Clinical Significance of Mycobacterium kansasii Isolates from Respiratory Specimens

The clinical significance of Mycobacterium kansasii respiratory isolates is uncertain. The aims of this study were to determine the clinical relevance of M. kansasii isolates and to identify the clinical features and outcomes of M. kansasii lung disease. We reviewed the medical records of 104 patients from whom at least one respiratory M. kansasii isolate was obtained from January 2003 to July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%) met the diagnostic criteria for nontuberculous mycobacterial lung disease; among them, 41 (76%) patients received antibiotic treatment for a median time of 15.0 months (interquartile range [IQR], 7.0–18.0 months). The remaining 13 (24%) without overt disease progression were observed for a median period of 24.0 months (IQR, 5.0–34.5 months). Patients with M. kansasii lung disease exhibited various radiographic findings of lung disease, including the fibrocavitary form (n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in patients who received treatment (n = 23, 56%), while the nodular bronchiectatic form was more common in patients with M. kansasii lung disease who did not receive treatment (n = 9, 70%). None of the patients with a single sputum isolate (n = 18) developed M. kansasii disease over a median follow-up period of 12.0 months (IQR, 4.0–26.5 months). In total, 52% of all patients with M. kansasii respiratory isolates exhibited clinically significant disease. Moreover, patients with M. kansasii lung disease displayed diverse radiographic findings in addition to the fibrocavitary form. The nodular bronchiectatic form was more common in patients with M. kansasii lung disease with an indolent clinical course. Thus, since the clinical significance of a single M. kansasii respiratory isolate is not definite, strict adherence to recommended diagnostic criteria is advised.     

A pulmonary paragonimiasis case mimicking metastatic pulmonary tumor

Pulmonary paragonimiasis is a relatively rare cause of lung disease revealing a wide variety of radiologic findings, such as air-space consolidation, nodules, and cysts. We describe here a case of pulmonary paragonimiasis in a 27-year-old woman who presented with a 2-month history of cough and sputum. Based on chest computed tomography (CT) scans and fluorodeoxyglucose positron emission tomography (FDG-PET) findings, the patient was suspected to have a metastatic lung tumor. However, she was diagnosed as having Paragonimus westermani infection by an immunoserological examination using ELISA. Follow-up chest X-ray and CT scans after chemotherapy with praziquantel showed an obvious improvement. There have been several reported cases of pulmonary paragonimiasis mimicking lung tumors on FDG-PET. However, all of them were suspected as primary lung tumors. To our knowledge, this patient represents the first case of paragonimiasis mimicking metastatic lung disease on FDG-PET CT imaging.     

Conservation of tissue and function in pulmonary resection the technique of the anatomical separation of segments

Total ablation of an entire limb to remove a small benign granuloma or tumor is unthinkable. Yet when an entire pulmonary lobe is removed for a similar lesion the sacrifice of normal tissue and function is taken for granted. Operations upon the lung commenced with pneumonectomy, were made more selective by lobectomy, and now can be confined to resection of single pulmonary segments when the diseased area is no more extensive, or to single segments in several lobes if necessary. Technically the pulmonary segment is the unit of pulmonary resection. The separation of one from another, or even a half of one from the other half, can be accomplished with anatomical accuracy. More widespread use of this operation will provide surgical aid to many bronchiectatic patients who otherwise are afflicted with disease too widespread for cure. It will conserve healthy lung tissue in benign conditions where removal of the diseased area is necessary. The technical steps of pulmonary segmental resection are outlined and illustrated.     

