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Hypersensitivity pneumonitis in a pleurotus mushroom grower
Abstract
A 47 year old woman presented to the emergency department due to persistent productive cough, accompanied by breathlessness on exertion, chest pain and weight loss during the last three months. She was an occasional smoker and had been working as a mushroom grower of the Pleurotus species during the past six months, with an otherwise unremarkable medical history. An earlier chest CT scan, performed forty days previously, revealed bilateral patchy ground glass opacities, more profound in the upper lobes. One month before presentation she underwent bronchoscopy in another hospital and the cytological examination of the collected bronchoalveolar lavage (BAL) demonstrated excessive neutrophilia. She received at that time a course of antibiotic therapy with doxy-cyclin and amoxicillin/clavulanate, without clinical improvement. During hospitalization in our department, the patient underwent again bronchoscopy with BAL, revealing significant lymphocytosis (32%), additionally to the previously observed neutrophilia (43%). Given the compatible occupational history, the radiologic pattern and the BAL subpopulation analysis, a diagnosis of hypersensitivity pneumonitis was made and the patient was discharged with a recommendation to withdraw from her current occupational activity. Six weeks later, the patient presented evident clinical, imaging and functional improvement.
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Hypersensitivity pneumonitis is defined as an allergic lung disease that occurs in response to inhalation of fungal antigens, bacterial antigens, chemicals, dusts, or animal proteins. The incidence of summer-type hypersensitivity pneumonitis is higher in the summer season, especially in Japan, due to the influence of the hot and humid environment and the common style of wood house or old concrete condominiums.
The present report describes a case of a middle-aged married couple who lived in the same house and who simultaneously suffered from summer-type hypersensitivity pneumonitis. This report analyzes these two cases in terms of environmental research and its microbiological, radiological, and pathological aspects. This case report is followed by a review of family occurrences of summer-type hypersensitivity pneumonitis from 22 studies with a total of 49 patients (including the two present cases) in Japan.
Summer-type hypersensitivity pneumonitis may be unrecognized and misdiagnosed as pneumonia or other respiratory diseases. A greater understanding of the clinical, pathologic, and environmental features of summer-type hypersensitivity pneumonitis might help improve diagnosis and delivery of appropriate management for this condition.
Aims:
To evaluate the histological characteristics differentiating chronic hypersensitivity pneumonitis (chronic HP) with a usual interstitial pneumonia (UIP)-like pattern from idiopathic pulmonary fibrosis (IPF)/UIP.
Methods and results:
Surgical lung biopsy specimens from 22 patients with chronic HP diagnosed as having a UIP-like pattern upon histological examination and 13 patients with IPF/UIP were examined and the incidences of bronchiolitis, perilobular fibrosis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, fibroblastic foci, honeycombing, granulomas, giant cells, lymphocytic alveolitis and lymphoid follicles were compared. Bronchiolitis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, granulomas, giant cells and lymphocytic alveolitis were significantly more frequent among patients with chronic HP than among patients with IPF (all P<0.01).
Conclusions:
Centrilobular fibrosis, bridging fibrosis and organizing pneumonia, in addition to bronchiolitis, granulomas and giant cells, are characteristic features of chronic HP with a UIP-like pattern. These features are therefore important in differentiating chronic HP from IPF/UIP, as management strategies differ for the two disorders.
So far, the association of lung cancer with chronic hypersensitivity pneumonitis (CHP) has not been studied. Objective: We examined the prevalence and revealed clinical features of lung cancer in CHP.
We retrospectively reviewed the medical records from 1994 through 2005 and identified 11 patients (15 lesions) with lung cancer among 104 patients with CHP. Their clinical features and histopathological findings were analyzed.
Ten men and 1 woman with a median age of 68.9 years were included. All patients had a smoking history. The most prevalent histopathological type of lung cancer was squamous cell carcinoma (53%), and all tumors were located in the peripheral region of the lung. Four patients suffered from lung cancer after the diagnosis of CHP and 1 patient had lung cancer before the diagnosis of CHP. The histological pattern of CHP showed a predominantly usual interstitial pneumonia-like lesion. Tumors were located adjacent to honeycombing in 7 (47%) of 15 lesions, bullae in 4 (27%) lesions, and relatively normal lung in 4 lesions.
Since the prevalence of lung cancer in CHP seems to be high (10.6%) as seen in idiopathic pulmonary fibrosis, physicians should be aware of the possible complication of lung cancer in CHP.
Four mushroom workers have developed an extrinsic allergic alveolitis, after working with the oyster mushroom (Pleurotus ostreatus). After provocation with aerosolized spores under laboratory conditions, the four patients showed the complaints of an extrinsic allergic alveolitis; a rise of body temperature, leucocytosis and changes of lung function parameters were observed. Antibodies against the spores were assessed in the blood of these patients.
