Accelerated ethanol elimination via the lungs.

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.

Proteomics of exhaled breath condensate in stable COPD and non-COPD controls using tandem mass tags (TMTs) quantitative mass spectrometry: A pilot study.

Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow. Exhaled breath condensate (EBC) is now a safe and clinically significant measurement which has a huge potential to measure biomarkers in COPD. Previous studies profiled the pooled EBC samples from COPD or control participants due to technological limitations. In our study, 32 COPD patients and 28 control individuals were enrolled, and their EBC were collected. After matching with sex, age and smoking history, EBC samples of 19 COPD patients and 19 control individuals were analyzed using tandem mass tags (TMTs) quantitative mass spectrometry individually. A total of 257 proteins were identified. Compared with control group, 24 proteins (15 upregulated and 9 downregulated) were differentially expressed in COPD patients. The GO analysis of these differential proteins expressed mostly in the cytoplasm, and the KEGG analysis showed they had a predominant role in inflammatory response. And ACTB, UBC, TUBB and CCT2 involving in cell motility and cytoskeleton played important role in the interaction-net of these proteins. To sum up, we found some proteins might be novel biomarkers of EBC in COPD and TMTs was available to analyze proteomics in individual EBC samples. SIGNIFICANCE: It is still difficult to understand the mechanism of airway inflammation in COPD. Exhaled breath condensate(EBC) might be a great study object, but due to technological limitations, researchers preferred to use pooled EBC samples. This study analyzed individual EBC samples, which would deepen our understanding of the pathogenesis of COPD. And this method can be applied to individual EBC samples for further airway investigations of different purpose and different complexity.

Fractional Exhaled Nitric Oxide (FeNO) Combined with Pulmonary Function Parameters Shows Increased Sensitivity and Specificity for the Diagnosis of Cough Variant Asthma in Children.

BACKGROUND Cough variant asthma in children presents with a dry nonproductive cough. This study aimed to investigate the diagnostic value of fractional exhaled nitric oxide (FeNO) combined with small airway functional parameters in cough variant asthma. MATERIAL AND METHODS Children with asthma (n=136) were divided into a cough variant asthma (CVA) group (n=57; mean age, 8.03±2.1 years) and a non-cough variant asthma (nCVA) group (n=79; mean age, 8.61±1.7 years). In both groups, FeNO and other pulmonary function parameters were measured including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF), forced expiratory flow (FEF), and maximum expiratory flow at 25%, 50%, and 75% expired volume (MEF25, MEF50, and MEF75). Receiver-operating characteristic (ROC) curve analysis compared the sensitivity and specificity between the diagnostic parameters. RESULTS The FeNO values were significantly increased in the CVA group compared with the nCVA group (Z=6.890, p<0.001). The MMEF, MEF25, MEF50, and MEF75 values were significantly lower in the CVA group compared with the nCVA group (p=0.000, p=0.014, p=0.000, and p=0.000, respectively). The FeNO values were negatively correlated with MEF25, MEF50, and MMEF (ρ=-0.334, ρ=-0.257 and ρ=-0.276, respectively). FeNO was significantly more efficient diagnosing cough variant asthma comparing with pulmonary parameters (p<0.05), and was most sensitive and specific when combined with MMEF/MEF50 compared with single diagnostic parameters (p<0.05). CONCLUSIONS FeNO combined with pulmonary function parameters of MMEF/MEF50 showed increased sensitivity and specificity for the diagnosis of cough variant asthma.

Oscillating Positive Expiratory Pressure Therapy May Be Performed Poorly by Children With Cystic Fibrosis.

