Transient hyperthermia during ex vivo lung perfusion has no protective effect in rat model.

BACKGROUND: Although ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation, EVLP itself can lead to inflammation in the lung. Heat shock proteins (HSPs) have anti-inflammatory effects and can reduce ischemic reperfusion injury in the donor's lungs after transplantation. In this study, the effects of transient hyperthermia during EVLP on the expression of HSPs and inflammatory pathways were examined. METHODS: Fifteen male Sprague-Dawley rats were randomly divided into three groups: sham (n = 5), normothermic EVLP (37 °C, n = 5), and transient hyperthermia during EVLP (42 °C, n = 5). Lung function analyses regarding PaO2/FiO2 ratio, compliance, and pulmonary vascular resistance were conducted. The expression levels of HSPs and inflammatory cytokines were also evaluated. The degree of lung injury was histopathologically evaluated. Transcriptome analysis was performed on lung tissues from the sham (n = 2), normothermic EVLP (n = 2), and heat stress-EVLP (n = 2) groups. RESULTS: There were no significant differences in functional or histological parameters between the three groups. The expression of HSPs had significantly increased, especially that of HSPs 40 and 60 in the heat stress EVLP group; this was consistent with the inflammatory response. Inflammatory cytokine levels were significantly higher during EVLP and intensified with transient hyperthermia. CONCLUSION: Transient hyperthermia during EVLP has no protective effect on the donor lung graft or activation of the inflammatory pathway at the gene level.

Pulmonary Function and Aerobic Capacity Responses to Equine Assisted Therapy in Adolescents with Idiopathic Scoliosis: A Randomized Controlled Trial.

BACKGROUND: Idiopathic scoliosis is a common spinal malalignment that negatively impacts the respiratory system and physical conditioning in adolescents. Equine-assisted therapy comprises therapeutic horseback riding that optimizes physical performance and mobility in a range of contexts. However, the influence of equine-assisted therapy on pulmonary function remains unclear. OBJECTIVE: To examine the impact of 10 weeks of hippotherapy combined with Schroth exercises on pulmonary function and aerobic capacity in adolescents with idiopathic scoliosis. METHODS: A randomized controlled trial including 45 patients, randomly assigned to experimental and control groups, was performed. Patients in the experimental group received 15 30-min sessions of hippotherapy over a period of 10 weeks. The 2 groups attended a 60-min session of Schroth exercises 3 times/week for 10 weeks. Pulmonary function and functional capacity were assessed before and after the intervention. RESULTS: Pre- and post-intervention variables (FVC, FEV1, FEV1/FVC, MVV and 6MWT) revealed significant improvement in both groups (p < 0.05). The improvement in the experimental group was significantly higher than in the control group (p < 0.05). CONCLUSION: The addition of hippotherapy to Schroth exercises resulted in improved pulmonary function and aerobic capacity in adolescents with idiopathic scoliosis.

Effects of yogic intervention on pulmonary function and respiratory muscle strength parameters: A systematic literature review and meta-analysis.

The aim of this systematic review and meta-analysis is to investigate the efficacy of yogic intervention (YI) on pulmonary functions (PFs) and respiratory muscle strength parameters in healthy individuals. PubMed/Medline, Embase, Google Scholar, SPORTdiscus databases as well as manual searches carried out until March 2020 on yoga AND pulmonary function were included based on Prisma guidelines. Twenty studies were identified potentially relevant. They were systematically reviewed and summarized in tabular form, listing yogic intervention (YI) significant improved forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1); FEV1/FVC; peak expiratory flow rate (PEFR), maximum voluntary volume (MVV), respiratory muscle strength parameters like maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP or PEmax). There are encouraging results elucidated that yogic intervention improves pulmonary functions and respiratory muscle strength parameters of healthy physically fit individuals significantly.

Effect of Perinatal Vitamin D Deficiency on Lung Mesenchymal Stem Cell Differentiation and Injury Repair Potential.

