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

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

Emphysema in active farmer's lung disease.

BACKGROUND: Farmer's lung (FL) is a common type of hypersensitivity pneumonitis. It is often considered that fibrosis is the most frequent finding in chronic FL. Nevertheless, three cohort studies have suggested that some patients with chronic FL may develop emphysema. We aimed to evaluate the current prevalence of emphysema in active FL, to describe the radiological and functional features of emphysema in active FL, and to identify risk factors associated with emphysema in this population. METHODS: Patients aged over 18 years with active FL were prospectively recruited through the SOPHIA study (CPP Est; P-2009-521), between 2007 and 2015. Each patient had complete medical history screening, clinical examination, high resolution computed tomodensitometry, bronchoalveolar lavage, pulmonary function tests and serum precipitins. RESULTS: Among 33 patients with active FL, the prevalence of emphysema in this series of incident active FL cases was higher (48.5%) than that of fibrosis (12%) and was not dependent on smoking habits. Most patients with emphysema did not have lung hyperinflation. The possible risk factors for emphysema in active FL were a longer duration of exposure to organic dusts, and at a higher level. CONCLUSION: Emphysema is found in half of patients with active FL and may be influenced by exposure patterns.

Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

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

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

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

Alveolitis alérgica extrínseca: forma de presentación inicial como fiebre de origen desconocido / Extrinsic allergic alveolitis: an initial form of presentation as a fever of unknown origin

La alveolitis alérgica extrínseca se caracteriza por un proceso inflamatorio inmunológico con afectación pulmonar producida por inhalación de polvo orgánico. Se considera una enfermedad laboral y es una causa muy importante de incapacidad transitoria y permanente que se puede evitar. Ocasionalmente el diagnóstico no es sencillo, pero es importante realizarlo en los primeros estadios, cuando todavía es reversible la enfermedad (AU)

Extrinsic allergic alveolitis is characterised by an inflammatory immune process with pulmonary impairment caused by inhalation of organic dust. It is considered an occupational disease and is a very significant cause of temporary and permanent disability that can be prevented. The diagnosis is not often easy, but it is important to make it in the early stages, when the disease is still reversible (AU)

Farmer's lung-induced hypersensitivity pneumonitis complicated by shock.

Hypersensitivity pneumonitis is an immunologic reaction to an inhaled antigen, with a wide spectrum of clinical presentations. The most common manifestations are fever, cough, and dyspnea. We describe a case of hypersensitivity pneumonitis with marked alveolar lymphocytosis; the patient presented with respiratory failure and shock requiring mechanical ventilation and vasopressive agents. We hypothesized that immune mediators implicated in the pathogenesis of hypersensitivity pneumonitis were responsible for the transient shock observed in this patient.

[Farmer's lung disease caused by straw or hay? Case report]. / Hálmsótt eda heysótt?

A young woman was admitted to Akranes Regional Hospital because of dyspnea, fatigue and fever. She was found to have bilateral pneumonia but etiology was not found. She was treated with antibiotics with good resolution and was discharged after eight days from the hospital. Four weeks later she noticed rapidly progressive dyspnea and was found to be hypoxemic, and to have restrictive spirometry and diffuse interstitial changes on chest radiography. Computerized tomography of the lungs showed diffuse ground glass changes. Transbronchial biopsies from the lungs showed numerous small granulomas. She was treated with prednisolone for a short time with excellent recovery. She stall-fed horses and underneath them was straw containing organic dust. This is important to keep in mind as a differential diagnosis to farmers lung disease that is caused by hay.

[An unusual cause of pulmonary cysts]. / Une cause inhabituelle de kystes pulmonaires.

