Mangiferin attenuates cigarette smoke-induced chronic obstructive pulmonary disease in male albino rats.

We analyzed the ability of mangiferin to suppress cigarette smoke-induced chronic obstructive pulmonary disease. Control rats showed a marked decrease in the ratio of the forced expiratory volume at 0.1 s to forced vital capacity. The decreases in the peak expiratory flow and maximal mid-expiratory flow indicated airway remodeling and enlargement. The expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase, nuclear factor erythroid 2-related factor 2, and activating transcription factor 4 were increased in the control rats. The levels of oxidative stress, malondialdehyde, and reactive oxygen species peaked after 24 weeks, whereas the SOD and HO-1 levels and the total antioxidant capacity were reduced in control rats. Mangiferin restored the levels of reactive oxygen species, malondialdehyde, SOD, HO-1, and T-AOC to near normal. Increased numbers of infiltrating inflammatory cells were observed in control rats but were significantly reduced by mangiferin. In addition, edema and airway inflammation were reduced by mangiferin.

Performance improvement of machine learning techniques predicting the association of exacerbation of peak expiratory flow ratio with short term exposure level to indoor air quality using adult asthmatics clustered data.

Large-scale data sources, remote sensing technologies, and superior computing power have tremendously benefitted to environmental health study. Recently, various machine-learning algorithms were introduced to provide mechanistic insights about the heterogeneity of clustered data pertaining to the symptoms of each asthma patient and potential environmental risk factors. However, there is limited information on the performance of these machine learning tools. In this study, we compared the performance of ten machine-learning techniques. Using an advanced method of imbalanced sampling (IS), we improved the performance of nine conventional machine learning techniques predicting the association between exposure level to indoor air quality and change in patients' peak expiratory flow rate (PEFR). We then proposed a deep learning method of transfer learning (TL) for further improvement in prediction accuracy. Our selected final prediction techniques (TL1_IS or TL2-IS) achieved a balanced accuracy median (interquartile range) of 66(56~76) % for TL1_IS and 68(63~78) % for TL2_IS. Precision levels for TL1_IS and TL2_IS were 68(62~72) % and 66(62~69) % while sensitivity levels were 58(50~67) % and 59(51~80) % from 25 patients which were approximately 1.08 (accuracy, precision) to 1.28 (sensitivity) times increased in terms of performance outcomes, compared to NN_IS. Our results indicate that the transfer machine learning technique with imbalanced sampling is a powerful tool to predict the change in PEFR due to exposure to indoor air including the concentration of particulate matter of 2.5 µm and carbon dioxide. This modeling technique is even applicable with small-sized or imbalanced dataset, which represents a personalized, real-world setting.

Statins for asthma.

BACKGROUND: Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and chest tightness, with or without a cough. Statins possess multiple therapeutic effects, including lowering lipid levels in the blood. Statins are reported to have a potential role as an adjunct treatment in asthma. However, comprehensive evidence of the benefits and harms of using statins is required to facilitate decision making. OBJECTIVES: To assess the benefits and harms of statins as an adjunct therapy for asthma in adults and children. SEARCH METHODS: We searched for studies in the Cochrane Airways Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP and Embase Ovid SP, from their inception dates We handsearched the proceedings of major respiratory conferences. We also searched clinical trials registries for completed, ongoing and unpublished studies, and scanned the reference lists of included studies and relevant reviews to identify additional studies. The search is current to 7 February 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a parallel-group design that assessed statins for at least 12 weeks' duration. We considered all participants with a clinical diagnosis of asthma to be eligible, regardless of age, sex, disease severity and previous or current treatment. We planned to include studies reported as full text, those published as abstract only, and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected the studies, extracted outcome data and intervention characteristics from included studies, and assessed risk of bias according to standard Cochrane methodological procedures. We resolved any disagreement through discussion. MAIN RESULTS: We found only one trial involving a total of 60 people living with asthma. The trial compared the effect of atorvastatin with a placebo (dummy treatment containing lactose) in treating people with chronic asthma. The trial did not report data for the primary outcomes or adverse events. There was uncertainty about the relative effect on forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in the atorvastatin group compared with the placebo group. The study did not report serious adverse effects for the interventions. The included study had internal discrepancies in its reported data. AUTHORS' CONCLUSIONS: The evidence was of very low certainty, so we are unable to draw conclusions about the effectiveness and safety of statins to treat asthma. High-quality RCTs are needed to assess the effect of statins on people with asthma. Well-designed multicentre trials with larger samples and longer duration of treatment are required, which assess outcomes such as adverse events, hospital utilisation and costs, to provide better quality evidence. Future studies that include subgroups of obese people with asthma are also required.

Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020. OBJECTIVES: To evaluate the efficacy and safety of oral PDE4 inhibitors for management of stable COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations). MAIN RESULTS: We found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years. We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials. Lung function Treatment with a PDE4 inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV1) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence). Quality of life Trials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence). Incidence of exacerbations Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found. Adverse events More participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE4 inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms. Participants treated with PDE4 inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups. Mortality No effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials. AUTHORS' CONCLUSIONS: For this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review. PDE4 inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg. The findings of this review provide cautious support for the use of PDE4 inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation, or mortality in COPD.

A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease.

The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O2 pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O2 delivery through improvements in primary cardiocirculatory and muscular crosstalk.

Efficacy of tiotropium in treating patients with moderate-to-severe asthma: A meta-analysis and systematic review based on 14 randomized controlled trials.

BACKGROUND: The goal of the current meta-analysis and systematic review was to explore the efficacy of tiotropium in treating patients with moderate-to-severe asthma on the basis of qualified randomized controlled trials (RCTs). METHODS: The following online electronic databases, such as Cochrane, PubMed, and Embase database were screened to identify qualified studies updated to January 2019 through the use of index words. Several literatures that were relevant to the present analysis were also included. To further analyze the main outcomes, we utilized the odds rations (OR), and mean difference (MD) along with its 95% confidence interval (95% CI). RESULTS: A total of 14 RCTs with 4998 patients in the tiotropium group and 5074 patients in the control group were included in the present study. On the basis of the pooled results, tiotropium was significantly associated with improved morning PEF (SMD: 3.29, 95%CI: 2.03-4.55), evening PEF (SMD: 3.36, 95%CI: 2.24-4.48), peak FEV (SMD: 2.67, 95%CI: 1.47-3.88), and trough FEV (SMD: 1.90, 95%CI: 0.87-2.92) vs the control group. Nevertheless, no significant difference was observed in peak FVC (SMD: 0.77, 95%CI: -0.21-1.76), trough FVC (SMD: 0.67, 95%CI: -0.18-1.53), AE (RR: 0.98, 95%CI: 0.94-1.02) and serious AE (RR: 1.08, 95%CI: 0.77-1.52) between the 2 groups. CONCLUSIONS: In this review, we summarized the significant effect of tiotropium for the treatment of moderate-to-severe asthma, mainly in increasing morning PEF, evening PEF, peak FEV and trough FEV based on high-quality RCTs. Nevertheless, no significant difference in peak FVC, trough FVC, AE and serious AE was found between the 2 groups. A close comparison of the 2 groups revealed that more high-quality larger-sample RCTs are needed to gather more strong evidence on the therapeutic efficacy and safety of tiotropium for clinical practice.

Effects of Short-term Exposure to Ambient Particulate Matter on the Lung Function of School Children in Dhaka, Bangladesh.

