Farmer's Lung Disease Research Articles

Farmer’s Lung Disease and Microbiological Composition of Hay: A Case–Control Study

Previous studies performed in France have suggested that handling hay contaminated with high amounts of moulds, and especially Absidia corymbifera and Eurotium amstelodami, may favour farmer's lung disease. The circumstances favouring farmer's lung disease and the distinctive microbiological composition of hay samples that provoke attacks need to be specified. We present a case-control study which investigates the agricultural practices and the microbiological composition of hay handled in patients with farmer's lung disease as compared to those of a representative control population. Ten cases identified the hay they were handling at the onset of symptoms. The location, type of farm and working conditions were similar to those of the control farms. Conversely, the microbiological composition of hay differed, with significantly higher amounts of E. amstelodami (P < 0.01), A. corymbifera (P = 0.003), mesophilic Streptomyces (P < 0.01), thermophilic Streptomyces (P < 0.01) and Saccharomonospora viridis (P < 0.01) than in the control population. Our results demonstrate that hay identified by patients as having a harmful effect is characterized by a higher total amount of microorganisms, notably five microorganisms that seem discriminative. Mean concentrations are 2- to 115-fold higher in hay suspected to cause symptoms than in hay from a representative panel of farms. Handling hay with high amounts of these five microorganisms constitutes a risk factor for farmer's lung disease that should be considered for the development of prophylactic measures.

Detection and Quantification ofWallemia sebiin Aerosols by Real-Time PCR, Conventional PCR, and Cultivation

Wallemia sebi is a deuteromycete fungus commonly found in agricultural environments in many parts of the world and is suspected to be a causative agent of farmer's lung disease. The fungus grows slowly on commonly used culture media and is often obscured by the fast-growing fungi. Thus, its occurrence in different environments has often been underestimated. In this study, we developed two sets of PCR primers specific to W. sebi that can be applied in either conventional PCR or real-time PCR for rapid detection and quantification of the fungus in environmental samples. Both PCR systems proved to be highly specific and sensitive for W. sebi detection even in a high background of other fungal DNAs. These methods were employed to investigate the presence of W. sebi in the aerosols of a farm. The results revealed a high concentration of W. sebi spores, 10(7) m(-3) by real-time PCR and 10(6) m(-3) by cultivation, which indicates the prevalence of W. sebi in farms handling hay and grain and in cow barns. The methods developed in this study could serve as rapid, specific, and sensitive means of detecting W. sebi in aerosol and surface samples and could thus facilitate investigations of its distribution, ecology, clinical diagnosis, and exposure risk assessment.

Fatal Intra-Alveolar Hemorrhage After Rituximab in a Patient with non-Hodgkin Lymphoma

A 65-year-old male developed progressive dry cough and digital clubbing after starting rituximab-CHOP chemotherapy for non-Hodgkin lymphoma. A lung biopsy showed loose non-necrotic granulomas in a background of mild fibrosis and rare eosinophils, compatible with a drug-induced hypersensitivity pneumonia. Associated manifestations of this hypersensitivity reaction were a high eosinophil count, elevated serum levels of immunoglobulin E, and a skin rash consistent with pigmented purpuric dermatitis (Schamberg disease). Corticosteroids were marginally efficacious in treating this reaction. Few similar reactions have since been described, 2 of them ultimately fatal, but none was associated with pulmonary hemorrhage. A 2.5 : 1 ratio between the interstitial alveolar T4/T8 lymphocytes in our case is similar to the findings in methotrexate-induced pneumonitis and farmer lung disease. This report documents the serologic and immunohistologic findings associated with a pulmonary interstitial reaction to rituximab. A review of the pertinent literature is provided. The possible pathogenetic mechanisms, including the role of cytokines, cytotoxic T-lymphocytes and CD 20 positive T-cells in relation to the administration of rituximab are discussed.

