非特异性间质性肺炎患者的高分辨率CT表现及其病理学特点

目的探讨非特异性间质性肺炎（NSIP）的高分辨率CT（HRCT）影像学特点及其病理学改变。方法对9例经开胸肺活组织检查（简称肺活检）证实为NSIP患者的HRCT与病理表现进行回顾性分析。结果9例NSIP患者HRCT主要表现为两侧斑片状磨玻璃影、实变影、伴或不伴不规则线影和牵拉性支气管和细支气管扩张，分布在中、下肺的外周，但未见蜂窝影。HRCT表现为磨玻璃影伴或不伴不规则线影和牵拉性支气管和细支气管扩张的区域，其相应的病理改变为不同程度的炎性细胞浸润和纤维化引起的肺间质增厚，病变时相基本一致；在HRCT表现为实变影的区域，其病理改变表现为间质纤维化病变程度重于间质炎症；也可表现为闭塞性细支气管炎伴机化性肺炎样改变，肺泡腔内泡沫状细胞聚集，镜下可见蜂窝肺内有黏液潴留等病理改变。结论NSIP患者的HRCT表现有一定的特征性；根据病理特点并结合临床资料及HRCT表现可初步诊断为NSIP。     

硬金属致巨细胞间质性肺炎一例并文献复习

目的 提高对硬金属粉尘致巨细胞间质性肺炎的临床、胸部影像学和病理表现的认识.方法 对1例经胸腔镜肺活检证实的巨细胞间质性肺炎患者的硬金属粉尘职业史、临床、胸部x线、CT、病理资料并结合有关文献进行回顾性分析.结果 患者女,30岁,钨棒磨削工,接触含钴和钨等硬金属粉尘3年,咳嗽和活动后喘息40 d.肺功能检查示混合性通气功能障碍,弥散功能明显下降(D<,L>CO占预计值%为39%),X线胸片和高分辨率CT示两肺弥漫性分布的磨玻璃影和边界不清的小结节影.肺活检病理表现为巨细胞间质性肺炎,肺泡腔内可见巨噬细胞和大量的多核巨细胞聚集,位于肺泡腔内的多核巨细胞内可见被吞噬的炎症细胞;细支气管及周围肺泡腔可见慢性炎症细胞浸润和肺间质纤维化.结合患者的职业史及特征性病理改变,诊断为硬金属致巨细胞间质性肺炎和硬金属肺疾病.患者脱离接触金属粉尘工作后,经糖皮质激素治疗临床症状缓解,胸部异常阴影明显吸收.结论 巨细胞间质性肺炎是硬金属肺疾病的特征性病理改变.在间质性肺疾病的诊断和鉴别诊断中需重视患者的职业暴露史.     

巨细胞间质性肺炎一例及文献复习

目的提高对巨细胞间质性肺炎（GIP）的临床、胸部影像学和病理改变的认识。方法对1例经开胸肺活检证实的GIP患者的职业史、临床表现、胸部X线、CT和病理资料并结合有关文献进行回顾性分析。结果GIP主要的临床表现有咳嗽和活动后呼吸困难；肺功能检查表现为限制性通气功能障碍；胸部X线和HRCT表现为两肺磨玻璃样影、实变影、弥漫性的小结节影、网状影和牵拉性支气管扩张。GIP主要病理表现有脱屑性间质性肺炎样反应，即在肺泡腔内有巨噬细胞和大量的多核巨细胞聚集，位于肺泡腔内的多核巨细胞内可见被吞噬的炎性细胞，是GIP的特点。GIP是硬金属尘肺的特征性病理改变。结论GIP是非常罕见的慢性间质性肺炎，无特异性的临床表现，影像学表现类似于特发性间质性肺炎。在GIP诊断中，仔细收集患者的职业史非常重要。     

