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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amiodarone-induced interstitial pneumonitis is a serious, frequently fatal untoward effect of a commonly used antiarrhythmic agent. Recent reports suggest that bronchoalveolar lavage (BAL) fluid cellular analysis might be used to diagnose amiodarone-induced pneumonitis. The purpose of this study was to determine if the diagnosis of amiodarone-induced pneumonitis could be made by patient history, pulmonary function evaluation, and examination of BAL fluid. We studied five groups of patients. Three of the five groups received amiodarone: patients receiving amiodarone without evident lung toxic reaction, patients with amiodarone-induced pneumonitis, and amiodarone-treated patients diagnosed as having other pathologic processes involving the lung. The two other groups examined were healthy volunteers and patients with interstitial lung disease from causes other than amiodarone. Pulmonary function tests included vital capacity (FVC), first second forced exhaled volume (FEV1), total lung capacity (TLC), and diffusing capacity for carbon monoxide (DCO). BAL fluid analysis included total and differential cell counts. We found that amiodarone-induced interstitial pneumonitis was not associated with an alteration in pulmonary function or BAL cellular composition which could permit its distinction from amiodarone-treated patients diagnosed as having an unrelated pulmonary process or patients with interstitial lung disease from other causes. The most frequent abnormality encountered in patients with amiodarone toxicity was a reduction in the percentage of macrophages in the differential cell count. The sensitivity, specificity, and predictive value of this finding was 82 percent, 69 percent, and 69 percent, respectively. The sensitivity, specificity, and predictive value of a > or = 15 percent reduction in DCO was 44 percent, 50 percent, and 36 percent, respectively. We conclude that amiodarone-induced interstitial pneumonitis remains a diagnosis of exclusion, and the role of BAL fluid analysis is to narrow the differential diagnosis through microbiologic culture and cytologic examination.
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PMID:Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis. 139 16

Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients.
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PMID:Amiodarone pulmonary toxicity. 159 83

Amiodarone is an amphiphilic drug that penetrates easily through the plasmatic membrane and can induce the production of lysosome lamellar bodies in virtually all cells of the organism, independently of toxic effects. This study determines the value of searching for lamellar bodies in peripheric leucocytes as a method of prevention of pulmonary toxic effects in long term amiodarone treated patients. The rate of leucocytes with lamellar bodies was determined in three groups of patients. The group I was composed of 8 patients with amiodarone induced pneumonia who were taking the drug for an average of 16.88 months (average of 386.60 mg a day). The group II was composed of 19 patients not presenting any toxic effects, and who were taking amiodarone for an average of 38.32 months (average of 260.62 mg a day). The group III consisted by 8 healthy volunteers. The leucocyte layer was sampled from centrifuged peripheric blood and examined by transmission electron microscopy. The average percentage of leucocytes with lamellar bodies was 1.82 in group I, 1.65 in group II and 3.47 in group III. The lamellar inclusions were seen in all groups. There were no significant qualitative or quantitative differences between the groups. The inclusions couldn't be differentiated from other previously described non amiodarone lamellar bodies, such as artifacts and those produced by cellular degeneration. Although lamellar bodies can be observed in leucocytes of patients taking amiodarone, the determination of the rate of affected leucocytes is of no help for predicting amiodarone pulmonary toxicity.
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PMID:[Value of lamellar body quantification in leukocytes in amiodarone toxicity]. 166 61

Amiodarone pneumonitis is a serious complication that may lead to fatal lung fibrosis. In an attempt to diagnose this condition as early as possible, the technetium-99m-labelled diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol washout rates of 10 non-smoking normal volunteers (group 1), 10 non-smoking patients on a long-term amiodarone regimen with dilated cardiomyopathy but no congestive heart failure (group II) and 10 patients with amiodarone pneumonitis (group III) were compared. Spirometric measurements, as percentage predicted, were higher in group I than in group III (P less than 0.05). The global mean effective half-lives of 99mTc-DTPA aerosol for both lungs together in minutes were 65 +/- 14, 55 +/- 16 and 27 +/- 4 for groups I, II and III, respectively. Group III values were significantly lower than those of groups I and II (P less than 0.05). Our results demonstrated that amiodarone pneumonitis alters the alveolar-capillary membrane permeability to hydrophilic molecules. The pulmonary clearance of 99mTc-DTPA aerosol is a useful test in the differentiation of patients on a long-term amiodarone regimen without side effects from patients with amiodarone pneumonitis. The test is rapid, easy to perform and has the potential for playing an important role in deciding which patients should discontinue therapy.
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PMID:Pulmonary clearance of technetium 99m diethylene triamine penta-acetic acid aerosol in patients with amiodarone pneumonitis. 228 6

