Bronchial Lesions Research Articles

Invasive fungal tracheobronchitis in mechanically ventilated critically ill patients: underlying conditions, diagnosis, and outcomes

BackgroundInvasive fungal tracheobronchitis (IFT) is a severe form of pulmonary fungal infection that is not limited to immunocompromised patients. Although respiratory failure is a crucial predictor of death, information regarding IFT in critically ill patients is limited.MethodsIn this retrospective, multicenter, observational study, we enrolled adults diagnosed as having IFT who had been admitted to the intensive care unit between January 2007 and December 2015. Their demographics, clinical imaging data, bronchoscopic and histopathological findings, and outcomes were recorded.Results This study included 31 patients who had been diagnosed as having IFT, comprising 24 men and 7 women with a mean age of 64.7 ± 13.7 years. All patients developed respiratory failure and received mechanical ventilation before diagnosis. Eighteen (58.1%) patients had diabetes mellitus, and 12 (38.7%) had chronic lung disease. Four (12.9%) patients had hematologic disease, and none of the patients had neutropenia. Twenty-five (80.6%) patients were diagnosed as having proven IFT, and the remaining patients had probable IFT. Aspergillus spp. (61.3%) were the most common pathogenic species, followed by Mucorales (25.8%) and Candida spp. (6.5%). The diagnoses in six (19.4%) patients were confirmed only through bronchial biopsy and histopathological examination, whereas their cultures of bronchoalveolar lavage fluid were negative for fungi. The overall in-hospital mortality rate was 93.5%.ConclusionsIFT in critically ill patients results in a high mortality rate. Diabetes mellitus is the most prevalent underlying disease, followed by chronic lung disease. In addition to Aspergillus spp., Mucorales is another crucial pathogenic species. Bronchial lesion biopsy is the key diagnostic strategy.

Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants.

This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. • Lung cancer within a year of a negative CT screen was rare. • Abnormalities likely due to lung cancer were identified retrospectively in most patients. • Awareness of error types may help identify lung cancer sooner.

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of low-dose-rate brachytherapy

Brachytherapy is the use of radionuclides to treat malignancies or benign conditions by means of a radiation source placed close to or into the tumor or treatment site. This practice parameter refers only to the use of radionuclide brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. Low-dose-rate (LDR) brachytherapy has traditionally been used for treating prostate, head and neck, breast, cervical, and endometrial cancers as well as obstructive bile duct, esophageal, or bronchial lesions. It has been practiced for over a century with a variety of sources including radium-226, cesium-137, and, more recently, iridium- 192, iodine-125, and palladium-103. Low-dose-rate (LDR) brachytherapy can be given as interstitial, intracavitary, intraluminal, and/or plesiotherapy to a wide variety of treatment sites. This practice parameter addresses sealed sources as they are used for LDR brachytherapy. It is recognized that unsealed sources (e.g., yttrium-90) are also a form of LDR brachytherapy.

P1.04-004 Bronchocopic Cryosurgery with Carbon Dioxide; Experience in an Oncology Clinic in Colombia

The bronchoscopic cryosurgery with carbon dioxide is a groundbreaking tool in the diagnostic treatment of respiratory diseases. It has shown to be of great usefulness at a reasonable cost, with multiple indications and few side effects. We described the experience in an oncology institution in Colombia. Medical histories, Bronchoscopies and images were review from patients subjected to Bronchoscopic Cryosurgery. The procedures were performed at the “High-Tech Western Oncologist Clinic” in Pereira, Colombia with a highly trained medical staff from this clinic and from Neumovida Clinic from Armenia. Rigid and flexible Bronchoscopy video was made, and the equipment used in the cryotherapy was the Erbe Cryo 2 with the cryoprobe of 1.9 and 2.4 mm. 71 patients were found, 44 men, 27 women. Tracheal Recanalization to 11 patients, Bronchial Cryorecanalization to 24, Bronchial Cryobiopsy to 13, Tracheal Cryobiopsy to 7 and Pulmonary Cryobiopsy to 16 patients. Cryorecanalization was performed to 15 patients with tumors in the right lung and 9 in the left lung. Permeabilization of the Bronchial lumen was achieved to 22 patients at the same time the Bronchoscopy was being done. In 2 patients with Bronchial Obstruction the same procedure was achieved a week later. Pulmonary re-expansion and symptomatic control were achieved in 31 patients. Permeabilization of the bronchial lumen was achieved in 2 patients but not pulmonary re expansion. Silicone prosthesis were implanted to 9 patients with Tracheal lesions and 18 patients with Bronchial lesions. Differences between genders were not shown. There were not any important clinical complications associated with the procedures. Moderate bleeding with the pulmonary biopsy was control locally. In general the post-operative evolution of the patients was satisfactory. The Bronchoscopic Cryosurgery has clear indications in patients with Central Airway Tumors, just as the diagnostic, therapeutic and palliatives purposes and in patients with interstitial compromise of presumable neoplasic or infectious origin. In our casuistry, the objective was achieved in all the patients that underwent the procedures such as tracheobronchial recanalization and extraction of tracheal, bronchial or pulmonary tissue with a significant symptomatic improvement with a low risk and low morbidity