BACKGROUND: Ambient particulate pollution may adversely affect children's lung function. However, evidence on this association remains scarce in Asia despite this region having the greatest burden of disease due to air pollution. OBJECTIVES: To investigate the effect of short-term exposure to ambient particulate matter (PM) on the lung function of school children in Dhaka city, Bangladesh. The possible seasonal modification of this association was also examined. METHODS: A panel of 315 school children who were 9-16 years of age were recruited from three schools in and around Dhaka. Lung function was assessed using a spirometry test during the cool and warm seasons in 2013, yielding six measurements per child. Daily PM data were retrieved from nearby air monitoring stations. Linear mixed effects models were used to examine associations. Seasonal modification was examined by stratification. RESULTS: An inverse association was observed for the lung function parameters with PM2.5; peak expiratory flow (PEF) and forced expiratory volume within 1 second (FEV1) decreased with increasing PM2.5. The percent deviation from the personal median was -4.19% [95% confidence interval (CI): -5.72, -2.66] for PEF and -2.05% (95% CI: -2.92, -1.18) for FEV1 for a 20 µg/m increase in PM2.5 on the previous day. Results for PM10 were less consistent. The estimated effects of PM on lung functions were generally greater in the warm season. CONCLUSIONS: Short-term exposure to PM is associated with worse lung function in children living in highly polluted settings, with the strength of these adverse PM effects varying by season.

Sanao decoction for asthma: Protocol of a systematic review.

BACKGROUND: Asthma is a chronic inflammatory disease characterized by recurrent attacks of breathlessness and wheezing, which often worsen at night or in the early morning and vary from person to person in severity and frequency. Sanao decoction (SAD), as a traditional Chinese medicine compound, has a long history of clinical application in the treatment of respiratory diseases. Whereas neither systematic nor meta-analysis of randomized controlled articles explain the efficacy of SAD in treating asthma. Therefore, we provide a protocol to evaluate the efficacy and safety of SAD for asthma. METHODS: From the beginning to December 2018, the following electronic databases will be searched for studies in English or Chinese: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and the Wanfang Database. Total effective rate, peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC will be measured as primary outcomes. Meta-analysis will be performed using the Stata 15. RESULTS: This study will provide the current evidence of asthma treated with SAD from the several points including PEF, FEV1, FVC, and FEV1/FVC. CONCLUSION: The consequence of this summary will furnish proof to evaluate if SAD is effective in the treatment of asthma. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018117923.

Tidal breathing flow volume profiles during sleep in wheezing infants measured by impedance pneumography.

Overnight analysis of tidal breathing flow volume (TBFV) loops, recorded by impedance pneumography (IP), has been successfully applied in the home monitoring of children with wheezing disorders. However, little is known on how sleep physiology modifies the relationship between TBFV profiles and wheeze. We studied such interactions in wheezing infants. Forty-three infants recruited because of recurrent lower airway symptoms were divided into three groups based on their risk of asthma: high (HR), intermediate (IR), or low (LR). Sedated patients underwent infant lung function testing including assessment of airway responsiveness to methacholine at the hospital and a full-night recording of TBFV profiles at home with IP during natural sleep. Overnight TBFV indexes were estimated from periods of higher and lower respiration variability, presumably belonging to active [rapid eye movement (REM)] and quiet [non-REM (NREM)] sleep, respectively. From 35 valid recordings, absolute time indexes showed intrasubject sleep phase differences. Peak flow relative to time and volume was lower in HR compared with LR only during REM, suggesting altered expiratory control. Indexes estimating the concavity/convexity of flow decrease during exhalation suggested limited flow during passive exhale in HR compared with IR and LR, similarly during NREM and REM. Moreover, during REM convexity was negatively correlated with maximal flow at functional residual capacity and methacholine responsiveness. We conclude that TBFV profiles determined from overnight IP recordings vary because of sleep phase and asthma risk. Physiological changes during REM, most likely decrease in respiratory muscle tone, accentuate the changes in TBFV profiles caused by airway obstruction. NEW & NOTEWORTHY Impedance pneumography was used to investigate overnight tidal breathing flow volume (TBFV) indexes and their interactions with sleep phase [rapid eye movement (REM) vs. non-REM] at home in wheezing infants. The study shows that TBFV indexes vary significantly because of sleep phase and asthma risk of the infant and that during REM the changes in TBFV indexes caused by airway obstruction are accentuated and better associated with lung function of the infant.

LA phonospirometry technique compared to pediatric respiratory assessment measure and peak expiratory flow measurement as a novel technique to assess the severity of an asthma exacerbation.