BACKGROUND: Oscillating positive expiratory pressure devices aid removal of excess secretions and reduce gas trapping in patients with hypersecretory pulmonary diseases, for example, cystic fibrosis. Oscillating positive expiratory pressure works when the patient exhales actively against a fixed resistor, which generates mean intrapulmonary pressures of 10-20 cm H2O with rapid fluctuations of at least 1 cm H2O from the mean. In this study, we evaluated the performance of oscillating positive expiratory pressure therapy by pediatric subjects with cystic fibrosis to determine adherence to target therapeutic pressures. METHODS: Twenty-one pediatric subjects were recruited. Each had a history of using an oscillating positive expiratory pressure device twice daily and had received standardized training and instructions from the same specialist physiotherapist. Performance was evaluated by using a flow and pressure sensor placed in-line between the participant's mouth and the device. The participants performed expirations as per their normal routine. RESULTS: None of the participants achieved target therapeutic pressure ranges during expiration. The mean ± SD pressure generated was 16.2 ± 6.8 cm H2O, whereas mean ± SD flow was 31.3 ± 8.9 L/min. The mean ± SD expiration length was 2.5 ± 1.4 s. CONCLUSIONS: Despite standardized instruction, the results demonstrated considerable variation among the participants and overall poor technique during use. Outcomes of this study indicated that airway clearance effects of oscillating positive expiratory pressure were compromised due to poor technique.

Exhaled acetone and isoprene in perioperative lung cancer patients under intensive oral care: possible indicators of inflammatory responses and metabolic changes.

One of the most severe complications of lung resection is postoperative pneumonia, and its prevention and prediction are critical. Exhaled acetone and isoprene are thought to be related to metabolism; however, little is known on their relationship with bacteria living in the oral cavity or their meaning in the acute phase in perioperative lung cancer patients. We measured acetone and isoprene in exhaled breath of 13 Japanese patients with lung cancer (3 women and 10 men, age range 62-82 years, mean 72.4 years) before breakfast during hospitalization, and compared with two acute-phase proteins, C-reactive protein (CRP) and albumin in blood serum, as well as the total number of bacteria in saliva and their activity to produce acetone and isoprene. Before operation, intensive oral care was carried out for each patient to prevent postoperative pneumonia, and swallowing and cough reflexes were measured for 12 of 13 patients to assess risk of postoperative pneumonia. Breath and saliva were sampled before intensive oral care (T1), after oral care but before operation (T2), and after operation (T3) during hospitalization. The total number of oral bacteria in saliva decreased significantly from T1 to T2 among 13 patients. No acetone or isoprene was detected from saliva after in vitro incubation under anaerobic or aerobic conditions, but both acetone and isoprene were detected in breath. After operation, breath acetone correlated significantly with CRP (Spearman's ρ = 0.559, P = 0.03), but not with albumin. Breath isoprene correlated significantly with albumin (Spearman's ρ = 0.659, P = 0.008), but not with CRP after operation. Although the number of subjects was small, our results support the hypothesis that breath acetone and isoprene may be related with these acute-phase proteins, which reflect inflammatory reactions and subsequent changes in metabolism in the early postoperative phase of lung resection.

An Artificial Cough Maneuver to Remove Secretions From Below the Endotracheal Tube Cuff.

BACKGROUND: Endotracheal suctioning is mandatory to prevent complications caused by the retention of tracheal secretions. Endotracheal suctioning is often performed late, when patients show signs of respiratory and hemodynamic alterations. We conceived a prototype device that, when synchronized with the ventilator, automatically removes secretions collected below the endotracheal tube (ETT) cuff, thus avoiding endotracheal suctioning. The aim of our investigation was to assess the performance of this novel prototype in vitro. METHODS: Three studies were performed to examine the characteristics of the prototype. We tested device's ability to generate an effective artificial cough flow (artificial cough maneuver) > 1 L/s by rapidly deflating the ETT cuff within the time of a sustained inflation (at 30 and at 40 cm H2O) (cough flow study). We also tested the prototype's ability to remove the fluid positioned below the ETT cuff using saline dye (fluid removal study), and to prevent the aspiration of saline dye from above the ETT cuff during the deflation phase of the ETT cuff (aspiration study). The trachea model was positioned at 45° in the aspiration study, and horizontally in the other two studies. RESULTS: In the cough flow study, the prototype provided an effective artificial cough maneuver, with a mean ± SD of 1.78 ± 0.19 L/s (range, 1.42-2.14 L/s). The tracheal pressure after ETT cuff deflation never decreased below the PEEP level. In the fluid removal study, the prototype cleared the fluid from below the ETT cuff and the experimental trachea. No fluid was aspirated from the area above the ETT cuff toward the lower airways. CONCLUSIONS: We conceived an system capable of automatically expelling fluid from below the ETT cuff outside an experimental trachea by generating an artificial cough maneuver. This system may decrease the use of endotracheal suctioning and its complications. Future in vivo studies are needed to confirm this first in vitro evaluation.