HOSPITAL-ACQUIRED PNEUMONIA ASSOCIATED WITH THE CAUSATIVE AGENT STENOTROPHOMONAS MALTOPHILIA, IN NEWBORN INFANTS

Objective: to analyze the clinical course of ventilator-associated pneumonia caused by Stenotrophomonas maltophilia in infants as a high-risk group for the development of hospital acquired infection, as well as a study of the sensitivity of the pathogen to antibiotics. Eighteen infants (14 premature and 4 mature infants) with ventilator -associated pneumonia due to (Stenotrophomonas maltophilia) were monitored. The disease occurred in the majority (72%) of infants as a monoinfection, more often in severe and acute form with severe toxicosis, trophic disorders, severe respiratory failure, bilateral lung and bronchial lesions. In 33% of children, mostly premature, there was a change in the pathogen, which increased the severity and duration of the disease. Pneumonia had complications in the form of sepsis (6%) and bronchopulmonary dysplasia (28%). Most Stenotrophomonas maltophilia retained sensitivity to ticarcillin + clavulanate, ciprofloxacin, chloramphenicol and co-trimoxazol.

A Case of Peripheral Lung Tumor Adjacent to Subsegmental Bronchus Diagnosed by EBUS-TBNA: Approaches to Subsegmental Bronchial Lesions with EBUS-TBNA Through the R-EBUS Reference Method

A Case of Peripheral Lung Tumor Adjacent to Subsegmental Bronchus Diagnosed by EBUS-TBNA: Approaches to Subsegmental Bronchial Lesions with EBUS-TBNA Through the R-EBUS Reference Method

Two years of surveillance of influenza a virus infection in a swine herd. Results of virological, serological and pathological studies.

Swine farms provide a dynamic environment for the evolution of influenza A viruses (IAVs). The present report shows the results of a surveillance effort of IAV infection in one commercial swine farm in Argentina. Two cross-sectional serological and virological studies (n=480) were carried out in 2011 and 2012. Virus shedding was detected in nasal samples from pigs from ages 7, 21 and 42-days old. More than 90% of sows and gilts but less than 40% of 21-days old piglets had antibodies against IAV. In addition, IAV was detected in 8/17 nasal swabs and 10/15 lung samples taken from necropsied pigs. A subset of these samples was further processed for virus isolation resulting in 6 viruses of the H1N2 subtype (δ2 cluster). Pathological studies revealed an association between suppurative bronchopneumonia and necrotizing bronchiolitis with IAV positive samples. Statistical analyses showed that the degree of lesions in bronchi, bronchiole, and alveoli was higher in lungs positive to IAV. The results of this study depict the relevance of continuing long-term active surveillance of IAV in swine populations to establish IAV evolution relevant to swine and humans.