Objective: Asthma is a common chronic disease treated in emergency departments. The measurements of Peak Expiratory Flow (PEF) and Pediatric Respiratory Assessment Measure (PRAM) scores have been recommended as objective techniques in the assessment of acute asthma exacerbations, but have multiple barriers limiting their use. The Los Angeles phonospirometry technique is an easier, trans-cultural technique. The technique assesses dyspnea by measuring how many seconds a child is able to chant "LA LA LA" in a single breath. The objective of this study is to determine the correlation of this technique with PEF measurements and PRAM scores in children with acute asthma exacerbations, both before and after nebulized bronchodilator treatment. Methods: A convenient sample of children aged 5-17 years being treated for asthma in the ED was enrolled. Phonospirometry, PRAM, and PEF measurements were obtained through pre and post inhaled bronchodilator treatments. The highest values from each measurement were correlated using Spearman's correlation coefficient. Results: A total of 91 children were enrolled. The correlations at pre-treatment, after first, second, and third treatments between phonospirometry and PEF were 0.38 (p < 0.001), 0.60 (p < 0.001), 0.54 (p < 0.001), 0.52 (p < 0.01), respectively; between phonospirometry and PRAM were -0.37 (p < 0.001), -0.42 (p < 0.001), -0.26 (p < 0.05), and -0.06 (p > 0.05), respectively; and between PEF and PRAM were -0.6 (p < 0.01), -0.54 (p < 0.001), -0.38 (p < 0.01), and -0.36 (p - 0.05), respectively. Conclusions: This novel technique correlates mild to moderately with PEF, and shows promising aide in the assessment of children with acute asthma exacerbations.

The effect of inhaled heliox on peak flow rates in normal and brachycephalic dogs.

BACKGROUND: Heliox, a mixture of helium and oxygen, alleviates airway obstruction in people and improves air flow, and its use has been proposed in dogs. Brachycephalic dogs have naturally occurring airway obstruction where heliox might be a useful therapeutic option. OBJECTIVE: The purposes of this study were to (1) determine the impact of breathing heliox on peak inspiratory and expiratory flows (PIF/PEF) in healthy dogs and (2) determine if brachycephalic dogs and mesocephalic dogs have similar responses to inhaled heliox. ANIMALS: Eleven healthy dogs: 5 mesocephalic and 6 brachycephalic dogs. METHODS: A prospective study. Tidal breathing flow-volume loops were recorded when dogs were breathing room air (nitrogen-oxygen) and heliox. Peak inspiratory and expiratory flow rates were recorded and the subjective shape of loops assessed. Peak inspiratory and expiratory flows pre- and post-heliox were compared using a Mann-Whitney Rank sum test with a P-value of <.05 considered significant. RESULTS: In inhaled heliox, PIF and PEF were evaluated by tidal breathing flow-volume loops. In mesocephalic dogs, PIF increased from a median of 820 mL/s (range, 494-1010 mL/s) to 1386 mL/s; P = .02; and for PEF from 688 mL/s to 1793 mL/s (P = .04), whereas in brachycephalic dogs, the median PIF increased from 282 mL/s to 694 mL/s; P = .01 and the median PEF increased from 212 mL/s to 517 mL/sec; P = .03. Brachycephalic dogs showed normalization of loop shapes. CONCLUSIONS AND CLINICAL IMPORTANCE: Heliox improves flow rate and appears to improve flow patterns in brachycephalic dogs.

Blood pressure and pulmonary health effects of ozone and black carbon exposure in young adult runners.

