Farmer's Lung Disease Research Articles

Farmer’s Lung Disease

Occupational lung disease is a lung disease or disorder that occurs due to the inhalation of dangerous particles, mist, vapors, or gases while a person is working. The materials accumulate in the respiratory tract or lungs. The type of lung disease that occurs depends on the size and type of the inhaled material. Substances that cause occupational lung disease are toxic materials called noksa. Noksa is a substance that can cause damage to the anatomical structure of body organs and cause respiratory tract function disorders. The lung disease that many farmers experience is often called farmer's lung disease (FLD). FLD is part of hypersensitivity pneumonitis (HP). HP, also known as extrinsic allergic alveolitis, is a group of lung diseases caused by the inhalation of various antigenic organic materials. The most common cause is exposure to agricultural biological dust derived from straw, mold spores, or other dust. HP can be a secondary reaction due to repeated and prolonged inhalation of specific antigens in sensitive individuals. Diagnosis of FLD is often inaccurate. Many of these cases are diagnosed as idiopathic interstitial lung disease. A complete anamnesis should be performed, especially regarding the history of exposure to moldy hay, previous work, and domestic animals, to determine the existence of a history of exposure to the antigen and to confirm the diagnosis.

Farmer's lung disease: Analysis of 75 cases

IntroductionFarmer'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 methodsA 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 sensitization was demonstrated and/or a concordant pathology. ResultsWe 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=0.0018). In the ASF group, DLco showed an improvement during follow-up (p=0.047). The determination of specific IgG antibodies was positive in 39 patients (78%) with ASF (44% of them against Aspergillus) and CF 12 (48%). The realization of antigenic avoidance (OR 9.26, 95% CI 1.3–66.7, p=0.026) and the administration of immunosuppressive therapy (OR 16.13, 95% CI 1.26–200, p=0.033) were predictors of better disease progression. ConclusionsFLD 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 realization 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

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.

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.

Draft Genome Sequence of the Principal Etiological Agent of Farmer's Lung Disease, Saccharopolyspora rectivirgula.

Saccharopolyspora rectivirgula is the main cause of farmer’s lung disease. The development of recombinant antigens to standardize the serodiagnosis of the disease requires knowledge of the S. rectivirgula genome. We sequenced the genome of an environmental strain, S. rectivirgula DSM 43113. A total of 3,221 proteins were found to be encoded in a short 3.9-Mb genome.

Immunoreactive proteins of Saccharopolyspora rectivirgula for farmer's lung serodiagnosis

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. 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. 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%. The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.

Prevalence and risk factors for farmer's lung in greenhouse farmers: an epidemiological study of 5,880 farmers from Northeast China.

The objectives of this epidemiological study were to evaluate the prevalence of farmer's lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m(2) but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced.

Draft Genome Sequence of Saccharopolyspora rectivirgula

We have sequenced the genome of Saccharopolyspora rectivirgula, the causative agent of farmer’s lung disease. The draft genome consists of 182 contigs totaling 3,977,051 bp, with a GC content of 68.9%.

Quantification of <italic>Saccharopolyspora rectivirgula</italic> in Composting Plants: Assessment of the Relevance of <italic>S. rectivirgula</italic>