Amiodarone (ADR), a new antiarrhythmic drug for life-threatening cardiac arrhythmias, causes pneumonitis or lung fibrosis in a sizeable minority of patients. The cause of lung damage is not known. We have shown that infusion of 10 mg amiodarone into the inflow circuit of ventilated and perfused rabbit lungs causes immediate increase in pulmonary artery pressure (mean +/- SEM) (from 13.6 +/- 1.2 to 40.6 +/- 9.5 mm Hg, p less than 0.01) and pulmonary edema with marked increase in the pulmonary generation of thromboxane and leukotrienes C4 and/or D4. Albumin (2 g%) in the perfusate prevents any increase in lung perfusion pressure or edema formation. When lung perfusion pressure increase is blocked with the combined cyclooxygenase and lipoxygenase inhibitor enolicam sodium (CG5391B, 35 microM in perfusate), significant lung edema still occurs after amiodarone, indicating that amiodarone causes increased alveolar-capillary membrane permeability. Addition of catalase (100 U/ml) or superoxide dismutase and catalase (100 U/ml each) to perfusate fails to protect from amiodarone lung injury. Immediate infusion of amiodarone (10 mg) into lungs ventilated with room air (ADR + RA) causes an increase in lung weight gain from baseline (delta W) of 5.7 +/- 1.5 g/min. Compared with ADR + RA, ventilation of lungs with 4% O2 (delta W = 0.7 +/- 0.3 g/min, p less than 0.05), pretreatment of rabbits for 3 days with butylated hydroxyanisole (BHA, 100 mg/kg/day i.p., delta W = 0.05 +/- 0.02 g/min, p less than 0.01), pretreatment of rabbits for 3 days with vitamin E (Vit E, 300 U/day orally, delta W = 0.6 +/- 0.2 g/min, p less than 0.05), or addition of N-acetylcysteine to the lung perfusate (NAC, 5 mM, delta W = 0.1 +/- 0.08 g/min, p less than 0.01) all protect from lung edema formation after amiodarone. Amiodarone (100 mg) also caused a marked increase in luminol-enhanced lung chemiluminescence, lung production of superoxide anion (O2-), and tissue levels of lung glutathione disulfide. These results suggest that amiodarone causes lung injury by an oxidant mechanism.
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PMID:Amiodarone causes acute oxidant lung injury in ventilated and perfused rabbit lungs. 245 31

Fifteen patients, eleven males and four females, with amiodarone induced pulmonary disease were studied. Their ages ranged between 52 and 79 (mean = 64.0) years. 66% of the patients were taking a daily dose of 200 mg of amiodarone. The time elapsed between the initial dose and the diagnosis of the pneumonitis varied from 2 to 84 (mean = 23.3) months. Premature ventricular beats and recurrent episodes of paroxistic supra ventricular tachycardia were the most common indications for the use of the drug. The most frequent clinical complaints were progressive dyspnea and cough. Weight loss was observed in five patients, fever in six and chest pain in two. The most habitual thoracic physical sign was diffuse crepitation. Chest roentgenograms disclosed bilateral interstitial infiltrates in all patients, associated to pleural effusions in two. An increased diffuse uptake of 67 gallium citrate was observed in the nine patients to whom it was done. Lung function tests showed a pattern of restrictive ventilatory respiratory insufficiency and hypoxemia. Lung tissue specimens were obtained in ten patients, bronchoalveolar lavage in one and pleural fluid in one. The material was examined by light and electron microscopy. Amiodarone was discontinued in all patients and corticosteroids were introduced in thirteen. Five patients (33.3%) died, eight improved and two remained with radiographic scars.
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PMID:[Pneumonitis induced by amiodarone]. 248 1

