Acute amiodarone-induced pulmonary toxicity following lung resection

Amiodarone-induced pulmonary toxicity has been described mostly in patients receiving large doses of the drug over prolonged periods. In this report, we describe the early onset of acute pulmonary toxicity leading to acute respiratory distress syndrome after a short course of amiodarone treatment following middle-lobe non-small-cell lung cancer resection.     

SP-D as a marker of amiodarone-induced pulmonary toxicity

Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated.     

Serum KL-6 as a possible marker for amiodarone-induced pulmonary toxicity

Amiodarone is a useful drug for the treatment of life-threatening cardiac arrhythmias. However, amiodarone can induced pulmonary toxicity (APT) and may cause life-threatening lung damage. APT can be difficult to diagnose, but early diagnosis is important. Here, in a 51-year-old man with APT, the high serum KL-6 level was correlated with the severity of symptoms and chest X-ray findings, and it was inversely correlated with PaO2 and diffusion capacity for carbon monoxide levels. The findings suggest that the serum KL-6 level may be increased in APT and that therefore it's the determination of serum KL-6 may provide a useful indicator and/or monitoring marker of APT. KL-6 is believed to be produced and secreted by type II pneumocytes. Typical pathological findings of APT include proliferation of type II pneumocytes which may produce KL-6, and result in increased serum KL-6 levels.     

Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity

Amiodarone is an effective anti-arrhythmic agent. However, during long-term therapy, patients can develop severe adverse pulmonary reactions that are potentially life-threatening. A case of amiodarone-induced pulmonary toxicity is presented in a 78-year-old woman. She developed dyspnea and a pulmonary mass with associated multiple lung nodules mimicking a lung cancer following 5 years of treatment with amiodarone for atrial fibrillation. After drug withdrawal, and without any additional treatment, clinical and radiological improvement was observed, and radiological findings resolved completely within 6 months.     

Clinical features of acetaminophen toxicity

Thirteen patients met our criteria for severe acetaminophen hepatotoxicity over a 5-year study period. Six patients had therapeutic misadventures (not attempting suicide), and seven were attempting suicide. Five of six patients in the therapeutic misadventure group were chronic alcoholics, and three were taking other drugs reported to cause hepatic microsomal enzyme induction. In the suicide group, two of seven patients were alcoholics, and one patient was taking another inducing drug. All six patients in the therapeutic misadventure group had nausea, vomiting, or starvation, whereas two of seven patients in the suicide group had similar characteristics. Starvation could deplete the protective factor glutathione, thus augmenting hepatotoxicity. In the therapeutic misadventure group, four of six patients developed acute tubular necrosis, as compared to two of seven in the suicide group. One patient died in each group. Clinicians should be aware of these features as part of the spectrum of acetaminophen toxicity.     

Susceptibility to amiodarone-induced pulmonary toxicity: Relationship to the uptake of amiodarone by isolated lung cells

In previous studies, we showed that Fischer rats fed 175 mg/kg of amiodarone accumulated large amounts of drug and metabolite in the lung and developed pulmonary toxicity, whereas Wistar rats fed the same drug dose had significantly less amiodarone in the lung and did not develop pulmonary inflammation. The present study was designed to determine whether this difference in susceptibility between the strains was related to differences in uptake of amiodarone by lung cells. We found that isolated mixed lung cells of Fischer rats sequester significantly more drug than cells from Wistar rats. This difference in uptake cannot be due to drug metabolism because the lung is not capable of metabolizing amiodarone. We also found that the alveolar macrophage is one of the cell types in the mixed cell population that is partially responsible for the difference in drug uptake and that fibroblasts and type II pneumocytes are not involved. In addition, despite the fact that there was no difference in drug uptake, we found that fibroblasts isolated from Fischer rats were more susceptible to amiodarone-induced cytotoxicity than were Wistar fibroblasts. We conclude that genetic differences in lung drug sequestration and possibly the sensitivity to cytotoxicity may explain differences in susceptibility to amiodarone-induced pulmonary toxicity.     

Detection of amiodarone-induced pulmonary toxicity in supine and prone positions: high-resolution computed tomography study.

