Asthma Lung Function Research Articles

Вплив любительських занять спортом на якість здоров’я

In recent years, there has been a trend in society for a healthy lifestyle. According to the World Health Organization recommendations, exercise is considered a key element in the prevention of many non-communicable diseases, including obesity, diabetes mellitus, cardiovascular disease, tumors, chronic respiratory diseases and others. The purpose of the study was to analyze the sources of modern literature on the effects of exercise, including yoga and resistance training, on health. Both types of training were considered as preventive measures or non-drug treatments. Materials and methods. The search for scientific information was conducted using PubMed and Web of Science databases. For the analysis, it was decided to include mainly review articles, meta-analyzes and systematic reviews published in English. An analysis of the scientific literature, which presents views on the features of the use of yoga and resistance training in chronic non-communicable diseases was carried out. Results and discussion. Modern scientists are actively discussing the impact of exercise on quality of life, because the World Health Organization defines health as a state of complete physical, mental and social well-being, and not just the absence of disease or physical disabilities. It is determined that yoga and resistance training are popular and accessible to most young and middle-aged people. People who practice yoga tend to have a lower body mass index and show a commitment to a healthy lifestyle. Yoga-based exercises are a safe and effective tool for treating patients with hypertension and diabetes. Breathing exercises during yoga have shown a positive effect on quality of life, symptoms of hyperventilation and lung function in asthma. Yoga, as monotherapy or adjunctive therapy, has positive effects on depression and chronic stress. Resistance exercises can promote bone, muscle, and metabolic health, and are associated with a reduced risk of cardiovascular events. The data revealed as a result of this review indicate that a healthy lifestyle, regular exercise can significantly reduce the level of chronic non-communicable diseases, significantly increase the duration and quality of life. However, the authors emphasize that compliance with the recommended levels of physical activity remains extremely low, so it is important to monitor the level of physical activity by health professionals. Conclusion. The analysis allows us to conclude that both types of amateur leisure sports, yoga and resistance training, can be recommended as preventive measures or non-drug treatments for chronic non-communicable diseases

The Oral Eosinophil-lowering Drug Dexpramipexole Improves FEV1 Largely Thorough its Effect on FVC

Airflow obstruction in asthma (measured by FEV1) can be partitioned into components of air trapping in small airways (measured by FVC) and airway narrowing (measured by FEV1/FVC). Anti-eosinophil treatments improve lung function in asthma, but the effect of eosinophil depletion on individual components of airflow obstruction, i.e. FEV1/FVC vs FVC, are not established and may provide insight into the effects of eosinophils on pulmonary physiology.