First-in-Man Emergency Use of Plasminogen Replacement for Respiratory Failure Due to Congenital Hypoplasminogenemia

Congenital hypoplasminogenemia (HPG) is characterized by markedly impaired extracellular fibrinolysis leading to the formation of ligneous (woody) pseudomembranes on mucosal surfaces, including the eye, mouth, bronchopulmonary tree, and genitourinary tract. HPG is caused by homozygous or compound-heterozygous mutations in the plasminogen gene (PLG; 6q26).We present a report of the first therapeutic use of replacement therapy with plasminogen purified from human plasma. A male of Turkish descent was diagnosed at 4 weeks of age with congenital hypoplasminogenemia following presentation with typical ligneous conjunctivitis. The serum plasminogen activity level was < 2% (Reference range 75-140%), and the diagnosis was confirmed by genetic testing showing a novel homozygous splice-site mutation in PLG (c.1587+1 G>A).At 2 months of age he suffered a severe respiratory syncytial virus (RSV) infection requiring ventilatory support for 5 days and a 1 month hospitalization. From this time he had recurrent respiratory problems. From 4 months of age he was treated with fresh frozen plasma (FFP) 20 mL/kg/week. At 18 months of age he was found to have exophytic lesions within both the right and left main bronchi. He had one incident of acute severe dyspnea with cyanosis which responded to non- invasive oxygen insufflation. Subsequently he had repeated bronchoscopies with laser removal of bronchial lesions with FFP cover. At 20 months of age during preparation for bronchoscopy he had an episode of acute cyanosis and cardiac arrest with asystole and was resuscitated after 30 minutes. CXR showed atelectasis of the left lung and of the right lower lobe. He was admitted to the ICU and required both ventilatory and circulatory support. Profuse viscous lung secretions were aspirated.One week later he was given a dose of plasminogen of 4 mg/kg, with a second dose of 6 mg/kg and subsequent doses of 6.5 mg/kg every 48 hours. The pharmacokinetics are shown in the Figure. Note that baseline level before the first dose is 21% due to FFP therapy.Progressive dissolution of the membranes and exophytic lesions with some blood spotting, was noted, and was associated with decreased oxygen requirements. Improvement in the ligneous eye lesions was also observed. After 4 days he was extubated., but required reintubation after 36 hours due to exhaustion; he was finally extubated 1 week after receiving the first dose of plasminogen. Plasminogen replacement has continued with a regimen of 6.5 mg/kg every second day. There has been progressive dissolution of the membranes with greatly reduced lesions seen after 6 weeks of treatment.CXR before administration of plasminogen showed atelectasis of the left lung and of the right lower lobe (left panel). Six weeks after initiation of regulalar plasminogen substitution ventilation in both lungs had improved significantly (right panel)In this patient substitution with plasminogen was effective and showed no significant side effects. Patients with severe plasminogen deficiency might benefit from prophylactic or early treatment to prevent severe complications such as occurred in this patient. [Display omitted] [Display omitted] [Display omitted] DisclosuresMoran:ProMetic Life Sciences, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Schneppenheim:Baxalta, now part of Shire: Membership on an entity's Board of Directors or advisory committees.

電子蛍光気管支鏡(AFI)による気管気管支粘膜病変の診断(第27回日本呼吸器内視鏡学会総会 : プレナリーセッション1)

電子蛍光気管支鏡(AFI)による気管気管支粘膜病変の診断(第27回日本呼吸器内視鏡学会総会 : プレナリーセッション1)

気管支内多発性隆起病変を呈した電撃傷の 1 例

気管支内多発性隆起病変を呈した電撃傷の 1 例

Application of Quantitative Autofluorescence Bronchoscopy Image Analysis Method in Identifying Bronchopulmonary Cancer.

Autofluorescence bronchoscopy shows good sensitivity and poor specificity in detecting dysplasia and cancer of the bronchus. Through quantitative analysis on the target area of autofluorescence bronchoscopy image, determine the optimal identification index and reference value for identifying different types of diseases and explore the value of autofluorescence bronchoscopy in diagnosis of lung cancer. Patients with 1 or more preinvasive bronchial lesions were enrolled and followed up by white-light bronchoscope and autofluorescence bronchoscopy. Color space quantitative image analysis was conducted on the lesion shown in the autofluorescence image using MATLAB image measurement software. A retrospective analysis was conducted on 218 cases with 1208 biopsies. One hundred seventy-three cases were diagnosed as positive, which included 151 true-positive cases and 22 false-positive cases. White-light bronchoscope associated with autofluorescence bronchoscopy was able to differentiate between benign and malignant lesion with a high sensitivity, specificity, positive predictive value, and negative predictive value (92.1%, 59.3%, 87.3%, and 71.1%, respectively). Taking 1.485 as the cutoff value of receiver operating characteristic of red-to-green value to differentiate benign and malignant diseases, the diagnostic sensitivity reached 82.3% and the specificity reached 80.5%. U values could differentiate invasive carcinoma and other groups well. Quantitative image analysis method of autofluorescence bronchoscopy provided effective scientific basis for the diagnosis of lung cancer and precancerous lesions.

