A case of hypersensitivity pneumonitis in which serum specific antibodies for three species of isocyanate molecules were demonstrated]

A 64-year-old male was admitted to our hospital with complaints of the development of high fever, cough and dyspnea 5-6 hours after painting automobiles. His chest X-ray film showed interstitial shadows in both lungs. Pulmonary function test demonstrated reduction of diffusion capacity; and blood gas analysis demonstrated hypoxemia and an increase in alveolar-arterial oxygen tension difference. Marked lymphocytosis and a striking decrease in CD4/CD8 ratio were observed in the bronchoalveolar lavage fluid. Transbronchial lung biopsy specimens showed alveolitis and Masson's bodies. We suspected that the patient was suffering from hypersensitivity pneumonitis induced by isocyanates contained in the urethane paint he used. Immunological studies were performed using chemical compounds of three species of isocyanate molecules (TDI, MDI, HDI) and human serum albumin (HSA). The results were as follows: skin tests were positive for TDI-HSA and MDI-HSA; lymphocyte-stimulation tests on peripheral blood were positive for TDI-HSA; precipitation reaction was negative for all the isocyanates studies; enzyme-linked immunosorbent assay (ELISA) demonstrated the existence of specific IgG antibodies for TDI, MDI and HDI; inhalation challenge test by TDI-HSA was negative, but environmental provocation was considered to be positive. We diagnosed his pulmonary disorder as hypersensitivity pneumonitis due to isocyanates. Type III and Type IV allergic reactions of Gell-Coombs were suggested to be involved in the pathogenesis, however, there remains the possibility that the instability of isocyanate compounds as antigen modified the results of our immunological studies.     

A case of lung sarcoidosis which was clinically difficult to distinguish from hypersensitivity pneumonitis

A case of pulmonary sarcoidosis (stage III), in which the abnormal chest shadow disappeared within two weeks was reported. A 35-year-old male was admitted for further examination of bronchial asthma. He stayed overnight at home after he received inhalation provocation test of sulpyrin. Returning to the hospital, he had a fever (38 degrees C) with diffuse small nodular shadows on the chest roentgenogram. The onset and clinical features of the disease suggested hypersensitivity or drug induced pneumonitis rather than sarcoidosis. Bronchoalveolar lavage fluid (BALF) analysis showed an increase of total cell counts and lymphocytes. The surface marker of lymphocytes in BALF revealed that the CD4/8 ratio was remarkably elevated to 6.2. Both transbronchial lung and scalene node biopsy specimens revealed numerous non-caseous granulomas, and a diagnosis of sarcoidosis was confirmed. The chest infiltrates disappeared spontaneously within two weeks. This case was reported because of its rare natural course as stage III pulmonary sarcoidosis.     

A case of chronic bird fancier's lung in which VATS biopsy was diagnostically useful]

A 72-year-old woman was admitted to our hospital complaining of dry cough and dyspnea on effort for 9 months. Her chest HRCT findings showed diffuse reticular opacities, ground-glass opacities, and interlobular septal thickening with subpleural and peribronchovascular distribution, not typical of IPF/UIP. BAL revealed mild lymphocytosis and elevated CD4/CD8 ratio. Since TBLB was not diagnostic, we performed VATS biopsy. The pathological finding by VATS biopsy revealed collapse, fibrosis, and scar formation in both subpleural and intralobular regions with small granuloma, consistent with chronic hypersensitivity pneumonitis. Both antibodies in serum to pigeon dropping extract and inhalation provocation test using avian dropping extracts were positive. and therefore we diagnosed chronic bird fancier's lung. We should suspect chronic hypersensitivity pneumonitis in cases with HRCT findings atypical of IPF/UIP. and examine antibodies against specific antigens and perform VATS biopsy.     