STAMINA A NOVEL PROSPECT IN ASTHMA MANAGEMENT

Background: Current therapy for asthma includes bronchodilators and anti-inflammatory drugs. Inhibition ofRhoA/ROCK pathway to control hyperresponsiveness presents a novel area in asthma therapy.Study Design: Experimental randomized control trial. “To examine the effect of statins on the airway hyperresponsiveness.” Statins are lipid-lowering agents exhibiting pleiotropic effects in decreasing oxidative stress and inflammation. Several published studies have reported using statins in treating asthma patients, but their results could bemore consistent. This study aims to determine whether statins are beneficial for asthma administration and explorethe covariables that may affect their clinical effectiveness.Materials and Maths: Five groups of six similar guinea pigs animals under similar laboratory conditions wereselected. The animal model of asthma was reproduced via intraperitoneal ova albumin in all except negative controlgroup 1. These groups were Group I negative control, II positive- control, III atorvastatin treated, IV Simvastatintreated, and V lovastatin treated group. After 28 days, animals were sacrificed. Bronchoalveolar fluid (B.A.L.)analysis was taken, and Smooth muscle contractions in tracheal strips to increasing concentrations of acetylcholinewere recorded by isometric transducers using a computerized data recording system. The effects of statins were assessedby comparing concentration-response curves of experimental groups with those of controls.A systematic literature search was performed in PubMed, Embase, and Cochrane Center Register of ControlledTrials from inception to September 2012. Randomized controlled trials (R.C.T.), retrospective studies, and controlledclinical trials that reported the use of statins in the treatment of asthma patients were eligible. Quality evaluation wasconducted for R.C.T. using Jadad criteria.Results: Comparison of B.A.L. of positive control with that of negative confirmed the induction of allergic inflammatory model. The concentration-response curve was significantly shifted upward in positive control compared to negativecontrol (P<0.05).In the case of statin-treated groups, there was a significant downward shift in concentration-responsecurves compared to positive control, showing inhibition of airways hyperresponsiveness by statins. Significant differenceswere observed between them and positive control (P<0.05A total of 18 articles were included. Our study found noconclusive evidence to demonstrate that statins could enhance lung function in asthmatics, although they may reduceairway inflammation. The results were inconsistent across studies concerning symptoms, quality of life, maintenancemedication, and asthma hospitalization/emergency department (E.D.) visits. The present study demonstrates thatstatins inhibit hyperresponsiveness in the allergic airway inflammatory model of the guinea pig. Statins may have atherapeutic potential to ameliorate airway hyperresponsiveness in allergic bronchial asthma. Human trials are neededto include these drugs in asthma treatment guidelinesKeywords: Asthma Guinea pig Model Statin B.A.L

Boysenberry and apple juice concentrate reduced acute lung inflammation and increased M2 macrophage-associated cytokines in an acute mouse model of allergic airways disease.

Bioactive compounds including anthocyanins and other polyphenols are associated with reduced lung inflammation and improved lung function in asthma and other lung diseases. This study investigated the effects of a Boysenberry and apple juice concentrate, high in cyanidin glycosides, ellagitannins, and chlorogenic acid, on a mouse model of allergic airways inflammation. Male C57BL/6J mice were orally gavaged with 2.5 mg/kg of total anthocyanins (TAC) from BerriQi® Boysenberry and apple juice concentrate (0.2 mg/kg human equivalent dose) or water control 1 hr before an acute intranasal ovalbumin (OVA) challenge and were gavaged again 2 days after the intranasal challenge. Consumption of BerriQi® Boysenberry and apple juice concentrate significantly decreased OVA‐induced infiltrating eosinophils, neutrophils, and T cells in the lung, and mucous production. Quantification of gene expression for arginase (Arg1), chitinase 3‐like 3 (Ym‐1), found in inflammatory zone (Fizz1), which have been associated with an anti‐inflammatory macrophage phenotype (M2), found significantly increased Arg1 expression in the lung in the Boysenberry and apple juice concentrate treatment group. There was also increased production of M2‐associated cytokines C‐X‐C motif chemokine ligand (CXCL) 10 and C‐C motif chemokine ligand (CCL) 4. These results suggest that consumption of BerriQi® Boysenberry and apple juice concentrate promoted a shift toward an anti‐inflammatory environment within the lung leading to reduced immune cell infiltration and tissue damage.

Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.

Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin derived from a traditional Chinese medicine, in preclinical models of asthma. In mouse precision-cut lung slices, osthole relaxed preconstricted airways, irrespective of β2-adrenoceptor desensitization. Osthole administered in murine asthma models attenuated airway hyperresponsiveness, a hallmark of asthma. Osthole inhibited phosphodiesterase 4D (PDE4D) activity to amplify autocrine prostaglandin E2 signaling in airway smooth muscle cells that eventually triggered cAMP/PKA-dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole revealed that osthole bound to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation. Identification of osthole binding sites on PDE4D will guide further development of bronchodilators that are not subject to tachyphylaxis and would thus avoid β2-adrenoceptor agonist resistance.

ABO blood group genotypes and ventilatory dysfunction in patients with allergic and nonallergic asthma.