Stem cells, including the resident lung mesenchymal stem cells (LMSCs), are critically important for injury repair. Compelling evidence links perinatal vitamin D (VD) deficiency to reactive airway disease; however, the effects of perinatal VD deficiency on LMSC function is unknown. We tested the hypothesis that perinatal VD deficiency alters LMSC proliferation, differentiation, and function, leading to an enhanced myogenic phenotype. We also determined whether LMSCs' effects on alveolar type II (ATII) cell function are paracrine. Using an established rat model of perinatal VD deficiency, we studied the effects of four dietary regimens (0, 250, 500, or 1,000 IU/kg cholecalciferol-supplemented groups). At Postnatal Day 21, LMSCs were isolated, and cell proliferation and differentiation (under basal and adipogenic induction conditions) were determined. LMSC paracrine effects on ATII cell proliferation and differentiation were determined by culturing ATII cells in LMSC-conditioned media from different experimental groups. Using flow cytometry, >95% of cells were CD45-ve, >90% were CD90 + ve, >58% were CD105 + ve, and >64% were Stro-1 + ve, indicating their stem cell phenotype. Compared with the VD-supplemented groups, LMSCs from the VD-deficient group demonstrated suppressed PPARγ, but enhanced Wnt signaling, under basal and adipogenic induction conditions. LMSCs from 250 VD- and 500 VD-supplemented groups effectively blocked the effects of perinatal VD deficiency. LMSC-conditioned media from the VD-deficient group inhibited ATII cell proliferation and differentiation compared with those from the 250 VD- and 500 VD-supplemented groups. These data support the concept that perinatal VD deficiency alters LMSC proliferation and differentiation, potentially contributing to increased respiratory morbidity seen in children born to mothers with VD deficiency.

Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan.

BACKGROUND: The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. METHODS: BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. RESULTS: After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. CONCLUSIONS: NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

Efectos de la suplementación con vitamina D en el control del asma en pacientes adultos: una revisión sistemática / Effects of vitamin D supplementation on asthma control in adult patients: a systematic review

INTRODUCCIÓN: El asma es una enfermedad crónica inflamatoria de la vía aérea e inmunomediada en su patogénesis. La vitamina D es un inmunomodulador que regula el perfil secretor de citoquinas, entre otras funciones celulares. Una asociación entre la suficiencia de vitamina D y mejoría en la función pulmonar, control de asma y número de exacerbaciones se ha propuesto en adultos, importante dada la elevada prevalencia de insuficiencia de vitamina D globalmente. OBJETIVO: Conocer los efectos de la suplementación con vitamina D en el control del asma en adultos. MÉTODOS: Se realizó una revisión sistemática de la literatura a través de una búsqueda en la base de datos PubMed y EMBASE. Los desenlaces primarios fueron cambios en VEF1, control sintomático, frecuencia de exacerbaciones, además de eventos adversos y FEM como desenlaces secundarios. La calidad de evidencia de los desenlaces fue evaluada a través del modelo GRADE. RESULTADOS: Siete estudios fueron seleccionados después de remover duplicados y aplicar los criterios de inclusión y exclusión, con calidad de evidencia muy baja aplicando sistema GRADE. DISCUSIÓN: No se encontraron diferencias estadísticamente significativas tras la suplementación con vitamina D en los desenlaces evaluados en general, pero dada la calidad de evidencia muy baja y que no se reportaron efectos adversos serios, es necesario tomar cautelosamente estos resultados. Asímismo no se puede descartar la utilidad de esta terapia como tratamiento auxiliar a los pacientes asmáticos con este déficit vitamínico.

