Radiologic Characteristics of Non-tuberculous Mycobacteria Infection in Patients with Bronchiectasis.

INTRODUCTION: Non-tuberculous mycobacteria pulmonary disease (NTM-pd) commonly complicates bronchiectasis. However, clinical and radiological features of NTM-pd and bronchiectasis are very similar. We aimed to develop a radiologic prediction tool for bronchiectasis to identify NTM-pd. METHODS: We reviewed clinical, laboratory and radiological data in patients with bronchiectasis. Radiologic features on CT scans and the individual components of the Bhalla scoring system were compared between people with and without NTM-pd. Logistic regression and receiver-operating curve (ROC) analysis were performed to predict NTM-pd. RESULTS: People with NTM-pd had more pulmonary segments with bronchiectasis (13 ± 5 vs. 11 ± 5, p = 0.03), presence of mucus plugging (47% vs. 19%, p < 0.0001) and tree in bud infiltrates (53% vs. 28%, p = 0.004). The total modified- Bhalla score was worse among people with NTM-pd (median [IQR] 11[9,13] vs. 9[8,12], p = 0.03). Logistic regression identified the number of pulmonary segments involved, presence of bullae, consolidations, and a total score of 10 or more to be independently associated with presence of NTM-pd. ROC analysis with radiographic variables only identified an AUC of 0.706 (95% CI 0.644-0.762). When people with chronic Pseudomonas infection were excluded from the ROC analysis, prediction for NTM was improved: AUC = 0.87 (95% CI 0.796-0.945). DISCUSSION AND CONCLUSIONS: Radiological features together with advanced age and female gender may predict NTM-pd among people with bronchiectasis. Infection with Pseudomonas aeruginosa may resemble NTM radiographically, and this prediction rule may better differentiate people with and without NTM-pd when Pseudomonas infection is not present.

Pulmonary Langerhans cell histiocytosis and diabetes insipidus in pregnant women: our experience.

Pulmonary Langerhans cell histiocytosis (PLCH) occurs predominantly in young adult smokers. Diabetes insipidus occurs in up to 15 % patients with PLCH. Information on PLCH in pregnancy is sparse, especially associated with diabetes insipidus. We report three patients with these conditions and describe the disease history and pregnancy outcomes.

[Pulmonary hyper IgG4 disease].

Hyper IgG4 syndrome (HIDI is a multisystem disease characterized by high levels of immunoglobulin IgG4 with possible involvement of the pancreas, lung and lymph nodes as well as other organs. It was first described in connection to autoimmune pancreatitis but since then, it became clear that it can also affect many other organs. The disease involves the thorax and lesions were described in the mediastinum, airways, lung parenchyma and pleura. it can simultaneously involve multiple organs or be localized in just one. HID can develop in part of the fibro-inflammatory diseases of the chest without clear etiology like pseudo tumors, mediastinal and pleural fibrosis or inflammation. HID was also found in connection with various diseases in the airways. The HID lesion is typically rich in plasma cells positive to IgG4, fibrosis and vascutitis. This disease is rare and until now there were almost no cases reported in Israel. High clinical suspicion can make the diagnosis and prescribe the right therapy. The prognosis is favorable if the diagnosis is made on time. New studies are needed to understand the connection and the importance of this pathology to the lungs and also the most suitable treatments available for it.

Minor and intermediate surgeries in lung transplant recipients.

BACKGROUND: Only limited data exist regarding the incidence and outcome of surgical procedures following lung transplantation (LTX). METHODS: A retrospective analysis of surgical procedures performed in all LTX patients (n = 250) between 1997 and 2008. RESULTS: Of 250 patients who underwent LTX, 68 (27.2%) required 154 surgical procedures. Mean age was 53 ± 13 yr. Mean interval between LTX and surgery was 41 ± 40 months. Mean follow-up was 21 ± 9.4 months. Fourteen (9.1%) emergency operations were performed. Sixty patients (39%) underwent general anesthesia, 12 (7.8%) regional anesthesia, and 82 (53%) local anesthesia. Two patients required a major surgical procedure, while 76 of the procedures (49.4%) were intermediate, and 76 were minor surgeries. Only two patients (0.8%) developed complications (one infectious and one bronchospasm). One patient (0.4%) died following surgery as a result of septic shock. CONCLUSIONS: Minor and intermediate procedures can be performed safely in LTX patients without associated morbidity or mortality.

Voriconazole and itraconazole in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction.