BACKGROUND: The aim of the present study was to describe the effectiveness and feasibility of high-resolution computed tomography (HRCT) in patients in supine and prone positions to detect amiodarone-induced pulmonary toxicity (APT). With regard to the possible differential diagnosis, our second goal was to emphasize the clinical value of HRCT with the patients in supine and prone positions compared with other paraclinical tests. METHODS AND RESULTS: Thoracic HRCT taken in both positions for 23 patients who were administrated amiodarone were prospectively evaluated in the current study. High-resolution computed tomography scans obtained with the patient in a prone position were helpful in differentiating dependent opacity from lung disease in 11 out of 23 patients. In another 4 patients, HRCT scans obtained with the patient in a prone position were useful in confirming the presence of subtle ground-glass opacities, considered as APT. Combination of HRCT in supine and prone positions provided a more reproducible method for evaluating the global extent of APT than other paraclinical tests. CONCLUSIONS: High-resolution computed tomography used in prone positions as well as a supine position could be an effective technique for reducing false-positive results in detection of APT and preventing the clinically serious pulmonary adverse effects by amiodanone.     

Clinical aspects of amiodarone pulmonary toxicity

Amiodarone pulmonary toxicity is a major clinical problem limiting the utility of this powerful therapeutic agent. The clinical manifestations of amiodarone lung toxicity are protean, but the most common presentation is that of an indolent illness characterized by dyspnea and often associated with cough and/or fever. Diffuse radiographic abnormalities are common, but localized infiltrates can be seen as well. The typical physiologic changes are the development of diffusing impairment and a restrictive ventilatory defect. In the absence of a 15% decline in DLCO from the pretreatment value, significant amiodarone toxicity appears to be unlikely. The diagnosis is made by the careful exclusion of other causes for the observed illness and the finding of clinical, radiographic, physiologic, and pathologic abnormalities compatible with amiodarone toxicity. Although the pathologic findings of amiodarone lung can be distinctive, the histologic demonstration of foam cells and ultrastructural lamellar inclusions alone does not distinguish toxic from nontoxic patients receiving amiodarone. If reasonable alternative antiarrhythmic therapy is available, amiodarone should be withdrawn. If the severity of illness warrants, a trial of corticosteroid therapy is reasonable. Some patients can be maintained on continued therapy despite toxicity, if the drug is deemed to be absolutely essential and clinical deterioration does not continue. The prognosis of patients who develop amiodarone pulmonary toxicity seems to be poor, but may be largely determined by the underlying cardiac disease.     

Value of technetium-99m diethyltriamine pentaaceticacid radioaerosol inhalation lung scintigraphy for the stage of amiodarone-induced pulmonary toxicity

BACKGROUND: Amiodarone is a potent antiarrhythmic agent that is limited in clinical use by its adverse effects, including potentially life threatening amiodarone-induced pulmonary toxicity (AIPT). The alteration of technetium-99m diethyltriaminepentaaceticacid (Tc-99m DTPA) radioaerosol lung clearance in AIPT was experimentally investigated. METHODS: Eighteen white New Zealand rabbits (initial weight 4.1+/-0.2 kg) were divided into two groups. AIPT group (n=13) was administered amiodarone (20 mg/kg BW) ip as a 5% aqueous solution for 6 week. The controls (n=5) were administered the same amount of 0.9% saline ip. Four rabbits of AIPT group died due to AIPT. The reminders of AIPT group (n=9) and controls underwent Tc-99m DTPA radioaerosol lung scintigraphy at the end of the treatment period. AIPT group was divided into two subgroups according to histopathologic evaluation. AIPT-I had interstitial pneumonitis (n=4) and AIPT-II had interstitial pneumonitis with fibrosis (n=5). RESULTS: The mean T(1/2) values of in control, AIPT-I, and AIPT-II groups were found 54+/-4.4, 39.2+/-11.7 and 114.6+/-16.7 min, respectively. The mean T(1/2) values of Tc-99m DTPA significantly differ than other groups (X(2)=11.78, P=0.02). The significantly increased T(1/2) values was noted in AIPT-II group when compared with control (P=0.001). In contrast, AIPT-I group has significantly lower T(1/2) values than control group (P=0.03). CONCLUSION: We suggested that Tc-99m DTPA radioaerosol inhalation lung scintigraphy provides an accurate evaluation about stage of lung toxicity and therefore may be a useful tool for the monitoring of AIPT.     

