60-Year-Old Man with Non-resolving Pneumonia
Submitted by
Nicholas C. James, MD, Timothy N. Liesching, MD
Department of Pulmonary and Critical Care Medicine
Lahey Hospital & Medical Center
Burlington, Massachusetts
from https://www.thoracic.org/professionals/clinical-resources/clinical-cases/01-15.php
History 病史
A 60 year-old man with a past medical history for coronary artery disease requiring four vessel coronary artery bypass grafting, hypertension, hyperlipidemia, nephrolithiasis and cirrhosis related to alcohol abuse was deemed a liver transplant candidate after complications of several episodes of hepatic encephalopathy and esophageal variceal bleeding. He remained abstinent from alcohol.
一名60岁男性患者曾因冠心病接受冠脉搭桥手术(4根血管),此外,既往史包括高血压,高脂血症,肾结石及酒精性肝硬化。患者还曾数次发生肝性脑病及食道静脉曲张出血,因而等待肝移植。
He underwent a living donor liver transplant using the right hepatic lobe graft donated by his son. His immunosuppression regimen included sirolimus, mycophenolate, and prednisone. Valgancyclovir and trimethoprim/sulfamethoxazole included his prophylactic therapy. There were no peri-operative complications noted. Post-operatively, the patient noted mild dyspnea and a non-productive cough. His postoperative course was complicated by cholangitis secondary to biliary stricture necessitating percutaneous trans-hepatic cholangiography (PTC) and biliary dilation. Work up for his cholangitis included an abdominal CT that incidentally demonstrated a dense pulmonary infiltrate of the right middle lobe (RML) (Figure 1). He also developed acute renal insufficiency, but did not require renal replacement therapy. It was determined by the surgical team that the patient had pneumonia and was treated amoxicillin/clavulanate. His respiratory symptoms resolved and followed up in clinic.
患者接受了活体肝移植(儿子捐献的肝脏右叶)。免疫抑制剂包括西罗莫司,麦考酚酯和强的松。同时预防性使用缬更昔洛韦和复方新诺明。术后,患者出现轻度呼吸困难及干咳。术后患者因胆道狭窄继发胆管炎行经皮经肝胆管造影(PTC)及胆管扩张。有关胆管炎的诊断检查包括腹部CT,CT检查意外发现右中叶(RML)致密性浸润影(图1)。患者还发生急性肾脏功能不全,但无需接受肾脏替代治疗。外科医生认为患者发生肺炎,并使用阿莫西林/克拉维酸治疗。患者呼吸道症状缓解,随后在门诊随访。
As an outpatient, the patient required one additional biliary dilation procedure for biliary stricture. A follow up chest CT (Figure 2) 7 weeks after initial imaging demonstrated a persistent RML infiltrate. The patient was completely without respiratory complaint at the time. A pulmonary consultation is requested.
门诊随访期间,患者因胆道狭窄再次进行胆道扩张。7周后复查胸部CT(图2)显示RML浸润影持续存在。此时患者没有任何呼吸道主诉,遂请呼吸科医生会诊。
Physical Exam 体格检查
Physical examination revealed the patient to be afebrile with an oxygen saturation of 99% on room air. The remaining vitals were also unremarkable. The patient was not in acute distress and could talk in complete sentences. Auscultation of the lungs was clear throughout and cardiac examination revealed a 3/6 systolic murmur. The extremities were void of edema and there was no clubbing.
体格检查显示患者不发热,吸入空气时氧饱和度99%。其余生命体征无明显异常。患者没有急性呼吸窘迫的症状,且能够说出完整的话。肺部听诊呼吸音清晰,心脏检查发现有3/6级收缩期杂音。四肢没有水肿,没有杵状指。
Figure 1: CT chest showing right middle lobe dense consolidation with associated ground glass opacities
图1:胸部CT显示右中叶致密实变影伴磨玻璃影
Figure 2: Persistent, more consolidated right middle lobe infiltrate with increased ground glass opacities
图2:右中叶浸润影持续存在且实变更明显,磨玻璃影加重
Question 1 问题1
What would be the next best diagnostic approach for this patient’s non-resolving opacity?
对于肺部病变,下一步应选择以下哪种诊断措施?
正确答案1
Flexible bronchoscopy with bronchoalveolar lavage (BAL) and trans-bronchial biopsies
纤支镜下行肺泡支气管灌洗(BAL)及经支气管活检
Identification of potentially treatable pulmonary complications is important in patients who are immunosuppressed. The differential diagnosis of non-resolving pulmonary infiltrates includes both infectious and non-infectious etiologies. Recent advances in urine antigen testing, induced sputum analysis, and other rapid non-invasive studies have aided in the diagnosis of pulmonary infiltrates in immunosuppressed patients1.