Comparing the Performance Characteristics of Different Positive Expiratory Pressure Devices.

BACKGROUND: Positive expiratory pressure (PEP) devices are widely used in clinical settings, yet the performance characteristics of these devices remain relatively unknown. This study compared the performance characteristics of 6 airway clearance devices by varying resistance and flow. METHODS: Mean PEP, peak PEP, oscillation frequency, and amplitude PEP of the Flutter, Pari PEP S, Acapella Choice, Acapella DM, Acapella DH, and Aerobika devices were obtained across flows of 5, 10, 15, 20, 25 and 30 L/min and at low, medium, and high resistance using an experimental apparatus custom-built for this bench study. RESULTS: Performance characteristics of the devices differed across flows and resistance settings (device × flow/resistance interaction; P < .001). At a fixed resistance, increasing flows increased mean PEP produced by the Acapella Choice, Acapella DH, Aerobika, and Pari PEP S. Increasing flow resulted in minimal change in mean PEP produced by the Flutter and Acapella DM. Increasing flow increased peak PEP and amplitude PEP produced by all devices except the Acapella DH and Acapella Choice. Increasing flow maintained or increased oscillation frequency for all devices except the Flutter. At a fixed flow, increasing resistance increased mean PEP produced by all devices except the Acapella Choice. Increasing resistance increased peak PEP produced by the Acapella DM, Aerobika, and Pari PEP S but resulted in minimal change in peak PEP for the Flutter and Acapella Choice. Increasing resistance either maintained or increased oscillation frequency for all devices. Amplitude PEP was either maintained or increased during oscillations when increasing resistance for all devices except the Flutter. CONCLUSIONS: PEP devices produced small but statistically significant variations in performance characteristics across a range of flows and resistance settings. There appear to be flow-dependent and non-flow-dependent devices. Varying flow or resistance typically maintained or increased the production of mean, peak, and amplitude PEP and oscillation frequency.

Relationship of genetic determinants of height with cardiometabolic and pulmonary traits in the Hispanic Community Health Study/Study of Latinos.

Background: Associations of adult height with cardiometabolic and pulmonary traits have been studied in majority European ancestry populations using Mendelian randomization and polygenic risk score (PRS) analysis. The standard PRS approach entails creating a PRS for height using variants identified in prior genome-wide association studies (GWAS). It is unclear how well the standard PRS approach performs in non-European populations and whether height-trait associations observed in Europeans are also observed in other populations. Methods: In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we used: (i) the standard approach to create a PRS for height (PRS1) and (ii) a novel approach to optimize the selection of variants from previously established height association loci to better explain height in HCHS/SOL (PRS2). We also estimated the extent to which PRS-trait associations were independent or mediated by the PRS effect on height. Results: In 7539 women and 5245 men, PRS1 and PRS2 explained 9 and 29% of the variance in measured height, respectively. Both PRS1 and PRS2 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/ FVC ratio, total cholesterol and 2-hour oral glucose-tolerance test insulin levels. Additionally, PRS2 was associated with estimated glomerular filtration rate and ankle brachial index. Both PRS1 and PRS2 had pleiotropic associations with FEV1/ FVC ratio in mediation analyses. Conclusions: Associations of polygenic scores of height with measures of lung function and cholesterol were consistent with those observed in prior studies of majority European ancestry populations. Mediation analysis may augment standard PRS approaches to disentangle pleiotropic and mediated effects.