急性纤维蛋白性机化性肺炎的临床病理特征

目的介绍一种新近定义的弥漫性急性肺损伤类型-急性纤维蛋白性机化性肺炎,以提高临床医生对其的认识方法分析南京市鼓楼医院确诊的1例患者以及国外有关文献的报道,总结其临床特征。结果急性纤维蛋白性机化性肺炎患者表现为急性或亚急性起病,主要临床表现为呼吸困难、咳嗽、咳痰,肺功能为限制性通气功能障碍和弥散降低,CT可见两肺斑片状实变影,主要病理表现为肺泡腔内可以看到特征性纤维蛋白球以及机化的疏松结缔组织,而没有DAD中的经典透明膜形成。结论急性纤维蛋白性机化性肺炎的病理组织学特点决定了它是一种不同于弥漫性肺泡损伤、机化性肺炎和嗜酸细胞性肺炎的新的肺损伤类型,但其是否为一个独特的疾病综合征有待进一步明确。     

隐源性机化性肺炎18例的临床病理特征

目的回顾分析经病理确诊的隐源性机化性肺炎临床、病理和影像学特征,以提高临床诊断水平。方法1993年4月至2005年10月在北京协和医院住院、经病理确诊的机化性肺炎23例,对其进行临床、影像学和病理学综合分析。结果23例机化性肺炎中5例为药物引起或合并结缔组织病,18例为隐源性机化性肺炎(cryptogen ic organ izing pneumon itis,COP)。其中10例经皮肺活检或经支气管肺活检,8例开胸肺活检或经胸腔镜肺活检,男8例,女10例,年龄(53.5±11.0)岁。气短、咳嗽及肺部爆裂音及湿性啰音是主要的症状和体征。肺功能显示限制性通气功能障碍(11例)及弥散障碍(18例)。胸部CT表现为磨玻璃样变(4例),肺实变(13例)伴支气管充气征(3例),胸腔积液(4例)。支气管肺泡灌洗液中淋巴细胞占细胞总数的0.40±0.16,中性粒细胞为0.15±0.08,嗜酸粒细胞为0.05±0.03;CD4/CD8为0.43±0.21。所有患者均给予糖皮质激素治疗。16例患者经随诊(8.67±6.21)个月仍存活,临床缓解或病情稳定。1例患者对糖皮质激素反应差,死于进行性加重的呼吸衰竭。另1例患者糖皮质激素治疗后出现肺部感染,死于感染性休克。结论临床表现及影像学特征对COP的诊断有一定的提示作用,但确诊需依靠病理检查。经皮肺活检或经支气管镜肺活检结合支气管肺泡灌洗液检查,对临床诊断隐源性机化性肺炎有较高的价值。     

淋巴细胞间质性肺炎临床病理分析1例并文献复习

目的了解淋巴细胞性间质性肺炎的临床及病理表现。方法1例淋巴细胞性间质性肺炎行开胸肺活检,标本送检病理及免疫组化。结果本病的病理表现主要为受累部位弥漫性间质浸润,显著地肺泡间隔分布,浸润成分大多为T淋巴细胞、浆细胞和巨噬细胞,与支气管黏膜相关的淋巴组织增生常见。结论本病少见,确诊有赖于胸腔镜或开胸肺活检。治疗为类固醇激素,或免疫抑制剂,治疗反应不一。     

隐源性机化性肺炎16例临床分析

目的 分析隐源性机化性肺炎16例患者的临床、影像和病理特征.方法 在我院确诊的16例患者,对其病例资料进行分析.结果 气短、咳嗽、肺部爆裂音及湿啰音为主要临床表现;肺功能检查主要为限制性通气障碍;胸部CT示肺实变为主伴间质性改变.支气管肺泡灌洗液细胞混合性增高,CD+4/CD+8降低.所有患者经肺活检证实为机化性肺炎.15例患者7.9±5.8个月仍存活、临床缓解或病情稳定;1例死于呼吸衰竭.结论 临床表现及影像学特点对隐源性机化性肺炎的诊断有提示作用,但确诊仍依靠病理活检.     

