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.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Locating and quantifying multiple landfills methane emissions using aircraft data.

A mass balance approach to quantify methane (CH4) emission of four co-located landfills by means of airborne measurements and dispersion modelling was proposed and assessed. By flying grids at different heights above the landfills, atmospheric CH4 densities and wind components were measured along the edges and inside the study atmospheric volume, in order to calculate mass flows in the along- and across-wind directions. A steady-state Gaussian dispersion model was applied to build the concentration fields associated to unit emission from each landfill, while the contribution of each one to the total emission was assessed using a General Linear Model approach, minimizing the difference between measured and modeled mass flows. Results showed that wind spatial and temporal variability is the main factor controlling the accuracy of the method, as a good agreement between measured and modeled mass flows was mainly found for flights made in steady wind conditions. CH4 emissions of the entire area ranged from 213.5 ±â€¯33.5 to 317.9 ±â€¯90.4 g s-1 with a mean value of 252.5 ±â€¯54.2 g s-1. Contributions from individual sources varied from 17.5 to 40.1 g m-2 day-1 indicating a substantial heterogeneity of the different landfills, which differed in age and waste composition. The proposed method was validated against tower eddy covariance flux measurements made at one of the landfills, revealing an overall agreement within 20%.

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.

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.

Swimming pool-induced asthma.

A 13-year-old elite swimmer presented with wheezing after indoor swimming training. On the basis of her clinical history and the tests performed, exercise-induced asthma and mold-induced asthma were ruled out and a diagnosis of chlorine-induced asthma was made.

Vardenafil and weaning from inhaled nitric oxide: effect on pulmonary hypertension in ARDS.

We report a 66-year-old patient with refractory pulmonary hypertension secondary to ARDS who was being treated with inhaled nitric oxide. Enteral vardenafil (phosphodiesterase-5 inhibitor) was tried at two different doses (10 mg and 5 mg), in order to wean the patient from nitric oxide. The higher dose decreased pulmonary pressure but caused systemic hypotension and the drug was discontinued. Subsequently, a 5 mg dose of vardenafil decreased pulmonary pressure without hypotension. Pulmonary hypertension was controlled using vardenafil 10-15 mg divided in 2-3 daily doses. This therapy allowed nitric oxide withdrawal, weaning from mechanical ventilation and discharge from ICU Vardenafil acted in synergy with inhaled nitric oxide, permitted nitric oxide reduction and discontinuation and proved to be effective as a single, long-term treatment for pulmonary hypertension.

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.

Bronchodilator effect of an inhaled combination therapy with salmeterol + fluticasone and formoterol + budesonide in patients with COPD.

In the present trial, we compared the broncholytic efficacy of the combination therapy with 50 microg salmeterol + 250 microg fluticasone and 12 microg formoterol + 400 microg budesonide, both in a single inhaler device, in 16 patients with moderate-to-severe COPD. The study was performed using a single-blind crossover randomized study. Lung function, pulse oximetry (SpO2) and heart rate were monitored before and 15, 30, 60, 120, 180, 240, 300, 360, 480, 600, and 720 min after bronchodilator inhalation. Both combinations were effective in reducing airflow obstruction. FEV1 AUC(0-12 h) was 2.83 l (95% CI: 2.13-3.54) after salmeterol/fluticasone and 2.57 l (95% CI: 1.97-3.2) after formoterol/budesonide. Formoterol/budesonide elicited the mean maximum improvement in FEV1 above baseline after 120 min (0.29 l; 95% CI: 0.21-0.37) and salmeterol/fluticasone after 300 min (0.32 l; 95% CI: 0.23-0.41). At 720 min, the increase in FEV1 over baseline values was 0.10 l (95% CI: 0.07-0.12) after salmeterol/fluticasone and 0.10 l (95% CI: 0.07-0.13) after formoterol/budesonide. The mean peak increase in heart rate occurred 300 min after formoterol/budesonide (1.5 b/min; 95% CI--2.3 to 5.3) and 360 min after salmeterol/fluticasone (2.6 b/min; 95% CI--1.9 to 7.0). SpO2 did not change. All differences between salmeterol/fluticasone and formoterol/budesonide were not significant (P > 0.05) except those in FEV1 at 120 and 360 min. The results indicate that an inhaled combination therapy with a long-acting beta2-agonist and an inhaled corticosteroid appears to be effective in improving airway limitation after acute administration in patients suffering from COPD.