Change of Exhaled Acetone Concentration Levels in Patients with Acute Decompensated Heart Failure.

Exhaled acetone concentration is one of the expected compounds to be a breath biomarker in heart failure. However, it has not been clarified how exhaled acetone concentration changes in clinical course of heart failure.To investigate whether exhaled acetone concentration changes after treatment in acute decompensated heart failure (ADHF).This study included 19 patients with ADHF (ADHF group) and eight patients with stable heart failure (control group). Exhaled acetone was collected from these patients, and the concentration was measured with gas chromatography.The ADHF group had higher heart rates (P = 0.046), higher New York Heart Association class (P < 0.001), higher levels of brain natriuretic peptide (P = 0.026), blood total ketone bodies (P = 0.015), and exhaled acetone concentration (P < 0.001), compared with the control group. In ADHF group, exhaled acetone concentration significantly decreased after treatment (median: 2.40 versus 0.92 ppm, P < 0.001). However, in the control group, exhaled acetone concentration did not significantly change (median: 0.73 versus 0.49 ppm, P = 0.141).In these preliminary findings, exhaled acetone concentration in patients with ADHF drastically decreased by treatment. Serial exhaled acetone measurement might be useful to evaluate the course of ADHF.

Toxicokinetics of the neonicotinoid insecticide imidacloprid in rainbow trout (Oncorhynchus mykiss).

Studies were conducted to determine the distribution and elimination of imidacloprid (IMI) in rainbow trout. Animals were injected with a low (47.6 µg/kg), medium (117.5 µg/kg) or high (232.7 µg/kg) dose directly into the bloodstream and allowed to depurate. The fish were then sampled to characterize the loss of IMI from plasma and its appearance in expired water (all dose groups) and urine (medium dose only). In vitro biotransformation of IMI was evaluated using trout liver S9 fractions. Mean total clearance (CLT) values determined by non-compartmental analysis of plasma time-course data were 21.8, 27.0 and 19.5 mL/h/kg for the low, medium and high dose groups, respectively. Estimated half-lives for the same groups were 67.0, 68.4 and 68.1 h, while fitted values for the steady-state volume of distribution (VSS) were 1.72, 2.23 and 1.81 L/kg. Branchial elimination rates were much lower than expected, suggesting that IMI is highly bound in blood. Renal clearance rates were greater than measured rates of branchial clearance (60% of CLT in the medium dose group), possibly indicating a role for renal membrane transporters. There was no evidence for hepatic biotransformation of IMI. Collectively, these findings suggest that IMI would accumulate in trout in continuous waterborne exposures.

Excessive alcohol consumption induces methane production in humans and rats.

Various studies have established the possibility of non-bacterial methane (CH4) generation in oxido-reductive stress conditions in plants and animals. Increased ethanol input is leading to oxido-reductive imbalance in eukaryotes, thus our aim was to provide evidence for the possibility of ethanol-induced methanogenesis in non-CH4 producer humans, and to corroborate the in vivo relevance of this pathway in rodents. Healthy volunteers consumed 1.15 g/kg/day alcohol for 4 days and the amount of exhaled CH4 was recorded by high sensitivity photoacoustic spectroscopy. Additionally, Sprague-Dawley rats were allocated into control, 1.15 g/kg/day and 2.7 g/kg/day ethanol-consuming groups to detect the whole-body CH4 emissions and mitochondrial functions in liver and hippocampus samples with high-resolution respirometry. Mitochondria-targeted L-alpha-glycerylphosphorylcholine (GPC) can increase tolerance to liver injury, thus the effects of GPC supplementations were tested in further ethanol-fed groups. Alcohol consumption was accompanied by significant CH4 emissions in both human and rat series of experiments. 2.7 g/kg/day ethanol feeding reduced the oxidative phosphorylation capacity of rat liver mitochondria, while GPC significantly decreased the alcohol-induced CH4 formation and hepatic mitochondrial dysfunction as well. These data demonstrate a potential for ethanol to influence human methanogenesis, and suggest a biomarker role for exhaled CH4 in association with mitochondrial dysfunction.