Over 8 1/2 years, we observed 27 patients with drug-induced respiratory disease (DIRD). The inducer drugs were mainly those used in cardiology (9 patients, of whom 8 had amiodarone pneumonitis), in oncology (8 patients), in rheumatology (4 patients; 3 from d-penicillamine and 1 from gold), and in neurology (4 cases from ergoline derivatives). The main pattern of DIRD was a diffuse interstitial lung disease having either a rapid, a slowly progressive or a chronic course. Only the two former patterns offered clearing following withdrawal of the drug. Severe bronchiolitis obliterans from d-penicillamine (2 cases) and pulmonary eosinophilia (2 cases) was also observed. The onset of DIRD occurred earlier, i.e. following shorter periods of drug administration (months), in the acute interstitial lung disease variant, while it occurred after years of drug exposure in subacute and chronic forms. In contrast to other reports, bronchoalveolar lavage lymphocytosis was not a prominent feature in amiodarone pneumonitis. The outcome was favourable in 16 patients; deaths was encountered during the florid phase of DIRD in 3; incapacitating sequelae were noted in 6 patients, leading to subsequent death in 2; the underlying disease accounted for 7 additional deaths. Therefore, DIRD are relatively common, develop often in patients with severe underlying conditions, and interstitial pneumonitis is their pattern of predilection. Amiodarone emerges as a common inducer, and accounted for more cases than all chemotherapeutic agents grouped together in our series.
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PMID:[Drug-induced respiratory complications. Study of 27 cases]. 278 7

Associated with amiodarone use is pneumonitis which may progress to life-threatening pulmonary fibrosis. Desethylamiodarone, a metabolite, whose role in the etiology of amiodarone-induced pulmonary toxicity has been unclear, also possesses antiarrhythmic activity and could potentially be used as an antiarrhythmic drug itself. We have used a single intratracheal administration of equimolar amounts of amiodarone or desethylamiodarone (1.83 mumol) to male golden Syrian hamsters to investigate the fibrogenicity of desethylamiodarone. Animals were terminated at 1, 7, 14, 21, and 28 days post-treatment, and toxicity was assessed by measurement of lung hydroxyproline content and by histological techniques. Amiodarone and desethylamiodarone significantly increased lung hydroxyproline content over vehicle control animals by 21 days (33 and 58% respectively). While amiodarone-treated lungs had hydroxyproline contents similar to control levels at 28 days, desethylamiodarone-treated lungs remained elevated (44% over control values). Quantitative histologic examination revealed that lungs from desethylamiodarone-treated animals displayed a greater toxic effect, while trichrome staining confirmed the increased deposition of interstitial collagen in these same animals. These results may be due to the higher affinity of the lung for desethylamiodarone and thus a prolonged exposure. The findings indicate that, in the hamster, both compounds are toxic by this route and that desethylamiodarone is not a nontoxic metabolite. Further, use of desethylamiodarone as an antiarrhythmic agent may not be devoid of the adverse effects associated with amiodarone.
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PMID:Pulmonary fibrosis induced in the hamster by amiodarone and desethylamiodarone. 278 62

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.
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PMID:Leukocyte migration inhibition in amiodarone-associated pneumonitis. 305 57

Amiodarone is an iodinated antiarrhythmic agent that is effective in the treatment of atrial and ventricular arrhythmias. A number of side effects are seen, including pulmonary toxicity and thyroid dysfunction. A patient with both amiodarone-induced pneumonitis and hyperthyroidism who exhibited abnormal gallium activity in the lungs, as well as diffuse gallium uptake in the thyroid gland is presented. The latter has not been previously reported and supports the concept of iodide-induced "thyroiditis" with gallium uptake reflecting the inflammatory response.
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PMID:Gallium uptake in the thyroid gland in amiodarone-induced hyperthyroidism. 316 35


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