BACKGROUND: Asthma is an airway chronic disease, with an important inflammatory component within its pathogenesis, driven by a dysregulated immune response. Vitamin D is an immunomodulator that regulates cell proliferation, differentiation and cytokine secretion profile. An association between vitamin D sufficiency and improvement in pulmonary function, asthma control and a decrease in exacerbations have been proposed in the adult population, which falls into importance given the high prevalence of vitamin D insufficiency globally. OBJECTIVE: To know vitamin D supplementation effects in asthma control in adults. METHODS: Through a PubMed and EMBASE database search, a systematic review of the literature was conducted. Primary outcomes were: changes in FEV1, symptomatic control, exacerbation frequency and PEF and adverse events as secondary outcomes. Outcome evidence quality assessment was made using the GRADE model. Results: Seven studies were selected after taking out duplicates, applying inclusion and exclusion criteria. In all cases, evidence quality assessed by the GRADE system yielded very low quality. CONCLUSIONS: No statistically significant differences were found after vitamin D supplementation in the overall evaluated outcomes. Nonetheless, a cautious interpretation of studies is mandatory, because evidence quality was very low and no serious adverse events were reported. Hence this treatment usefulness as an ancillary therapy for vitamin D deficient asthmatic patients cannot be dismissed.

Performance characteristics of high-frequency percussive ventilation under hyperbaric conditions.

Introduction: Safe administration of critical care hyperbaric medicine requires specialized equipment and advanced training. Equipment must be tested in order to evaluate function in the hyperbaric environment. High-frequency percussive ventilation (HFPV) has been used in intensive care settings effectively, but it has never been tested in a hyperbaric chamber. Methods: Following a modified U.S. Navy testing protocol used to evaluate hyperbaric ventilators, we evaluated an HFPV transport ventilator in a multiplace hyperbaric chamber at 1.0, 1.9, and 2.8 atmospheres absolute (ATA). We used a test lung with analytical software for data collection. The ventilator uses simultaneous cyclic pressure-controlled ventilation at a pulsatile flow rate (PFR)/oscillatory continuous positive airway pressure (oCPAP) ratio of 30/10 with a high-frequency oscillation percussive rate of 500 beats per minute. Inspiratory and expiratory times were maintained at two seconds throughout each breathing cycle. Results: During manned studies, the PFR/oCPAP ratios were 26/6, 22/7, and 22.5/8 at an airway resistance of 20cm H2O/L/second and 18/9, 15.2/8.5, and 13.6/7 at an airway resistance of 50 cm/H2O/L/second at 1, 1.9, and 2.8 ATA. The resulting release volumes were 800, 547, and 513 mL at airway resistance of 20 cm H2O/L/sec and 400, 253, and 180 mL at airway resistance of 50 cm/H2O/L/sec at 1, 1.9, and 2.8 ATA. Unmanned testing showed similar changes. The mean airway pressure (MAP) remained stable throughout all test conditions; theoretically, supporting adequate lung recruitment and gas exchange. A case where HFPV was used to treat a patient for CO poisoning was presented to illustrate that HFPV worked well under HBO2 conditions and no complications occurred during HBO2 treatment. Conclusion: The HFPV transport ventilator performed adequately under hyperbaric conditions and should be considered a viable option for hyperbaric critical care. This ventilator has atypical terminology and produces unique pulmonary physiology, thus requiring specialized training prior to use.

Amelioration of pulmonary aflatoxicosis by green tea extract: An in vivo study.

