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11/29. sirolimus-associated pulmonary toxicity.

    BACKGROUND: Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. methods: We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched pubmed for all previously reported cases. RESULTS: Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. CONCLUSION: The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.
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keywords = exposure
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12/29. Respiratory bronchiolitis associated with interstitial lung disease.

    Respiratory bronchiolitis associated with interstitial lung disease (RB-ILD), first described by Niewoehner et al in an autopsy study of cigarette smokers who died from non pulmonary causes in 1974, is a rare entity that should be distinguished from the other interstitial lung diseases and in particular from desquamative interstitial pneumonia, although the two conditions share a similar histopathological pattern. RB-ILD is clearly connected with tobacco smoking and has been inserted in the "smoking related interstitial lung diseases" together with DIP and Cell histiocytosis of Langerhans; it may also be associated with occupational exposure to machine fumes. The following is a case report of a patient with both smoking and occupational exposure.
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keywords = occupational exposure, exposure
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13/29. sirolimus-associated interstitial pneumonitis in solid organ transplant recipients.

    sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart-lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving.
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14/29. Hard metal lung disease: high resolution CT and histologic correlation of the initial findings and demonstration of interval improvement.

    Hard metal lung disease (HMLD) is a rare form of interstitial lung disease caused by sensitization to cobalt. It occurs in patients exposed to hard metal (tungsten carbide) and in diamond workers who use cobalt-containing polishes. The chest radiograph may be normal or show a nodular, reticulonodular, or reticular pattern. The high-resolution CT findings have been described in a small number of patients. Reported abnormalities include patchy lobular ground glass opacities, consolidation, reticulation, centrilobular nodularity, and, occasionally, honeycombing.We describe the high-resolution CT findings in a patient with pathologically proven HMLD who demonstrated interval improvement in the ground glass opacities and persistence of the centrilobular nodules following cessation of exposure to hard metal and treatment with corticosteroids. To our knowledge, this is the first described case of HMLD with follow-up CT examination.
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15/29. Giant cell interstitial pneumonia associated with nitrofurantoin.

    A case of giant cell interstitial pneumonia (GIF) that occurred in association with exposure to nitrofurantoin is presented. While the diagnosis of GIP is confirmed by histopathology, this diagnosis can be supported by the findings of bizarre multinucleated giant cells (MGC), elevated T lymphocytes, and a low T lymphocyte helper/suppressor ratio in the bronchoalveolar lavage fluid (BALF). Recognition of GIP as a rare manifestation of nitrofurantoin toxicity is important because prompt therapy may be associated with a favorable outcome.
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keywords = exposure
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16/29. Hill walkers' lung.

    A previously healthy female presented with a 7-week history of dyspnoea on exertion following inhalation of a fluorochemical-based water repellent spray, which was applied to footwear, in the living area that she shared with 8 members of her family while on a hill walking holiday. Clinical examination, serial lung function studies, bronchoalveolar lavage, transbronchial biopsies and high-resolution CT thorax confirmed a sub-acute interstitial pneumonitis, which did not resolve until 15 weeks following exposure. None of her family members were affected despite similar exposure. Interstitial pneumonitis due to inhalation of fluorochemical-based water repellent, though rarely described, usually presents in an acute severe form necessitating immediate therapy and resolves in 1-4 weeks. pulmonary fibrosis can also occur. Sub-acute interstitial pneumonitis following inhalation of fluorochemical-based water repellent spray should always be considered as a cause of unexplained persistent respiratory symptoms in otherwise healthy individuals involved in outdoor pursuits.
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keywords = exposure
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17/29. Chronic interstitial lung disease in a welder of galvanized steel.

    A 32-year-old man who took pride in his skill and speed as a welder suffered two relatively brief intense exposures (three months each) to welding fumes under relatively confined space conditions. He developed shortness of breath within 18 months of beginning work, with severe impairment of his diffusion capacity. This remains some months later despite discontinuing his welding activities.
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18/29. Hard metal disease: eight workers with interstitial lung fibrosis due to cobalt exposure.

    Eight hard metal workers exposed to cobalt containing dust (four producers of stone-cutting cobalt-diamond wheels and four grinders of hard metal tools) and affected by interstitial lung fibrosis have been examined. A close relationship between cobalt exposure and clinical findings was observed in six patients who were still working. The clinical picture ranged from minor symptoms to manifestations resembling those of hypersensitivity pneumonitis, with fever, weight-loss, non-productive cough and dyspnea. A restrictive impairment of the ventilatory function was prevalent. The chest roentgenogram of one patient showed a diffuse reticular nodular pattern, while the others presented a mild reticular accentuation of the interstitium. In five patients, bioptic specimens of the lung parenchyma showed interstitial collagenic fibrosis with inflammatory cells infiltrating the alveolar septa. An increased number of lymphocytes and polymorphs was reported in the bronchoalveolar lavage (BAL) fluid from seven patients. Giant multinucleated cells were present in the BAL of four subjects while an inversion of the helper-suppressor ratio was evident in those patients who were still exposed to cobalt when BAL was performed. In this study, the causal role of metallic cobalt inhalation in the etiology of the lung disease is examined and discussed.
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ranking = 5
keywords = exposure
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19/29. piroxicam induced pulmonary infiltrates and eosinophilia.

    We describe 2 patients who developed pulmonary infiltrates while being treated with piroxicam. There was no satisfactory explanation other than drug induced lung disease for their illness. They had no exposure to pneumotoxic drugs or aerocontaminants. Microorganisms were not cultured in sputum or bronchoaveolar lavage. There was no underlying illness with possible lung involvement. Pulmonary infiltrates developed during piroxicam therapy, disappeared after drug withdrawal and recurred following rechallenge.
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20/29. Giant cell interstitial pneumonitis. Disease recurrence in the transplanted lung.

    recurrence of the original disease in the transplanted organ is well reported in renal transplant recipients. There have been no previously fully documented cases of recurrence of the original disease after lung transplantation. We report a patient who underwent single-lung transplant in 1990 for end-stage respiratory failure secondary to biopsy-proved giant cell interstitial pneumonitis (GIP). There was no further industrial exposure. Surveillance bronchoscopies and biopsies post-transplant demonstrated eosinophils and giant cells in the bronchoalveolar lavage of both lungs, and in biopsies of the transplanted organ. Two years after successful transplantation the patient deteriorated and underwent open lung biopsy, which demonstrated not only bronchiolitis obliterans but also the classic features of GIP. There was no evidence of inorganic particles in the transplanted lung. autopsy confirmed the presence of numerous giant cells characteristic of GIP with associated fibrosis throughout the transplanted lung. Although tungsten and other inorganic particles were again demonstrated in the native lung, there was no evidence of tungsten particles in the transplanted lungs. We believe that this case documents recurrence of the original disease after lung transplantation. The absence of unusual inorganic particles in the transplanted lung in the face of the classic picture of GIP is highly suggestive of an autoimmune mechanism for this occupation-associated disease. The appropriateness of transplant in the management of this lung disease should be reviewed further.
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ranking = 1
keywords = exposure
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