Specific bronchoalveolar lavage IgG antibody in hypersensitivity pneumonitis from diphenylmethane diisocyanate

We evaluated a patient for dyspnea, fever, malaise, and hypoxemia that developed after exposure to diphenylmethane diisocyanate (MDI). Specific inhalation challenge with MDI caused fever, leukocytosis, a restrictive decline in forced vital capacity, and a decrease in Pao2 several hours after challenge. Bronchoalveolar lavage 24 h after challenge showed lymphocytic alveolitis. Specific IgG antibodies to MDI human serum albumin (MDI-HSA) conjugate were demonstrated in serum and bronchial lavage fluid using the enzyme-linked immunoabsorbent (ELISA) technique. These findings suggest participation of both humoral and cellular immunity in the pathogenesis of hypersensitivity pneumonitis from isocyanate exposure.     

A familial case of summer-type hypersensitivity pneumonitis possibly associated with bird breeder's lung diagnosed by bronchoalveolar lavage fluid]

Case 1: A 32-year-old woman had cough and exertional dyspnea in August 2002, and chest computed tomographic scan revealed diffuse centrilobular nodules. Bronchoalveolar lavage fluid (BALF) showed a high proportion of lymphocytes with a decreased CD 4/CD 8 ratio. Transbronchial lung biopsy (TBLB) specimens showed alveolitis. Summer-type hypersensitivity pneumonitis was diagnosed on the basis of positive findings of anti-Trichosporon antibodies in the serum. Case 2: A 64-year-old man, the father of Case 1, also had cough and exertional dyspnea in August 2003. He had been in close contact with pigeons. Chest computed tomographic scan revealed bilateral map-like ground-glass opacities predominantly in the upper lobes. BALF showed a high proportion of lymphocytes with a decreased CD 4/CD 8 ratio. TBLB specimens showed alveolitis, granuloma and Masson body in the air spaces. Specific IgG and IgA antibodies against Trichosporon asahii, IgA antibodies against Trichosporon mucoides, and IgA antibodies against pigeon dropping extracts were found only in the BALF but not in the serum. Although a positive finding of returning-home provocation test was definitive in diagnosing summer-type hypersensitivity pneumonitis, he was also suspected of having bird fancier's lung.     

Hypersensitivity pneumonitis induced by spores of Lyophyllum aggregatum

OBJECTIVES: Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment all year round. This study aimed to clarify the clinical features of hypersensitivity pneumonitis (HP) induced by LA. PATIENTS AND SETTING: Ten patients showed mild respiratory symptoms including dry cough, sputum, and low-grade fever. We tried to characterize the clinical features and the findings using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte stimulation tests (LSTs) for LA. RESULTS: Laboratory findings showed mean (+/- SD) elevated levels of C-reactive protein (0.78 +/- 1.3 mg/dL), erythrocyte sedimentation rate (48 +/- 23 mm/h), and gamma-globulin (26.9 +/- 7.6%). PFTs revealed a slight decrease in the percentage diffusing capacity of the lung for carbon monoxide, possibly due to the presence of epithelial granulomas in the alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph (CXR), chest HRCT findings of all patients showed centrilobular small nodules and diffuse ground-glass opacities. The BALF testing revealed an increase in total cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell ratio was significantly decreased (0.5 +/- 0.3). The results of the LSTs were positive in seven of seven cases. CONCLUSIONS: Since patients with HP induced by LA typically have mild respiratory symptoms and sometimes normal CXR findings, their conditions might remain undiagnosed. However, the chest HRCT images showed the typical subacute phase of HP.     

A case of summer-type hypersensitivity pneumonitis with bronchoalveolar lavage performed 4 years before onset

A 51-year-old man with chief complaints of cough, fever, and dyspnea was admitted to our hospital. Based on a home provocation test, transbronchial lung biopsy specimens, and a serum antibody, we diagnosed summer-type hypersensitivity pneumonitis. In 1983 when the patient was 46 years old, thymectomy was performed for thymoma. Prior to surgery, bronchoalveolar lavage (BAL) was performed. Total cell count and neutrophils had already increased in BALF. Furthermore, the increase in BALF cell neutrophil count was also seen at the time of admission and after the home provocation test. Because an increase of neutrophils in BALF cells was seen not only at onset but before onset, further studies are required to clarify the role of neutrophils and the factors that increase them in hypersensitivity pneumonitis.     