Biological effects of inhaled nitrogen dioxide in healthy human subjects.

PURPOSE: Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques. METHODS: Twenty-five subjects were exposed for 3 h to NO2 concentrations 0, 0.1, 0.5, and 1.5 ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate. RESULTS: From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5 ppm (p = 0.048) compared to 0.1 ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p = 0.05). CONCLUSION: These results do not suggest a considerable acute adverse response in human subjects after 3 h of exposure to NO2 in the NO2 concentration range investigated in this study.

Effect of exercise duration on pro-oxidants and pH in exhaled breath condensate in humans.

Exercise promotes pulmonary oxidative imbalance. In this regard, some evidence has been obtained from the study of exhaled breath condensate (EBC) during urban races, in which the factors involved in the occurrence of this process are still not characterized. In this paper, under laboratory conditions, both the role of time of exercise on the generation of pro-oxidants (H2O2, NO2 (-)) and pH have been assessed in EBC of 16 under-trained subjects who completed three tests of cycloergometric exercise at low intensity (30 % of VO2 max) with a duration of 10, 30, and 90 min. Samples were obtained as follows: immediately before and at 80 min post exertion in each test. In the 90-min test, an increase in H2O2, NO2 (-) concentration in EBC at 80 min post exertion with no changes in the pH was observed. Total O2 consumption and total ventilation weakly correlated with the changes in H2O2 and NO2 (-). In conclusion, the concentration of pro-oxidants in the EBC depends on the duration of the exercise when it is performed at low intensity under laboratory conditions.

Recent Marijuana Use and Associations With Exhaled Nitric Oxide and Pulmonary Function in Adults in the United States.

BACKGROUND: The medical and recreational use of marijuana is now legal in some parts of the United States; the health effects are unknown. We aimed to evaluate associations between recent marijuana use and exhaled nitric oxide (eNO) and pulmonary function. METHODS: We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey in the years 2007 to 2012. We examined associations between marijuana use and eNO, FEV1, FVC, the FEV1/FVC ratio, and forced expiratory flow (midexpiratory phase) (FEF25%-75%) by weighted linear regression. RESULTS: In the study population, there were 4,797 never users, 4,084 past marijuana users, 555 participants who used marijuana 5 to 30 days before the examination, and 891 participants who used marijuana 0 to 4 days before the examination. Current marijuana use in the past 4 days was associated with 13% lower eNO (95% CI, -18% to 8%). FVC was higher in past users (75 mL; 95% CI, 38-112) and current users in the past 5 to 30 days (159 mL; 95% CI, 80-237) and in users within 0 to 4 days of the examination (204 mL; 95% CI, 139-270) compared with never users. All associations remained unchanged and statistically significant in sensitivity analyses excluding current and past tobacco users. CONCLUSIONS: Current marijuana use was associated with lower levels of eNO and higher FVC. The lower eNO in marijuana smokers suggests that short-term exposure to marijuana may, like tobacco, acutely affect the pulmonary vascular endothelium and impair airflow through the small airways.

Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review.

Oxidative stress has a recognized role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflammation, and asthma severity. Levels of oxidative stress markers in the EBC have been systematically evaluated in children with asthma; however, there is no such systematic review conducted for adult asthma. A systematic review of oxidative stress markers measured in EBC of adult asthma was conducted, and studies were identified by searching MEDLINE and SCOPUS databases. Sixteen papers met the inclusion criteria. Concentrations of exhaled hydrogen ions, nitric oxide products, hydrogen peroxide and 8-isoprostanes were generally elevated and related to lower lung function tests in adults with asthma compared to healthy subjects. Assessment of EBC markers may be a noninvasive approach to evaluate airway inflammation, exacerbations, and disease severity of asthma, and to monitor the effectiveness of anti-inflammatory treatment regimens. Longitudinal studies, using standardized analytical techniques for EBC collection, are required to establish reference values for the interpretation of EBC markers in the context of asthma.