Abstract 896: The airway field of injury reflects gene expression changes associated with the presence of lung squamous premalignant lesions

Abstract Lung squamous cell carcinoma (SCC) arises in the epithelial layer of the bronchial airways and is preceded by the development of premalignant lesions (PMLs). The molecular events involved in the progression of PMLs to lung SCC are not clearly understood as not all PMLs that develop go on to form carcinoma. In addition, the majority of lung cancer chemoprevention agents tested to date are ineffective. Molecular characterization of the airway field of injury in individuals with PMLs could provide novel insights into the earliest molecular events associated with carcinogenesis and identify biomarkers to guide lung cancer detection and chemoprevention. RNA-sequencing was conducted on cytologically normal airway brushings from current and former smokers with (n = 50) and without (n = 25) PMLs as part of the British Columbia Lung Health Study. Linear modeling strategies were used to identify 280 differentialy expressed genes at FDR&amp;lt;0.002 between subjects with and without PMLs. Pathway analysis using GSEA and ROAST revealed enrichment of genes involved in the electron transport chain and oxidative phosphorylation pathways in subjects with PMLs. These findings were validated by measuring the cellular bioenergetics of cultured epithelial cells from biopsies of PMLs and non-lesion areas. Baseline oxygen consumption rates were 2.5 fold higher (p&amp;lt;0.001) and the spare respiratory capacity was 1.5 fold higher (p&amp;lt;0.001) in PML cultures. These data suggest that metabolism-associated gene expression observed in the field of injury of PMLs is correlated with PMLs. In addition, there is a significant concordant enrichment (FDR&amp;lt;0.05) between the signature and gene expression in PMLs adjacent to SCC tumors, in SCC tumors, and in the field of individuals with lung cancer. This concordance led to the development of a 200-gene biomarker that accurately predicts the presence of PMLs (AUC = 0.90 n = 17 independent samples). Importantly, this biomarker was also predictive (AUC -.72) of progression/stability vs. regression of these premalignant lesions in an independent cohort of cytologically normal airway brushings collected as part of the RPCI screening clinic (n = 18). This is the first study to comprehensively profile gene expression changes in airway epithelial cells in the presence of PMLs. A subset of these changes reflects the earliest changes in the process of lung squamous cell carcinogenesis including the genes involved in cellular metabolism. However, the molecular alterations in the field of injury are dynamic as bronchial lesions either progress or regress these changes may be leveraged to monitor efficacy in chemoprevention trials. In addition monitoring molecular changes in high-risk smokers may identify smokers with PMLs that should receive lung cancer screening as well as lay the foundation for personalized lung cancer chemoprevention. Citation Format: Sarah A. Mazzilli, Ania Tassinari, Yaron Gethalter, Gang Lui, Mary Pine, Stephen Lam, Mary Reid, Suso Platero, Marc Lenburg, Avrum Spira, Jennifer Beane. The airway field of injury reflects gene expression changes associated with the presence of lung squamous premalignant lesions. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 896.

Abstract 1419: Characterization of the evolution of immune response in lung squamous carcinogenesis