Exposure to bioaerosols in composting plants can lead to negative health effects on compost workers. Health complaints vary between cough, irritation of the eyes and the skin, sinusitis, or dyspnea among others. It is fact that compost materials harbor high concentrations of microorganisms, which were aerosolized during handling compost. Within the present study, total cell numbers between 3.4 × 10(4) and 1.6 × 10(8) cell counts per m(3) air were determined after 4',6-Diamidin-2-phenylindol DAPI staining in 124 samples from German composting plants. Special attention should be paid to some specific microorganisms, which are able to cause health complaints. Saccharopolyspora rectivirgula, known to be one of the major causes of extrinsic allergic alveolitis (EAA, also called hypersensitivity pneumonitis, HP), was often found in environments of agricultural production, where the classical form of EAA ('farmer's lung disease') is common, but also in composting plants. In Germany, cases are known where workers had to terminate their work due to this disease. However, up to now, the relevance of S. rectivirgula at composting plants is unexplained. This study showed that high concentrations of airborne S. rectivirgula were found in composting plants similar to that found in agricultural production. Altogether, in 86.7% of the 124 analyzed samples, S. rectivirgula was detected using quantitative real-time polymerase chain reaction (PCR). Estimated concentrations ranged between 1.24 × 10(2) cell counts of S. rectivirgula per cubic meter air next to the rotted residues and 1.5 × 10(7) cell counts next to a converter. Furthermore, our methodical proceedings were verified. To analyze DNA extraction limits through the amount of cells within one sample, the DNA concentration was compared with total cell counts (TCCs). Altogether, when TCC was <1.4 × 10(5) cells per DNA extraction assay, no DNA was measurable; when TCC reached 3.5 × 10(6) cells, DNA was always detectable by fluorometric method. To overcome limitation of DNA measurement using fluorometric method, samples without measurable DNA were inserted in a PCR assay with universal primers. Results showed that a gain of 37% was possible, when samples were additionally analyzed by universal PCR. Hence, cell counts >2.0 × 10(6) cells were necessary to measure DNA concentrations in 90% of the analyzed samples, whereas cell counts <3.0 × 10(5) are sufficient to detect PCR products. Therefore, sampling of bioaerosols should be done in consideration of the expected cell count per cubic meter air. Note, to get measurable DNA using a fluorometer, >3.5 × 10(6) cells must be sampled for one DNA extraction assay. With this study, the real-time PCR approach for the detection of S. rectivirgula at workplaces in compost plants was revised, and the results revealed that this method is suitable for occupational exposure measurements.

Aspergillus species recombinant antigens for serodiagnosis of farmer's lung disease

Farmer's lung disease (FLD) is the most frequent occupational hypersensitivity pneumonitis. In the East of France and Finland, various genera of mold (Aspergillus, Absidia = Lichtheimia, and Wallemia) have been suggested as the main causative agents of FLD.1,2 Immunologic studies have also shown that sera from patients with FLD specifically react with Aspergillus species from the glaucus group (Aspergillus vitis/Eurotium amstelodami).1,3

Salt induces biosynthesis of hemolytically active compounds in the xerotolerant food-borne fungus Wallemia sebi

Wallemia sebi is a xerotolerant, ubiquitous, food-borne, mycotoxigenic fungus. An ethanol extract of its mycelium demonstrated a strong hemolytic activity, which was further enhanced at high salt concentrations in the growth medium. Characterization of the extract using gas chromatography-mass spectrometry revealed a mixture of sterols and unsaturated fatty acids, indicating the latter as responsible for the hemolytic activity. The lytic activity of the extract is here studied using red blood cells and artificial small lipid vesicles with various lipid compositions. This shows concentration-dependent hemolysis and preferential activity toward lipid membranes with greater fluidity. The W.sebi lytic activity on mammalian erythrocytes shows its potential involvement in the formation of lesions in subcutaneous infections, in farmer's lung disease, and in consumption of food and feed that are contaminated with food-borne W.sebi.

Genomics and the ancient origins of the daptomycin biosynthetic gene cluster

Daptomycin is a clinically useful lipopeptide antibiotic produced by Streptomyces roseosporus. The antibiotic is assembled by a nonribosomal peptide synthetase (NRPS) mechanism, and the cyclized tridecapeptide contains three non-proteinogenic-amino acids: ornithine (Orn), 3-methyl-glutamic acid (3mGlu) and kynurinine (Kyn). Daptomycin also has three D-amino acids. The two genes that encode proteins involved in the formation of 3mGlu and Kyn have no known orthologs, and hence they are good probes to search for daptomycin-like gene clusters among newly sequenced actinomycete genomes. A recent search with these genes revealed a daptomycin-like gene cluster in Saccharomonospora viridis, a causative agent for farmer's lung disease. S. viridis has a genome of 4.3 Mb, which is about one half the size of Streptomyces genomes. Searches for other NRPS and polyketide synthase (PKS) genes revealed only one other NRPS gene and no PKS genes in S. viridis. The orthologous lipopeptide biosynthetic genes and gene products in S. viridis and S. roseosporus have diverged extensively from a last common ancestor dating back to a pathway that had evolved over 1 billion years ago.