Role of polymorphic variants of cytochrome P450 genes (CYP1A1, CYP2E1) and microsomal epoxide hydrolase (mEPHX) in pathogenesis of cystic fibrosis and chronic respiratory tract diseases

Frequencies of CYP1A1, CYP2E1, and mEPHX polymorphic variants were analyzed in cystic fibrosis, chronic obstructive lung disease, bronchiectatic disease, chronic nonobstructive bronchitis, and recurring bronchitis. Mutations in CYP1A1 and mEPHX were shown to modify the severity of respiratory disorders in cystic fibrosis, the combination of CYP1A1 genotype Val/Val with the "very slow" mEPHX phenotype being most unfavorable (odds ratio OR = 12.30). Heterozygosity at both CYP1A1 and CYP2E1 was associated with chronic obstructive lung disease and recurring bronchitis (OR = 4.08 and 11.72, respectively). The "very slow" phenotype of mEPHX was predisposing to chronic respiratory disorders regardless of the CYP1A1 or CYP2E1 alleles (OR = 4.06). Basing on the above correlations, a combination of the "very slow" mEPHX phenotype with elevated cytochrome P450 (CYP1A1 and CYP2E1) activities was assumed to expedite severe respiratory disorders.     

Utility of bronchoalveolar lavage in the diagnosis of drug-induced pulmonary toxicity

Two hundred consecutive bronchoalveolar lavages (BALs) performed at Mayo Clinic were retrospectively reviewed. The BAL specimens were evaluated for nuclear enlargement, hyperchromasia and increased cytoplasmic staining density as possible cytologic markers of cytotoxic drug effects. Of the 200 patients whose lavages were examined, 178 had sufficient clinical data for study. Thirty-six BAL specimens had cytologic changes consistent with drug-induced pulmonary toxic effects. Twenty-three of the 36 patients had concurrent or subsequent lung tissue available for evaluation; 10 of the 23 showed histologic evidence of cytotoxic effects. The results indicate that BAL is a safe and useful procedure, not only for the assessment of suspected pulmonary infection in immunocompromised patients, but also for the investigation of drug-induced pulmonary disease.     

非结核分枝杆菌肺病临床分离株的菌种鉴定及临床特征分析

为探究非结核分枝杆菌（nontuberculous mycobacterium,NTM）肺病临床分离株的菌种分布及临床特征, 对2017年5月―2018年10月就诊于复旦大学附属中山医院的90例NTM肺病患者的样本进行分析。采用快速全自动分枝杆菌培养和药物敏感检测系统（BACTEC MGIT960 System）或改良罗氏培养法对90例患者的采集样本进行培养,利用基质辅助激光解析/电离飞行时间质谱（matrix assisted laser desorption/ionization time of flight mass spectrometry,MALDI-TOF MS）进行菌种鉴定,并对回顾性分析收集的90例患者的临床资料进行分析。结果NTM菌种鉴定为9种,其中慢速生长分枝杆菌65例,以胞内分枝杆菌（54.4%,49/90）占多数;快速生长分枝杆菌25例,以脓肿分枝杆菌（22.2%,20/90）占多数。90例患者中确诊67例、疑似23例。确诊患者中少见菌种所占比例较低（6.0% vs 26.1%,P = 0.016）。确诊与疑似患者在临床表现方面未见显著差异,但确诊患者有抗NTM治疗史的比例显著高于疑似患者（85.1% vs 4.3%,P < 0.001）。确诊患者中,快速生长NTM肺病患者既往抗结核治疗史的比例显著高于慢速生长组（52.9% vs 24.0%,P = 0.036）。本研究结果为NTM肺病的临床诊治提供了数据参考。     

The Adventures and Times of Eosilred,Prince of Elfour: A Bloodtime Story: Part IV

Eighty patients with carcinoma of the lung have been treated at the Nova Scotia Sanatorium since 1940; in 15, coexisting active pulmonary tuberculosis was present. No characteristic clinical or roentgenological findings indicated that the tuberculous individual also had lung cancer. In four cases cancer was not diagnosed until the lung was examined by the pathologist. In the others a considerable interval elapsed before carcinoma was suspected.Only four patients with known cancer were considered suitable for thoracotomy. In three, an attempt at curative resection was made. One survived over seven years before accidental death; one is alive less than one year after operation; the third died as a result of the surgery. Bronchogenic carcinoma should be suspected in every tuberculous patient over the age of 50; diagnostic investigations should include bronchoscopy and cytological studies of bronchial secretion and sputum. Suspicion of carcinoma in any such patient constitutes an indication for early resection of the tuberculous disease.     