The Role of MIP-1? in Experimental Hypersensitivity Pneumonitis

S. rectivirgula (SR) causes Farmer's Lung Disease, a classic example of hypersensitivity pneumonitis (HP). We utilized a model of experimental hypersensitivity pneumonitis (EHP), antibody to MIP-1alpha and MIP-1alpha -/- mice, to test the hypothesis that MIP-1alpha is essential in the development of EHP. Treatment of C57BI/6 mice with anti-MIP-1alpha antibody did not change the extent of pulmonary histology abnormalities, BALF cell number or characteristics, or BALF concentration of IL12p40, TNF, IL1alpha and IL6, after an i.t. challenge with SR. MIP-1alpha -/- animals responded similarly to wild-type (wt) animals in the extent and nature of pulmonary histologic changes and BALF cell number and type after a single i.t. injection of SR There was a dose-response relationship between the amount of SR and BALF IL12p40, MCP-1 and IL6 in both strains, and MIP-1alpha in wild-type animals. We next transferred SR cultured spleen cells from SR sensitized mice (both wt and MIP-1alpha -/-) to naive recipients. Lung histology and BALF characteristics after SR i.t. challenge of the recipients were used to determine if adoptive transfer had occurred. Cultured cells from MIP-1alpha -/- animals were fully capable of transferring EHP to recipients. There was no difference of BALF TNF, IL6 and IL1alpha between the strains, but there was more MCP-1 and IL12p40 in the MIP-1alpha -/- mice than in the control mice. MIP-1alpha is not necessary for the recruitment of cells into the lung and BALF after i.t. administration of SR, or the development of cells able to adoptively transfer EHP.

Long-term sequelae of Farmer's lung disease in HRCT: a 14-year follow-up study of 88 patients and 83 matched control farmers.

The aim of this study was to compare high-resolution computed tomography (HRCT) findings of long-term farmer's lung (FL) patients and control farmers. We studied 88 FL patients and 83 matched control farmers with a mean follow-up time of 14 years. Emphysematous, fibrotic, and miliary changes were recorded by HRCT. The pattern of emphysema and location and distribution of other findings were evaluated in detail. Emphysema was found in 20 (23%) FL patients and in 6 (7%) controls (p=0.005). Recurrences of FL attacks increased (p=0.021) the risk of emphysema. Prevalence of fibrosis (17 vs 10%, p=0.16) and miliary changes (11 vs 4%, p=0.06) did not differ significantly in patients and controls. Among FL patients, emphysematous, fibrous, and miliary changes were more pronounced at the base than in the upper parts of the lung (p<0.02). In slice analysis, the pattern of emphysema was more polymorphous (p=0.001) and the distribution of fibrotic and miliary changes was more variable among FL patients than controls. Emphysema in HRCT is more common in FL patients than matched control farmers, and the occurrence is increased by recurrences of FL. Emphysematous, fibrous, and miliary changes in FL patients HRCT are multiform and predominate in the lower parts of the lung.

The risk of asthma among Finnish patients with farmer's lung.

To assess the incidence and risk of asthma in patients with farmer's lung in comparison with farm workers without farmer's lung. The details of farmers and animal-husbandry workers notified in 1988-1999 for farmer's lung ( n=1,272) or other occupational disease ( n=5,045) to the Finnish Register of Occupational Diseases were followed until 31 December 2000 through two national registries of individuals eligible for reimbursement of the cost of asthma medication and the Population Register Center. Incidence rates of asthma were calculated, and a log-linear model adjusted for age, gender and occupation was used to estimate relative risks of asthma among those with farmer's lung compared to those with other occupational disease. Of the patients with farmer's lung, 109 (8.6%) were diagnosed with asthma during the follow-up compared with 202 (4.0%) incident cases of asthma among those in the reference population. The crude relative risk of asthma was 2.1 (95% CI 1.6-2.6) among those with farmer's lung compared with the reference population. The age- and occupation-adjusted relative risk of asthma among patients with farmer's lung was 2.5 (1.8-3.5) in men and 1.4 (1.0-1.9) in women. The rate of asthma was especially high during the first 2 years after notification of farmer's lung. Patients with farmer's lung have an increased risk of developing asthma in comparison to farm workers in general. Most of the cases of asthma occur relatively shortly after the diagnosis of farmer's lung, which should be taken into account in medical follow-up of patients with farmer's lung.