Vast numbers of spores of the thermophilic actinomycetes Excellospora flexuosa, Thermomonospora alba, T. curvata and T. fusca were collected from the air in fermentation tunnels during the spawning of mushroom compost, i.e. over 10(9) CFU m-3 of air. Five different genera of fungi, namely, Aspergillus, Aureobasidium, Cladosporium, Penicillium and Scytalidium, were found at only 10(3) CFU m-3 of air. Agaricus bisporus, used for spawning, was absent. Sera of 10 mushroom growers affected by Mushroom Worker's Lung (MWL) were tested by a qualitative dot-ELISA for antibodies against the spores of these micro-organisms. All 10 were positive for one or more of the actinomycetes E. flexuosa, T. alba, T. curvata and T. fusca. No antibodies were found against Streptomyces thermovulgaris, Thermoactinomyces vulgaris and T. sacchari nor against the fungi Aspergillus fumigatus, Penicillium brevicompactum, P. chrysogenum, Scytalidium thermophilum and Trichoderma viride. Sera of 11 of 14 workers engaged in routine spawning of compost in tunnels reacted positively with 1 or more of the actinomycetes. Their 10log serum titres increased with the duration of employment to an upper limit of 2.5. The sera of 19 non-exposed individuals were negative. Because high numbers of spores of E. flexuosa, T. alba, T. curvata and T. fusca were present in the air that was used for successful inhalation provocation of mushroom workers with MWL and because of the elevated serum titres of these workers, we presume these organisms to contribute in the occurrence of MWL.
We reported the first case of hypersensitivity pneumonitis (HP) by an edible mushroom, Pleurotus Eryngii (Eringi). A 54-year-old woman had worked in a Bunashimeji mushroom factory for 42 months, and she moved to a new factory producing Eringi. Two months after, she was found to have HP by the spore of Eringi. Although no radiological finding was detected 6 months before the onset of HP, serum surfactant protein D (SP-D) had been elevated. We speculated that type II pneumocyte activation might prepare the ground for HP during the former exposure to Bunashimeji, and serum SP-D levels might reflect their conditions.
We characterized by immunoblotting the antigenicity of the most frequent fungi colonizing cork during its industrial processing, Penicillium glabrum and Chrysonilia sitophila. Penicillium glabrum is the main causative agent of Suberosis, a hypersensitivity pneumonitis of cork workers. Chrysonilia sitophila induces both IgE sensitization and occupational asthma in the wood processing industry.
Serum-specific IgG, IgG4 and IgE to P. glabrum and C. sitophila from nine cork workers with hypersensitivity pneumonitis (HP) and seven with asthma (four with occupational asthma) were analysed by immunoblotting.
Both HP and asthmatic patients' sera showed immunoreactivity to several proteins resolved in the specific immunoblot strips. The frequency of specific IgG recognition to 12-13.5 and 33 kDa proteins of P. glabrum was significantly higher in HP patients. The sera of HP patients had significantly higher specific IgG recognition to 16 and 51-55 kDa proteins of C. sitophila. There was no specific IgE recognition in the sera of HP or asthmatic patients to both fungi.
Different patterns of antibody reactivity to P. glabrum and C. sitophila are seen in cork workers with hypersensitivity pneumonitis or asthma. The 12-13.5 and 33 kDa proteins of P. glabrum and the 16 and 51-55 kDa proteins of C. sitophila may be major antigens in Suberosis.
Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to improve detection and diagnosis are needed, and treatment options, principally avoidance, are limited. A workshop recommended: a population-based study to more accurately document the incidence and prevalence of HP; better classification of disease stages, including natural history; evaluation of diagnostic tests and biomarkers used to detect disease; better correlation of computerized tomography lung imaging and pathologic changes; more study of inflammatory and immune mechanisms; and improvement of animal models that are more relevant for human disease.
Extrinsic allergic alveolitis (EAA) is an important clinical entity, but its incidence and significance in the general population are uncertain.
To estimate the incidence of EAA, and resulting mortality, in the UK.
General-population-based cohort study in a UK primary care database (THIN).
THIN patients with an incident diagnosis of EAA were compared with a general population cohort whose members were 4:1 matched with EAA patients by age, sex and GP practice. Follow-up started at the first diagnosis of EAA (and at the same date in the matched controls) and ended at death or end of follow-up, whichever came first. Poisson, logistic, and Cox proportional hazard regression models were used; mortality rate, odd ratios, and hazard ratios were calculated.