Proposed Definitions for Epidemiologic and Clinical Studies of Mycobacterium avium Complex Pulmonary Disease

Background

Epidemiologic and clinical studies of Mycobacterium avium complex (MAC) pulmonary disease typically use strict ATS/IDSA definitions designed for decisions about treatment. Studies based on these criteria may exclude a substantial number of patients with true disease. We reviewed patients treated for MAC pulmonary disease at an academic medical center to propose revised definitions encompass the full spectrum of MAC pulmonary disease.

Methods

We conducted a retrospective review of patients with MAC pulmonary disease treated from 1993–2006 by pulmonary or infectious disease specialists to assess whether treated patients met current ATS/IDSA microbiologic criteria and dichotomous radiologic classification as nodular/bronchiectatic (NB) or fibrocavitary (FC) disease. We propose a revised set of definitions that include categories of both probable and definite disease to include all treated patients. We further classify patients into dichotomous clinical categories as: “primary MAC” (without antecedent lung disease) or “secondary MAC” (smoking history or antecedent lung disease).

Results

Among 72 treated patients, 74% were female. Median age at diagnosis was 64 years; 41(57%) met ATS/IDSA criteria and 31 (43%) did not, most often for lack of multiple positive cultures. Dichotomous radiologic criteria were met by 48 (67%) patients (36 NB, 12 FC); the remaining 24 (33%) had both NB and FC findings or other abnormalities. Nineteen (26%) were classified as primary and 53 (74%) as secondary MAC (21 COPD, 4 bronchiectasis, 44 smoking history).

Conclusions

We propose revised definitions for epidemiologic and clinical studies of MAC pulmonary disease that describe the full spectrum of disease.     

Cytology of secondary vulvar Paget's disease of urothelial origin: a case report

BACKGROUND: Primary cutaneous Paget's disease of the vulva is an intraepithelial adenocarcinoma most likely arising from a cutaneous stem cell with sweat gland epithelial differentiation or can be of sweat gland origin. Primary vulvar Paget's disease, however, can be mimicked by an internal noncutaneous neoplasm htat has extended to secondarily involve the vulva. Most commonly, this is due to an anal or rectal adenocarcinoma or a urothelial carcinoma. These malignancies may be detected in a vaginal or vulvar cytologic smear. CASE: An 81-year-old woman with a past history of urothelial carcinoma in situ of the bladder presented severalyears subsequent to treatment for bladder cancer with extensive vulvar and vaginal disease, clinically interpreted as primary vulvar Paget's disease involving the vagina. Vaginal cytology showed a high grade malignancy. The patient subsequently underwent radical (total deep) vulvectomy and vaginal excision. Subsequent investigation of her bladder showed recurrent urothelial carcinoma in situ with extensive spread to the vagina and vulva, simulating primary cutaneous vulvar Paget's disease. CONCLUSION: It is important to recognize secondary vulvar Paget's disease, although uncommon, because of the difference in therapy for primary and secondary vulvar Paget's disease. Certain cytologic characteristics in a vaginal or vulvar smear in a patient with suspected vulvar Paget's disease may aid in distinguishing them.     

