Abstract Background The aim of this work was to evaluate the effect of high-intensity interval exercise (i.e., 30 s at 100% of max workload, followed by 30 s at rest, 45 min 3 days/week working-out ...schedule for 12 weeks) on left ventricular function and aortic elastic properties among chronic heart failure (CHF) patients. Methods This study is a phase III clinical trial. Of the 100 consecutive CHF patients (NYHA classes II–IV, ejection fraction < 50%) that were randomly allocated, 72 completed the study (exercise training group, n = 33, 63 ± 9 years, 88% men, and control group, n = 39, 56 ± 11 years, 82% men). All patients underwent cardiopulmonary stress test, non-invasive high-fidelity tonometry of the radial artery, pulse wave velocity measurement using a SphygmoCor device and echocardiography before and after the completion of the training program. Results Both groups reported similar medical characteristics and physical activity status. General mixed effects models revealed that the intervention group reduced pulse wave velocity by 9% (p = 0.05); Emv/Vp by 14% (p = 0.06); E to A ratio by 24% (p = 0.004), E to Emv ratio by 8% (p = 0.05), MLHFQ score by 66% (p = 0.003) and the depression score by 19% (p = 0.5); increased augmentation index by 29%; VTI by 4% (p = 0.05), 6-minute-walk distance up to 13% (p = 0.05), peak oxygen uptake by 28% (p = 0.001) and peak power by 25% (p = 0.005). There were no significant changes in the control group. Conclusion Interval high-intensity aerobic training, combined with strength exercise, seems to benefit aortic dilatation capacity and augmented systolic pressure in parallel with improvement in left ventricular diastolic function and quality of life.
ABSTRACT
Background and objective
This study investigated the duration of immediate respiratory effects of e‐cigarette smoking (ECS) and tested the hypothesis that ECS has more prominent effects in ...asthmatics compared with healthy smokers (HS).
Methods
Fifty‐four smokers, 27 healthy (HS group) and 27 with intermittent asthma (mild asthma (MA) group) underwent a control session (no liquid, no resistor coil inside e‐cigarette cartridge) and an experimental session of ECS using standardized puffing settings. Impulse oscillometry impedance (Z), resistance (R), reactance (X) and fractional exhaled nitric oxide (FeNO) were measured before and 0, 15 and 30 min after control and experimental sessions.
Results
Control session revealed no significant changes. In the experimental session, immediately post‐ECS, both groups exhibited a significant increase in respiratory system total impedance at 5 Hz (Z5) (P < 0.001), respiratory system resistance at 5 Hz (R5) (P < 0.001), respiratory system resistance at 10 Hz (R10) (P < 0.001), respiratory system resistance at 20 Hz (R20) (P < 0.05), resonant frequency (P < 0.001) and reactance area (P < 0.05).
MA exhibited higher baseline values and a more prominent effect immediately after ECS compared with HS for Z5 (P = 0.022), R5 (P = 0.010) and R10 (P = 0.013).
FeNO decreased significantly in both groups (P < 0.001); HS returned to baseline values in ≤15 min while the MA maintained significantly lower values for an additional 15 min (P < 0.05) and returned to baseline values at 30 min post‐ECS.
Conclusion
A single session of ECS had respiratory mechanical and inflammatory effects, which were more prominent in smokers with asthma.
E‐cigarette smoking (ECS) has immediate mechanical and inflammatory consequences in smokers, with more prominent duration and intensity in mild asthma (MA). ECS and MA also had synergistic effects on respiratory function. These findings have implications for asthma management and tobacco control.
•COPD is characterized by chronic inflammation and emphysematous alveolar destruction.•Studies provide strong support for the involvement of IL-18 in the pathogenesis of COPD.•Neutralizing antibodies ...to IL-18 have efficacy in preclinical models of inflammation and injury.•IL-18 is suggested as a potential therapeutic target in COPD limiting destruction and remodeling.