Aim ABO blood group genotypes are established as a genetic factor in pathophysiology of various diseases, such as cardiovascular disorders, cancers, infectious diseases and there is rising evidence of their involvement in other conditions. The aim of this study was to determine if ventilatory changes of lung function in asthma, measured by biomarkers/parameters, are connected to certain ABO blood group genotypes in Croatia. Methods A case-control study included 149 patients with asthma and 153 healthy individuals (blood donors). ABO genotyping on five main alleles was performed using PCR-SSP method. All patients had spirometry performed and severity of asthma was estimated. Clinical parameters of spirometry (FEV1, FEV/FVC, PEF), biomarkers FeNO, IgE and pO2 were measured. The χ2 test, Fisher's test, Kruskal-Wallis test and Spearman's correlation coefficients with p<0.05 were used as statistically significant. Results There was no determined statistically significant difference in both ABO genotypes and phenotypes between patient and control groups. Comparison of the lung function in different ABO phenotypes in asthmatic patients also did not show any statistically significant differences in FEV1 values, FEV/FVC ratio or PEF. Statistically significant differences in oxygenation between different ABO blood types have not been noticed (p=0.326). Differences in quantitative values of biomarkers (FeNO and IgE) between different ABO blood phenotypes in patients with asthma were not significant, except for IgE that had marginal values (p=0.074). Conclusion No correlation was found between certain ABO blood group genotypes and parameters/biomarkers of ventilatory dysfunction in patients with allergic and nonallergic asthma.

Methylation of cysteinyl leukotriene receptor 1 genes associates with lung function in asthmatics exposed to traffic-related air pollution

ABSTRACT Air pollution is associated with early declines in lung function and increased levels of asthma-related cysteinyl leukotrienes (CysLT) but a biological pathway linking this rapid response has not been delineated. In this randomized controlled diesel exhaust (DE) challenge study of 16 adult asthmatics, increased exposure-attributable urinary leukotriene E4 (uLTE4, a biomarker of cysteinyl leukotriene production) was correlated (p = 0.04) with declines in forced expiratory volume in 1-second (FEV1) within 6 hours of exposure. Exposure-attributable uLTE4 increases were correlated (p = 0.02) with increased CysLT receptor 1 (CysLTR1) methylation in peripheral blood mononuclear cells which, in turn, was marginally correlated (p = 0.06) with decreased CysLTR1 expression. Decreased CysLTR1 expression was, in turn, correlated (p = 0.0007) with FEV1 declines. During the same time period, increased methylation of GPR17 (a negative regulator of CysLTR1) was observed after DE exposure (p = 0.02); this methylation increase was correlated (p = 0.001) with decreased CysLTR1 methylation which, in turn, was marginally correlated (p = 0.06) with increased CysLTR1 expression; increased CysLTR1 expression was correlated (p = 0.0007) with FEV1 increases. Collectively, these data delineate a potential mechanistic pathway linking increased DE exposure-attributable CysLT levels to lung function declines through changes in CysLTR1-related methylation and gene expression.

Discrepancy between Lung Function Measurements at Home and in the Hospital in Children with Asthma and CF.

The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV1) measurements with a monitor at home. Paired FEV1 measurements were included if the measurement on the home monitor was performed on the same day as the FEV1 measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV1 was 0.18 L in CF (95% confidence interval (CI) 0.08–0.27 L; p < 0.001) and 0.12 L in asthma (95%CI 0.05–0.19 L; p < 0.001). FEV1 measurements at home were significantly lower than clinically obtained FEV1 measurements, which has implications for the application of this technique in the daily clinical situation.