Physical activity has been shown to promote health and well-being, however, exercising in environments with high level of air pollution might increase the risk of cardio-respiratory impairments. In this crossover study, we constructed linear mixed models to investigate the impact of short-term exposure to black carbon (BC) and ozone on blood pressure and pulmonary functions among 30 healthy adult runners after 30-minute run on a clean and polluted route on separate days in August 2015 in Hong Kong. Runners were on average 20.6 years old, with mean body mass index of 20.3 kg/m2. Air pollution concentrations were higher in the polluted route than in the clean route, with the highest difference in BC (5.4 µg/m3 versus 1.3 µg/m3). In single-pollutant models, no significant association was found between air pollution and changes in blood pressures, forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow and fractional exhaled nitric oxide, after adjusting for gender, type of route, temperature and relative humidity. When further adjusting for both BC and ozone simultaneously, increment in BC became statistically significantly associated with increase in systolic blood pressure (relative risk = 3.18; 95% CI: 0.24, 6.13) after running exercise. Stratified analysis further shows that the significant adverse association between systolic blood pressure and BC was only observed in the polluted route (e.g., relative risk = 4.51, 95% CI: 0.75, 8.27 in two-pollutant). Our finding of BC is consistent with existing literature, while further studies with greater sample size and longer exposure time are needed to investigate the effects of ozone to cardio-respiratory functions in runners. Given that exercise has clear health benefits, one should consider ways to minimize the air pollution exposure.

Exposure to phthalates aggravates pulmonary function and airway inflammation in asthmatic children.

INTRODUCTION: Studies on the associations between phthalate exposures and respiratory outcomes are limited. We investigated the association of phthalates exposure with pulmonary function and airway inflammation in asthmatic children. METHODS: Fifty-six children with asthma living in Seoul Metropolitan Area, Korea aged 6-16 years were enrolled. Their pulmonary function including forced expiratory volume in 1 sec (FEV1) and peak expiratory flow rate (PEFR) were measured, and the fractional exhaled nitric oxide (FeNO) as a marker of airway inflammation was examined repeatedly up to four times during the study period. Urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), metabolites for di-(2-ethylhexyl) phthalate (DEHP), and mono-n-butyl phthalate (MnBP), a metabolite of di-n-butyl phthalate (DnBP), were also measured on the same days. The effects of phthalate metabolites on the respiratory symptoms were analyzed using linear mixed effect models with adjustment for potential cofounders. RESULTS: An increase in phthalate metabolites was associated with a decrease in pulmonary function and an increase in FeNO in asthmatic children. As one natural log-unit (ln-unit) levels of urinary MEHHP and MEOHP increased, FeNO levels on the same day increased by 19.47 ppb [95% confidence interval (CI): 9.28, 29.67] and 17.93 ppb (95% CI: 5.86, 30.01), respectively. An increases in the urinary level of MEHHP, MEOHP, and MnBP by one ln-unit was associated with a decrease in PEFR on the next day by 12.17 L/min (95% CI: 2.59, 21.74), 10.80 L/min (95% CI: 0.29, 21.32), and 13.65 L/min (95% CI: 5.07, 22.24), respectively. CONCLUSION: Phthalates, especially DEHP, may worsen pulmonary function and airway inflammation in asthmatic children. To control asthma symptoms, exposure to phthalates needs to be avoided.

The use of 5% lidocaine medicated plaster for acute postoperative pain after gynecological surgery: A pilot randomized controlled feasibility trial.

OBJECTIVES: To examine the feasibility and potential efficacy of 5% lidocaine medicated plaster for acute postoperative pain in a parallel, blinded, randomized controlled pilot trial. METHODS: Twenty-eight women undergoing elective gynecological surgery with midline incisions were randomly allocated 5% lidocaine medicated patch (Lignopad) or placebo plasters. Postoperative pain at rest and on movement at 24 hours were the primary study endpoints, with secondary endpoints of postoperative pain within the first 48 hours, cumulative morphine consumption (mg), predicted peak flow rate (PFR) (%) and adverse effects. We assessed pain scores at rest and on movement using the visual analogue scale (0-100). RESULTS: The lidocaine patch group had lower postoperative pain scores at rest at 24 hours (mean difference [MD] -15.1, 95% confidence interval [95% CI] -28.3 to -2.0; P = .024) but not on movement at 24 hours (MD -6.4, 95% CI -22.7 to 9.9; P = .445). Compared to placebo, lidocaine may slightly lower cumulative morphine consumption (mg) over time (MD -3.4, 95% CI -6.9 to 0.2; group*time interaction P = .065). The difference in improvement in the PFR over time after surgery between groups appeared small (group*time P = .0980). No adverse effects occurred. CONCLUSIONS: Lidocaine patch may provide a clinically important reduction in postoperative pain intensity. A larger trial to confirm the efficacy and safety of lidocaine patch is feasible after modifying the inclusion criteria and collecting patient-centered outcomes, such as quality of recovery and patient satisfaction.