抗组织纤维化多肽药物研究进展

组织纤维化是一种慢性疾病,多发于肝、肺、心脏、肾脏等部位,全球有 1/3 的人死于组织纤维化以及由其产生的器官衰竭。当组 织受到损伤后,损伤部位发生一系列细胞反应,最终导致细胞外基质过度沉积,发生组织纤维化。纤维化治疗的策略和药物开发围绕着抑 制纤维化过程中关键细胞通路和蛋白的分泌而展开。在药物开发过程中,多肽药物因其高效性、毒副作用低,可以根据治疗目的进行针对 性设计,成为研究人员进行抗纤维化药物开发的良好选择,现已有部分药物进入临床研究。综述抗纤维化治疗中的多肽药物及其治疗的机制, 为其他相关药物开发提供思路。     

Proteomic study of human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification

Bronchoalveolar lavage fluid (BALF) is an important diagnostic source to investigate cellular and molecular changes in the course of lung disorders. The pattern of soluble proteins in BALF obtained from patients at different stages of respiratory disorders may provide deeper insights in the molecular mechanisms of the disease. We used surface-enhanced laser desorption/ionization mass spectrometry (MS) for differential protein display combined with reversed-phase chromatography and subsequent matrix-assisted laser desorption/ionization-MS or nanoliquid chromatography MS/MS analysis for protein identification to compare the protein pattern of BALF samples obtained from ten smokers suffering from chronic obstructive pulmonary disease (COPD), eight clinically asymptomatic smokers, and eight nonsmokers without pulmonary disease. In this context, we were able to identify small proteins and peptides, either differentially expressed or secreted in the course of COPD or in a direct response to cigarette smoke. The concentrations of neutrophil defensins 1 and 2, S100A8 (calgranulin A), and S100A9 (calgranulin B) were elevated in BALFs of smokers with COPD when compared to asymptomatic smokers. Increased concentrations in S100A8 (Calgranulin A), salivary proline-rich peptide P-C, and lysozyme C were detected in BALFs of asymptomatic smokers when compared to nonsmokers, whereas salivary proline-rich peptide P-D and Clara cell phospholipid-binding protein (CC10) were reduced in their concentration. The identified proteins and peptides might be useful in the future as diagnostic markers for smoke-induced lung irritations and COPD.     

Herpetic eye disease: immunopathogenesis and therapeutic measures

Infection of the cornea with herpes simplex virus (HSV) can result in a chronic disease called herpetic stromal keratitis (HSK). The disease represents one of the leading causes of infectious blindness in the Western world. Immune-mediated cellular damage is suspected in the pathogenesis of human HSK. The murine model has been pivotal in further establishing HSK as an immunopathological disease. This article reviews understanding of HSK, both in humans and in the mouse model, with an emphasis on possible future therapeutic strategies to counteract this blinding immunoinflammatory disease.     

Programmatic change: lung disease research in the era of induced pluripotency

Human lung research has made remarkable progress over the last century largely through the use of animal models of disease. The challenge for the future is to translate these findings into human disease and bring about meaningful disease modification or even cure. The ability to generate transformative therapies in the future will require human tissue, currently scarce under the best of circumstances. Unfortunately, patient-derived somatic cells are often poorly characterized and have a limited life span in culture. Moreover, these cells are frequently obtained from patients with end-stage disease exposed to multiple drug therapies, leaving researchers with questions about whether their findings recapitulate disease-initiating processes or are simply the result of pharmacological intervention or subsequent host responses. The goal of studying early disease in multiple cell and tissue types has driven interest in the use of induced pluripotent stem cells (iPSCs) to model lung disease. These cells provide an alternative model for relevant lung research and hold promise in particular for studying the initiation of disease processes in genetic conditions such as heritable pulmonary arterial hypertension as well as other lung diseases. In this Perspective, we focus on potential iPSC use in pulmonary vascular disease research as a model for iPSC use in many types of advanced lung disease.     

Bronchoscopic Cryobiopsy for the Diagnosis of Diffuse Parenchymal Lung Disease

Background

Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease.

Methods

A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist.

Results

Twenty-five eligible subjects were identified. With a mean area of 64.2 mm², cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25). The most frequent diagnosis was usual interstitial pneumonia (UIP) (n = 7). Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications.

Conclusion

In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.     