Aflatoxins (AFB1) are mycotoxins known to be associated with human and animal diseases. The lung is a at risk from AFB1exposure either via inhalation or circulation. Green tea consumption is increasing over time due to widespread popularity as antioxidants, anti-inflammatory, and cytoprotective agents. Therefore, we attempted to study the lung toxicity caused by AFB1 and the possible ameliorating effect of green tea extract. Forty adult male albino rats were divided into five groups; Group I: Untreated control group, Group II (vehicle): Each rat received 1 ml of olive oil, Group III (GTE): Each rat received Camellia sinensis, green tea extract (30 mg/kg/day), Group IV(AFB1): Each rat received (50 µg/kg/day of AFB1). Group V (AFB1+ GTE): Each rat received the same previously mentioned doses of AFB1 in addition to GTE concomitantly. All treatments were orally gavaged for 8 weeks then rats were sacrificed. Serum levels of pro-inflammatory (IL-1ß, TNF-α, IL-6) and anti-inflammatory (IL-10) cytokines were measured, lung tissues' oxidative stress indices were also measured in addition to the histopathological study which was performed by using hematoxylin & eosin and Masson trichrome stains. Morphometric and statistical analyses were also performed. Oral gavage of AFB1 resulted in significant histopathological changes in the lung tissues, in the form of variable degrees of congestion, hemorrhage, interstitial inflammation with infiltration by chronic inflammatory cells, interstitial fibrosis, bronchitis, vasculitis and fibrous thickening of arterial walls. Inflammation was evident by elevated levels of pro-inflammatory cytokines and a declined level of anti-inflammatory cytokines. Also, oxidative stress was evident by increased levels of Malondialdehyde (MDA), Myeloperoxidase (MPO), and decreased levels of total glutathione (tGSH) and Catalase (CAT). The histopathological changes, inflammatory cytokines, and oxidative stress markers were significantly decreased during concomitant administration of green tea extract in (AFB1+ GTE) group. Aflatoxin B1 has deleterious effects on the lung tissue that could be minimized by concomitant administration of Green tea extract owing to its anti-inflammatory, antioxidant, and protective properties.

Inspiratory Muscle Training on Glucose Control in Diabetes: A Randomized Clinical Trial.

This study evaluated the effects of inspiratory muscle training (IMT) in glucose control and respiratory muscle function in patients with diabetes. It was a randomized clinical trial conducted at the Physiopathology Laboratory of the Hospital de Clínicas de Porto Alegre. Patients with Type 2 diabetes were randomly assigned to IMT or placebo-IMT (P-IMT), performed at 30% and 2% of maximal inspiratory pressure, respectively, every day for 12 weeks. The main outcome measures were HbA1c, glycemia, and respiratory muscle function. Thirty patients were included: 73.3% women, 59.6 ± 10.7 years old, HbA1c 8.7 ± 0.9% (71.6 ± 9.8 mmol/mol), and glycemia 181.8 ± 57.8 mg/dl (10.5 ± 3.2 mmol/L). At the end of the training, HbA1c was 8.2 ±0.3% (66.1 ± 3.3 mmol/mol) and 8.7 ± 0.3% (71.6 ± 3.3 mmol/mol) for the IMT and P-IMT groups, respectively (p = .8). Fasting glycemia decreased in both groups with no difference after training although it was lower in IMT at 8 weeks: 170.0 ± 11.4 mg/dl(9.4 ± 0.6 mmol/L) and 184.4 ± 15.0 mg/dl (10.2 ± 0.8 mmol/L) for IMT and P-IMT, respectively (p < .05). Respiratory endurance time improved in the IMT group (baseline = 325.9 ± 51.1 s and 305.0 ± 37.8 s; after 12 weeks = 441.1 ± 61.7 s and 250.7 ± 39.0 s for the IMT and P-IMT groups, respectively; p < .05). Considering that glucose control did not improve, IMT should not be used as an alternative to other types of exercise in diabetes. Higher exercise intensities or longer training periods might produce better results. The clinical trials identifier is NCT03191435.

Chest Wall Mobility: Identification of Underlying Predictors.