Abstract Molecular profiling of from pre-invasive bronchial lesions, and particularly the evolution of immune response, may identify promising new biomarkers for early detection and targets for chemoprevention/treatment of lung cancer. mRNA expression was analyzed (Agilent microarrays) from fresh frozen human bronchial biopsies (N = 122, 77 patients) at successive morphological stages of lung squamous carcinogenesis. Modules of co-expressed genes were identified among the stage associated genes, selected using a linear mixed-effects model adjusting for smoking status, gender, and history of cancer as fixed effects and patient as a random effect. Cell type specific signatures were applied to the genes co-expressed in these modules in order to identify the immune response signal through the stages of lung carcinogenesis. Genes expression alterations were grouped into 4 successive molecular steps. Based on their behavior across the 4 steps, 8 modules of genes with different patterns were observed: gene modules primarily up-regulated among the early or late steps, up-regulated in a linearly across the 4 steps, as well as down- then up-regulated (biphasic). Genes signing the presence of activating CD8 and CD4 T cells, as well as some memory B cells were progressively and linearly up-regulated from metaplasia through all stages of carcinogenesis. At the later stages, the transition to high-grade dysplasia, the most significant gene expression changes included immune/inflammatory response genes. At this stage a very strong adaptive immune response is noted involving T cells - mainly Th1 and T regulators - and dendritic cells. In addition, immunosuppressive signals, corresponding to negative co-inhibitory molecules, also significantly appears at the high-grade dysplasia stage. The adaptive CD4/CD8 related immune response starts from the earlier stages (metaplasia) of lung carcinogenesis. The significant modification of inflammatory/immune response genes in association with high-grade lesions suggests, at this critical stage of carcinogenesis, a major role of the surrounding microenvironment with an adaptive immune response, driven by Th1 and Treg cells, and but also, before tumor invasion across the basal membrane, a tumor versus host immunosuppressive response. Citation Format: Celine Mascaux, Mihaela Angelova, Jennifer Beane, Kahkeshan Hijazi, Geraldine Antoine, Karen Willard Gallo, Vincent Ninane, Arsène Burny, Jean-Paul Sculier, Avrum Spira, Jérôme Galon. Characterization of the evolution of immune response in lung squamous carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1419.

An Unusual Cause of Dysphagia with Bronchoesophageal Fistula

A 57-year-old man presented with a 4-week history of dysphagia and cough. Physical examination revealed mucocutaneous pallor, and laboratory tests showed a slight anemia (hemoglobin level 12,5 g/dL). An upper gastrointestinal endoscopy reveled an obstructive neoplasm in the midesophagus (Fig. 1); biopsy specimens showed fibrinonecrotic and granulation tissue. Chest computed tomography showed a large peribronchial mass with bronchoesophageal fistula (BEF) (Fig. 2), and bronchoscopy reveled bronchial infiltration and marked caliber reduction of the left main bronchus. The results of examinations of samples from repeat biopsies of esophageal and bronchial lesions were negative for dysplasia or neoplasia. The results of polymerase chain reaction testing for Mycobacterium tuberculosis were positive, so we began administration of tuberculostatics and systemic corticosteroids, assuming lymph node tuberculosis with mediastinal involvement. However, there was a worsening of dyspnea and weight loss, and the results of the Xpert MTB/RIF Assay (Cepheid, Sunnyvale, CA) and Lowenstein–Jensen culture were both negative, leading to the assumption of a false-positive result of the first test. Endoscopic reassessment showed increase esophageal lesion and extensive tracheobronchial destruction, forming a large necrotic cavity in the mediastinum (Fig. 3). Histopathological analysis revealed large lymphocytes with a diffuse growth pattern with negative immunostaining for cytokeratin AE1, cytokeratin AE3, and for cluster of

AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

Invasive tracheobronchial aspergillosis progressing from bronchial to diffuse lung parenchymal lesions

Invasive tracheobronchial aspergillosis that is entirely limited or predominantly confined to tracheobronchial lesions is a relatively rare form of invasive pulmonary aspergillosis. Extended parenchymal opacities that are radiological manifestations of invasive aspergillosis sometimes occur following invasive tracheobronchial aspergillosis. However, it remains unclear whether or not invasive tracheobronchial aspergillosis is the initial stage of invasive pulmonary aspergillosis. A 61-year-old woman was admitted because of severe diarrhea and dehydration. Three days after admission, she complained of dyspnea. A computed tomography (CT) scan of the chest showed bronchial wall thickening. She developed respiratory failure despite antibiotic therapy. A CT scan showed obstructions of bronchial lumens and bronchiectasis in the right upper lobe. A spergillus fumigatus was identified from samples obtained in bronchoscopic examination. Bronchial lesions rapidly progressed to be extended. A spergillus infection with multiple parenchymal opacities was observed on CT scan. She responded to treatment with antifungal drugs.