成人肺朗格汉斯细胞组织细胞增多症五例临床分析

目的 探讨成人肺朗格汉斯细胞组织细胞增多症(PLCH)患者的临床、影像、肺功能和组织病理特点.方法 回顾性分析2006年6月至2007年10月北京朝阳医院收治的5例PLCH患者的临床资料.结果 5例均为男性吸烟者,以肺部损害为主,其中2例以自发性气胸为首发症状,1例为肺脏终末期病变合并肺动脉高压.胸部高分辨率CT示大小不一的多发囊腔阴影,病变以双上肺为著,终末期病例囊腔影遍及全肺.5例均经外科肺活检获得组织病理学资料,显示囊腔样改变和朗格汉斯细胞聚集(免疫组织化学CD1a和S-100染色阳性).肺功能检查示V50占预计值%为53.6%～77.6%,V25占预计值%为38.5%～70.5%,V50和V25的降低与组织病理学所见小气道受累相符合.治疗以戒烟为主,疾病有自然缓解倾向.结论 PLCH是朗格汉斯细胞组织细胞增多症的一种特殊类型,主要发生于吸烟者,多呈良性经过.     

肺血管炎的临床与影像学特点解析

肺部血管炎包括原发性与继发性两大类.继发性血管炎包括感染性疾病、结缔组织病、恶性肿瘤和过敏性疾病所致肺血管炎.原发性血管炎的分类通常根据受累血管的大小分为大血管炎、中血管炎和小血管炎.肺部血管受累常见于原发性大血管炎[大动脉炎(Takayasu arteritis),巨细胞动脉炎(giant cell arteritis,GCA),白塞病(Behcetdisease)]和原发性抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasmic antibody,ANCA)相关性小血管炎[肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA),显微镜下多血管炎(microscopic polyangiitis),嗜酸性肉芽肿性多血管炎(eosinophilic granulomatosis with polyangiitis,EGPA)].原发性肺血管炎的影像学表现极具多样性,包括血管壁增厚、结节影、空洞、磨玻璃影和实变影等.原发性肺部小血管炎常导致弥漫性肺泡出血(diffuse alveolar hemorrhage,DAH).相比于胸片,胸部CT更能够显示肺血管炎的病变特征和侵及范围.肺部血管炎的诊断极具挑战性,需要通过患者的临床特征、影像学特点、实验室检查结果和组织病理学特征作出综合判断.     

肺黏膜相关淋巴组织淋巴瘤临床特征分析

目的：提高肺黏膜相关淋巴组织淋巴瘤诊治水平。方法回顾性分析江西省人民医院及南昌大学第二附属医院自2005年1月至2015年1月确诊的8例肺黏膜相关淋巴组织淋巴瘤的临床表现、影像学特点、诊断手段、误诊情况、治疗及预后。结果8例肺黏膜相关淋巴组织淋巴瘤中男6例,女2例,年龄38~75岁,中位年龄65岁。主要症状：咳嗽(5例)、咳痰(4例)、发热(2例)、胸闷(4例)、乏力(3例)、消瘦(3例),无症状2例。胸部 CT 表现：双肺分布5例,单肺分布3例,实变影5例,肿块及结节影4例,斑片状浸润影3例,支气管充气征5例,钙化1例,空洞2例。确诊方法：经气管镜活检1例,CT 引导下经皮肺穿刺5例,外科手术2例。误诊分析：5例误诊为细菌性肺炎,1例误诊为肺真菌病,1例误诊为肺癌,1例误诊为肺转移癌。治疗及预后：2例外科手术患者术后未行放化疗,4例转入血液内科行化疗(CHOP 方案),2例放弃治疗。8例患者随访时间2~105个月,2例死亡,6例存活。结论肺黏膜相关淋巴组织淋巴瘤临床表现不典型,容易误诊,诊断需要组织病理活检。     