We identified 271 incident cases of EAA (mean age at diagnosis 57 years, 51% male). Between 1991 and 2003, the incident rate for EAA was stable at approximately 0.9 cases per 100000 person-years. In comparison to the 1084 general population controls, patients with EAA were less likely to smoke (odds ratio 0.56, 95%CI 0.39-0.81), but had a marked increase in the risk of death (hazard ratio 2.98, 95%CI 2.05-4.33).
The incidence of EAA in the UK population appears to be stable overtime, and suggests about 600 new cases of EAA each year. People with EAA are less likely to smoke than the general population, but have a markedly increased mortality rate.
Hypersensitivity pneumonitis (HP) is a disease of immune-mediated inflammation of the lungs after exposure to specific antigens. Patients are often exposed at work or at home to antigens that lead acutely to symptoms of cough, fever, and dyspnea. If the patient is no longer exposed to these antigens, there is usually a recovery without any long-term sequelae. However, chronic exposure can lead to chronic dyspnea and irreversible lung disease. Recent studies have shown the importance of T helper 1 cells and other inflammatory mediators like interleukin-17 in driving the acute inflammatory process. A transition to chronic stages of HP seems to be secondary to T helper 2-mediated inflammation. Symptoms of HP can be acutely controlled with steroids but the definitive treatment involves considering the diagnosis and identifying and stopping continued antigen exposure.
The distinction of chronic hypersensitivity pneumonitis (HP) or advanced-stage sarcoidosis from idiopathic pulmonary fibrosis or usual interstitial pneumonia is important because each disease is managed differently and may have a different prognosis. The analyses of pattern and distribution of lung parenchymal abnormalities on high-resolution computed tomography scans help differentiate among the 3 diseases. In chronic HP, the presence of lobular areas of decreased attenuation and centrilobular small nodules and the absence of lower lung zone predominance are characteristically observed. In advanced-stage sarcoidosis, patchy areas of reticulation, traction bronchiectasis, architectural distortion, honeycomblike cysts, bullae, and paracicatricial emphysema are observed in the upper and middle lung zones. Lung bases are usually spared. In idiopathic pulmonary fibrosis or usual interstitial pneumonia, however, the presence of honeycombing with lower lung zone predominance and the absence of centrilobular small nodules are important findings that allow us to differentiate the disease from chronic HP or advanced-stage sarcoidosis. In the 3 diseases, most important prognosis-predicting factor is the extent of fibrotic score (the extent of honeycombing and reticulation) calculated on high-resolution computed tomography scans or fibrosis estimated on chest radiographs.
Clinical observations of 16 patients were collected to exemplify a possible new disease entity. Each was a Puerto Rican migratory worker engaged in the handling of compost used as soil for growing mushrooms in Pennsylvania. The disease has not, as yet, been observed or identified in other persons. Immunity was not conferred by a single episode or successive episodes. The disease recurred with reexposure. Treatment was nonspecific and supportive. Removal of contact from the compost was necessary for cure. The consistent findings were respiratory signs and symptoms, characteristic roentgenographic appearance of lung fields, eosinophil count elevation, nationality of patient, and contact with the compost. The natural pattern of the disease resembles that of "farmer's lung" and "silo-filler's disease." The etiology remains undetermined.
Clinical manifestations of hypersensitivity pneumonitis may closely mimic other interstitial lung diseases, and the disease onset is usually insidious. High-resolution computed tomography and bronchoalveolar lavage are the sensitive and characteristic diagnostic tests for hypersensitivity pneumonitis. The relevant antigen to hypersensitivity pneumonitis cannot be identified in up to 20% to 30% of patients. Clinicians should be aware that hypersensitivity pneumonitis must be considered in all cases of interstitial lung disease, and a detailed environmental exposure history is mandatory.
Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP.
The fine structure of Aspergillus fumigatus and Aspergillus umbrosus by transmission electron microscopy (TEM) is described. The fine structure of the ascosporic and asexual stages of A. umbrosus is described for the first time. Dense, homogenous material and fibers were detected on the outer hyphal cell wall of the Aspergilli. Septal pores were found in the hypha of A. umbrosus. Two wall layers were detected in the cell wall of the conidia of the both Aspergilli. The ascospores of A. umbrosus contained thick cell wall and the surface of which was smoother than that of the conidia.