INTRODUCTION: Multiple pathologies may be associated with cystic appearances in the lungs. Lymphangioleiomyomatosis, Langerhans cell histiocytosis and lymphocytic interstitial pneumonia are the principal causes of thin walled pulmonary cysts. CASE REPORT: We report the case of a non-smoking woman of 71 years, a retired farmer, who was admitted on account of cough, increasing dyspnoea, fever and loss of weight that developed following exposure to hay. The thoracic CT scan revealed diffuse ground glass opacities and centrilobular nodules. Multiple thin walled cystic shadows were distributed homogeneously throughout both lung fields. Broncho-alveolar lavage revealed a marked lymphocytosis (63%) and precipitins for Microsporum Faeni were strongly positive (6 arcs). The respiratory symptoms resolved spontaneously during the stay in hospital, allowing the patient to be discharged after 3 weeks with the advice to avoid all contact with hay. One month later she remained symptom free, the repeat CT scan showed a diminution ofthe ground glass opacities and the nodules but persistence of the pulmonary cysts. CONCLUSION: The diagnosis of hypersensitivity pneumonitis should be considered in the presence of a diffuse pulmonary infiltrate with multiple thin walled cysts in a patient with a suggestive history and clinical picture.

[A case of Farmer's lung accompaign with caseous granuloma, monitored with serum KL-6 and SP-D].

A 65-year-old man was admitted to our hospital with a productive cough, fever, and dyspnea; his chest radiographs revealed diffuse nodular and ground-glass opacities. He had worked on a farm for 11 years. Six months earlier, he had presented with similar symptoms at another hospital, and was admitted with suspected atypical pneumonia. After treatment with antibiotics, his condition improved and he was discharged. Examination on admission to our hospital revealed markedly elevated serum KL-6 levels. Histological findings from specimens obtained by video-assisted thoracic surgical lung biopsy showed caseating and non-caseating epitheloid cell granuloma, lymphocyte infiltration, and alveolitis. Bacteriological tests for mycobacteria and fungi were all negative. Farmer's lung was diagnosed in accordance with the criteria for hypersensitive pneumonia. It is generally accepted that the distinguishing histological finding for Farmer's lung disease is non-caseating epitheloid cell granuloma, but in this case, caseous granuloma was also present.

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.

OBJECTIVES: To assess the incidence and risk of asthma in patients with farmer's lung in comparison with farm workers without farmer's lung. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Reproducibility of scoring emphysema by HRCT.

PURPOSE: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. MATERIAL AND METHODS: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. RESULTS: Intraobserver kappa-values for all three methods were good (0.51-0.74). Interobserver kappa varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. CONCLUSION: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests.

IgG antibodies, chronic bronchitis, and pulmonary function values in farmer's lung patients and matched controls.

We measured IgG antibody levels against eight different microbes in farmer's lung (FL) patients an average of 14 years after the first diagnosed episode of FL and in matched controls. The study population consisted of 87 FL patients and 81 control farmers, matched by age, sex, and smoking habits. Clinical studies included the measurement of IgG antibody levels against Absidia corymbifera, Aspergillus umbrosus, A. fumigatus, Humicola grisea, Saccharopolyspora rectivirgula, Penicillium brevicompactum, Rhodotorula glutinis, and Thermoactinomyces vulgaris, in addition to spirometry, pulmonary diffusing capacity (DL(CO)), and the evaluation of chronic bronchitis. Median IgG antibody levels were two or more times higher in FL patients than control farmers against Ab. corymbifera, S. rectivirgula, and T. vulgaris (P<0.001). Against A. fumigatus, H. grisea, and R. glutinis, FL patients also had significantly higher antibody levels. FL patients often had positive antibody titers against several microbes, whereas control farmers usually had a positive titer against one or two microbes. A positive association between IgG antibody levels and chronic bronchitis and DL(CO) was observed in FL patients, but not in control farmers. It is suggested that the high antibody levels noted in FL patients were due not only to high exposure but also to individual sensitivity to environmental microbes.

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.

[Farmer's lung complicated by bilateral pneumothorax and mediastinal emphysema].