Chronic hypersensitivity pneumonitis caused by Aspergillus complicated with pulmonary aspergilloma

A 57-year-old man consulted our hospital with a history of the gradual onset of dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass opacities in the bilateral lung fields with honeycombing. He was diagnosed as having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an outpatient, he suffered from dyspnea upon physical exertion with exacerbation of the high-resolution CT (HRCT) opacities. An inhalation provocation test for Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis of a detailed history, specific HRCT findings, and lymphocyte-dominant bronchoalveolar lavage fluid cell findings.     

Hypersensitivity pneumonitis and bronchial asthma attacks caused by environmental fungi.

We report a case of hypersensitivity pneumonitis and asthma attacks caused by environmental fungi in a 75-year-old man. The diagnosis was established by inhalation challenge with Bjerkandera adusta and Aspergillus fumigatus. The patient was admitted for treatment of fever, wheezing, and dyspnea. Chest computed tomography showed small nodular shadows with diffuse, partially patchy, ground-glass opacities. The findings of bronchoalveolar lavage fluid were compatible with hypersensitivity pneumonitis. His symptoms and objective findings, including chest radiographs, worsened after returning home, suggesting the existence of causative antigens in his house. B. adusta and A. fumigatus were isolated from the living room and bedroom. Based on the results of antigen inhalation bronchoprovocation test, he was given a diagnosis of hypersensitivity pneumonitis caused by B. adusta and bronchial asthma attacks caused by B. adusta and A. fumigatus. After cleaning the entire house, the patient has had no recurrence of the symptoms on returning home.     

A case of Japanese summer-type hypersensitivity pneumonitis: monitoring with serum KL-6 and examination of the phenotype of HLA]

A 55-year-old woman was admitted with a cough and fever in August. A diagnosis of Japanese summer-type hypersensitivity pneumonitis was made on the basis of radiological, serological and pathological findings, in addition to positive returning home provocation. Serum KL-6 was monitored during the clinical course. Although KL-6 fluctuated slowly in comparison with the clinical symptoms and HRCT findings, it was considered useful for confirming the effects of treatment. Serum anti-Trichosporon antibody and the phenotype of HLA were studied in both the patient and her asymptomatic roommate, with whom she had no blood relationship. Though both were sensitized immunologically, HLA-DQ 3, which was reported to be associated with Japanese summer-type hypersensitivity pneumonitis, was detected in the patient but not in her roommate. It was suggested that HLA plays a role in the development of this disease.     

A case of hypersensitivity pneumonitis showing acute respiratory distress syndrome due to exposure to dust containing diphenylmethane diisocyanate]

The patient was a 61-year-old man who reported coughing and fever that occurred immediately after the work of breaking up a large refrigerator containing diphenylmethane diisocyanate (MDI). He was brought to our medical center with respiratory distress ten days after onset. Acute respiratory distress syndrome was diagnosed on the basis of a P/F oxygen ratio of less than 200 and chest CT findings of extended consolidation in both lung fields. He was intubated and ventilated mechanically. Steroid pulse therapy was started because of an elevated lymphocyte count found through bronchoalveolar lavage (BAL). After that, arterial blood gas and chest radiography findings improved gradually, and high-resolution chest findings on the 4th day of hospitalization showed centrilobular and uncleared shadows of marginated acini in both lung fields. The patient was extubated ten days after admission, the steroid therapy was withdrawn, and he was discharged from the intensive care unit on the 22nd day of hospitalization. Transbronchial lung biopsy on admission revealed alveolitis, Masson bodies and activated macrophages in the air spaces. The dismantled refrigerator was known to contain MDI, and because of the IgE and the IgG to MDI present in the serum, and of the IgG to MDI in the BAL fluid, we diagnosed hypersensitivity pneumonitis with acute respiratory distress syndrome due to exposure to dust containing MDI. There are many reports of painters with hypersensitivity pneumonitis following exposure to isocyanates, but care should be taken to avoid the possibility of acute respiratory distress syndrome arising because of the inhalation of dust mixed with isocyanates.     