Hypersensitivity pneumonitis (HP) is a complex syndrome resulting from repeated exposure to a variety of organic particles. HP may present as acute, subacute, or chronic clinical forms but with frequent overlap of these various forms. An intriguing question is why only few of the exposed individuals develop the disease. According to a two-hit model, antigen exposure associated with genetic or environmental promoting factors provokes an immunopathological response. This response is mediated by immune complexes in the acute form and by Th1 and likely Th17 T cells in subacute/chronic cases. Pathologically, HP is characterized by a bronchiolocentric granulomatous lymphocytic alveolitis, which evolves to fibrosis in chronic advanced cases. On high-resolution computed tomography scan, ground-glass and poorly defined nodules, with patchy areas of air trapping, are seen in acute/subacute cases, whereas reticular opacities, volume loss, and traction bronchiectasis superimposed on subacute changes are observed in chronic cases. Importantly, subacute and chronic HP may mimic several interstitial lung diseases, including nonspecific interstitial pneumonia and usual interstitial pneumonia, making diagnosis extremely difficult. Thus, the diagnosis of HP requires a high index of suspicion and should be considered in any patient presenting with clinical evidence of interstitial lung disease. The definitive diagnosis requires exposure to known antigen, and the assemblage of clinical, radiologic, laboratory, and pathologic findings. Early diagnosis and avoidance of further exposure are keys in management of the disease. Corticosteroids are generally used, although their long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness.
The purpose of this study was to evaluate the prevalence and outcomes of pulmonary hypertension in chronic hypersensitivity pneumonitis and to examine the relationship between pulmonary function tests and pulmonary hypertension.
We conducted a retrospective review of 120 patients with hypersensitivity pneumonitis seen at two centers for pulmonary diseases over a 5-year interval and identified patients with chronic hypersensitivity pneumonitis for whom both pulmonary function tests and Doppler echocardiography data were available.
Chronic hypersensitivity pneumonitis was identified in 83 patients and Doppler echocardiography data were available for 73 of them. Pulmonary hypertension (sPAP ≥ 50 mmHg) was detected in 14 patients (19%), and was associated with a greater risk of death (median survival = 23 months vs. 98 months; P=0.003). Patients with pulmonary hypertension were older and had a significantly decreased PaO(2). There was a weak correlation between pulmonary function parameters and the underlying sPAP, with significance for FVC, FEV(1), and PaO(2) and inversely with PaCO(2).
Using Doppler echocardiography for evaluation, pulmonary hypertension seems to be common in patients with chronic hypersensitivity pneumonitis, significantly impacts survival, and correlates with FVC, FEV(1), and PaO(2) and inversely with PaCO(2).
Hypersensitivity pneumonitis (HP) is a complex syndrome caused by an exaggerated immune response to the inhalation of a large variety of organic particles. The most frequent antigens that cause HP worldwide are bird proteins (pigeon breeders' disease) and bacteria (Saccharopolyspora rectivirgula). However, fungi are also implicated in many cases, including occupational and nonoccupational outbreaks. The clinical course of the disease is highly variable and its diagnosis clinically challenging since no specific test or biomarker allows a consistent diagnosis. Therefore, a combination of symptoms, bronchoalveolar lavage findings, chest imaging, lab tests, and often biopsies are needed for an accurate diagnosis. Regardless of the cause or the responsible environment, the histopathology is similar and usually consists of a granulomatous interstitial bronchiolocentric pneumonitis characterized by the presence of poorly formed granulomas and a prominent interstitial infiltrate composed of lymphocytes, plasma cells, and macrophages. However, some patients may show a "nonspecific interstitial pneumonia" pattern, or even a usual interstitial pneumonia-like pattern. Importantly, patients with chronic HP may evolve to interstitial fibrosis or develop emphysematous changes, although the reason(s) for these different pathological responses are presently unclear. This review provides a general overview of HP, emphasizing its fungal etiologies, and also examines the currently used clinical criteria for diagnosis and proposes an alternative classification. Challenges for future research include identification of biomarkers that may predict outcome and progression (primarily of chronic HP), and the need for a better understanding of the underlying molecular and genetic mechanisms of the disease.
Most cases of hypersensitivity pneumonitis develop only after many years of inhaling allergens, which include microbes, animal or plant proteins, and certain chemicals that form haptens. The initial clinical presentation is either episodes of acute illness with dyspnea and prominent constitutional symptoms, such as fever, or an insidious onset of dyspnea, coughing, and weight loss, sometimes with superimposed acute episodes. The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli. Fibrosis and emphysema may develop. The radiologic findings include diffuse ground-glass opacification, centrilobular ground-glass opacities, air trapping, fibrosis, lung cysts, and emphysema. The histologic and radiologic features in some cases may resemble those of usual interstitial pneumonia or nonspecific interstitial pneumonia. The diagnosis usually rests on a variable combination of findings from history, serology, radiography, lung biopsy, and bronchoalveolar lavage, which characteristically reveals a lymphocyte content of more than 30%, often with an increased CD4-to-CD8 ratio of T cells. Treatment includes avoiding the allergen, if possible, and, in severe cases, systemic corticosteroids. The long-term prognosis is usually good, but some patients develop severe respiratory insufficiency, and a few die of the disease.