Interleukin (IL)-18 is a pro-inflammatory cytokine that was firstly described as an interferon (IFN)-γ-inducing factor. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. The platform for activating caspase-1 is known as the inflammasome, a multiple protein complex. Macrophages and dendritic cells are the primary sources for the release of active IL-18, whereas the inactive precursor remains in the intracellular compartment of mesenchymal cells. Finally, the IL-18 precursor is released from dying cells and processed extracellularly.
IL-18 has crucial host defense and antitumor activities, and gene therapy to increase IL-18 levels in tissues protects experimental animals from infection and tumor growth and metastasis. Moreover, multiple studies in experimental animal models have shown that IL-18 over-expression results to emphysematous lesions in mice. The published data prompt to the hypothesis that IL-18 induces a broad spectrum of COPD-like inflammatory and remodeling responses in the murine lung and also induces a mixed type 1, type 2, and type 17 cytokine responses. The majority of studies identify IL-18 as a potential target for future COPD therapeutics to limit both the destructive and remodeling processes occurring in COPD lungs.
Sestrins (Sesns) are a family of highly conserved stress-inducible proteins and various stresses have been shown to strongly up-regulate them. Sestrin 2 (Sesn2) deficiency has been shown to partially ...suppress pulmonary emphysema. The aim of this study was to evaluate Sesn2 levels in COPD patients and its possible associations with the presence of emphysema and blood eosinophils. All patients underwent lung function testing and high-resolution computed tomography (HRCT) of the chest. The presence of emphysematous lesions in >15% of the pulmonary parenchyma was considered as significant emphysema. Sixty-seven patients were included in the study. 40/67 patients were characterized as having significant emphysema. Patients with significant emphysema had higher levels of Sesn2 (ng/ml) median (IQR) 6.7 (2.7,10.3 vs 1.09 (0.9,1.9), p<0.001) and significantly lower % and absolute blood eosinophil counts (cells/muL) compared to patients without emphysema 1 (0, 2) vs 4 (2, 4) p<0.001 and 62 (0, 110) vs 248 (180, 300), p<0.001 respectively. Sesn2 presented a significant positive correlation to the score of emphysema in HRCT (r.sub.s = 0.87, p<0.001) and similar positive but weaker correlation to FRC (r.sub.s = 0.27, p = 0.024). Negative correlations were observed between Sesn2 and either the % of blood eosinophils and/or the absolute blood eosinophil count (r.sub.s = -0.79, p<0.001, and r.sub.s = -0.78, p<0.001 respectively). Sesn2 levels above 1.87 ng/ml showed a high diagnostic performance for the presence of significant emphysema in HRCT with an AUC 0.93, 95% CI (0.85,0.98), p<0.001. Sesn2 could serve as a potential biomarker of emphysema.
Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF).
To investigate the safety and efficacy of nintedanib in ...patients with IPF in a real-life setting.
This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016.
We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73.8 ± 7.5, mean%FVC±SD = 68.1 ± 18.3, mean%DLCo±SD = 44.4 ± 14.5). Diarrhea (n = 52, 55.3%) was the most commonly reported adverse event. Twenty patients (21.2%) had to permanently discontinue nintedanib due to severe adverse events. In the 6-months follow-up, median decline in %FVC predicted and %DLCO predicted were 1.36 (95%Cl: 0 to 2.97) and 4.00 (95%Cl: 2.01 to 6.20), respectively, when deaths were censored and excluded from the analysis. At 12 months, mean%FVC±SD and mean%DLCo±SD were 64.5 ± 19.1 and 43.7 ± 15.4, respectively. With regards to mortality, 17 patients (18.1%) died over a study period of 730 days.
Nintedanib demonstrated an acceptable safety and efficacy profile in our real-world observational study. Prospective observational studies in the context of registries that collect well-defined supporting data over time are sorely needed to answer residual questions on drug's performance.
