Serum leptin and tumor necrosis factor - alpha levels and maximal exercise performance in patients with chronic obstructive pulmonary disease

Systemic inflammation plays an important role in skeletal muscle dysfunction in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this study is to determine whether serum leptin and tumor necrosis factor- alpha (TNF-a) levels, as markers of systemic inflammation, affect the maximal exercise performance of COPD patients.Methods: Thirty male COPD patients underwent pulmonary function and progressive exercise testing for maximal exercise and for VO2max determination. Fat Free Mass (FFM), Fat Mass (FM) and Thigh Muscle Area (TMA) were estimated by measuring skinfold thickness. Serum leptin and TNF-a levels were determined in morning blood samples.Results: Significant correlations were found between serum leptin levels and Body Mass Index (BMI) (r = 0.421, p < 0.02), FM (r = 0.551, p < 0.01) and TNF-a (r = 0.521, p < 0.001). Exercise performance, expressed as VO2max, correlated significantly with % FEV1 (r = 0.563, p < 0.001), BMI (r = 0.636, p < 0.001), FFM (r = 0.415, p < 0.02), TMA (r = 0.651, p < 0.001), but not with serum leptin or TNF-a levels. By stepwise regression analysis TMA appeared to be a significant predictor of VO2max in COPD patients.Conclusion: Serum leptin and TNF-a levels were poor predictors of maximal exercise capacity (VO2max) in COPD patients. The best predictors of VO2max during exercise were airflow limitation (%FEV1) and thigh muscle mass expressed by TMA.Results: Significant correlations were found between serum leptin levels and Body Mass Index (BMI) (r = 0.421, p < 0.02)

Does combined training of biofeedback and neurofeedback affect smoking status, behavior, and longitudinal brain plasticity?

Introduction: Investigations of biofeedback (BF) and neurofeedback (NF) training for nicotine addiction have been long documented to lead to positive gains in smoking status, behavior and to changes in brain activity. We aimed to: (a) evaluate a multi-visit combined BF/NF intervention as an alternative smoking cessation approach, (b) validate training-induced feedback learning, and (c) document effects on resting-state functional connectivity networks (rsFCN); considering gender and degree of nicotine dependence in a longitudinal design.Methods: We analyzed clinical, behavioral, and electrophysiological data from 17 smokers who completed five BF and 20 NF sessions and three evaluation stages. Possible neuroplastic effects were explored comparing whole-brain rsFCN by phase-lag index (PLI) for different brain rhythms. PLI connections with significant change across time were investigated according to different resting-state networks (RSNs).Results: Improvements in smoking status were observed as exhaled carbon monoxide levels, Total Oxidative Stress, and Fageström scores decreased while Vitamin E levels increased across time. BF/NF promoted gains in anxiety, self-esteem, and several aspects of cognitive performance. BF learning in temperature enhancement was observed within sessions. NF learning in theta/alpha ratio increase was achieved across baselines and within sessions. PLI network connections significantly changed across time mainly between or within visual, default mode and frontoparietal networks in theta and alpha rhythms, while beta band RSNs mostly changed significantly after BF sessions.Discussion: Combined BF/NF training positively affects the clinical and behavioral status of smokers, displays benefit in smoking harm reduction, plays a neuroprotective role, leads to learning effects and to positive reorganization of RSNs across time.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02991781

Does Smoking Affect OSA? What about Smoking Cessation?

The connection between smoking and Obstructive sleep apnea (OSA) is not yet clear. There are studies that have confirmed the effect of smoking on sleep disordered breathing, whereas others did not. Nicotine affects sleep, as smokers have prolonged total sleep and REM latency, reduced sleep efficiency, total sleep time, and slow wave sleep. Smoking cessation has been related with impaired sleep. The health consequences of cigarette smoking are well documented, but the effect of smoking cessation on OSA has not been extensively studied. Smoking cessation should improve OSA as upper airway oedema may reduce, but there is limited data to support this hypothesis. The impact of smoking cessation pharmacotherapy on OSA has been studied, especially for nicotine replacement therapy (NRT). However, there are limited data on other smoking cessation medications as bupropion, varenicline, nortriptyline, clonidine, and cytisine. The aim of this review was to explore the current evidence on the association between smoking and OSA, to evaluate if smoking cessation affects OSA, and to investigate the possible effects of different pharmacologic strategies offered for smoking cessation on OSA

Sleep Disorders and Mental Stress of Healthcare Workers during the Two First Waves of COVID-19 Pandemic: Separate Analysis for Primary Care

Background: During the recent pandemic, Healthcare Professionals (HCPs) presented a significant prevalence of psychological health problems and sleep disturbances. The aim of this study was to assess the impact of COVID-19 on HCPs&rsquo; sleep and mental stress with a separate analysis for primary care HCPs. Methods: A cross-sectional observational study with an online anonymized, self-reported questionnaire was conducted in May 2020 (1st wave) and repeated in December 2020 (2nd wave). Patient health questionnaire-4 (PHQ-4), dimensions of anger reactions-5 (DAR-5) scale, 3-item UCLA loneliness scale (LS) and sleep condition indicator (SCI) were used. Results: Overall, 574 participants were included from the 1st wave, 514 from the 2nd and 469 were followed during both. Anxiety and depression were significantly higher during the 2nd wave vs. the 1st (32.8% vs. 12.7%, p &lt; 0.001 and 37.7% vs. 15.8%, p &lt; 0.001). During the 2nd wave, HCPs scored significantly higher in DAR-5 (9.23 &plusmn; 3.82 vs. 7.3 &plusmn; 3.3, p &lt; 0.001) and LS (5.88 &plusmn; 1.90 vs. 4.9 &plusmn; 1.9, p &lt; 0.001) with worse sleep quality SCI (23.7 &plusmn; 6.6 vs. 25.4 &plusmn; 3.2, p &lt; 0.001). This was more evident in primary care HCPs. Significant correlations were found between SCI and PHQ4, DAR5 and LS. Conclusion: There is a need to support HCPs&rsquo; mental health and sleep, especially in those working in primary care

Pharmacokinetics of Ciprofloxacin and Its Penetration into Bronchial Secretions of Mechanically Ventilated Patients with Chronic Obstructive Pulmonary Disease▿

We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (Cmax) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC0–24) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a mean Cmax of 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC0–24/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 μg/ml, respectively. Slightly better results were obtained for the ratio Cmax/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 μg/ml

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624)