The objective of the study was to examine the relationship of pathologic pattern and prognosis in hypersensitivity pneumonitis (HP). We analyzed 24 cases of subacute (cellular, nonfibrotic) and 25 cases of chronic (fibrotic) HP. Nineteen (79%) of the subacute cases showed a pattern of bronchiolocentric interstitial pneumonia and 5 (21%) a pattern mimicking cellular nonspecific interstitial pneumonia (NSIP). Giant cells or granulomas or Schaumann bodies were present in 19 cases (79%). Eighteen (72%) chronic cases showed a pattern resembling usual interstitial pneumonia (UIP), but, in most cases, with more peribronchiolar fibrosis than one would expect in UIP. Three fibrotic cases (12%) had only peribronchiolar fibrosis, whereas 4 (16%) resembled fibrotic NSIP. Giant cells or granulomas or Schaumann bodies were present in 22 (88%) cases. Areas of subacute HP were present in 12 cases with a UIP-like pattern. Only 2 UIP-like cases could not be morphologically distinguished from idiopathic UIP. The median survival for patients who had no fibrosis was 22.4 years; for patients with a fibrotic NSIP pattern was 2.1 years; and for those with a UIP-like pattern 2.8 years (not statistically different). Patients with a pattern of only peribronchiolar fibrosis had a median survival of 11.3 years. These data confirm that the presence of fibrosis is associated with a generally poor prognosis in patients with HP, and suggest that pure peribronchiolar fibrosis may portend a longer survival than does a UIP-like or fibrotic NSIP-like pattern of fibrosis. Most cases of chronic HP have distinctive pathologic features, but a small percentage of cases cannot be pathologically distinguished from UIP.
Regardless of the causative antigen, hypersensitivity pneumonitis (HP) is usually classified as 'acute', 'subacute' or 'chronic'. Considerable confusion still surrounds this classification because there are no widely accepted criteria to distinguish the various stages. The objective of this study was to determine whether the current classification of HP truly reflects categories of patients with distinct clinical features.
Data obtained from a large prospective multicenter cohort study (the HP Study) were used to divide a cohort of patients with HP into a limited number of categories (clusters) with maximally differing clinical patterns, without prejudgment. The results of this cluster analysis were compared with the current classification of HP (acute, subacute or chronic).
168 patients were included in the analysis. A 2-cluster solution best fitted the data. Patients in cluster 1 (41 patients) had more recurrent systemic symptoms (chills and body aches) and normal chest radiographs than those in cluster 2 (127 patients) who showed significantly more clubbing, hypoxemia, restrictive patterns on pulmonary function tests and fibrosis on high-resolution computed tomography (HRCT). All p values were <0.0001, using Fisher's exact test. Nodular opacities were seen on HRCT as often in cluster 1 as in cluster 2. There was considerable disagreement between the current classification of HP and the results of our analysis.
The current classification of acute, subacute and chronic HP is not supported by our analysis. Subacute HP is particularly difficult to define.
Acute exacerbations (AEs) in idiopathic pulmonary fibrosis (IPF) are critical factors for its clinical course and prognosis. We have seen AEs and poor prognosis consequent to AE in patients with chronic hypersensitivity pneumonitis (HP), as has been seen in patients with IPF. The aim of this study was to evaluate the clinical features of the patients with AE in those with chronic HP.
We reviewed 100 consecutive patients with chronic bird fancier lung (BFL) from 1993 to 2006, and analyzed the clinical characteristics, including history, and laboratory and immunologic, imaging, BAL, and histologic findings.
AE developed in 14 patients during this observation period (AE group), whereas 86 patients remained stable (non-AE [NAE] group). The 2-year frequency of AE among patients with chronic BFL having usual interstitial pneumonia (UIP)-like lesions seen on surgical lung specimens was 11.5%. Patients with AE were more likely to be smokers (p = 0.003). In pulmonary function test results, the mean total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) were lower in patients with AEs (TLC: AE patients, 63.0 +/- 16.8%; NAE patients, 81.6 +/- 20.0%; Dlco: AE patients, 41.9 +/- 19.0%; NAE patients, 60.0 +/- 19.4%). The mean number of lymphocytes in BAL fluid were lower (AE patients, 13.7 +/- 7.5 lymphocytes; NAE patients, 37.2 +/- 29.7 lymphocytes), while the number of neutrophils were greater in AE patients (AE patients, 10.7 +/- 17.6 neutrophils; NAE patients, 3.6 +/- 4.4 neutrophils). Histologic and/or radiologic findings revealed that all AE patients had UIP-like lesions. Diffuse alveolar damage was observed in six cases, whereas organizing pneumonia superimposed on preexistent fibrotic lesions was observed in two cases.