OBJECTIVE: The purpose of this study was to identify factors contributing to normal mobility or hypermobility of the chest wall. METHODS: Seventy-eight young adults were divided into 2 groups: patients with normal mobility (group 1, n = 40) and hypermobility of the chest wall (group 2, n = 38). The mean mobility of the chest wall in groups 1 and 2 was 9.9 and 6.1 cm, respectively. The mean age of groups 1 and 2 was 22.2 and 21.5 years, respectively. The Brief Symptom Inventory, State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale were used to evaluate the psychometric properties. Quality of life was assessed using 12-Item Short Form Health Survey. Smoking status was determined via self-report of current smoking status. Chest wall mobility was measured using thoracic and axillary cirtometry. Pulmonary functions were evaluated using a Spirobank II device. Subsequently, forced vital capacity (FVC), forced expiratory volume in 1 second, peak expiratory flow, and forced expiratory flow 25% to 75% were verified. Carefusion Micro RPM and the 6-minute walk test were used to evaluate maximal respiratory pressures and functional capacity, respectively. RESULTS: With backward linear regression models, FVC and obsessive-compulsive traits were significant predictors of chest wall mobility (R²â€¯= 0.27; P < .001 and P = .01, respectively). In logistic regression models, FVC, maximum inspiratory pressure, and obsessive-compulsive traits were significant predictors of normal mobility/hypermobility of the chest wall (R²â€¯= 0.42; P < .001, P = .01, and P = .03, respectively). CONCLUSION: Forced vital capacity, maximum inspiratory pressure, and obsessive-compulsive traits are significant predictors of chest wall mobility and normal mobility or hypermobility of the chest wall.

Inspiratory Muscle Training in Patients With Heart Failure: What Is New? Systematic Review and Meta-Analysis.

OBJECTIVE: The benefits of inspiratory muscle training (IMT) have already been demonstrated in patients with heart failure (HF), but the best mode of training and which patients benefit from this intervention are not clear. The purpose of this study was to review the effects of IMT on respiratory muscle strength, functional capacity, pulmonary function, quality of life, and dyspnea in patients with HF; IMT isolated or combined with another intervention (combined IMT), the presence of inspiratory muscle weakness, training load, and intervention time were considered. METHODS: The search included the databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, and LILACS database through September 2019. The review included randomized studies that assessed IMT in isolation or combined with another intervention-in comparison with a control group, a placebo, or another intervention-in patients with HF. Fourteen studies were included, 13 for meta-analysis (10 for isolated IMT and 3 for combined IMT). RESULTS: Isolated IMT demonstrated an increase in maximal inspiratory pressure (MIP) (25.12 cm H2O; 95% CI = 15.29 - 34.95), 6-Minute Walk Test (81.18 m; 95% CI = 9.73 - 152.63), maximum oxygen consumption (12 weeks: 3.75 mL/kg/min; 95% CI = 2.98 to 4.51), and quality of life (-20.68; 95% CI = -29.03 to -12.32). The presence of inspiratory muscle weakness, higher loads, and longer intervention times resulted in greater increases in MIP. IMT combined with another intervention demonstrated an increase only in MIP. CONCLUSIONS: Isolated IMT resulted in an increase in inspiratory muscle strength, functional capacity, and quality of life. IMT combined with another intervention resulted only in a small increase in inspiratory strength. Isolated IMT with higher loads can be considered an adjuvant intervention, especially for those who do not adhere to conventional rehabilitation and who have respiratory muscle weakness. IMPACT: A systematic review was necessary to review the effects of IMT on respiratory muscle strength, lung function, functional capacity, quality of life, and dyspnea in patients with HF. Various clinical issues important for a better training prescription were considered; these included whether the performance of the training IMT as a form of isolated training benefits patients with HF, whether the combination of IMT with another intervention has additional effects, whether any patient with HF can benefit from IMT (alone or combined with another intervention), and whether only patients who already have respiratory muscle weakness benefit. Also important was establishing which training load provides the best result and the best intervention time, so that health care can be provided more efficiently. LAY SUMMARY: For people with heart failure, IMT by itself, without being combined with other exercise, can improve ease of breathing, increase the amount of distance that they can walk, and improve quality of life. Inspiratory training with higher loads might be helpful for those with respiratory muscle weakness who are unable to do conventional exercise.

The Impact of the Deepwater Horizon Oil Spill upon Lung Health-Mouse Model-Based RNA-Seq Analyses.