隐源性机化性肺炎的临床病理特征和影像学表现

目的探讨隐源性机化性肺炎(COP)的临床病理特征和影像学表现。方法分析5例隐源性机化性肺炎病例的临床特点、影像学表现、肺活检的病理特征,并复习相关文献。结果 COP常见的临床表现为咳嗽、进行性呼吸困难和吸气末肺部爆裂音。肺活检病理检查显示肺泡管、肺泡腔内见肉芽组织栓。胸部CT表现为含支气管充气征的实变阴影,伴或不伴磨玻璃影。患者对糖皮质激素治疗有显著疗效。结论临床表现结合影像学特点可提示COP临床诊断,肺活检是诊断COP有效的检查方法。     

胺碘酮性肺炎合并超鞭毛虫肺部感染一例及文献复习

目的提高对胺碘酮性肺炎、超鞭毛虫肺部感染及两病合并临床特点的认识。方法结合1例胺碘酮性肺炎合并超鞭毛虫肺部感染患者的临床资料及文献复习，对本病的临床表现、实验室检查、影像学、诊断和治疗进行分析。结果该患者在胺碘酮性肺炎基础上合并超鞭毛虫感染，临床症状为活动后胸闷、气急；实验室检查主要为肺弥散能力下降，支气管肺泡灌洗液中查到泡沫样巨噬细胞和超鞭毛虫；影像表现既有间质性改变又有肺泡渗出；因难以取得病理，诊断主要依赖临床；通过停用胺碘酮及应用抗原虫药物治疗超鞭毛虫感染，患者的临床症状明显缓解。结论胺碘酮性肺炎合并超鞭毛虫肺部感染非常罕见，其原因可能为胺碘酮性肺炎患者局部免疫功能下降，易并发肺部感染。     

淋巴细胞间质性肺炎7例临床、CT影像学及病理特征分析

［摘要］　目的　分析淋巴细胞间质性肺炎（LIP）的临床、CT影像学及病理特征。方法　回顾性分析7例经病理确诊的LIP患者的临床、影像资料,所有病例均进行胸部薄层CT检查。结果　7例LIP患者均为女性,4例表现为弥漫分布的斑片状磨玻璃影,其中3例伴有网格状影、小结节影;3例表现为局灶分布的斑片状磨玻璃影,其中1例局部夹杂小结节影。5例有多发薄壁含气肺囊肿,4例伴有纵隔淋巴结肿大。病理活检组织HE染色主要表现为肺间质内弥漫性淋巴细胞浸润,免疫组织化学染色主要提示CD3细胞和多克隆CD20细胞的增加。结论　LIP为罕见病,好发生于女性干燥综合征患者,当肺部高分辨率CT呈斑片状磨玻璃影并多发薄壁含气肺囊肿改变,病理表现为肺间质弥漫性淋巴细胞浸润时,高度提示LIP。     

Pathologic characteristics of drug-induced lung disease

The surgical pathologist's role in the diagnosis of adverse pulmonary and pleural drug effect requires an appreciation of the clinico-radiologic scenario and particular knowledge of morphologic patterns of lung injury. Bronchoscopic biopsies may be helpful in some cases of DAD, eosinophilic pneumonia, or OP. Extrapolating patterns of lung involvement from small biopsies and cytologic preparations often is difficult and surgical lung biopsy is required. Although lung biopsies are not pathognomonic for drug toxicity and correlation with clinical, laboratory, and radiologic data is required, they can be a powerful tool in the evaluation of suspected drug-induced pulmonary disease by helping to exclude underlying disease or infection and documenting the pattern of lung injury. The latter information is helpful in making the diagnosis of drug toxicity as well as guiding the optimal management of the patient.     

Pulmonary infiltrates associated with noncytotoxic drugs

A wide variety of noncytotoxic drugs, including antibiotics, analgesics, narcotics, and psychotrophic and cardiovascular agents, may cause lung injury accompanied by roentgenographic infiltrates. The clinical manifestations of drug-induced lung disease are protean. Patients may present with acute injury resembling the adult respiratory distress syndrome, which must initially be distinguished from bacterial sepsis. Other drug-associated lung injury is characterized by a more subacute pneumonitis similar to an atypical infectious pneumonia. Finally, some drugs may cause insidiously progressive pulmonary infiltrates that share features with granulomatous infections. The more common drug reactions are discussed in this review, and, although the features of drug-induced lung disease are often relatively nonspecific, those features that either mimic infectious causes or may be helpful in differentiating these processes from infections are given particular emphasis.     

