Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Bronchoscopic sampling techniques in the era of technological bronchoscopy.

Flexible bronchoscopy is a key diagnostic and therapeutic tool. New endoscopes and technologically advanced navigational modalities have been recently introduced on the market and in clinical practice, mainly for the diagnosis of mediastinal lymph adenopathies and peripheral lung nodules. Bronchoscopic sampling tools have not changed significantly in the last three decades, with the sole exception of cryobiopsy. We carried out a non-systematic, narrative literature review aimed at summarizing the scientific evidence on the main indications/contraindications, diagnostic yield, and safety of the available bronchoscopic sampling techniques. Performance of bronchoalveolar lavage, bronchial washing, brushing, forceps biopsy, cryobiopsy and needle aspiration techniques are described, focusing on indications and diagnostic accuracy in the work-up of endobronchial lesions, peripheral pulmonary abnormalities, interstitial lung diseases, and/or hilar-mediastinal lymph adenopathies. Main factors affecting the diagnostic yield and the navigational methods are evaluated. Preliminary data on the utility of the newest sampling techniques (i.e., new needles, triple cytology needle brush, core biopsy system, and cautery-assisted transbronchial forceps biopsy) are shown. TAKE HOME MESSAGE: A deep knowledge of bronchoscopic sampling techniques is crucial in the era of technological bronchoscopy for an optimal management of respiratory diseases.

Choose the best route: ultrasound-guided transbronchial and transesophageal needle aspiration with echobronchoscope in the diagnosis of mediastinal and pulmonary lesions.

Nodal mediastinal staging is a crucial part of the diagnostic workup of patients with nonsmall- cell lung cancer (NSCLC) for planning optimal treatment. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and real-time endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) are accurate, minimally invasive and safe diagnostic techniques for mediastinal staging. Because of the different accessibility to the mediastinum, they are considered complementary and their combination increases the diagnostic yield as compared with the either alone. Recent studies have shown that endosonography represents the best initial test for invasive mediastinal evaluation in NSCLC. Endoscopic ultrasound (with bronchoscope)-guided fine needle aspiration (EUS-B-FNA) is a recently introduced procedure consisting of a transesophageal needle aspiration using an ultrasound bronchoscope. It allows to perform both transbronchial and transesophageal needle sampling with the same instrument, in the same session and by one operator only, thus maximizing time and costs savings. In a recent study Oki et al. randomized 110 patients with hilar/mediastinal adenopathies or lung abnormalities adjoining both the esophagus and the bronchi, to undergo EBUSTBNA or EUS-FNA performed by pulmonologists with an echobronchoscope. The Authors demonstrated that both procedures provide a high diagnostic yield, without any difference in the number of adverse events and a good comparable tolerance. Nevertheless, the transesophageal approach guaranteed a significantly lower dose of anesthetics and sedatives, a shorter procedural time, fewer oxygen desaturations, a significantly lower cough score and a higher operator satisfaction. In this review our aim was to discuss the findings by Oki et al. in the context of medical literature, highlighting the importance of the EUS-B needle aspiration technique in diagnosing mediastinal and lung lesions, when EBUS-TBNA is deemed less suitable. Finally, we pointed out the importance of interventional pulmonologists being trained to perform mediastinal sampling by the esophageal route, to choose the best solution in every technical and clinical occurence.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Bronchoscopy in sarcoidosis: union is strength.