BACKGROUND: The aim of this study was to compare the extent of interaction between tacrolimus and itraconazole vs. voriconazole. PATIENTS AND METHODS: This retrospective study included 60 lung transplant recipients who were treated with a tacrolimus-based regimen; 40 received prophylactic itraconazole for the first six months following lung transplantation (LTX), and 20 were treated with voriconazole. All patients had at least 12 months of follow-up. Tacrolimus levels and dosage requirements were compared during and after azole therapy. We assessed the rejection rate, fungal infection rate, and renal function during the study period. RESULTS: The mean tacrolimus dose during itraconazole treatment was 3.26 ± 2.1 mg/d compared with 5.74 ± 2.9 mg/d after itraconazole was stopped, p < 0.0001. Similarly, the mean tacrolimus dose during voriconazole treatment was 1.75 ± 0.9 mg/d compared with 4.85 ± 0.38 mg/d after voriconazole was stopped (p = 0.002). Thus, the mean increase in the total daily dose of tacrolimus after itraconazole and voriconazole withdrawal was 76% and 64%, respectively. No differences in the rejection or fungal infection rates or renal toxicity were observed during the study period, although an increase in positive fungal isolates was noted during itraconazole therapy. CONCLUSION: The tacrolimus dose was reduced more with itraconazole than with voriconazole, without an increase in the rejection rate and with renal function preservation.

Pulmonary epithelioid hemangioendothelioma.

Pulmonary epithelioid hemangioendothelioma (PEH), previously known as "intravascular bronchoalveolar tumor," is a rare vascular malignancy with an unpredictable prognosis. Treatment can vary from observation in asymptomatic patients to surgery in patients with resectable disease or chemotherapy in patients with disseminated disease. This report describes the clinical, radiological and pathological features of three cases of PEH and a review of the current literature.

Endobronchial drainage of lung abscess: the use of laser.

The management of lung abscess is usually conservative. However, in some cases drainage is necessary, commonly performed transcutaneously. Endobronchial catheter drainage is a potential alternative, though reported only sporadically. Transbronchial pigtail catheter drainage was used in 3 patients with refractory lung abscesses at our centre. The catheter was introduced endobronchially under bronchoscopic procedure. Laser was used to perforate the abscess wall through the airway into the abscess in order to provide a pathway for catheter insertion. An improvement in clinical and radiological parameters was noted immediately after catheter placement. The catheters were extracted after 4-6 days. All patients had a complete clinical recovery. Endobronchial catheters with the use of laser appear to be relatively safe and effective for the treatment of pulmonary abscess in selected patients in whom the abscess is adjacent to the central airway. When necessary, a bulge in an adjacent airway can be perforated with laser. To the best of our knowledge, there have been no previous reports of endobronchial drainage with the use of laser.

The QuantiFERON-TB-GOLD assay for tuberculosis screening in healthcare workers: a cost-comparison analysis.

The aim of this study was to assess the costs of screening healthcare workers (HCWs) for tuberculosis (TB) using the novel interferon-gamma release assay QuantiFERON((R))-TB Gold In-tube (QFT) versus the tuberculin skin test (TST). We used a prospective observational study with a cost-comparison analysis. The study was conducted at a regional center for ambulatory TB treatment. The study included 100 Israeli HCWs who were referred for routine TB screening. The participants were tested with both TST and QFT. For the TST, induration of 10 mm or more was considered a positive test. For the QFT, a threshold of 0.35 IU/ml interferon-gamma above background levels was a positive test. We developed a computerized model of the present TST-only screening method versus the QFT either alone (instead of the TST) or as a confirmatory test for a positive TST. Of the 100 subjects, 34 had a positive TST result and 17 had a positive QFT result. There was poor agreement between the TST and the QFT (kappa = 0.19). Assuming adherence to treatment of 50%, costs were minimized by using the QFT to confirm a positive TST (4155). The QFT-only model was cheaper than the TST-only model (7280 vs. 8217, respectively). The QFT-only method required the fewest clinic visits (121) compared to the TST (344). Adherence to treatment in the QFT-positive group was 47% compared with 12% for the TST-positive group. Screening HCWs with the QFT test compared to the TST resulted in fewer possible cases being identified, lower costs, and increased adherence to treatment. Costs were minimized by using the QFT to confirm a positive TST. A QFT-based screening program for HCWs is feasible and should be evaluated systematically.

Long-term pulmonary function after recovery from pulmonary contusion due to blunt chest trauma.