胺碘酮致老年患者甲状腺功能异常临床病例分析

目的长期服用胺碘酮引起甲状腺功能异常增高,且在不同地区胺碘酮引起甲状腺功能异常的类型差异很大。本文观察广东地区老年心律失常患者长期口服胺碘酮导致甲状腺功能异常的临床特征及转归。方法263例口服胺碘酮老年患者,其中男性184例,女性79例,年龄60~87平均(74.6±11.3)岁。在服药前均经放射免疫法测定血液甲状腺功能,排除了甲状腺功能异常。在服药中和停药后半年多次测定甲状腺功能,并同时测定自身免疫学指标TGA、MCA、TG。结果随访过程中出现甲状腺功能异常的老年患者62例,其中男性45例,女性17例。本组患者中,服用胺碘酮后甲状腺功能异常出现时间最短为3周,最长为2.5年。11例服药后出现甲状腺功能亢进,51例出现甲状腺功能减退,82%的患者在停药3个月后T3、T4、FT3、FT4恢复正常,而只有23%的患者TSH恢复。所有患者服药前、服药中和停药后自身免疫学指标甲状腺球蛋白(TGA)、甲状腺球蛋白抗体(MCA)、甲状腺微粒体抗体(TG)均未发现明显改变。结论在广东地区,胺碘酮引起甲状腺功能异常以甲状腺功能减退为主,临床病程个体差异较大;自身免疫在胺碘酮所致的甲状腺功能异常中不起主要作用;胺碘酮引起的甲状腺功能异常在停药后均可恢复,无需长期治疗。     

Clinical and imaging features of pulmonary veno-occlusive disease and pulmonary capillary hemangioma

正Objective To improve the diagnosis and treatment of the pulmonary veno-occlusive disease(PVOD)and pulmonary eapillary hemangioma(PCH).Methods The clinical features,radiological findings,laboratory testing and treatment in 8 cases of PVOD/PCH which was diagnosed from 2013 to 2017 were described.Results     

哮喘-COPD重叠综合征的临床特征

目的 探讨哮喘-COPD重叠综合征(asthma-COPD overlap syndrome,ACOS)的临床特征.方法 根据2014年全球哮喘防治创议(the Global Initiative for Asthma,GINA)标准,回顾性分析2014年1月至2016年4月中国医科大学附属盛京医院呼吸科病房及门诊受试者中支气管哮喘(简称哮喘)患者566例.在入选的哮喘患者中,选取年龄≥40岁,符合纳入标准的ACOS患者65例,单纯哮喘组75例.入院开始1周内收集如下资料:一般临床特征、血清嗜酸粒细胞计数、血清总IgE、肺功能.结果 ACOS组平均年龄(58.80±9.00)岁,单纯哮喘组平均年龄(55.10±9.40)岁,ACOS组年龄高于单纯哮喘组(t=2.46,P＜0.05);ACOS组患者吸烟的比例高于哮喘组(55.4％ vs29.3％,x2=9.74,P＜0.01);ACOS组患者血清总IgE较高[(481.60±784.80) U/ml vs(153.90±139.10) U/ml,t=3.05,P＜0.01];ACOS组患者有较低的FEV1(t=6.65,P＜0.01),差异有统计学意义.结论 本研究发现ACOS组患者年龄较大,大部分患者有长期吸烟史,血清总IgE明显升高.ACOS组患者FEV1明显降低,造成2组差异的主要因素是年龄、吸烟和气道重塑.     

老年性特发性肺纤维化的临床特征

目的总结老年性特发性肺纤维化的临床特征。方法对47例老年患者的诊断资料、病史及体征、肺功能、胸部高分辨率CT（HRCT）、血气分析以及其它指标进行分析。结果有外科肺活检资料的8例;男性患者35例;平均诊断年龄69.23±6.76岁,诊断时中位病程14月;诊断以前,被误诊、漏诊共29例;有合并症30人/次;主要临床表现为干咳、进行性呼吸困难,肺部听诊闻及爆裂音,肺功能限制性通气功能障碍及弥散降低为主,HRCT以两肺网状影、蜂窝肺,牵拉性支气管和细支气管扩张为主,血气分析显示一定程度的低氧血症,部分可有肺动脉高压等表现。结论老年性特发性肺纤维化以男性居多,临床误诊漏诊较多,临床表现具有自己的特征,其诊断多以无外科肺活检资料标准来确定。