Cytotoxic drug-induced lung injury

Cytotoxic drug-induced pulmonary disease is a major cause of morbidity and mortality in immunocompromised patients. It is estimated that 20% of all patients receiving cytotoxic drugs will develop a symptomatic pulmonary reaction. Therefore, the possibility of a toxic drug reaction must be considered in all patients developing pulmonary disease during or following treatment with these agents. Clinical manifestations of lung toxicity are nonspecific and parallel the signs and symptoms of diffuse lung infection and malignant disease in the chest. For this reason, the diagnosis of cytotoxic drug-induced lung damage is one of exclusion of the various opportunistic infections that afflict this patient population. This typically requires careful microbiologic studies of bronchoalveolar lavage (BAL) samples and lung tissue. The diagnosis of cytotoxic drug-induced lung injury is often vexing. In the future, (BAL) may assume a more prominent diagnostic role and suggest insights into the pathogenesis of this entity.     

Mechanisms of amiodarone pulmonary toxicity

Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that patients may clinically present with an acute illness suggestive of a hypersensitivity picture or with a more chronic indolent course mimicking a malignant process. Likewise, the mechanism of amiodarone pulmonary toxicity suggests that at least two different pathways of toxicity exist: (1) an indirect mechanism characterized by influx of inflammatory or immune effector cells to the lung and (2) a direct toxic mechanism that results in lung parenchymal cell injury and a subsequent fibrotic response. Clearly, there is the potential for much crossover and interaction between the proposed pathways of toxicity in any given patient. A better understanding of the mechanism of amiodarone pulmonary toxicity will not only improve our diagnostic approaches to patients with this serious lung disorder, but will also provide the opportunity to develop unique therapeutic strategies that control the toxicity and potentially not interfere with the intended therapeutic efficacy of the drug.     

Significant pulmonary toxicity associated with interferon and ribavirin therapy for hepatitis C

OBJECTIVE: The aim of this study was to analyze the clinical presentation and outcomes of significant pulmonary toxicity associated with interferon and ribavirin. METHODS: We conducted a retrospective review of patients enrolled in four clinical trials at three sites, two academic medical centers and one community practice, and reviewed the literature. RESULTS: Four patients, while on therapy with interferon a and ribavirin for chronic hepatitis C, developed significant pulmonary signs and symptoms. Further workup, which included lung biopsy in three, revealed bronchiolitis obliterans organizing pneumonia in two, and interstitial pneumonitis in two other cases. There were no other predisposing factors for lung disease identified. Resolution of symptoms occurred in all patients upon discontinuation of interferon and ribavirin, with or without corticosteroid therapy. One of the patients developed pulmonary complications while on a clinical trial of pegylated interferon and represents the first reported case associated with the use of long-acting interferon in chronic hepatitis C infection. CONCLUSIONS: A spectrum of significant pulmonary toxicity, including bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis, can occur with interferon or pegylated interferon in combination with ribavirin. Though pulmonary toxicity of interferon is well known, these cases represent the first cases reported in the literature with combination therapy. It is likely that pulmonary toxicity may not be investigated in patients on combination therapy because of the frequent pulmonary symptoms with ribavirin. Though usually reversible, at least one case has required long-term steroids with inadequate resolution. Though pulmonary toxicity is rare, symptoms which are more than mild or progressive in nature should likely be investigated.     

Drug-induced interstitial lung diseases

Any discussion of drug-induced interstitial lung disease is fraught with the problem of having a syndrome in which information is composed predominantly of case reports. When the information is taken as a whole, however, the picture becomes clearer: (1) Some drugs can produce significant pulmonary toxicity; (2) the clinical history, physical examination, and chest roentgenogram are not unique or specific for drug-induced interstitial lung disease; and (3) the lung reacts in limited ways to various insults, producing pathologic changes that are not unique for drug-induced interstitial lung disease. The work of Crystal et al. has shed new light on interstitial lung disease. Their concept that the alveolitis is the key initiating step in interstitial lung disease fits with the pathologic findings in many situations of drug-induced interstitial lung disease. Furthermore, as they proposed, if the primary alveolitis has not progressed to derangement of alveolar structures, then the process can be reversed. This may explain the variable response seen with drug withdrawal and the use of corticosteroids. These concepts have not been extensively studied in drug-induced interstitial lung disease and this needs to be done to fully evaluate their ideas. A keen awareness of the potential for any drug to cause drug-induced interstitial lung disease can be of immense benefit to the patient, for early discontinuation of the agent is likely to increase the chance of reversing the pulmonary toxicity.     