A single high dose of formoterol is as effective as the same dose administered in a cumulative manner in patients with acute exacerbation of COPD.

Several clinical trials have shown that the inhaled beta2-agonists with long-acting properties, formoterol and salmeterol, may be effective in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, there is a great deal of controversy regarding the timing and optimal dose of inhaled beta2-agonists in this pathologic condition. In this double-blind, randomised, crossover study, we have compared the bronchodilating effect and the safety of inhaled formoterol administered via Turbuhaler using either a cumulative dose regimen or the equivalent single dose in 16 patients with acute exacerbations of COPD. On the two consecutive days, the patients received, in a randomised order, each of the following active dose regimens: (A): 9 + 9 + 18 microg of formoterol via Turbuhaler (36 microg cumulative delivered dose) or (B): 36 + 0 + 0 microg of formoterol via Turbuhaler. The three doses on each treatment day were administered at 30-mm intervals, with measurements being made 5 and 30 min after each dose. Contemporaneously, we also measured oxygen saturation by pulse oximetry (SpO2) and pulse rate. Both the high dose and the cumulative one induced a significant bronchodilation expressed as change in FEV1. The difference between the two regimens was significant (P=0.0332) only 60 min after the first inhalation. The trend of FVC and IC was similar to that of FEV1. All treatment regimens were well tolerated and no adverse events were reported. Neither the administration ofthe high dose nor that of the cumulative one modified heart rate in a significant manner. Also they did not influence SpO2. This study indicates that a single high dose offormoterol is as effective as the same dose administered in a cumulative manner in patients with acute exacerbation of COPD.

Bronchodilation test in COPD: effect of inspiratory manoeuvre preceding forced expiration.

The effects of an inspiratory manoeuvre preceding forced expiration on functional tests performed under routine conditions before and after inhalation of a bronchodilator drug (salbutamol) were assessed on 150 consecutive chronic obstructive pulmonary disease outpatients. The patients performed forced vital capacity manoeuvres either immediately after a rapid inspiration (manoeuvre no. 1) or after a slow inspiration with a 4-6 s pause (manoeuvre no. 2). Under baseline conditions, forced expiratory volume in one second (FEV1) values were 8% (% control) larger with manoeuvre no. 1 than no. 2. FEV1 values increased with salbutamol administration by approximately 8% and were, on average, still 7% larger with manoeuvre no. 1 than no. 2. The incidence of reversibility, assessed according to American Thoracic Society criteria, was 76% when manoeuvre no. 2 was selected to represent baseline conditions and manoeuvre no. 1 was chosen to represent the effects of bronchodilator administration, whereas the lowest incidence (2%) was found when manoeuvre no. 1 was selected to represent baseline conditions and manoeuvre no. 2 was chosen to represent the effects of bronchodilator administration. These results indicate that the time dependence of the forced vital capacity manoeuvre has an important impact on the assessment of routine lung function in a clinical setting and supports the notion that the time course of the inspiration preceding the forced vital capacity manoeuvre should be standardised.

Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD.

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol. The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients. Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration. The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population.

Bronchodilating effect of oxitropium bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study.

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.

RNA polymerase III transcription complexes on chromosomal 5S rRNA genes in vivo: TFIIIB occupancy and promoter opening.

Quantitative analysis of multiple-hit potassium permanganate (KMnO(4)) footprinting has been carried out in vivo on Saccharomyces cerevisiae 5S rRNA genes. The results fix the number of open complexes at steady state in exponentially growing cells at between 8 and 17% of the 150 to 200 chromosomal copies. UV and dimethyl sulfate footprinting set the transcription factor TFIIIB occupancy at 23 to 47%. The comparison between the two values suggests that RNA polymerase III binding or promoter opening is the rate-limiting step in 5S rRNA transcription in vivo. Inhibition of RNA elongation in vivo by cordycepin confirms this result. An experimental system that is capable of providing information on the mechanistic steps involved in regulatory events in S. cerevisiae cells has been established.