New evidence of the involvement ofLichtheimia corymbiferain farmer's lung disease

Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis resulting from recurrent exposure to moldy plant materials. We investigated and compared the initial response of respiratory epithelium after exposure to extracts of Sacharopolyspora rectivirgula, Lichtheimia corymbifera (formerly Absidia corymbifera), Eurotium amstelodami and Wallemia sebi. The two criteria for selection of these species were their high prevalence in the hay handled by FLD patients and the presence of high levels of specific precipitins to these molds in FLD patients&#x2019; sera. Hydrosoluble extracts were prepared from spores and hyphae grown in culture under optimal conditions for each of the four species. Confluent A549 cells were inoculated with one of the four calibrated soluble extracts. Two mediators, one inflammatory (Interleukin (IL)-8) and one allergic (IL-13), were quantified using real-time PCR and ELISA assay, after four exposure periods (30 min, 2 h, 4 h and 8 h). S. rectivirgula and L. corymbifera extracts were the only ones which induced a marked upregulation of IL-8, as shown by both real-time PCR and ELISA assay 8 h after the initial contact. This study adds to the growing body of evidence that L. corymbifera should be recognized as an etiologic agent of FLD along with S. rectivirgula.

A clinical and epidemiological study of farmer's lung disease

A clinical and epidemiological study of farmer's lung disease

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.

Complete genome sequence of Saccharomonospora viridis type strain (P101T)

Saccharomonospora viridis (Schuurmans et al. 1956) Nonomurea and Ohara 1971 is the type species of the genus Saccharomonospora which belongs to the family Pseudonocardiaceae. S. viridis is of interest because it is a Gram-negative organism classified among the usually Gram-positive actinomycetes. Members of the species are frequently found in hot compost and hay, and its spores can cause farmer’s lung disease, bagassosis, and humidifier fever. Strains of the species S. viridis have been found to metabolize the xenobiotic pentachlorophenol (PCP). The strain described in this study has been isolated from peat-bog in Ireland. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the family Pseudonocardiaceae, and the 4,308,349 bp long single replicon genome with its 3906 protein-coding and 64 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.

Avidity of Aspergillus umbrosus IgG antibodies in farmer's lung disease.

Farmer's lung disease (FL), the commonest form of allergic alveolitis caused by repeated inhalation of mouldy hay, is associated with exposure to the fungus Aspergillus umbrosus among Finnish farmers. The antigen-binding avidity of A. umbrosus-specific IgG antibodies was measured in 12 FL patients in acute phases of initial and recurrent attacks and during 1 year follow up as well as in 12 healthy farmers and five healthy urban controls. The farmers' groups were further divided into two subgroups: subjects with short exposure (< 7 years) and subjects with long exposure (> 25 years). During the first acute phase FL patients with long exposure exhibited a high avidity of A. umbrosus-specific IgG antibodies that remained high during the 1 year follow up, although the A. umbrosus-specific IgG antibody titre decreased. A re-exposure to mouldy hay leading to a recurrence further enhanced the maturation of the antibody avidity, so that an even higher A. umbrosus-specific IgG avidity with a less significant increase of antibody titre occurred than during the first acute attack. Notably higher IgG antibody avidity was observed in FL patients with long exposure than in healthy farmers or in healthy controls.

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.

Causes and Presenting Features in 85 Consecutive Patients With Hypersensitivity Pneumonitis

To assess the current spectrum of causes and clinical features associated with hypersensitivity pneumonitis (HP). We studied consecutive patients with HP diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1997, through December 31, 2002. Diagnostic criteria for HP included the following: (1) presence of respiratory symptoms, (2) radiologic evidence of diffuse lung disease, (3) known exposure or a positive serologic test result to an inciting antigen, and (4) no other identifiable cause for the lung disease. If there was no identifiable inciting antigen, 1 of the following 2 criteria was required: (1) lung biopsy specimen that demonstrated features of HP or (2) bronchoalveolar lavage lymphocytosis and high-resolution computed tomographic evidence of ground-glass opacities or centrilobular nodules bilaterally. The mean +/- SD age of the 85 study patients was 53 +/- 14 years; 53 patients (62%) were women. Only 2 patients (2%) were current smokers. Chronic (> or = 4 months) respiratory symptoms were present in 66 patients (78%). Histopathologic confirmation was obtained in 64 patients (75%). The cause was identified in 64 patients (75%), and the most common causes were avian antigens (34%) and Mycobacterium avium complex in hot tub water (21%). Farmer's lung disease accounted for 11% of cases, and an additional 9% were related to household mold exposure. The inciting antigen was not identifiable in 25% of patients. Most patients with HP seen at this tertiary care referral center in the Midwest region of the United States had chronic HP, and the most common causes were exposure to birds and exposure to hot tubs.