BACKGROUND: Blunt chest trauma can cause severe acute pulmonary dysfunction due to hemo/pneumothorax, rib fractures and lung contusion. OBJECTIVES: To study the long-term effects on lung function tests after patients' recovery from severe chest trauma. METHODS: We investigated the outcome and lung function tests in 13 patients with severe blunt chest trauma and lung contusion. RESULTS: The study group comprised 9 men and 4 women with an average age of 44.6 +/- 13 years (median 45 years). Ten had been injured in motor vehicle accidents and 3 had fallen from a height. In addition to lung contusion most of them had fractures of more than three ribs and hemo/pneumothorax. Ten patients were treated with chest drains. Mean intensive care unit stay was 11 days (range 0-90) and mechanical ventilation 19 (0-60) days. Ten patients had other concomitant injuries. Mean forced expiratory volume in the first second was 81.2 +/- 15.3%, mean forced vital capacity was 85 +/- 13%, residual volume was 143 +/- 33.4%, total lung capacity was 101 +/- 14% and carbon monoxide diffusion capacity 87 +/- 24. Post-exercise oxygen saturation was normal in all patients (97 +/- 1.5%), and mean oxygen consumption max/kg was 18 +/- 4.3 ml/kg/min (60.2 +/- 15%). FEV1 was significantly lower among smokers (71.1 +/- 12.2 vs. 89.2 +/- 13.6%, P = 0.017). There was a non-significant tendency towards lower FEV1 among patients who underwent mechanical ventilation. CONCLUSIONS: Late after severe trauma involving lung contusion, substantial recovery was demonstrated with improved pulmonary function tests. These results encourage maximal intensive care in these patients. Further larger studies are required to investigate different factors affecting prognosis.

Step oximetry test: a validation study.

INTRODUCTION: Step climbing is a potentially useful modality for testing exercise capacity. However, there are significant variations between test protocols and lack of consistent validation against gold standard cycle ergometry cardiopulmonary exercise testing (CPET). The purpose of the study was to validate a novel technique of exercise testing using a dedicated device. METHODS: We built a step oximetry device from an adapted aerobics step and pulse oximeter connected to a computer. Subjects performed lung function tests, a standard incremental cycle CPET and also a CPET while stepping on and off the step oximetry device to maximal exertion. Data from the step oximetry device were processed and correlated with standard measurements of pulmonary function and cycle CPET. RESULTS: We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9 mL/kg/min (95% CI -3.6 to 5.4) higher in the step test compared with the gold standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated negatively with diffusion capacity for carbon monoxide (r=-0.43, p<0.005). No adverse events occurred. CONCLUSIONS: The step oximetry test was a maximal test of exertion in the subjects studied, achieving slightly higher VO2 than during the standard test. The test was safe to perform and well tolerated by the patients. Parameters derived from the step oximetry device correlated well with gold standard measurements. The step oximetry test could become a useful and standardisable exercise test for clinical settings where advanced testing is not available or appropriate.

Limitations in exercise and functional capacity in long-term postpneumonectomy patients.

INTRODUCTION: Pneumonectomy results in impairments of pulmonary function and exercise intolerance associated with respiratory limitations. However, exercise capacity and functional capacity are less known at long-term followup. The aims of this study were to assess exercise tolerance and functional capacity among long-term postpneumonectomy patients and to identify the limiting factors in exercise related to comorbidities and which lung was involved. METHODS: Seventeen postpneumonectomy patients aged 59 ± 13 years and 5.5 ± 4.2 years postoperation were prospectively studied. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), Doppler-echocardiography, 6-minute walk test (6MWT) distance, and "senior fitness tests" (SFTs) were conducted with all patients. RESULTS: Exercise capacity and PFT were diminished ((Equation is included in full-text article.)O2 peak; 11.5 ± 3.3 mL·kg·min, 48 ± 17% predicted, forced vital capacity % predicted; 55 ± 13, FEV1% predicted; 46 ± 14, respectively). Most patients presented with low exercise cardiovascular parameters and normal breathing reserve (17 ± 12 L) during CPET. No significant differences were shown between right and left pneumonectomy and comorbidities related to exercise limitations (χ= 1.96, P = .376). Functional capacity in walking and SFTs were near normal (6MWT distance; 490 ± 15 m, 89 ± 25% predicted). Echocardiography showed normal left ventricle systolic function (ejection fraction, 60 ± 4%) with mildly elevated systolic pulmonary arterial pressure (38 ± 12 mm Hg). CONCLUSIONS: Long-term postpneumonectomy patients demonstrated decreased exercise capacity, limited primarily by the cardiovascular system regardless of lung resection side or comorbidities, although tests of functional capacity were near normal. Most patients can maintain near normal life in activities of daily living, but the long-term cardiopulmonary exercise function should be considered for meticulous evaluation and clinical care to preserve physiological reserves.

Characterization of novel multiantigenic vaccine candidates with pan-HLA coverage against Mycobacterium tuberculosis.

The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis antigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44(high)/CD62L(+) activation/effector memory markers and gamma interferon (IFN-γ), but not interleukin-4 (IL-4), production in both CD4(+) and CD8(+) T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded or M. tuberculosis-infected macrophages. Lysis of M. tuberculosis-infected targets was accompanied by high IFN-γ secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity against M. tuberculosis-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.