Bronchiolitis obliterans organizing pneumonia

Bronchiolitis obliterans with organizing pneumonia (BOOP) is a pathological syndrome common to a variety of pulmonary inflammatory disorders. It is defined by the presence of buds of granulation tissue consisting of fibroblasts and collagen within the lumen of the distal airspaces. BOOP may be secondary to lung injury resulting especially from infection or drug toxicity or may develop in the context of connective tissue diseases or after lung or bone marrow transplantation. BOOP may also be idiopathic (and then preferentially called cryptogenic organizing pneumonia) and then is the hallmark of a distinct clinicoradiological syndrome of subacute pneumonia, with typical alveolar patchy and often migratory pulmonary opacities on imaging. Other imaging presentations consist of diffuse infiltrative opacities or focal pneumonia. Improvement with corticosteroids is usually spectacular, but relapses are common after stopping or while reducing treatment.     

A clinical study of twelve cases of drug-induced pneumonitis

Twelve cases of drug-induced pneumonitis were clinically investigated. Treatment of antimicrobial agents in 8 cases of drug-induced pneumonitis ranged from 7-21 days (mean 12 days) and that of other drugs in 4 cases from 18-150 days (mean 70 days). The patients developed fever and dyspnea at a high rate of frequency. Abnormal laboratory findings included increased IgE (44%), eosinophilia (36%), and increased GOT and GPT in 33%. Chest X-ray films revealed a large reticulo-nodular or ground glass shadows in both lung fields. The results of lymphocyte stimulation tests were positive in 5 of 11 cases (45%). Eight cases demonstrated a rapid improvement by discontinuation of the drug and corticosteroid was administered in 4 cases. The drug received by the patient and their known risk of pulmonary toxicity should be kept in mind in order to reach a diagnosis of drug-induced pneumonitis and grasp the clinical picture of this disease. A provocation test is potentially dangerous, therefore it should not be carried out lightly.     

Sulphasalazine and lung toxicity.

Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here. All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms "sulphasalazine" and "sulfasalazine" were combined with the terms "lung", "pulmonary disease", "pneumonitis" and "pleuritis" using Medline and PubMed databases. Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.     

Deterioration of oxygenation and abnormal lung microvascular permeability during resolution of leukopenia in patients with diffuse lung injury

To determine whether circulating leukocytes contribute to gas exchange abnormalities in diffuse lung injury, we retrospectively examined oxygenation in 6 patients who met 3 criteria: leukopenia caused by marrow aplasia from remission-inducing chemotherapy for myelogenous leukemia, the eventual resolution of leukopenia, and concurrent acute respiratory failure diagnosed clinically as increased permeability pulmonary edema. Four of the 6 patients abruptly developed overt clinical evidence of pulmonary dysfunction within the 96 h preceding the resolution of the peripheral leukopenia. In all 6 patients, the alveolar to arterial oxygen tension difference increased between leukocyte counts. The mean value for the alveolar to arterial oxygen tension difference for the group doubled during this period (148 +/- 37 mmHg 3 days prior to resolution; 290 +/- 37 mmHg 1 day after resolution; p less than 0.05). As an index of lung capillary permeability, we measured the lung permeability-surface area product for urea (PSu) for an additional patient with oxygen toxicity and drug-induced leukopenia whose hypoxemia increased immediately before the resolution of leukopenia. The PSu in this patient was high, in the range previously reported as being highly specific for increased permeability pulmonary edema with a fatal outcome. We conclude that such diffuse lung injury resembling the adult respiratory distress syndrome can occur in leukopenic patients, but the resolution of leukopenia in such patients may be associated with worsening oxygenation and with abnormally high pulmonary microvascular permeability. These observations do not prove a causal relationship but provide a clinical parallel to several leukocyte-depletion studies reported in animal models of increased permeability pulmonary edema that implicate white blood cells in the pathogenesis of hypoxemia and lung edema.