A case of pneumonitis due to sho-saiko-to

We reported a case of pneumonitis due to Sho-saiko-to. A 71-year-old woman was admitted to our hospital because of pneumonia. She complained of dry cough, pyrexia and severe dyspnea. Fine crepitation was heard on physical examination of the chest and a chest X-ray film revealed diffuse reticulo-nodular shadow in both lung fields. We suspected summer-type hypersensitivity pneumonitis and followed her up, however her condition deteriorated. Under a suspicion of drug-induced pneumonitis, all drugs were stopped and she was given prednisolone. Consequently her complaints, laboratory data and chest X-ray findings markedly improved. Microscopic examination of a transbronchial lung biopsy specimens showed interstitial pneumonitis. The results of a lymphocyte stimulation test were positive for sho-saiko-to. She gave informed consent after receiving an explanation of the challenge test. She was tested with 2.5 g sho-saiko-to twice and developed high fever and dyspnea with hypoxia, while the chest X-ray film also revealed diffuse infiltrative shadows similar that on admission. Based on these findings, we diagnosed this case as pneumonitis due to sho-saiko-to. To our knowledge, there has been no previous case of pulmonary hypersensitivity due to sho-saiko-to reported in the world.     

A case of acute hypersensitivity pneumonitis caused by contact with budgerigars (bird-breeder's lung)]

A 58-year-old woman was admitted to our hospital for repeated episodes of dry cough, low-grade fever, and gradual development of dyspnea on exertion. Chest computed tomography showed diffuse ground-glass opacities in both lung fields. Bronchoalveolar lavage fluid (BALF) showed an increased number of lymphocytes, and transbronchial lung biopsy revealed alveolitis and epithelioid cell granuloma. The acute onset and the patient's living environment suggested summer-type hypersensitivity pneumonitis. However, anti-Trichosporon antibody was negative and a definitive diagnosis could not be made. The patient's condition improved with corticosteroid treatment and, after discharge from the hospital, she moved to a new home. The following year, however, her symptoms returned, and she was readmitted to our hospital. Recurrence of the disease despite the change in environment ruled out summer-type hypersensitivity pneumonitis. Given the patient's history of budgerigar breeding five years earlier, bird breeder's lung was suspected. Anti-bird excreta antibody found in the patient's serum and BALF, along with a positive lymphocyte stimulation test against pigeon serum, strongly suggested an acute onset of bird breeder's lung. We report a rare case of acute bird breeder's lung with radiologic findings of ground-glass opacities, a one-year disease-free period and an acute relapse.     

Hypersensitivity pneumonitis related to medium-density fiberboard

Pneumonitis due to hypersensitivity to wood fiber is mainly associated with the fungus that colonizes it. We present the case of a male affected with hypersensitivity pneumonitis in which the agent implicated was medium-density fiberboard, an engineered product whose main component is pine wood fiber. The causal agent was identified by means of a specific bronchial provocation test.     

A case of flomoxef-induced pneumonitis]

We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.     

A case of chronic hypersensitivity pneumonitis due to wild pigeons]

A 61-year-old woman was admitted to the Oita Medical University Hospital because of a nonproductive cough and exertional dyspnea. Interstitial changes had been seen on her chest radiograph 5 years previously, but no respiratory symptoms were identified at that time. On admission, chest radiography revealed linear and ground-glass opacities in the middle and lower lung fields. Computed tomography provided evidence of bronchiectasis and micro-honeycombing of the lungs, while lymphocyte and neutrophil counts in the bronchoalveolar lavage fluid were increased. Transbronchial lung biopsy demonstrated alveolitis and Masson's bodies. The patient was not a pigeon breeder, but she could have been exposed to pigeons at her workplace. Indeed, she had specific antibodies against pigeon serum and droppings, and her peripheral lymphocytes showed proliferation in response to pigeon serum. A positive provocation test involving inhalation of pigeon serum confirmed that she had chronic hypersensitivity pneumonitis caused by allergy to pigeons. This is a rare case of chronic hypersensitivity pneumonitis associated with wild pigeons, that progressed to pulmonary fibrosis. Antigen provocation testing proved to be of great value.     