A 35-year-old woman was admitted to the hospital because of severe coughing and right-sided chest pain. She had worked on a farm for 13 years. For the preceding 2 years, she noticed a productive cough, a mild fever, and dyspnea after working in a barn for longer than 6 hours. Chest radiological examinations revealed low lung volumes, especially in the right upper lobe, and diffuse small granular shadows in both lung fields. Pathological examinations of lung specimens, which were obtained by transbronchial lung biopsy, showed alveolitis and granulomas in the interstitium. Micropolyspora faeni organisms were detected in hay from the barn. A M. faeni serum precipitation test revealed that her serum had antibodies against that organism. From these findings, we gave her a diagnosis of chronic farmer's lung. Prednisolone was given because her dyspnea and hypoxemia had increased. During the steroid treatment, bilateral pneumothorax and mediastinal emphysema developed. Bullae were removed surgically because she did not respond well to medical treatment. Although steroid administration may have caused these complications, bilateral pneumothorax and mediastinal emphysema are rare in patients with chronic farmer's lung.

Antioxidant therapy partially blocks immune-induced lung fibrosis.

A mouse model of hypersensitivity pneumonitis was generated by challenge with a thermophilic actinomycete. Oxygen radical scavengers were administered to challenged mice: vitamin E at 1000 units daily, polyethylene glycol-superoxide dismutase (SOD) at 500 units daily, polyethylene glycol-catalase at 10,000 units daily, 1,3,dimethyl-2-thiourea (DMTU) at 2 mg daily, and the biomimetic SOD, copper(II) [diisopropyl salicylate]2 (CuDIPS) at 1 mg daily. At three weeks after actinomycete challenge, a 10-fold increase in bronchoalveolar (BAL) cell number was observed. Treatments with catalase or DMTU were without effect on the BAL cell number in challenged mice. However, infusion of vitamin E was associated with an increased BAL cell influx (15-fold increase at two and three weeks). Similarly, treatment with PEG-SOD and CuDIPS resulted in an increase in cell number at two and three weeks. PEG-SOD or CuDIPS treatment resulted in a strong neutrophilia, whereas control challenged mice had a cellular influx mostly of macrophages and lymphocytes. Vitamin E treatment of challenged mice led to an increased T lymphocyte recruitment at two and three weeks. In vitro studies showed that actinomycete challenge was associated with an enhancement of alveolar macrophage O2- release, which was blocked by PEG-SOD, vitamin E, or DSC treatment but was unaffected by catalase or DMTU treatment. In control challenged mice, there was a 25-fold increase in the BAL albumin concentration at two weeks. PEG-SOD, vitamin E, or CuDIPS treatment all decreased the albumin concentration; the three modulators also diminished lung fibrosis at two or three weeks, as seen by a decrease in lung hydroxyproline and collagen synthesis by lung fibroblasts. Examination of sections from lungs of challenged animals showed evidence of cellular infiltrates around the bronchi and the blood vessels. Challenged mice given continuous infusions of vitamin E, SOD, or CuDIPS had lung histological scores that were significantly lower than control challenged mice or challenged mice treated with catalase or DMTU. Thus, therapies based on O2- scavenging or treatment with a general antioxidant such as vitamin E may hold some promise in the treatment of hypersensitivity pneumonitis.

[A case of chronic type farmer's lung which led to severe pulmonary fibrosis and spontaneous pneumothorax].

We present a case of chronic type farmer's lung which showed progressive pulmonary fibrosis and spontaneous pneumothorax 12 years after the first admission. A 56-year-old woman was diagnosed as having farmer's lung in 1981. After the first hospitalization, her chest roentgenogram showed regression with steroid therapy. After that, she sometimes worked at a dairy farm and required rehospitalization three times for recurrence. In April 1993, she was readmitted complaining of sudden chest pain and dyspnea after cough. Her chest roentgenogram on admission showed spontaneous pneumothorax. After treatment, her chest roentgenogram revealed severe pulmonary fibrosis and loss of lung volume.