Influence of buffered propionic acid on the development of micro‐organisms in hay

We tested the benefit of using buffered propionic acid (BPA) as a means of preventing farmer's lung disease (FLD). BPA, a new formulation of propionic acid, a hay preservative with no deleterious effect on farm machinery or cattle, reduces the development of micro-organisms in hay. Twenty pairs of round bales were analysed for concentration of micro-organisms measured in the winter following hay treatment. Each pair included one untreated bale and one bale treated with BPA during haymaking. Our results showed the following decreases in concentration in treated bales: total fungal species, 40% (P < 0.05); Eurotium amstelodami (the main species found), 65% (P < 0.01); and thermophilic actinomycetes, 60% (not significant), respectively. We conclude that BPA could be used to prevent FLD.

Occurrence of farmer's lung disease is relevant to meteorological conditions: a 20-year follow-up field survey analysis.

A field survey on farmer's lung disease (FLD) in a dairy farming community in the northernmost district of Japan has been in progress since 1978. The correlation between the number of FLD occurrences year by year and dairy farming conditions and meteorological data were compared. Thirty-four FLD cases had occurred in a 20 years period. Average number of days below freezing during the harvest season the year prior to FLD occurrence were significantly smaller than other years (2.1 +/- 0.7 [SE] days, 4.6 +/- 0.7 days, P < 0.05, respectively). Average annual sum of the sunlight hours in the years before the years with FLD occurrence was significantly smaller than those without FLD occurrence (1457.1 +/- 114.0 hr, 1811.3 +/- 97.7 hr, P < 0.05, respectively) and was also significantly smaller for the sunlight hours during a harvest season (821.9 +/- 60.2 hr, 1023.2 +/- 52.7 hr, P < 0.05, respectively). Temperature and sunlight hours closely associated with the FLD occurrence.

Role of molds in farmer's lung disease in Eastern France.

Farmer's lung disease (FLD) is common in the east of France. In the absence of the primary recognized FLD agent, Saccharopolyspora rectivirgula, its etiology remains unknown. A prospective case-control study was performed to find the etiology of FLD in this area. Eleven patients were matched with 11 healthy control farmers. Twenty-two urban subjects constituted the nonexposed control group. Microorganisms from cowshed air and fodder were identified and counted. The antigens of the microorganisms most frequently isolated at the 22 farms were used for serological tests. Farms of patients with FLD contained more Absidia corymbifera than those of healthy farmers (p < 0.05 in air, p < 0.01 in fodder). Electrosyneresis, performed with A. corymbifera somatic antigen, differentiated 9 of 11 patients with FLD from control subjects (p < 0.01). Other significant results were obtained with Eurotium amstelodami (p < 0.01) and Wallemia sebi (p < 0.05). In contrast, no significant results were obtained with the other seven antigens tested, including S. rectivirgula. Absidia corymbifera and, to a lesser degree, W. sebi or E. amstelodami are likely to be the main causes of FLD in this area. Modifications in working conditions over time could explain the emergence of these new contributing etiologies.

Serum KL-6 Concentrations in Dairy Farmers

Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease (FLD). A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. University hospital screening project for FLD within a dairy-farming community in Japan. Four hundred seventy-two dairy farmers were invited to attend a local clinic. We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/- 57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 +/- 288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab(+) group were significantly higher than those of the Ab(-) group (p < 0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease.

Mediators of hypersensitivity pneumonitis

Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula ) causes farmer's lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a well-described murine model of HP to determine the timing of the appearance of the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1α (IL-1α), and interleukin-6 (IL-6); and the Th1-differentiating cytokine interleukin-12 (IL-12) in BALF. After a single intratracheal administration of S. rectivirgula , there was remarkable BALF neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to 72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of MIP-1α in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72 hours). There was also an increase in BALF IL-6, IL-1α, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1α, MCP-1, IL-6, IL-1α, and IL-12 from the murine macrophage cell line J774A.1; MIP-1α, IL-6, IL-1α, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1α, IL-6, and TNF—but not IL-12—from BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by intratracheal administration of S. rectivirgula precede BALF neutrophilia and lymphocytosis and may cause differentiation of Th1 cells; we also conclude that pulmonary macrophages represent a potential source of these substances. (J Lab Clin Med 2000;136:29-38)

This month in J Lab Clin Med: Issue highlights for July 2000

This month in J Lab Clin Med: Issue highlights for July 2000

Saccharopolyspora rectivirgula from Quebec dairy barns: application of simplified criteria for the identification of an agent responsible for farmer's lung disease.