In patients who are not severely ill with pulmonary infiltrates, an empiric course of antibiotics can be considered. Persistent pulmonary infiltrates commonly represent bacterial or opportunistic infections, such as fungal pneumonia or Pneumocystis jerovecii pneumonia. Common bacterial pathogens include methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aureuginosa. Legionella pneumonia remains a challenging infection in solid organ transplant recipients as major outbreaks can be seen with water or inhaled aerosol contamination2. Viral infections are also common post-transplant, and are well described by the length of time since transplant. Cytomegalovirus (CMV), Herpes simplex viruses (HSV) and Ebstein-Barr virus (EBV) are among the most commonly encountered. Immunusuppressive medications have led to reactivation of Mycobacterium tuberculosis following solid organ transplantation.
Malignancy may also represent non-resolving pulmonary infiltrates. Post-transplant lymphoproliferative disorder (PTLD) is an example of a lymphoproliferative disorder related to immunosuppression following solid organ transplantation as well as hematopoetic stem cell transplantation. The pathophysiology is related to B-cell proliferation induced by Ebstein-Barr virus. Clinically, patients present with constitutional symptoms such as fever, malaise and weight loss. More than half of patients with this disorder develop extra-nodal masses in the GI tract, lungs, skin, or central nervous system. Diagnosis is made by high clinical suspicion followed by biopsy. Full excisional biopsy is preferred; however, needle biopsy is an acceptable alternative in certain situations. Treatment of PTLD necessitates a reduction in immunosuppressive medications transplant recipients receive2,3. Typically chemotherapy is given for the treatment of PTLD as well. Chemotherapy regimens are similar to treating non-Hodgkin’s lymphoma with CHOP and rituximab, a monoclonal antibody to CD20 expressed on mature and immature B lymphocytes. Alternative non-infectious etiologies include atelectasis from airway obstruction, cryptogenic organizing pneumonia, or pulmonary vasculitides, such as granulomatosis with polyangiitis.
Bronchoscopy with alveolar lavage remains an essential component of the diagnostic algorithm. A 1990 study evaluated a diagnostic team to rapidly diagnose pulmonary infections in solid organ transplant recipients. Fiberoptic bronchoscopy was performed on patients with clinical and radiographic evidence of pneumonia that could not readily expectorate an adequate sputum sample. Bronchoscopy with lavage and brushing was done within 24-hours if deemed necessary. A diagnosis was made in 92% of patients, the overwhelming majority related to infectious processes3. In immunocompromised hosts, non-invasive and bronchoscopic procedures early in the course of pulmonary infiltrates related to infectious etiologies had significantly lower mortality if therapy was tailored within seven days4.
While all of the listed diagnostic procedures are feasible, bronchoscopy is a semi-invasive, well-tolerated procedure with acceptable risks. Bronchoscopy allows for bronchoalveolar lavage, protected brush sampling, endobronchial biopsy and transbronchial biopsy, depending on the specific patient characteristics. Infection in transplant recipients is common. Recognition is often difficult with advances in immunosuppression to prevent allograft rejection.
A sputum culture may not provide the diagnostic yield in this patient and therefore, choice A is incorrect. A VATS biopsy (choice B) will most likely make a diagnosis; however, this would not be optimal next step in this patient. VATS procedures are more invasive and inherently have higher complication rates than flexible bronchoscopy.
In this patient, bronchoscopy with BAL, brushing, and trans-bronchial lung biopsy were performed. Cultures including bacterial, viral, and fungal were negative. Legionella, nocardia, AFB and pneumocystis were negative as well. Cytology examination of the BAL and bronchial brush samples revealed no evidence of malignancy. Transbronchial biopsies were taken and these also did not show malignant cells. Pathologic examination of the transbronchial biopsies revealed normal alveolar structures with crush artifact, mildly atypical cells, and submucosal calcifications. Specimens stained for AFB and fungus were negative as well.
此例患者在纤支镜下进行BAL,毛刷和经支气管肺活检。细菌、病毒和真菌培养均阴性。有关军团菌、奴卡菌、抗酸杆菌和肺孢子虫的检查也为阴性。BAL及支气管毛刷标本的细胞学检查未发现恶性肿瘤迹象。经支气管活检也未发现恶性肿瘤细胞,病理检查显示正常肺泡结构,轻度非典型细胞,粘膜下钙化。活检标本抗酸杆菌及真菌染色阴性。

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