Differential diagnosis of deforming bronchitis and the peribronchial form of central lung cancer

Bronchofibroscopy was performed in 4736 patients in the Moscow Endoscopic Center (S. P. Botkin Hospital) over the period of September 1984-December 1987. Central lung cancer was diagnosed in 139, of them peribronchial tumor growth was determined in 15. Deforming bronchitis was diagnosed in 283 patients, 23 of them were admitted to hospital with the diagnosis of central lung cancer. Differential diagnosis of peribronchial central lung cancer and deforming bronchitis is based on findings of a combined study including roentgenography, tomography, bronchofibroscopy with biopsy for subsequent cytological and histological investigation.     

TGF-beta1 induces progressive pleural scarring and subpleural fibrosis

Pleural fibrosis is a misunderstood disorder which can cause severe restrictive lung disease with high morbidity and even mortality. The condition can develop in response to a large variety of diseases and tissue injury, among them infectious disease, asbestos, drugs, and radiation therapy. There is no efficient treatment to reverse established pleural fibrosis. TGF-beta1 is suspected, even if not proven, as a key cytokine in this process. In this study, we used adenoviral gene transfer of TGF-beta1 to the pleural mesothelium in rats. We show that local and transient TGF-beta1 overexpression induces homogenous, prolonged, and progressive pleural fibrosis without pleurodesis, associated with severe impairment of pulmonary function. We further demonstrate that pleural fibrosis can expand into the lung parenchyma from the visceral layer, but not into the muscle from the parietal layer. We provide evidence that matrix accumulation and fibrosis within the parenchyma evolved through a process involving "mesothelial-fibroblastoid transformation" and suggest that the pleural mesothelial cell may be an important player involved in the development of the subpleural distribution pattern known to be a hallmark of pulmonary fibrosis. This new model of pleural fibrosis will allow us to better understand the mechanisms of progressive fibrogenesis, and to explore novel antifibrotic therapies in the pleural cavity.     

Allelic variants of the tumor necrosis factor superfamily as markers of the severity of the course of chronic obstructive lung disease and bronchiectatic disease

The distribution of allelic variants of genes of the TNF superfamily (TNFA and LTA) was studied in 172 patients with chronic obstructive pulmonary disease (COPD), bronchiectatic disease (n = 22), and in healthy individuals (n = 169). Analysis of the TNFA gene locus -308G-->A revealed no differences between the examined groups. Analysis of the LTA gene polymorphic locus +252A-->G showed that in patients with COPD, the frequency of the G allele was significantly higher than that in the control group (chi 2 = 3.98, p < 0.05). The presence of this allele in the genotype was correlated with the degree of COPD severity. Thus, in patients with stage II COPD, heterozygous AG genotype predominated (51.3%), whereas in patients with stage III COPD, the frequency of AG genotype was reduced to 32.7% at the expense of increased frequency of GG genotype (14.6%) (chi 2 = 6.78, p < 0.05; OR = 4.6, CI 1.37-15.96). The distribution of combined TNFA and LTA genotypes was also studied. In the group of COPD patients, the proportion of individuals with a combination of normal GG TNFA genotype and heterozygous AG LTA genotype was significantly higher (28.5% versus 18.4% in control; chi 2 = 4.14, p < 0.05; OR = 1.75, CI = 1.01-3.04). Genotype combinations were characterized at various clinical stages of COPD and bronchiectatic disease (BED). Thus, we have shown for the first time ever that LTA gene alleles and their combinations with the polymorphic variants of the TNFA gene are associated with predisposition to COPD and severity of this disease.     

Cytomorphology of granular-cell tumor of the bronchus. A case report

The cytologic features of a bronchial granular-cell tumor clinically mimicking a bronchogenic carcinoma are presented. Distinctive granular cells similar to the main cellular components of the surgical specimen were found in abundance in bronchial brushings and washings obtained during bronchoscopy. Our findings and conclusions confirm previously published studies. Granular-cell tumors of the bronchus can easily be diagnosed on cytologic examination if the entity is considered in the differential diagnosis of clinically suspected lung tumors.