The present study showed several predictive factors for AE at the time of diagnosis. Low TLC and Dlco, low lymphocyte levels in BAL fluid, and a UIP-like pattern in histology at the time of diagnosis may be the risk factors for AE.
Between April 1982 and August 1985, seven cases of mushroom worker's lung (MWL), a form of hypersensitivity pneumonitis, were diagnosed among workers at one mushroom farm in Florida. The cases suffered from episodic shortness of breath, cough, fever and chills, myalgia, malaise, and difficulty breathing. Pulmonary function testing revealed restrictive ventilatory impairment and reduced diffusing capacity; chest radiographs exhibited diffuse interstitial pulmonary infiltrates. The seven cases occurred among workers from different farm operations, suggesting that workers throughout the farm were exposed to the disease causing agent(s). Six of the affected workers left employment at the farm in order to remain free of symptoms. The other affected worker was able to continue working at the farm, but only by remaining in a maintenance shop which was physically separated from the rest of the farm facilities. An industrial hygiene survey demonstrated that farm workers from every work area were exposed to organic dust constituents suspected of causing MWL, but no specific antigens were identified as the cause of the cases. Of the remaining workers who participated in a cross-sectional respiratory morbidity survey at the farm, approximately 20% of the more heavily exposed workers reported occasionally experiencing symptoms consistent with MWL. Approximately 10% of the workers had below normal spirometry test results, but interpretation was hampered by the diverse racial makeup of the population and lack of an adequate comparison group. No abnormalities consistent with either acute or chronic MWL were seen on the chest radiographs. Serologic tests demonstrated that almost all workers had been exposed to antigens capable of causing MWL, but the results were not associated with health status. At the time of the cross-sectional survey, no workers were found to be suffering acute respiratory problems consistent with MWL.
Specific IgG antibodies against antigens of a contaminated air conditioner were estimated in serum of 134 workers of a printing company. Altogether 64% of the workers investigated revealed significantly elevated levels (> 3 U/ml) of IgG antibodies specific to these antigens as compared to a nonexposed control group. The occurrence of IgG antibodies for microbial extracts were 25% for Fusarium, 23% for Penicillium notatum, 13% for Alternaria tenuis, 12% for Aureobasidium pullulans, 9% for Sphaeropsidales species, 3% for Micropolyspora faeni, 2% for Aspergillus fumigatus and 2% for Thermoactionomyces vulgaris. Out of the 86 workers with elevated IgG antibodies for air conditioner antigens, 59 were nonsmokers. Considering a cut-off level of 10 U/ml IgG for high values, the proportion of smokers to nonsmokers becomes even more pronounced (6 to 36 respectively, binominal test p < 0.001). This is despite the fact that the distribution of smokers and nonsmokers among the 134 workers is approximately equal (60 to 74). All 3 workers with clinical diagnosis of humidifier lung or humidifier fever belonged to the nonsmoker group. Our findings indicate that crude water extracts of contaminated air conditioners are the best choice as antigen source for the diagnosis of humidifier lung in exposed workers. Nonsmokers are shown to have a high risk for immunological sensitization.
The effect of corticosteroid treatment on the course of farmer's lung (FL) was studied in 36 patients randomly allocated in a double-blind placebo-controlled study. All patients were in the acute stage of the disease and had had the first diagnosed attack of FL. Twenty patients were given prednisolone treatment for 8 wk. Sixteen patients received an 8-wk placebo treatment. One patient was withdrawn from the analysis when she terminated corticosteroid treatment because of side effects. After 1 month of treatment there was a significant difference (p = 0.03) in DLCO between the treatment groups. After a follow-up of 5 yr no statistically significant differences were found between the treatment groups in FVC, FEV1, or DLCO. FL recurred in six patients during the follow-up in the corticosteroid group and in one patient in the placebo group, but the difference was not statistically significant. In conclusion, in the corticosteroid group the improvement of pulmonary function was more rapid than in the placebo group, but no influence on the long-term result was found. The possibility that corticosteroid treatment may favor the occurrence of recurrent attacks of FL needs attention.