We used a transcriptomic approach to interrogate the effects of a saline-accommodated fraction from the Macondo 252 well (MC252) oil and Corexit dispersants on lung tissue. Wild-type C57BL/6 male and female mice were exposed on days 0, 7 and 13 by oropharyngeal aspiration to saline accommodated fractions (SAF) of crude oil from the Macondo (MC252) well, Corexit 9500, Corexit 9527, 9500+oil and 9527+oil or a saline solution as the vehicle control. These treatments did not cause overt toxicity, with the exception of the Corexit exposures which caused brief weight loss after the first exposure. On day 14, total RNA was isolated from the left lung for RNA-seq analyses. KEGG-pathway-based differential expression revealed that Corexit 9527 elicited the strongest changes involving the upregulation of 19 KEGG pathways (FDR < 0.10), followed by Corexit 9500 with the upregulation of seven pathways (FDR < 0.10). As an important signature, pathways related to a response to DNA damage (e.g., p53 signaling and mismatch repair) dominate those upregulated by Corexit 9527 and Corexit 9500. In addition, pro-inflammatory pathways (e.g., cytokine-cytokine receptor interaction, IL-17 signaling pathway and TNF signaling pathways) were upregulated selectively in oil-treated male mice. Surprisingly, oil + dispersant combinations caused lesser effects than the individual treatments at the transcriptomic level. Overall, these findings support potential genotoxicity, inflammation and cell death due to dispersant or oil exposures. Similar exposures to lung tumor bearing K-RasLA1 mice provided evidence for tumor promotion by oil and Corexit dispersant treatments. Our mouse RNA-seq analyses may be relevant to the pulmonary health hazards of MC252 oil and dispersants experienced in exposed populations.

Current strategies and opportunities to manufacture cells for modeling human lungs.

Chronic lung diseases remain major healthcare burdens, for which the only curative treatment is lung transplantation. In vitro human models are promising platforms for identifying and testing novel compounds to potentially decrease this burden. Directed differentiation of pluripotent stem cells is an important strategy to generate lung cells to create such models. Current lung directed differentiation protocols are limited as they do not 1) recapitulate the diversity of respiratory epithelium, 2) generate consistent or sufficient cell numbers for drug discovery platforms, and 3) establish the histologic tissue-level organization critical for modeling lung function. In this review, we describe how lung development has formed the basis for directed differentiation protocols, and discuss the utility of available protocols for lung epithelial cell generation and drug development. We further highlight tissue engineering strategies for manipulating biophysical signals during directed differentiation such that future protocols can recapitulate both chemical and physical cues present during lung development.

Measuring disease activity in COPD: is clinically important deterioration the answer?

Given the heterogeneity of chronic obstructive pulmonary disease (COPD), personalized clinical management is key to optimizing patient outcomes. Important treatment goals include minimizing disease activity and preventing disease progression; however, quantification of these components remains a challenge. Growing evidence suggests that decline over time in forced expiratory volume in 1 s (FEV1), traditionally the key marker of disease progression, may not be sufficient to fully determine deterioration across COPD populations. In addition, there is a lack of evidence showing that currently available multidimensional COPD indexes improve clinical decision-making, treatment, or patient outcomes. The composite clinically important deterioration (CID) endpoint was developed to assess disease worsening by detecting early deteriorations in lung function (measured by FEV1), health status (assessed by the St George's Respiratory Questionnaire), and the presence of exacerbations. Post hoc and prospective analyses of clinical trial data have confirmed that the multidimensional composite CID endpoint better predicts poorer medium-term outcomes compared with any single CID component alone, and that it can demonstrate differences in treatment efficacy in short-term trials. Given the widely acknowledged need for an individualized holistic approach to COPD management, monitoring short-term CID has the potential to facilitate early identification of suboptimal treatment responses and patients at risk of increased disease progression. CID monitoring may lead to better-informed clinical management decisions and potentially improved prognosis.