Saccharopolyspora rectivirgula (Micropolyspora faeni) is one of the major agents responsible for farmer's lung disease, a form of hypersensitivity pneumonitis. It is frequently isolated from the air of contaminated barns. The identification of this actinomycete is difficult because most of its phenotypic characteristics are variable and classical tests are not easy to perform on actinomycetes. Fatty acid analysis is very useful for the identification of these strains, but is not available except in some research or reference laboratories. Morphological (microscopic and macroscopic observations), physiological and biochemical tests (growth properties; macromolecules degraded; citrate utilisation and acid production from carbohydrates; resistance to antibiotics, lysozyme and heat), cell wall and fatty acid analyses and IgG analyses with serum from patients with farmer's lung were performed on 12 environmental isolates presumed to be S. rectivirgula and two control strains of S. rectivirgula. From this, a simple and rapid scheme for the identification of this actinomycete is proposed: optimal growth temperature (55 degrees C); colony appearance based on morphology (filamentous) and colour (beige to orange-brown); microscopic morphology (chains of spores on both aerial and substrate mycelium); growth on NaCl 10%; cell-wall analysis (type IV); and the verification of antibody response with serum from a patient with farmer's lung. This last criterion is important to confirm the immunogenicity of the strains identified as S. rectivirgula. This scheme provides an accurate and efficient way of identifying S. rectivirgula strains and evaluating exposure to this bacterium. The study shows the limited value and the lack of reproducibility of some classical biochemical tests.

Serum IgG antibodies against Wallemia sebi and Fusarium species in Finnish farmers.

Wallemia sebi and Fusarium species are common fungi in agricultural environments. Because Fusarium species are difficult to culture, and W. sebi has only recently been found in an agricultural environment with the use of a new culture medium, immunochemical methods may be important for evaluating exposure to these fungi. Immunoglobulin (Ig) G antibodies against W. sebi and two Fusarium species were measured in the sera of Finnish farmers to estimate exposure to fungi. Serum-specific IgG antibody levels against the fungi were determined in farmers with farmer's lung disease and asthma, as well as in asymptomatic farmers with low and high IgG antibody levels against other agricultural microorganisms, and in control persons (printing and office workers). Both enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunofiltration assay (ELIFA) techniques were used. Significantly higher IgG antibody levels against the fungi studied were observed in farmer's lung patients and asymptomatic farmers with high IgG levels against other agricultural fungi, than in the control group. On the other hand, the development of IgG antibodies to the fungi in asthmatic farmers remained unclear because of a discrepancy between the ELISA and ELIFA results. Cross-reactivity between Fusarium species was detected. The results indicate that Finnish farmers are exposed to W. sebi and Fusarium species in their work environment to a greater extent than has earlier been evaluated with air sampling and microbiologic methods.

75-Year-Old Man With Fever, Weight Loss, and Diarrhea

75-year-old retired farmer came to our institution because of anorexia, fever, weight loss, diarrhea, and occasional right upper quadrant pain. Three months ear­ lier, the patient had noticed decreased appetite and energy. A month later, coughing and expectoration of yellowish sputum were treated with an orally administered macrolide antibiotic. Despite completion of the course of antibiotic, fever (temperatures up to 38.9°C) developed, occurring primarily at night. One month before admission, the pa­ tient had diarrhea, with production of up to seven brown liquid stools per day without hematochezia or mucus; these bouts resolved spontaneously in 3 to 4 days. At that time, he was admitted to another hospital with the diagnosis of right lower lobe pneumonia, for which he received ceftriaxone, 1 g intravenously every 24 hours, and erythro­ mycin, 500 mg intravenously four times a day, for 8 days, after which he was dismissed with a 10-day oral regimen of antibiotics. Two days after completion of the antibiotic therapy, another episode of diarrhea occurred, with up to seven brown liquid stools per day, again without mucus or hematochezia. Four days later, he was admitted to our institution with the diagnosis of dehydration. Throughout this period, the patient continued to have nightly fevers (temperatures up to 40°C) with occasional drenching night sweats. The patient had a history of a monoclonal gammopathy of undetermined significance (MGUS) for at least 9 years, with low levels ofIgA, IgG, and IgM and an M peak in yof 0.8 g/dL (IgG K type). He had hypothyroidism and had also undergone a coronary artery bypass grafting procedure 2 years earlier. He had a history of farmer's lung and chronic obstructive pulmonary disease, with frequent use of antibi­ otics during the past few years for recurrent upper respira­ tory tract infections. Additionally, he had a history of paroxysmal atrial fibrillation, for which he was receiving

Long-term risk of emphysema in patients with farmer's lung and matched control farmers.