Clinical and radiological features of Mycobacterium kansasii and other NTM infections.

BACKGROUND: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically. METHODS: The sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated. RESULTS: In the M. kansasii group, n = 27 (42%) were native-born Israelis compared to 9.4% (n = 3) of all other NTM groups (p = 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p = 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p = 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group. CONCLUSION: Major differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications.

Postcoital hemoptysis: our experience and review of the literature.

Hemoptysis after physical activity is a well-known phenomenon. Hemoptysis following sexual intercourse is rarely reported. We describe three patients with hemoptysis occurring only after sexual activity and not following other types of physical effort. The underlying causes were congestive heart failure, uncontrolled hypertension and Takayasu arteritis. The literature is reviewed. We conclude that hemoptysis can present rarely following sexual activity and is usually associated with cardiovascular decompensation. It is always necessary to search for other underlying diseases. We suggest that patients with unexplained hemoptysis should be specifically asked about postcoital hemoptysis should be included in the differential diagnosis of every patient with unexplained hemoptysis.

Long-term follow-up of flexible bronchoscopic treatment for bronchial carcinoids with curative intent.

Background. Typical pulmonary carcinoids represent less than 5% of primary lung tumors. In patients with typical bronchial carcinoid, formal surgical resection still remains the gold-standard treatment. Data regarding long-term outcome in using flexible bronchoscope-based modalities under conscious sedation is very limited. Objectives. We sought to investigate, over extended follow-up period, the effectiveness of endobronchial resection for carcinoid tumors with curative intent using flexible bronchoscopy. Methods. Nd:YAG laser photoresection using flexible bronchoscope under conscious sedation. Follow-up included repeat bronchoscopy every 6 months and chest CT every year. Results. Ten patients aged 24 to 70 years with endobronchial carcinoid were treated. The tumor location was variable: 2 left Main bronchus, 1 left upper lobe bronchus, 2 right main bronchus, 2 right middle lobe bronchus and 3 right lower lobe bronchus. No major complications were observed. The patients required between 2 and 4 procedures. Patients were followed for a median period of 29 months with no evidence of tumor recurrence. Conclusions. Endobronchial laser photoresection of typical bronchial carcinoids using flexible bronchsocopy under conscious sedation is an effective treatment modality for a subgroup of patients that provides excellent long-term results that are similar to outcome obtained by more invasive procedures.

Herpes zoster after lung transplantation: incidence, timing, and outcome.

BACKGROUND: Although herpes zoster is a common complication of lung transplantation, the epidemiologic data are limited. The aims of the present study were to determine the incidence and clinical manifestations of herpes zoster in a large cohort of lung transplant recipients and to identify risk factors associated with its development. METHODS: The files of all adult patients who underwent lung transplantation at a major tertiary medical center from January 2001 to December 2007 were reviewed. Data were extracted on background, transplant-related, and posttransplantation factors. The occurrence and clinical characteristics of all episodes of herpes zoster were recorded. RESULTS: Of the 198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had herpes in a single dermatome. Disseminated cutaneous infection was documented in 4 cases (17%) and visceral involvement in 1. The median duration of follow-up was 34 months (range, 1 to 85 months). There were no recurrent infections. Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis, primarily for cytomegalovirus, was effective (during treatment) against herpes zoster. The incidence of herpes zoster was higher in patients treated with rabbit antithymocyte globulin. CONCLUSIONS: The occurrence of herpes zoster peaks between 12 and 36 months after lung transplantation. Additional immunosuppression may increase the risk. Further studies on preventive strategies against herpes zoster in this population are warranted.

The 15-step oximetry test: a reliable tool to identify candidates for lung transplantation among patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of approximately 3 years. Measurements of lung volumes and diffusion capacity at rest are generally used to monitor the clinical course of IPF. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as lung transplantation. This study was design to determine whether the simple 15-step climbing exercise oximetry test accurately characterizes disease severity and survival in patients with IPF. METHODS: The study population consisted of 51 patients with progressive IPF. Findings on the 15-step climbing test, pulmonary function tests, cardiopulmonary exercise test and 6-minute walk distance test were assessed at baseline. Participants were prospectively followed for >or=2 years to determine the relationship between the test parameters and survival. RESULTS: On univariate analysis, there were strong correlations between the 15-stair climbing test parameters and survival. On stepwise linear regression analysis, independent significant predictors of mortality were lowest saturation levels on the 15-step test and the 6-minute walk distance test. CONCLUSIONS: The lowest saturation and desaturation areas on the 15-step oximetry test are significantly associated with long-term outcome in patients with IPF. We suggest that the 15-step test be used as a simple and reliable tool to predict severity and prognosis in IPF and to identify candidates for lung transplantation.