Four workers, the total work force employed at a Shiitake farm, developed cough and sputum production following a variable period of exposure to Shiitake mushrooms. All four had abnormal diffusing capacity and three had abnormal spirometry values. Chest roentgenograms demonstrated an interstitial pattern in one worker. Pulmonary function tests performed before and during several days of work demonstrated a significant decrease (greater than 20%) in forced vital capacity (FVC) and/or maximal mid-expiratory flow (MMEF) in three workers. Although specific antibodies to an extract of Shiitake spores were detected in sera from three workers none were IgE. High levels of Shiitake spores were detected in growing rooms (greater than 10(6)/m3) as well as other locations at the farm. Shiitake spore airborne antigen, detected by an immunochemical assay, was present in dust collected with a volumetric sampler from different locations at the farm. Antigenic determinants of Shiitake spore antigens, in common with antigens from other cultivated mushrooms (Agaricus and Pleurotus) were demonstrated by ELISA inhibition assay. This study demonstrates that workers exposed to high levels of Shiitake spores develop symptoms and laboratory findings suggestive of hypersensitivity pneumonitis (HP). Strict environmental control and the wearing of a face mask is probably needed to reduce the high risk of sensitization and possible development of immunological lung disease. Shiitake spores must be considered as an aetiological agent of mushroom workers' lung.
In general, a history of exposure to "moldy" hay, birds, or other incriminated occupational or environmental inhalants in a patient with clinical and radiologic features consistent with HSP should lead to the demonstration of serum precipitins to the suspected antigen and an established diagnosis, confirmed by avoidance of the agent involved. Occasionally, other diagnostic procedures are required. The diagnosis is often difficult in domestic exposures, such as humidification and air conditioning systems. A careful environmental history is essential, and at times the physician must inspect the patient's environment personally. In most cases, the diagnosis is established if (1) the history and physical findings and pulmonary function tests indicate an interstitial lung disease, (2) the x-ray film is consistent, (3) there is exposure to a recognized cause, and (4) there is antibody to that antigen. In other exceptional circumstances, bronchoalveolar lavage may help. Biopsy is rarely needed. Special environmental studies and identification of new antigens require research facilities. Provocation tests are research procedures, not necessary for the diagnosis, and not needed in contested workmen's compensation adjudications.
We studied the clinical course of eighty-six patients with farmer's lung for a period of 5 years. The patients were first evaluated at an acute or sub-acute stage of the disease and 1, 3, 6, 12 and 60 months thereafter. Special attention was paid to the development of lung function and radiological findings with reference to corticosteroid treatment and antigen contact during the follow-up. Many of the patients were severely ill at the acute stage of the disease. Most of the recovery took place during the first month. Significant improvement of lung function happened up to 6 months, thereafter the improvement was insignificant. After 5 years, respiratory symptoms were reported by 65% and minor respiratory dysfunction (lowered diffusing capacity) was observed in about 40% of the farmers. Thirty-two per cent of the patients showed diffuse opacities in chest X-ray. Corticosteroid treatment had no effect on long term prognosis. There was no difference in the recovery of lung function between those who returned to work compared with those who did not. Exacerbations happened in 8% of the patients during the follow-up. We conclude that respiratory symptoms, minor airway dysfunction and mild radiological fibrosis are common findings after 5 years of an acute or sub-acute stage of the farmer's lung. However, in Finland two-thirds of the patients return back to their previous occupation of farming and cattle feeding.
A total of 888 randomly selected dairy farmers participated in an epidemiological study to evaluate the prevalence of precipitins to farmer's lung antigens, and the socioeconomic factors associated with their presence. Precipitins were present in 75 farmers (8.4%) (65 to Micropolyspora faeni, seven to Aspergillus spp, two to both Aspergillus and Micropolyspora faeni, and one to Aspergillus and Thermoactinomyces vulgaris). The titres ranged from a dilution of 1/32 to a concentration of X 2 (Ouchterlony's double diffusion method). In the study population there were 544 who had never smoked, 146 ex-smokers, and 198 smokers. Sixty nine precipitin positive subjects were either never smokers or ex-smokers; only six were smokers. The negative relationship between cigarette smoking and precipitins was highly significant (p = 0.004). Factors positively associated with positive precipitin reactions were: size of farm, time spent in the barn, and the presence of a family member previously diagnosed as having farmer's lung disease. Interestingly, positive precipitin reactions were not associated with any of the following: use of silos, hay conditioners, or hay dryers; the presence or quantity of mouldy hay; or the presence of respiratory symptoms. It is concluded that precipitin analysis is not useful as a screening method for farmer's lung, though it can be of diagnostic value in acute farmer's lung disease.
The aim of the present study was to investigate whether bronchoalveolar lavage (BAL) cell profile and immunoglobulin levels from patients with extrinsic allergic alveolitis (EAA) were related to the time elapsed between last antigen exposure and BAL. For this purpose, an analysis was performed of BAL fluid (BALF) obtained from 59 nonsmoking EAA patients at various time-points after termination of antigen exposure and BAL. BALF early after antigen provocation (group 1: < 24 h) contained high absolute and relative numbers of lymphocytes, neutrophils, eosinophils and mast cells, and a low relative number of alveolar macrophages. When obtained after recent antigen exposure (group 2: 2-7 days), BALF showed high numbers of lymphocytes, plasma cells and mast cells, and high levels of immunoglobulins M, G and A (IgM, IgG and IgA). In BAL obtained one week or more after the final antigen exposure, (Group 3: 8-30 days; Group 4: 1-12 months) the distribution of all constituents showed a tendency to return to normal values, with the exception of the lymphocytes. These results demonstrate that BAL cell profile and immunoglobulin levels in EAA are highly dependent on the time-point at which the material is obtained in relation to the last exposure to the causative antigen.