Acupoint Catgut Embedding Improves the Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: This study investigated the potential therapeutic effects of acupoint catgut embedding (ACE) at ST36 and BL13 on lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into the normal saline (NS group with a sham procedure), lipopolysaccharide (LPS group with a sham procedure), and LPS plus ACE (LPS+ACE with ACE at bilateral BL13 and ST36 acupoints one day before LPS injection) groups. After intratracheal instillation of normal saline or LPS (0.5 mg/kg), all rats were subjected to mechanical ventilation for 4 h. Their blood gas was analyzed before and after lung injury, and their lung pressure-volumes were measured longitudinally. The levels of TNF-α, IL-6, IL-10, and phosphatidylcholine (PC) and total proteins (TP) in bronchial alveolar lavage fluid (BALF) were assessed. Their wet to dry lung weight ratios, histology, myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were measured. Their lung aquaporin 1 (AQP1) and Occludin protein levels were analyzed. RESULTS: LPS administration significantly decreased the ratios of PaO2/FiO2 and pressure-volumes and induced lung inflammation and injury by increased concentrations of TNF-α, IL-6, IL-10, and TP in BALF and MPO and MDA in the lung but decreased PC in BALF and SOD activity in the lungs. LPS also reduced AQP1 and Occludin protein levels in the lung of rats. In contrast, ACE significantly mitigated the LPS-induced lung injury, inflammation, and oxidative stress and preserved the AQP1 and Occludin contents in the lung of rats. CONCLUSIONS: ACE significantly improved respiratory function by mitigating inflammation and oxidative stress and preserving AQP1 and Occludin expression in the lung in a rat model of LPS-induced ARDS.

Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials.

BACKGROUND: The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. METHODS: 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 µg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 µg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0-24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. RESULTS: The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [- 13, 43]; Study 207609: 11 mL [- 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. CONCLUSIONS: FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. TRIAL REGISTRATION: GSK (207608/207609; NCT03478683/NCT03478696).

The microcirculatory characteristics of the heart and lung meridians: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: The aim of the present study is to compare the microcirculatory difference of different meridians by using laser doppler flowmetry and investigate the specificity for the meridian-visceral association and site-to-site association between 2 specific meridians. METHODS AND ANALYSIS: The Lung and Heart meridians are chosen as 2 specific studied meridians. 120 participants will be enrolled and divided into the healthy control group, chronic stable angina pectoris group and healthy intervention group. Laser doppler flowmetry will be used to assess the blood perfusion of the Heart and Lung meridians. The specificity for the meridian-visceral association will be investigated by comparing the microcirculatory difference between the Heart and Lung meridians in the healthy control group and chronic stable angina pectoris group. Besides, participants in the healthy intervention group will receive 2 sessions of moxibustion in the Heart meridian and Lung meridian, respectively, to explore the specificity for the site-to-site association on the body surface. Primary outcomes will be blood flow curve and blood perfusion units of relevant sites along the Heart and Lung meridians. Statistical analysis will be conducted by third party statisticians. ETHICS AND DISSEMINATION: Ethics approval (approval No: ZSLL-KY-2019-001A-01) has been obtained from the Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University. The study findings will be disseminated through presentation at peer-reviewed medical journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04244812.

Effects of fixed oil of Caryocar coriaceum Wittm. Seeds on the respiratory system of rats in a short-term secondhand-smoke exposure model.