Home-Based Monitoring of Pulmonary Function in Patients with Duchenne Muscular Dystroph.

BACKGROUND: Loss of pulmonary function is a main cause of early morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Standard of care guidelines recommend regular assessment of pulmonary function by hospital-based spirometry to detect onset and monitor progression of pulmonary function decline. OBJECTIVE: To assess the feasibility of home-based monitoring of pulmonary function by a hand-held device (HHD) in adolescent and adult patients with DMD over a period of 12 months. METHODS: In the phase III randomized placebo-controlled DELOS trial in 10-18 year old DMD patients, peak expiratory flow (PEF) measurements were collected weekly at home by the patient (assisted by parent/caregiver) using a peak flow meter HHD. Adherence to the use of the HHD was assessed and 12-month changes in PEF as percent of predicted (PEF% p) for the idebenone (N = 31) and the placebo treatment groups (N = 33) from HHD-derived data were compared to results from hospital-based spirometry. RESULTS: A total of 2689 individual HHD assessments were analysed. Overall adherence to the use of the HHD over the course of the 12-month study duration was good (75.9%, SD 21.5%) and PEF% p data obtained at the same day by HHD and standard spirometry correlated well (Spearman's rho 0.80; p < 0.001). Several analysis methods of HHD-derived data for PEF% p consistently demonstrate that idebenone treatment slowed the decline in PEF% p compared to placebo, which supports the statistically significant difference in favour of idebenone for PEF% p measured by standard spirometry. CONCLUSIONS: This study demonstrates that home-based monitoring of pulmonary function in adolescent patients with DMD using a HHD is feasible, provides reliable data compared to hospital-based spirometry and is therefore suitable for use in clinical practice and for clinical trials.

Fluoxetine protects against OVA induced bronchial asthma and depression in rats.

Depression is very common in asthmatic patients and may increases risk for morbidity and mortality. The present work aimed to investigate the protective effect of fluoxetine, on behavioral and biochemical changes, associated with ovalbumin (OVA) - induced bronchial asthma and depression in rats. Rats were sensitized with intraperitoneal administration of OVA plus aluminum hydroxide for 3 consecutive days then at day 11 followed by OVA intranasal challenge at days 19, 20, 21. Rats were either pretreated with dexamethasone, fluoxetine10mg/kg or fluoxetine 20 mg/kg. At the end of the experiment, various tests were performed, including open field, forced swimming and respiratory function tests. Blood was drawn for serum IgE detection. Finally, rats were euthanized, brain-derived neurotrophic factor (BDNF) was estimated in bronchoalveolar lavage (BAL) fluid and lung content of reduced glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4) were determined. Histopathological study was also performed. The results showed that fluoxetine significantly ameliorated OVA- induced biochemical and behavioral changes. Fluoxetine may protect against OVA-induced asthma and depression in rats. This effect may be mediated at least in part by its antioxidant, anti-inflammatory and immunosuppressant effect.

Chinese herbal medicine formula for acute asthma: A multi-center, randomized, double-blind, proof-of-concept trial.