A nonsmoking 54-yr-old man, employed in a peat moss packaging plant, developed dyspnea and recurrent fever. The diagnosis of hypersensitivity pneumonitis (HP) was made. Thirteen of 14 coworkers and 13 nonexposed control subjects were studied. Five workers were nonsmokers, two were minimal smokers, and six were smokers. HP was found in another subject. Monocillium sp. and Penicillium citreonigrum, 4.6 x 10(7) CFU/g, were found in the peat moss. Three nonsmokers, the two minimal smokers (including the subject with HP), and the index case had antibodies to these microorganisms; none of the six heavy smokers had antibodies. Serum TNF-alpha was higher in the workers than in the control subjects (0.930 +/- 0.177 versus 0. 350 +/- 0.076). Three of the four asymptomatic seropositive workers and two seronegative smokers were further evaluated. All three seropositive workers had normal lung functions and CT but they all had a lymphocytic alveolitis (30, 34, and 68% lymphocytes in their bronchoalveolar lavage [BAL]). The smokers had normal lung functions, CT, and percentage of BAL lymphocytes (3 and 13%). This study identified a previously unrecognized work environment that can lead to HP and documented a protective effect of smoking on the response to antigens.
Indoor cultivation of oyster mushroom Pleurotus osteatus lead to an outbreak of extrinsic allergic alveolitis in two workers. High titer of indirect fluorescent antibody and positive
precipitins against basidiospores of P. osteatus were demonstrated in sera of the patients. Mushroom workers should protect themselves from the basidiospores, being aware
of their pathogenicity.
Lung biopsy has been proposed as a criterion for diagnosis of chronic hypersensitivity pneumonia (HP), especially in patients without proven antigen exposure. Histologic findings in some suspected HP patients overlap with usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). We reviewed our experience to determine the specificity of histologic findings in surgical lung biopsies from patients with clinical diagnoses of HP.
Surgical lung biopsies from patients with chronic HP, idiopathic pulmonary fibrosis, and idiopathic NSIP were reviewed retrospectively without knowledge of the clinical diagnosis. Each specimen was assigned a histologic diagnosis, and selected histologic findings were tabulated. Clinical data were abstracted from medical records.
Fifteen patients with clinical diagnoses of chronic HP underwent biopsy of one to three lobes. Ten showed features diagnostic of HP in all specimens. Two had discordant findings that included HP in one specimen and UIP or nonspecific changes in others. Biopsies from two showed only UIP, and one showed NSIP. Diagnostic features were present in all samples from 9 of the 11 patients with more than one biopsy site (81.8%). Three patients died of disease, including both patients from whom biopsies showed only UIP.
Most patients with a clinical diagnosis of chronic HP have supportive histologic findings in surgical lung biopsies. A subset of HP patients has findings indistinguishable from UIP. Sampling from more than one lobe may be helpful in separating HP from idiopathic pulmonary fibrosis.
Histopathologic evidence of fibrosis on surgical lung biopsy has been associated with reduced survival in patients with hypersensitivity pneumonitis (HP). Changes of pulmonary fibrosis detected on CT may also correlate with prognosis in patients with HP.
We identified 69 consecutive patients with HP diagnosed between January 1997 and December 2002 at Mayo Clinic, Rochester, MN. Patients were stratified into fibrotic and nonfibrotic groups based on the CT findings. Fibrosis was defined by the presence of irregular linear opacities, traction bronchiectasis, or honeycombing.
Of 69 patients, 26 were classified as fibrotic and 43 as nonfibrotic. Patients in the fibrotic group were older, had longer symptom duration, were more likely to have crackles on auscultation, more likely to be exposed to avian antigen, and had greater restrictive lung impairment (p<0.05 for all comparisons). There were 11 deaths in the fibrotic group and 1 death in the nonfibrotic group (p<0.0001). In the regression analysis, CT evidence of fibrosis, more severe pulmonary function abnormalities, and the presence of crackles on auscultation were predictive of reduced survival (p<0.05 for all). The presence as well as the extent of fibrosis on CT was associated with increased mortality. The age-adjusted hazard ratio for mortality in patients with fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p<0.0001).
CT findings of parenchymal fibrosis are associated with reduced survival in patients with HP and may serve as a useful prognostic indicator.