Airway Relaxation Mechanisms and Structural Basis of Osthole to Improve Lung Function in Asthma

Background and objectiveOveruse of β2‐adrenoceptor agonist bronchodilators causes receptor desensitization, resulting in decreased efficacy and an increased risk of death in asthma patients. This is a critical unmet problem in asthma management, and novel drugs are urgently needed. Here, we report that osthole, a coumarin derived from a traditional Chinese medicine, induces complete relaxation of preconstricted airways in mouse precision‐cut lung slices, irrespective of β2‐adrenoceptor desensitization.MethodsMouse precision‐cut lung slices as an in vitro model were used to analyze airway relaxation. The cAMP level in human airway smooth muscle (ASM) or HEK293 cells was determined by phosphorylation of vasodilator‐stimulated phosphoprotein using Western blot or cAMP dependent reporter luciferase assay. The secretion of prostaglandin E2 (PGE2) in ASM cells or lung slices was measured by ELISA assay. The effect of osthole on airway hyperresponsiveness (AHR) was measured in both house dust mite (HDM)‐sensitized mice and naïve regulator of G‐protein signaling 2 (RGS2) KO mice. The binding sites of osthole with PDE4D5 catalytic domain were analyzed by crystallization and X‐ray diffraction.ResultsOsthole administered in vivo ameliorates AHR, a hallmark of asthma, in murine asthma models. Mechanistic studies revealed that osthole inhibits phosphodiesterase 4D (PDE4D) activity to amplify endogenous PGE2 signaling in ASM cells, which eventually triggers cAMP/protein kinase A‐dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole reveals that osthole binds to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation.ConclusionIdentification of osthole binding sites on PDE4D will guide further development of novel therapeutics for β2‐adrenoceptor agonist‐resistant asthma.Support or Funding InformationThis work was supported in part by the National Institutes of Health (R01HL116849) and Nebraska State LB595 Research Program, USA; the National Laboratory of Biomacromolecules and the Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences (CAS); the CAS/SAFEA International Partnership Program for Creative Research Teams; the National Key R&amp;D Program of China (2017YFA0205501); the National Natural Science Foundation of China (21777192 and 31500623)

Long non-coding RNA NEAT1 overexpression associates with increased exacerbation risk, severity, and inflammation, as well as decreased lung function through the interaction with microRNA-124 in asthma.

BackgroundThis study aimed to explore the association of long non‐coding RNA nuclear‐enriched abundant transcript 1 (lncRNA NEAT1) with exacerbation risk, lung function, and inflammatory cytokines in asthma.MethodsA total of 170 patients with asthma in exacerbation, 170 patients with asthma in remission, and 170 healthy controls (HCs) were enrolled, and their plasma samples were collected. The expressions of lncRNA NEAT1 and microRNA‐124 (miRNA‐124) in plasma were detected by real‐time quantitative polymerase chain reaction; inflammatory cytokines in plasma were measured by the Enzyme‐linked immunosorbent assay (ELISA); and pulmonary ventilation function was detected by examination of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).Results LncRNA NEAT1 expression was upregulated in asthma patients in exacerbation compared with HCs and asthma patients in remission, and receiver operating characteristic curve exhibited that it was of good value in distinguishing asthma patients in exacerbation from HCs (AUC: 0.869 (0.830‐0.908)) and asthma patients in remission (AUC: 0.775 (0.724‐0.825)). Furthermore, lncRNA NEAT1 was positively correlated with exacerbation severity, TNF‐α, IL‐1β, and IL‐17, but negatively correlated with IL‐10, FEV1/FVC and FEV1%predicted in asthma patients. Additionally, lncRNA NEAT1 was negatively correlated with miR‐124, and miR‐124 was negatively associated with exacerbation risk, exacerbation severity, and inflammation, but positively associated with lung function in asthma patients.Conclusion Circulating lncRNA NEAT1 exhibits potential to be a new biomarker for elevated exacerbation risk and severity of asthma.

Lung clearance index: assessment and utility in children with asthma.