Onset of action of single doses of formoterol administered via Turbuhaler in patients with stable COPD.

We studied 16 patients with stable COPD in a double blind, double dummy, placebo-controlled, within patient study to see if formoterol could be used as a rescue drug. We compared the of onset of bronchodilation obtained with formoterol 12 microg (metered dose corresponding to 9 microg delivered dose) and formoterol 24 microg (metered dose corresponding to 18 microg delivered dose), both delivered via Turbuhaler, with that of salbutamol 400 microg and salbutamol 800 microg delivered via pressurized metered-dose inhaler (pMDI). Patients inhaled single doses of placebo, formoterol and salbutamol on five separate days. FEV1 was measured in baseline condition and 3, 6, 9, 12, 15, 18, 21, 24, 30, 40, 50, and 60 min after inhalation of each treatment. We examined two separate criteria for deciding if a response was greater than that expected by a random variation of the measurement: (1) a rise in FEV1 of at least 15% from the baseline value; (2) an absolute increase in FEV1 of at least 200 ml. Formoterol 12 microg (15.2 min; 95% CI 9.5-21.0) and formoterol 24 microg (15.1 min; 95% CI 8.9-21.2) caused a rise in FEV1 of at least 15% from the baseline value almost rapidly as salbutamol 400 microg (13.6 min; 95% CI 7.1-20.1) and salbutamol 800 microg (14.5 min; 95% CI 7.1-21.9). No significant difference (P=0.982) in onset of action was seen between the four active treatments. According to Criterion 2, the mean time to 200 ml increase in FEV1 was 11.1 min (95% CI: 7.0-15.2) after salbutamol 400 microg, 13.0 min (95% CI: 7.9-18.1) after salbutamol 800 microg, 14.7 min (95% CI: 7.1-22.4) after formoterol 12 microg, and 12.7 min (95% CI: 7.4-18.0) after formoterol 24 microg. Again, there was no significant difference (P= 0.817) between the four active treatments. Formoterol Turbuhaler 12 microg and 24 microg caused bronchodilation as rapidly as salbutamol 400 microg and 800 microg given via pMDI.

Lung function improvement in smokers suffering from COPD with zafirlukast, a CysLT(1)-receptor antagonist.

The present study was designed to evaluate the bronchodilating role of zafirlukast, a CysLT(1)receptor antagonist, at the standard dosage currently recommended in the marketing of this agent in smokers with COPD. The study was performed using a double-blind, cross-over, randomized design and was conducted on 2 non-consecutive days. Sixteen outpatients suffering from stable COPD received 40 mg oral zafirlukast, or placebo. Lung function was controlled before drug administration and 30, 60, 120, 180, 240 min thereafter. At the end of the 4-h period, each patient received 400 microg inhaled salbutamol and spirometric testing was performed 30 min later. Zafirlukast, but not placebo, produced a significant (P<0.05) bronchodilation between 30 min and 4 h following administration, with a maximum mean increase in FEV(1)of 0.134 l (11.2%) above baseline after 2 h. Nine of 16 patients showed an increase in FEV(1)of at least 15% above baseline after zafirlukast. The maximum mean increase in FEV(1)after zafirlukast in these subjects, who were considered responders, observed after 2 h, was 0.221 (19.4%). The mean difference of post-salbutamol FEV(1)values after zafirlukast and placebo (-0.036 l) was not significant (P<0.05). In responders, the mean of differences in pre- and post-salbutamol FEV(1)values after zafirlukast was 0.077 l, whereas the mean of differences between post-salbutamol values after zafirlukast and those after placebo was -0.064 l. The mean AUC(0-4 h)for all patients was 0.121 l for placebo and 0.385 l for zafirlukast. The difference between the placebo and zafirlukast AUC(0-4 h)was significant (P<0.05). The individual FEV(1)AUC(0-4 h)after zafirlukast were higher than those after placebo in 12 out of 16 patients. These findings suggest that cysteinyl leukotrienes might be one of the causes of persistent bronchoconstriction in COPD, at least in several smokers, but do not confirm the hypothesis that the effects of zafirlukast and salbutamol are independent and additive.