Endobronchial Involvement in Sarcoidosis

Endobronchial involvement is a common feature of sarcoidosis. The mucosa may appear normal or there may be inflammatory changes with erythematous lesions, miliary nodules, and, rarely, mass-like lesions leading to obstruction. In patients with bronchial lesions, the bronchial biopsy may be positive in three-quarters of patients. On the other hand, granulomas may be identified in one-third of patients with a normal mucosa. Current data on endobronchial sarcoidosis is primarily associated with the treatment and prognosis of obstructive mass-like granulomas. Data relevant to clinical features of superficial endobronchial involvement and its implications on prognosis and extrapulmonary organ involvement is lacking. The results of our two previous studies reveal that clinical findings of endobronchial disease may be different. These studies also suggest that there is a great difference between patients with no endobronchial involvement, limited and diffuse endobronchial disease in regard to clinical features, and prognosis. The incidence of extrapulmonary organ involvement is also significantly different between the three groups. In this short review, the clinical findings of endobronchial sarcoidosis have been defined, the effects of superficial endobronchial involvement on prognosis, and extrapulmonary organ involvement.

ЛОКАЛЬНЫЙ ТУБЕРКУЛЕЗ У ДЕТЕЙ РАННЕГО ВОЗРАСТА

The purpose is to study clinical and X-ray manifestations of local tuberculosis in children of the tender age and to detect risk factors promoting the development of the disease and complicating it, thus the analysis included 82 cases of children cases under 3 years old who had been treated in Children TB Hospital in 2013-2015. Tuberculosis of chest lymph nodes was diagnosed in 68.3%of them, and every fifth child had primary tuberculosis complex. Every other child was suffering from the complicated course of local tuberculosis (n = 42). The following forms were registered: bronchial pulmonary lesions (n = 27), lymphogenic progression (n = 13), including development of disseminated tuberculosis and meningitis. Positive results of sputum tests were observed in 14 (17.1%) children, of them 50% had multiple drug resistance. 10% of children suffering from tuberculosis manifested anergy. The predictors of such course of the disease included the absence of BCG vaccination and super infection with Mycobacterium tuberculosis.

Immunopathology of Experimental Models of Syphilis, Influenza, and Asthma.

The introduction of immunopathologic reaction classification in the 1960s led to a major advance in understanding immune effector mechanisms and how lesions of immunopathologic diseases developed. In this article, immunopathologic mechanisms are presented for experimental models of syphilis, influenza, and asthma. The chancre of syphilis is a delayed hypersensitivity skin reaction that is initiated by sensitized T cells that activate macrophages to phagocytose and kill the infecting organism, Treponema pallidum, in interstitial tissues. The primary immune effector mechanism in experimental influenza is T-cell-mediated cytotoxicity that kills infected epithelial cells, bronchial lining cells, and Type-II pneumocytes, in a manner similar to viral exanthema. The bronchial lesions of the experimental model of asthma in mice are preceded by an immune complex vasculitis and not an immunoglobulin E-mediated mast cell mechanism.

Electroporation ablation of bronchial smooth muscle cells: A novel non-thermal asthma therapy.

Asthma is a common disease which places significant burden on the US healthcare system and which can be associated with significant patient morbidity and mortality. Current medical therapies are costly and not curative. A new approach for a more permanent asthma treatment is the use of radiofrequency ablation. However, this radiofrequency approach is thermal-based and can result in deleterious effects to the airways, such as stenosis or ulceration. We describe a novel, improved therapeutic approach for smooth muscle ablation using non-thermal DC electroporation ablation. We developed and tested prototype electroporation ablation devices that access the airways both endoscopically and via a bronchoscope. We tested the feasibility of this approach and demonstrated proof-of-concept in 2 mongrel dogs. In order to assess for smooth muscle function, we performed functional studies pre and post ablation with methacholine challenge to assess for airway reversibility. We also evaluated bronchial lesions via direct vision with bronchoscopy. We developed novel electroporation catheters to delivery energy to the bronchial smooth muscle through an endoscopic approach. We tested these catheters in 2 acute canine studies and successfully demonstrated the ability to destroy smooth muscle tissue via novel prototypes and saline irrigation for widespread non-thermal electroporation ablation. Our functional studies demonstrate the efficacy of this approach. We report a novel method for non-thermal bronchial smooth muscle ablation using novel prototypes and electroporation with normal saline. These early findings require further evaluation in larger, chronic canine studies to assess for use as a potential curative therapy.