Biomarker-based detection of asthma-COPD overlap syndrome in COPD populations.

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD). However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient's symptoms or the physician's opinion, based on questionnaire testing. In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study. Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014. When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD. When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD. To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers. The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS.

Acute exercise is associated with reduced exhaled nitric oxide in physically inactive adults with asthma.

BACKGROUND: Although exercise has multiple health benefits, relatively little attention has been paid to its potential therapeutic effects in those with asthma. OBJECTIVE: To examine the effects of acute exercise on inflammation in physically inactive and active adults with asthma. METHODS: Fourteen adults with asthma (n = 6 physically inactive, n = 8 physically active) completed (1) 30 minutes of moderate-intensity exercise on a treadmill and (2) 30 minutes of rest in random order, with 4 weeks between sessions. Exhaled nitric oxide (eNO) was measured before and after the intervention (0, 0.5, 1, 2, 4, and 24 hours). Blood inflammatory mediators were measured before and after the intervention (0, 2, and 24 hours). RESULTS: Physically inactive participants had a significant decrease in eNO 4 hours after exercise (-4.8 ppb, -6.4 to -0.5 ppb, P = .028), which was not observed in physically active participants (P = .362). Interluekin-1 receptor antagonist increased in the physically inactive group 2 hours after exercise, with this increase strongly correlated with the decrease in eNO at 4 hours (R = -0.685, P = .007) and 24 hours (R = -0.659, P = .014) after exercise. Interleukin-6 was increased significantly 2 hours after exercise in physically inactive participants. Blood neutrophils and nuclear factor erythroid 2-like 2 gene expression were increased 2 hours after exercise in the overall cohort. CONCLUSION: This study demonstrates that acute moderate-intensity exercise is associated with decreased eNO in physically inactive adults with asthma and suggests that interluekin-1 receptor antagonist could have a role in mediating this effect. The attenuated response in physically active participants might be due to the sustained anti-inflammatory effects of exercise training. Future studies should investigate the impact of exercise intensity and exercise training on airway inflammation in those with asthma. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au), registration number ACTRN12613001014741.

Bronchial Reactivity, Inflammatory and Allergic Parameters, and Vitamin D Levels in Children With Asthma.

BACKGROUND: A low serum vitamin D level may represent a marker of other perplexing factors that may lead to increased asthma prevalence and severity. Our aim was to assess the correlation between vitamin D levels and asthma and allergy markers in a subgroup of children with fewer confounding factors. METHODS: Non-obese children (6-18 y old) with asthma who were not receiving anti-inflammatory treatment were recruited. Subjects underwent spirometry with a methacholine challenge test, and fractional exhaled nitric oxide (FENO), serum vitamin D levels, total immunoglobulin E (IgE) levels, blood eosinophil counts, and high-sensitivity C-reactive protein levels were determined. The primary end point was the correlation between vitamin D level and airway hyper-responsiveness as assessed by a methacholine challenge test. The secondary end point was the correlation between vitamin D level and FENO, systemic inflammatory markers, and allergy. RESULTS: Seventy-one children with asthma (25 females, 35%; 12.5 ± 3.6 y of age) were included. The median vitamin D level was 23 ng/mL (range of 6-48.5, mean of 23.02 ± 7.74), the median IgE level was 305 IU/mL (range of 4.3-4,240), the median provocational concentration of methacholine that produced a 20% decrease in FEV1 was 1.1 mg/mL (range of 0-13.9), and the median FENO was 26.5 ppb (range of 3.6-285). No correlation was found between vitamin D level and response to the methacholine challenge test, FENO, high-sensitivity C-reactive protein levels, IgE levels, eosinophil counts, and frequency of allergic rhinitis or atopic dermatitis. CONCLUSIONS: In our group of children with asthma, no correlation was found between the level of vitamin D and the degree of airway reactivity, airway inflammation, and allergy. The cause-and-effect relationship between vitamin D, asthma, and allergy should be further clarified. (ClinicalTrials.gov registration NCT01287455).