We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.

Diagnostic Accuracy of Transbronchial Biopsy in Acute Farmer's Lung Disease

To evaluate whether transbronchial biopsy (TBB) is useful for the diagnosis of acute farmer's lung (FL) by calculating the likelihood ratios (LHRs) of (1) simple pathologic criteria and (2) an overall assessment of the biopsy specimens. Retrospective study in which a blinded analysis of 105 TBBs with adequate material from patients with parenchymal diseases (55 cases of FL matched with 50 control samples) was performed by two independent pathologists. Respiratory clinic of a university-affiliated referral center. Three pathologic criteria were first studied: (1) diffuse lymphocytic infiltration (LI); (2) focal LI; and (3) granulomas. Then, an overall assessment or the TBB was done. Four diagnostic categories were considered: (1) probable FL; (2) possible FL; (3) nonspecific; and (4) alternative diagnosis. LHRs favoring the diagnosis of FL were calculated for the pathologic criteria and for each diagnostic category. For both the pathologic criteria and the overall assessments, the interobserver agreement was fair. As a pathologic criterion, "diffuse LI" was better than "loosely formed granuloma" to discriminate FL from control samples (LHR, 9.1 [confidence interval, 2.2 to 37.0] vs 1.8 [confidence interval, 0.5 to 6.9]). After the overall assessment, as many as 48.6% of the TBBs were read as nonspecific. The LHRs of the four diagnostic categories were as follows: (1) probable FL: 1.1 (observer 1) and 2.6 (observer 2); (2) possible FL: 2.2 and 1.7; (3) nonspecific: 0.9 and 0.6; and (4) alternative diagnosis: 0.4 and 0.0. Hematoxylin-eosin-stained TBB specimen is of limited usefulness for the diagnosis of FL and should be reserved for patients with intermediate pretest probability of FL. Diffuse LI best discriminates FL from control samples and should be specifically sought.

PHILIP HERRIES GREGORY 1907–1986: Pioneer Aerobiologist, Versatile Mycologist

Philip Gregory pioneered aerobiology as a topic for research, drawing together inputs from many disciplines to contribute to better understanding of fungal spore dispersal, plant disease epidemiology, and allergy. In childhood, he was interested in natural history and meteorology and frequently suffered from asthma. Initially, he worked with dermatophytes in Winnipeg, where he was influenced by Buller. Returning to Britain, he investigated the epidemiology first of flower bulb diseases and then of potato virus diseases, noting the occurrence of disease gradients in crops. He developed theories of spore dispersal during wartime air-raid duties and published these in his classic paper of 1945. The remainder of his career was largely spent obtaining data in support of his theories of spore dispersal and disease gradients, on understanding splash dispersal, in identifying the cause of farmer's lung disease, and in his retirement, in elucidating the epidemiology of black pod disease of cocoa in Nigeria.

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections. When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis.

IgE antibody response against Aspergillus umbrosus in farmer's lung disease.

IgG and IgA antibodies against fungus Aspergillus umbrosus have been found in the sera of patients with farmer's lung (FL) disease and healthy exposed farmers in Finland. To determine the IgE response to antigens of A. umbrosus and Candida albicans, sera from 20 patients with FL, 20 healthy farmers and 20 nonfarming controls were tested by nitrocellulose radioallergosorbent test (RAST). The values of RAST indices were low in each group and the only statistically significant difference was found between the groups of FL patients and nonfarming controls against A. umbrosus polysaccharide antigen. Individual IgE responses to polysaccharide antigens of A. umbrosus and C. albicans correlated among FL patients, however, no cross-reacting IgE antibodies could be shown. To conclude, the IgE antibody levels of A. umbrosus polysaccharide and crude antigens were low in FL patients, healthy exposed farmers and nonfarming controls. Neither polysaccharide nor crude antigen-specific IgE antibodies of A. umbrosus have any diagnostic value in FL disease.