farmers (60 percent) had PC20 of less than 256 mg/ml, compared with three (15 percent) of the control workers (p less than 0.01). Fewer swine farmers demonstrated atopy as measured by skin prick tests than did control workers (21 percent vs 56 percent; p less than 0.05). These findings suggested that occupational exposure in swine confinement buildings is associated with mild increases of nonspecific, nonatopic airways responsiveness in swine farmers.

Mast cells in bronchoalveolar lavage fluid and in transbronchial biopsy specimens of patients with farmer's lung disease.

Recently, an increased number of mast cells have been reported in bronchoalveolar lavage fluid (BAL) of patients with farmer's lung disease. Some authors pointed out the pathogenetic importance of mast cells in farmer's lung on the basis of their correlation with the activity of the disease, with the BAL lymphocyte counts, and with the markers of lung fibrosis. To determine whether BAL reflects the histologic aspects of the lung histologic features in patients with farmer's lung disease, mast cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 15 patients. Mast cell counts in BAL and lung biopsy specimens were significantly correlated (r = 0.88; p less than 0.01), while no other correlations between BAL inflammatory cells and tissue mast cells were found. In lung tissue, there were four times the increased number of mast cells in respect to the control group (84.4 +/- 28.8 vs 20.4 +/- 13.4 mast cells per square millimeter); 83.2 percent of mast cells were found in the alveolar septa, 14.9 percent within alveoli, 0.7 percent among alveolar lining cells, and 1 percent along blood vessels. No mast cells were located within alveoli in controls. In BAL, only lymphocyte and mast cell counts (56.4 +/- 18.6 percent, p less than 0.001; 3.9 +/- 1.5 5 percent, p less than 0.001, respectively) were significantly increased. Our data suggest that in farmer's lung disease, BAL correctly samples the alveolitis. Mast cells, such as lymphocytes, seem to be primary inflammatory cells involved at the site of the disease activity.

Fibrogenic activities in bronchoalveolar lavage fluid of farmer's lung.

Hyaluronic acid (HA), type III procollagen, fibronectin, and fibroblast growth factors (FGF) were measured in 43 bronchoalveolar lavage fluid (BALF) specimens obtained from 38 patients with farmer's lung (FL) and in BALF of 9 nonexposed normal control subjects. Bronchoalveolar lavage was done in 21 farmers with acute FL (acute) and in 22 with a history of previous FL (Ex) who were still in daily contact with dairy barns. All farmers from the acute and Ex groups had a lymphocytic alveolitis, respectively, 62.7 (3.5) percent (mean [SEM]) and 48.1 (4.3) percent. Hyaluronic acid, type III procollagen, fibronectin, and FGF were all highly increased in acute disease. These substances were also increased in the BALF of subjects of the Ex group who had no clinical symptoms or signs of acute disease at the time of lavage, but were actively farming. The increase in type III procollagen, however, was less in this group than in the subjects with acute disease. These observations suggest that the fibrosing activities and potentialities of the allergic alveolitis of FL are fully expressed at the time of clinical presentation and also in the subclinical phase of the disease in susceptible farmers who remain exposed after an initial acute phase of the disease.

Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.