Sarcoidosis is a benign disease of unknown etiology that is characterized by the formation of noncaseating epithelioid cell granulomas. Although a multisystemic disease, it primarily affects the lung and the lymphatic system of the body. When a histological diagnosis is required, bronchoscopy is frequently employed because allows tissue sampling from several anatomic sources, such as airways, lung parenchyma and hilar/mediastinal nodes. Transbronchial lung biopsies (TBLB), endobronchial biopsies (EBB) and conventional transbronchial needle aspiration (cTBNA) have long been the only bronchoscopic techniques to diagnose sarcoid granulomas, until the advent of endobronchial ultrasound guided needle aspiration (EBUS-TBNA). This technique shows excellent yield in sampling mediastinal adenopathies with a higher sensitivity than the conventional technique in sarcoidosis as well. Furthermore, non controlled studies, demonstrated its diagnostic superiority than EBB and TBLB in stages I (hilar adenopathies only) and II (hilar lymph nodes and parenchymal infiltrations) thoracic sarcoidosis. In a recent study, Gupta et al., randomized 130 patients with suspected stage I and II disease to undergo EBUS-TBNA or cTBNA in conjunction with transbronchial and endobronchial biopsies. The Authors demonstrated that the yield of cTBNA added to EBB and TBLB is similar to EBUS-TBNA plus transbronchial biopsies, although ultrasound guided transbronchial needle aspiration shows the best single diagnostic efficacy. In this review article we aimed to discuss the findings by Gupta in the context of medical literature, highlighting the importance of adding nodal aspirations (with or without ultrasound guidance) with bronchial and transbronchial samples to gain the optimal sensitivity in obtaining histological confirmation. We finally pointed out the need for future studies to evaluate the potential role of rapid on-site evaluation (ROSE) of needle aspirates in reducing additional sampling and related costs and complications.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Choose the best route: ultrasound-guided transbronchial and transesophageal needle aspiration with echobronchoscope in the diagnosis of mediastinal and pulmonary lesions.

Nodal mediastinal staging is a crucial part of the diagnostic workup of patients with non-small-cell lung cancer (NSCLC) for planning optimal treatment. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and real-time endobronchial ultrasounds transbronchial needle aspiration (EBUS-TBNA) are accurate, minimally invasive and safe diagnostic techniques for mediastinal staging. Because of the different accessibility to the mediastinum, they are considered complementary and their combination increases the diagnostic yield as compared with the either alone. Recent studies have shown that endosonography represents the best initial test for invasive mediastinal evaluation in NSCLC. Endoscopic ultrasound (with bronchoscope)-guided fine needle aspiration (EUS-B-FNA) is a recently introduced procedure consisting of a transesophageal needle aspiration using an ultrasound bronchoscope. It allows to perform both transbronchial and transesophageal needle sampling with the same instrument, in the same session and by one operator only, thus maximizing time and costs savings. In a recent study Oki et al. randomized 110 patients with hilar/mediastinal adenopathies or lung abnormalities adjoining both the esophagus and the bronchi, to undergo EBUS-TBNA or EUS-FNA performed by pulmonologists with an echobronchoscope. The Authors demonstrated that both procedures provide a high diagnostic yield, without any difference in the number of adverse events and a good comparable tolerance. Nevertheless, the transesophageal approach guaranteed a significantly lower dose of anesthetics and sedatives, a shorter procedural time, fewer oxygen desaturations, a significantly lower cough score and a higher operator satisfaction. In this review our aim was to discuss the findings by Oki et al. in the context of medical literature, highlighting the importance of the EUS-B needle aspiration technique in diagnosing mediastinal and lung lesions, when EBUS-TBNA is deemed less suitable. Finally, we pointed out the importance of interventional pulmonologists being trained to perform mediastinal sampling by the esophageal route, to choose the best solution in every technical and clinical occurence.

The functional impact of adding salmeterol and tiotropium in patients with stable COPD.