BACKGROUND: Despite advances in asthma management, exacerbations constitute a significant health economic burden. OBJECTIVE: To observe the efficacy and safety of Chinese herbal medicine formula entitled PingchuanYiqi (PCYQ) granule, on acute asthma and to explore its possible mechanism. MATERIALS AND METHODS: This proof-of-concept study consisted of a randomized, double-blind, placebo-controlled trial in patients with acute asthma (n = 300). Participants with acute mild-to-moderate asthma recruited from seven centers in China were randomly assigned to receive PCYQ or placebo. The primary outcomes were PEF (L/min) and total asthma symptom scores. Furthermore, a panel of cytokines including serum IL-4, IL-5, IL-6, IL-8, IL-1ß, IL-17A, IFN-α, IFN-ß, IFN-γ, CRP, CCL-5, IP-10, and PGD2 levels was detected using ELISA. RESULTS: The PCYQ (n = 139) significantly improved the morning PEF on day 4 (349.73 ±â€¯93.92 vs. 313.56 ±â€¯92.91 L/min, P = 0.004) and day 7 (360.42 ±â€¯94.39 vs. 329.52 ±â€¯95.97 L/min, P = 0.023), and the evening PEF on day 4 (352.65 ±â€¯95.47 vs. 320.58 ±â€¯95.30 L/min, P = 0.012) and day 7 (360.42 ±â€¯94.39 vs. 336.86 ±â€¯95.59 L/min, P = 0.029) in comparison with the placebo (n = 143). The PCYQ also improved the clinical symptoms scores and reduced the puffs of short-acting ß2-agonist (all P < 0.05). Furthermore, the PCYQ statistically reduced IL-5, IL-8, IL-1ß and PGD2 in serum. CONCLUSION: The PCYQ as the Chinese herbal medicine formula significantly improves lung function and symptoms of acute asthma, and reduces SABA dosage possibly via decrease of inflammatory biomarkers such as IL-5, IL-8, IL-1ß and PGD2. TRIAL REGISTRATION: ISRCTN61674768 (http://www.isrctn.com/).

Rapid and Consistent Improvements in Morning PEF in Patients with Severe Eosinophilic Asthma Treated with Mepolizumab.

INTRODUCTION: Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). METHODS: Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. RESULTS: Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p < 0.001. When the population was stratified by blood eosinophil thresholds the mean difference from placebo was 24 L/min (≥ 150 cells/µL), 27 L/min (≥ 300 cells/µL), and 34 L/min (≥ 500 cells/µL), p < 0.001 for all subgroups. The < 150 cells/µL (≥ 300 cells/µL in the previous year) group increased 13 L/min, while both 150 to < 300 cells/µL and 300 to < 500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively. CONCLUSION: Our analysis has shown early and consistent improvements in lung function measured by AM PEF using the study enrollment criterion of ≥ 150 eosinophils/µL. We also identified a relationship between baseline blood eosinophils and improvements in AM PEF with mepolizumab in patients with severe eosinophilic asthma. FUNDING: GlaxoSmithKline (study ID 208091).

Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta-analysis.

Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and application in asthma are controversial and not defined. A comprehensive search was performed in major databases (1946-2016) using the keywords: 'phosphodiesterase 4 inhibitor' or 'roflumilast' and 'asthma'. Placebo-controlled trials reporting lung function, airway hyperresponsiveness by direct challenge, asthma control and exacerbations, and adverse events were included. Random or fixed-effects models were used to calculate odds ratios (OR) and mean differences between the two treatment groups. Statistical analyses were conducted using Mann-Whitney U-tests and Cochrane systematic review software, Review Manager. Seventeen studies were included in the systematic review, of which 14 studies were included in the meta-analysis. Except for significant statistical heterogeneity in pre- and post-challenge predicted percentage of forced expiratory volume in 1 s (FEV1 %; I2 = 72%, χ2 = 3.35, P = 0.06), there was no heterogeneity in outcome measures. Roflumilast (500 µg) significantly improved FEV1 (mean difference: 0.05, 95% CI: 0.01-0.09, Z = 2.50, P = 0.01), peak expiratory flow, asthma control and exacerbations, but showed variable effects on airway responsiveness to methacholine and a 20% fall in FEV1 .Of note, PDE4 inhibitors were accompanied with significantly higher adverse events such as headache (OR: 3.99, 95% CI: 1.65-9.66, Z = 3.07, P = 0.002) and nausea (OR: 5.53, 95% CI: 1.38-22.17, Z = 2.41, P = 0.02). In patients with mild asthma, oral PDE4 inhibitors can be considered as an alternative treatment to regular bronchodilators and inhaled controllers.