For the various asthma-specific beneficial effects of physical activity, daily physical activity (DPA) and the potential of asthma therapies on DPA require better characterization. Hence, we aimed to ...determine (a) the DPA of asthma patients, and (b) the effect of add-on mepolizumab on the DPA of severe asthma patients. Methods: Adult outpatients with mild-to-moderate or severe asthma had accelerometer assessment of DPA. Severe asthma patients who were commenced on mepolizumab had their DPA reassessed after 12 months. Results: For the total cohort (n = 36), daily step count, time in moderate-to-vigorous physical activity (MVPA), MVPA volume and Movement Intensity (MI) were 7806 ± 3823 steps, 123 (interquartile range, 63) min, 657 ± 255 MET·min and 1.96 (0.45) m/s2, respectively. All patients met at least one recommendation for DPA but less than half met recommendations for vigorous DPA. Patients on mepolizumab therapy increased daily step count (646 steps; 9%), time in MVPA (20 min; 21%), MVPA volume (87 MET·min; 17%) and MI (0.11 m/s2; 6%) for the same amount of moving time; lung function, asthma control and health-related quality of life also improved. Conclusions: Analysis of the first national data on DPA in asthma and novel comparison against current applicable guidelines and identified beneficial thresholds showed borderline levels of DPA with room for improvement especially for severe asthma patients. In a non-sedentary cohort of severe asthma patients, mepolizumab conferred significant and meaningful improvements in DPA.
We performed metabolomic profiling to identify metabolites that correlate with disease progression and death.
We performed a study of adults hospitalized with Influenza A(H1N1)pdm09. Cases (n = 32) ...were defined by a composite outcome of death or transfer to the intensive care unit during the 60-day follow-up period. Controls (n = 64) were survivors who did not require transfer to the ICU. Four hundred and eight metabolites from eight families were measured on plasma sample at enrollment using a mass spectrometry based Biocrates platform. Conditional logistic regression was used to summarize the association of the individual metabolites and families with the composite outcome and its major two components.
The ten metabolites with the strongest association with disease progression belonged to five different metabolite families with sphingolipids being the most common. The acylcarnitines, glycerides, sphingolipids and biogenic metabolite families had the largest odds ratios based on the composite endpoint. The tryptophan odds ratio for the composite is largely associated with death (OR 17.33: 95% CI, 1.60-187.76).
Individuals that develop disease progression when infected with Influenza H1N1 have a metabolite signature that differs from survivors. Low levels of tryptophan had a strong association with death.
ClinicalTrials.gov Identifier: NCT01056185.
Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary ...abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece.
Methods
This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece).
Results
The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A.
Conclusion
Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.
Pirfenidone is a novel anti-fibrotic drug that has shown efficacy in five randomized multicenter clinical trials enrolling patients with Idiopathic Pulmonary Fibrosis of mild-to-moderate disease ...severity. Scarce data supports the use of pirfenidone in IPF patients with more advanced disease.
To investigate the safety and efficacy profile of pirfenidone in IPF patients with severe lung function impairment.
This was a retrospective study enrolling patients with advanced IPF (FVC%predicted < 50% and/or (DLco%predicted <35%) receiving pirfenidone for at least 6 months.
Between September 2011 and March 2013, we identified 43 patients with severe IPF (baseline meanFVC%predicted±SD: 63.8 ± 20.3, meanDLCO%predicted: 27.3 ± 8.2), of mean age±SD: 66.3 + 9.7, 34 males (81%) that received pirfenidone (2.403 mg/daily) for one year. Pirfenidone treatment was associated with a trend towards decrease in functional decline compared to 6-months before treatment initiation but failed to show any benefit after one year of treatment (ΔFVC: −3.3 ± 4.6 vs 0.49 ± 11.4 and vs. −5.8 ± 11.8, p = 0.06 and p = 0.04, respectively and ΔDLCO: −13.3 ± 15.2 vs. −10.1 ± 16.6 and vs. 28.3 ± 19.2, p = 0.39 and p = 0.002, respectively). Gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%) were the most common adverse events. Adverse events led to treatment discontinuation in 9 patients (20.9%) and dose reduction in 14 (32.5%).
Pirfenidone appears to be safe when administered in patients with advanced IPF. Pirfenidone efficacy in IPF patients with severe lung function impairment may diminish after 6 months of treatment.
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