The aim of this double-blind, double-dummy, crossover, randomised, pilot study was to explore the acute effects of adding salmeterol and tiotropium in patients with stable COPD. A total of 20 outpatients with stable COPD were enrolled. Single doses of 18-microg tiotropium, 50-microg salmeterol, and 18-microg tiotropium+ 50-microg salmeterol were given. Serial measurements of forced expiratory volume in 1 s (FEV1) were performed over 24h. The mean maximum increases in FEV1 from pre-dosing value on each of the dosing days were 0.165l (95% CI: 0.098-0.232) for tiotropium, 0.241 l (95% CI: 0.151-0.332) for salmeterol, and 0.290 l (95% CI: 0.228-0.353) for the combination and occurred 4 h after inhalation of tiotropium or salmeterol and 3 h after the combination. At 12h, the mean increases in FEV1 from pre-dosing value were 0.071 l (95% CI: 0.001-0.141; P = 0.047) for tiotropium, 0.069 l (95% CI: 0.018-0.120; P = 0.010) for salmeterol, and 0.108 l (95% CI: 0.047-0.170; P = 0.001) for the tiotropium + salmeterol combination. Only the difference between salmeterol and tiotropium + salmeterol was statistically significant (P = 0.009). At 24h, the mean FEV1 value was still higher than the mean pre-dosing value for tiotropium (0.042 l; 95% CI: -0.012-0.097; P=0.119) and the tiotropium+salmeterol combination (0.051 l; 95% CI: 0.01 5-0.087; P = 0.007), but not for salmeterol alone (-0.013 l; 95% CI: -0.041-0.014; P = 0.324). The FEV1 area under the curve (AUCs0-12h) were 1.657 l (95% CI: 1.152-2.162) for tiotropium, 2.068 (95l CI: 1.385-2.752) for salmeterol, and 2.541 l (95% CI: 1.954-3.129) for tiotropium + salmeterol. Only the difference between tiotropium and the tiotropium +salmeterol combination was statistically significant (P = 0.01). The FEV1 AUCs0-24h were 2.854 l (95% CI: 1.928-3.780) for tiotropium, 2.786 l (95% CI: 1.913-3.660) for salmeterol, and 3.640 l (95% CI: 2.674-4.605) for tiotropium + salmeterol. ALL differences between treatments were not statistically significant (P> 0.05). These results seem to indicate that the use of the tiotropium + salmeterol combination is more efficacious than the single agents alone, but the once-daily administration of the two drugs is inadvisable due to the broncholytic profile of salmeterol.

Onset of action of formoterol/budesonide in single inhaler vs. formoterol in patients with COPD.

Formoterol is a beta(2)-agonist bronchodilator that combines a fast onset of action with a long duration of broncholytic effect. An increasing documentation is showing that the combination of a long acting beta(2)-adrenoceptor agonist bronchodilator and an inhaled corticosteroid targets the airways obstruction in patients with COPD. In this study, we have explored whether the acute addition of an inhaled corticosteroid influences the fast bronchodilator response to formoterol. A total of 20 patients with stable COPD were randomized. Single doses of formoterol/budesonide 2 x (4.5/160)microg or formoterol 2 x 4.5 microg were given via Turbuhaler. Serial measurements of FEV(1) were performed over 60 min. Formoterol/budesonide elicited a significantly larger mean FEV(1)-AUC(0-15 min) than formoterol alone. Also the change in FEV(1) 15 min after inhalation of formoterol/budesonide combination (0.197 l; 95% CI: to 0.142-0.252) was greater than that induced by formoterol alone (0.147 l; 95% CI: to 0.092-0.201). The mean increases in FEV(1) were always higher after budesonide/formoterol than formoterol alone, although both treatments induced a significant improvement over baseline at each explored time point. Even the FEV(1)-AUC(0-60 min) after formoterol/budesonide was significantly larger than that after formoterol. Both treatments induced a significant reduction in VAS score but did not modify heart rate in a statistically significant manner. This study indicates that the addition of budesonide influences the fast onset of action of formoterol, but does not induce systemic effects, in patients with stable COPD.

Substituent effect on the stereochemistry of H2-receptor antagonists of the phenylformamidine series. A conformation-dependent mode of interaction with the H2 receptor.

The influence of alkyl substitution on the stereoisomerism of the formamidine cation (E,E vs E,Z) of several N-substituted (imidazolylphenyl)formamidines (1-10) was investigated. As (imidazolylphenyl)formamidines having alkyl substituents of more than three carbon atoms bind to H2-receptor preparations in a pseudoirreversible mode causing unsurmountable antagonism, the four isomeric butylformamidines (5-7 and 9) having comparable lipophilic character but different E,E/E,Z composition were investigated in H2-receptor assays to determine quantitatively any difference in their pseudoirreversible inhibitory pattern. It was found that the geometry of the formamidine cation is affected by the steric bulk of the substituent on the formamidine nitrogen. A relationship between the percentage of the E,E conformation of the formamidine cation and degree of pseudoirreversible antagonism was also found. The present studies support the hypothesis that bidentate hydrogen bonding plays an important role in the interaction of (imidazolylphenyl)formamidines with the H2 receptor.