There is increasing evidence that ventilation heterogeneity and small airway disease are significant factors in asthma, with evidence suggesting that the small airways are involved from an early stage in childhood asthma. Spirometry is commonly used to monitor lung function in asthmatics; however, it is not sensitive to small airway disease. There has been renewed interest in multibreath washout (MBW) tests, with recognition of the lung clearance index (LCI) as a global index of abnormality in gas mixing of the lungs that therefore also reflects small airway disease. This review summarises the technical and practical aspects of the MBW/LCI in children, and the differences between commercially available equipment. Children with severe asthma are more likely to have an abnormal LCI, whereas most children with mild-to-moderate asthma have an LCI within the normal range, but slightly higher than age-matched healthy controls. Monitoring children with asthma with MBW alongside standard spirometry may provide useful additional information.

Meta-analysis of vitamin D and lung function in patients with asthma

BackgroundThere is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients.MethodsMajor databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5.ResultsThis quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = − 0.1, 95% CI = − 0.11 to − 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = − 10.02, 95% CI = − 11 to − 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults.ConclusionsOur meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.

Associations of Th2, Th17, Treg cells, and IgA+ memory B cells with atopic disease in children: The Generation R Study.

New insights into immune cells could contribute to treatment and monitoring of atopic disease. Because nongenetic factors shape the human immune system, we here studied these immune cells in a large cohort with atopic children with adjustment for prenatal and postnatal confounders. Information on atopic dermatitis, inhalant- and food-allergic sensitization, asthma lung function scores was obtained from 855 10-year-old children within the Generation R cohort. 11-color flow cytometry was performed to determine CD27+ and CD27- IgG+ , IgE+ and IgA+ memory B cells, Th1, Th2, Th17, and Treg-memory cells from venous blood. Associations between any atopic disease, the individual atopic diseases, and immune cell numbers were determined. Children with any atopic disease had higher Th2, Treg, Treg-memory, and CD27+ IgA+ memory B-cell numbers compared to children without atopic disease. When studying the individual diseases compared to children without the individual diseases, children with atopic dermatitis, inhalant-, and food-allergic sensitization had higher memory Treg cell numbers 12.3% (95% CI 4.2; 21.0), (11.1% (95% CI 3.0; 19.8), (23.7% (95% CI 7.9; 41.8), respectively. Children with food-allergic sensitization had higher total B and CD27+ IgA+ memory B-cell numbers (15.2% [95% CI 3.2; 28.7], 22.5% [95% CI 3.9; 44.3], respectively). No associations were observed between asthma and B- or T-cell numbers. Children with any atopic disease and children with inhalant- and food-allergic sensitization or atopic dermatitis had higher circulating memory Treg cells, but not higher IgE+ B-cell numbers. The associations of higher Treg and CD27+ IgA+ B-cell numbers in children with food-allergic sensitization are suggestive of TGF-β-mediated compensation for chronic inflammation.

Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma.

Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.

Prevalence of Vitamin D deficiency in patients with acute exacerbations of bronchial asthma: A one-year hospital-based cross-sectional study

BACKGROUND AND OBJECTIVES: Bronchial asthma is one of the most common chronic diseases. In India, bronchial asthma has 66% frequency of reported exacerbations. Vitamin D has action on pro-inflammatory mediators and smooth muscle function and proliferation, which has a direct relevance for lung function in asthma. This study was done to investigate the prevalence of Vitamin D deficiency in patients presenting with asthma exacerbations and to assess the correlation between decreased levels and various indicators of severity of exacerbations. MATERIALS AND METHODS: A total of 118 participants of whom 93 patients had acute exacerbations of bronchial asthma were included in this study. Vitamin D levels were analyzed among different subgroups based on asthma control, severity, and severity of exacerbations. Vitamin D levels were correlated to forced expiratory volume in 1 s (FEV1)% predicted, body mass index (BMI), steroid use, and number of exacerbations in the previous 1 year. RESULTS: Prevalence of Vitamin D deficiency was 88.2%. Mean Vitamin D (± standard deviation [SD]) level was 12.50 ± 6.41 ng/ml, which was lower than that of patients in remissions (30.61 ± 4.00 ng/ml). Mean FEV1% predicted (±SD) was 54.06% ±15.39%. Patients with severe asthma and uncontrolled asthma had the lowest Vitamin D levels compared to the other subgroups (P CONCLUSION: Vitamin D deficiency is highly prevalent in patients during exacerbations of bronchial asthma. It is also associated with lower lung functions and increased number of exacerbations. Thus, improving Vitamin D status might be effective in the prevention and treatment of bronchial asthma and exacerbations.

Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children

BackgroundFew longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships.MethodsChildren underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection.ResultsAs anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1.ConclusionsIn asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.

Measuring Airway Obstruction in Severe Asthma in Children.

Lung function is an important tool in the diagnosis and monitoring of patients with asthma at all ages. Airway obstruction is a typical feature of asthma and it can be assessed with several lung function techniques. Spirometry, respiratory resistance and reactance, and lung volumes are available to measure it at different ages and in children. The assessment of a bronchodilator response is always recommended to show the reversibility of the obstruction. Poor lung function is a predictor of poor asthma outcome and a low Forced Expiratory Volume in the first second of expiration percent predicted measured with spirometry, has been shown to be associated with a higher risk of having an exacerbation during the following year independently of the presence of asthma symptoms. In severe asthma lung function assessment is used to distinguish different phenotypes, children with severe asthma have worse airflow limitation prior to administration of a bronchodilator than children with non severe asthma. Airway resistance and reactance are indirect measurements of airway obstruction and they can be measured with the forced oscillation technique, which is feasible also in non-collaborative children. This technique can be more informative in discriminating patients with asthma from healthy controls and is able to indicate a more peripheral involvement of the airways. The role of this technique in severe asthma is still debated. In conclusion lung function is useful in the clinical management of children with severe asthma.

Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in asthmatics from NHANES 2007-12.

Fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count are biomarkers for type 2 inflammation. However, they signal different inflammatory pathways. Simultaneously elevated, they are related to more asthma events in a general population and among younger asthmatics. To investigate if simultaneously elevated FeNO and B-Eos relate to asthma outcomes and lung function among subjects with asthma at a wide age span, and how different cut-offs for the markers affect these relations. FeNO, B-Eos and forced expiratory volume in 1 second (FEV1 ) were assessed in 1419 subjects with asthma, aged 6-79 years old, from the National Health and Nutrition Examination Survey (NHANES) 2007-12. Elevated levels were defined as FeNO ≥20 p.p.b. for children <12 years and ≥25 p.p.b. for subjects ≥12 years and B-Eos count ≥300 cells/μL. Additional analyses were performed for the cut-offs FeNO >35/30 and >50/35 p.p.b., and for B-Eos ≥400 and ≥ 500 cells/μL, as well as for different age subgroups (6-17, 18-44, >44 years old). Asthma events during the past year were self-reported. Subjects with simultaneously elevated FeNO and B-Eos compared with normal levels of both markers had a higher adjusted odds ratio (aOR (95%CI)) for having FEV1 <80% of predicted (2.15 (1.28-3.59), wheeze disturbing sleep (1.88 (1.27, 2.78)) but did not differ regarding asthma attacks past year. Elevated B-Eos, but not FeNO, was related to higher aOR for asthma attack (1.57 (1.14, 2.18) or emergency room (ER) visit due to asthma (1.88 (1.33, 2.64) when elevated FeNO and elevated B-Eos were studied as independent predictors. Simultaneously elevated FeNO and B-Eos related to reduced lung function in asthmatics, wheezing symptoms, but not to a history of asthma attacks. Asthma attacks and ER-visit due to asthma were related to increased B-Eos levels.

Serum periostin relates to type-2 inflammation and lung function in asthma: Data from the large population-based cohort Swedish GA(2)LEN.

Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.