Humidifier lung: possible contribution of endotoxin-induced lung injury

A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest computed tomography demonstrated bilateral diffuse ground-glass opacities predominantly in the upper lungs. Subpleural non-segmental consolidation was observed in the late phase. Hypersensitivity pneumonitis was suspected, and an environmental provocation test with the incidental use of a home ultrasonic humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6 levels were normal. Although several microorganisms were isolated from the humidifier water, there was no evidence for immune sensitization. We detected high amounts of endotoxin in the humidifier water, which may have contributed to the lung injury of this patient.     

Saccharomyces-induced hypersensitivity pneumonitis in a dairy farmer: a case report]

A 58-year-old man, a dairy farmer, was admitted to Engaru Kosei Hospital because of cough, fever and dyspnea following repeated exposure to moldy silage in a silo. Chest radiography showed ground-glass opacity and tiny nodules in both lung fields. Arterial blood gas analysis showed severe hypoxia (PaO2, 30.8 torr). The patient was referred to Asahikawa Medical College Hospital for a diagnostic evaluation. At the time of admission, his symptoms were slightly resolved and the lung density on the chest radiograph was decreased. Pulmonary function tests revealed restrictive ventilatory impairment with a reduction in diffusing capacity. Bronchoscopic examination revealed mild lymphocytosis in the bronchoalveolar lavage fluid (BALF). Neither bacteria nor fungi were cultured from the BALF. Transbronchial lung biopsy specimens showed alveolitis with lymphocyte infiltration. The symptoms and signs disappeared spontaneously without any specific treatment, such as corticosteroids or antibiotics. A provocation test consisting of silage handling elicited recurrence of his symptoms, a decrease in diffusing capacity, and hypoxia. A definitive diagnosis of hypersensitivity pneumonitis (HP) was made from these findings. Samplings from the silage revealed a gross growth of the yeast Saccharomyces cerevisiae. A serum-precipitating antibody gave a positive reaction for an extract of S. cerevisiae. These results suggested that repetitive exposure to S. cerevisiae had led to sensitization through the patient's occupational environment, resulting in the development of HP.     

A case of hard metal lung disease presenting a type of chronic hypersensitivity pneumonitis

A 35-year-old man was admitted to our hospital because of abnormal shadows on the chest radiograph and dry cough and exertional dyspnea. He was given a diagnosis of hard metal lung disease 15 years previously and was treated with corticosteroid. Laboratory examination revealed hypoxemia and reduced pulmonary vital capacity. Chest radiograph and high-resolution computed tomography (HRCT) on admission showed ground-glass opacities with volume loss and small cystic spaces. Bronchoalveolar lavage fluid (BALF) demonstrated bizarre multinucleated giant cells and transbronchial lung biopsy (TBLB) specimens showed interstitial pneumonia with multinucleated giant cells. He has worked as a metal grinder, and tungsten was detected in his BALF metal analysis. His illness was diagnosed as hard metal lung disease with giant cell interstitial pneumonia (GIP). We considered this case as a type of chronic hypersensitivity pneumonitis due to his high sensitivity and his disease worsened gradually for four years. Since hard metal lung disease may recur in individuals with high sensitivity, we should always be aware of the possibility of recurrence of this disease.     

Chronic hypersensitivity pneumonitis induced by Shiitake mushroom cultivation: case report and review of literature]

A 72-year-old man, a Shiitake mushroom grower over fifty years, was admitted to our hospital because of bilateral chest interstitial shadow with chronic cough and breathlessness. Chest computed tomography showed traction bronchiectasis, subpleural micro-cystic changes and partial ground-glass opacities in both lungs, and mild mediastinal lymphadenopathy. A diagnosis of chronic hypersensitivity pneumonitis induced by Shiitake mushrooms was comprehensively confirmed by occupational history, radiological findings, and positive findings of an incidental environmental provocation test and lymphocyte stimulation test for Shiitake mushroom extracts. We reviewed the clinical features in five patients with chronic hypersensitivity pneumonitis induced by Shiitake mushrooms reported in Japan. There was a tendency toward increasing lymphocytes and high CD4/CD8 ratio in bronchoalveolar lavage fluids. Treatment with steroids seems to have a limited effect, while avoidance of the antigen is important.