ETHNOPHARMACOLOGICAL RELEVANCE: Pequi fruit are obtained from the pequi tree (Caryocar coriaceum), from which the pulp and nut are used in order to extract an oil that is commonly used in popular medicine as an antiinflammatory agent, particularly for the treatment of colds, bronchitis and bronchopulmonary infections. Making use of the fixed oil of Caryocar coriaceum (FOCC), an attractive alternative for the treatment of diseases caused by exposure to environmental tobacco smoke. AIM OF THE STUDY: To evaluate whether oral intake FOCC provides beneficial effects in the respiratory system of rats submitted to a short-term secondhand smoke (SHS) exposure model. MATERIALS AND METHODS: The experiments were performed on Wistar rats divided into 4 groups; in the SHS + O and SHS + T groups, the animals were pretreated orally with 0.5 mL of FOCC (SHS + O) or vehicle (Tween-80 [1%] solution) (SHS + T). Immediately after pretreatment, the animals were submitted to the SHS exposure protocol, for a total period of 14 days. Exposures were performed 6 times per day, with a duration of 40 min per exposure (5 cigarettes per exposure), followed by a 1-h interval between subsequent exposures. In the AA + O and AA + T groups, animals were submitted to daily oral pretreatment with 0.5 mL of FOCC (AA + O) or vehicle (AA + T). These animals were then subjected to the aforementioned exposure protocol, but using ambient air. After the exposure period, we investigated the effects of FOCC in respiratory mechanics in vivo (Newtonian resistance -RN, tissue elastance -H, tissue resistance -G, static compliance -CST, inspiratory capacity -IC, PV loop area) histopathology and lung parenchymal morphometry in vitro (polymorphonuclear cells -PMN, mean alveolar diameter -Lm, bronchoconstriction index -BCI), temporal evolution of subjects' masses, and percent composition of the FOCC. RESULTS: Regarding the body mass of the animals, the results demonstrated an average body mass gain of 10.5 g for the animals in the AA + T group, and 15.5 g for those in the AA + O group. On the other hand, the body mass of animals in the SHS + T and SHS + O suffered an average loss of 14.4 and 4.75 g, respectively. Regarding respiratory system analyzes, our results demonstrated significant changes in all respiratory mechanics variables and lung parenchyma morphometry analyzed for the SHS + T group when compared to the AA + T group (p < 0,05), confirming the establishment of pulmonary injury induced by SHS exposure. We also observed that rats pretreated orally with FOCC (SHS + O) showed improvement in all variables when compared to the SHS + T group (p < 0,05), thus demonstrating the effectiveness of FOCC in preventing lung damage induced by short-term SHS exposure. CONCLUSION: In conclusion, our results demonstrate that FOCC was able to prevent lung injury in rats submitted to short-term SHS exposure.

Acute and daily effects of repeated voluntary hyperpnea on pulmonary function in healthy adults.

PURPOSE: Hyperpnea training has been used as a method for both improving exercise performance in healthy persons and improving ventilatory capacity in patients with pulmonary disease. However, voluntary hyperpnea causes acute declines in pulmonary function, but the effects of repeated days of hyperpnea on airway function are not known. The purpose of this study was to determine the effects of repeated normocapnic hyperpnea on daily and post-hyperpnea pulmonary function in healthy adults. METHODS: Ten healthy adults (21 years; 170 cm; 66 kg) completed ten hyperpnea training sessions within 17-days (TR). Training sessions consisted of 20-minutes of normocapnic hyperpnea with gradually increased minute ventilation over the 10 days. Spirometry was assessed at baseline and serially following hyperpnea during each experimental day. A control group (24 years; 171 cm; 66 kg) completed 10 days of spirometry with no hyperpnea training (CON). RESULTS: In both CON and TR subjects, baseline pulmonary function was unchanged during the 10 days. In TR subjects, pulmonary function was decreased at 5 mins after hyperpnea but thereafter increased to pre-hyperpnea values by 30 mins. Furthermore, these changes in pulmonary function were consistent during the 10 training days. In TR subjects, maximal voluntary ventilation decreased by 10.4 ± 8.9% (168-150 L min-1) over the 10 days (P < 0.05), whereas it was unchanged in CON subjects. CONCLUSIONS: These findings demonstrate that voluntary hyperpnea acutely decreases airway function in healthy subjects. However, there does not appear to be a cumulative effect of repeated hyperpnea, as daily pulmonary function was unchanged.

Lung-on-a-chip: the future of respiratory disease models and pharmacological studies.

Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.