Risk Factor For Development Of Asthma Research Articles

Inflammatory related plasma proteins involved in acute preschool wheeze.

Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood. Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3months. Additionally, to investigate the relationship between protein expression and clinical parameters. We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3months (PW-R, n=113/145) and 101 healthy controls (HC) aged 6-48months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala). Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins. Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.

Prevalence of bronchial asthma and correlation between the chemokine receptor 3 gene polymorphism and clinical asthma phenotypes among Egyptian asthmatic children

BackgroundAsthma is a chronic inflammatory airway disease characterized by episodic reversible airway obstruction that variably presents with cough, wheezing, shortness of breath, or chest tightness. It is a multigenetic disease, where both genetic and environmental factors have significant roles in pathogenesis. As regard asthma pathogenesis, the chemokine/chemokine receptor system is considered a key point of the immune response in most allergic diseases. This study was done to estimate the prevalence of bronchial asthma among school age children and explore the association between the underlying gene polymorphisms in chemokine receptor 3 (CCR3) and symptom-based clinical asthma phenotypes among a cohort of Egyptian children.ResultsPrevalence of asthma is increasing (20.6%). There are male asthma predominance. Family history of bronchial asthma and allergic diseases are predominant risk factors for asthma development. Sixty asthmatic cases with different clinical phenotypes were compared to 100 healthy controls, results explored that eosinophilic percent and total serum IgE are significantly higher among asthmatic cases versus controls. There are no significant difference regarding eosinophilic percent, serum IgE, and CCR3 T51C gene polymorphism among different clinical asthma phenotypes. There is no significant difference as regards degree of severity of asthma and level of asthma control between CCR3 T51C gene polymorphism.ConclusionWe conclude the prevalence of bronchial asthma is increasing. Also, eosinophilic percent and serum IgE are elevated in asthma patients, while CCR3 T51C gene polymorphism frequency seemed to be more prevalent among asthmatic subjects however without statistical significance. We recommend a prospective study on larger sample size to validate our results.

Serum Interleukin 4 Level in Asthma Patient in Relation to Body Mass Index (BMI)

Abstract Background The association between obesity and bronchial asthma has been demonstrated by many studies, either observational or interventional studies in both children and adults. The interrelationship between obesity and asthma derives from a complex interplay of biologic, physiologic, and environmental factors. Obesity considered as an important risk factor for asthma development and this mediated by release of proinflammatory mediators, such as interleukin (IL-6) (IL-4), tumor necrosis factor-alpha, and leptin, into the circulation, while release of anti-inflammatory adipokines, such as adiponectin, is decreased. Aim To determine relation between serum interleukin (IL-4) level and body mass index (BMI) in asthmatic patients. Methods This study was conducted on 86 individuals. They were equally classified into two groups: group 1 (overweight and obese asthmatics) group 2 (average weight asthmatics) all of them were subjected to full history and examination, chest x ray, measurement of BMI, CBC, serum total IgE level, serum IL-4 level and pulmonary function test. Results Serum IL-4 level is significantly elevated in group 1(overweight and obese asthmatics) rather than group 2(average weight asthmatics) at p-value 0.000. There was no statistically significant difference between the two groups as regard eosinophils, total igE level, FEV1, FVC and FEV1/FVC%. Conclusion IL-4 level is significantly elevated in overweight and obese asthmatics rather than average weight asthmatics this may be indicate a pathogenic role in development of asthma in overweight and obese asthmatics.

Small airway dysfunction and obesity in asthmatic patients: a dangerous liaison?

Asthma is a chronic condition characterized by inflammation throughout the entire bronchial airways. Recent findings suggest that ventilation inhomogeneity and small airway dysfunction (SAD) play a particularly significant role in asthma development and clinical manifestations. Obesity is a considerable risk factor for asthma development and morbidity in children and adults. A growing body of evidence suggests that SAD is linked to more severe asthma and poor asthma control in obese patients. However, the knowledge about the relationship between peripheral airway compromise and obesity in asthma is limited, mainly because of the historical lack of access to non-invasive assessment methods for studying SAD. Conventional lung function measurements, like spirometry, cannot accurately assess small airway function. However, in recent years, new specialized tests available in outpatient settings have been found to distinguish SAD from large airway obstruction more accurately compared to spirometry. Therefore, understanding the degree of peripheral airway implication in the underlying pathology is critical for effective asthma control and therapeutic decisions. This review highlights recent findings on the impact of SAD on asthma patients who are obese. Additionally, it explores how new diagnostic methods, such as impulse oscillometry (IOS), may be used in outpatient settings to detect small airway impairment in obese asthma at an early stage, potentially leading to improved asthma treatment.

Household adult smoking behaviors and prevalence of asthma in Greek schoolchildren: five surveys during 1998-2018.

Environmental tobacco smoke exposure is a well-recognized risk factor for asthma development and poor asthma control in children. However, the relationship between changes in parental smoking habits over time and the prevalence of childhood asthma remains largely unknown. Our objective was to investigate the trends of parental smoking behaviors in relation to childhood wheeze/asthma rates over a 20-year period. A standardized questionnaire on household overall smoking and household indoor tobacco smoking (HITS) habits was distributed to 8-9-years-old school children in the context of five cross-sectional surveys conducted in 1998 (n=3,076), 2003 (n=2,725), 2008 (n=2,688), 2013 (n=2,554) and 2018 (n=2,648). The parental overall smoking and HITS rates have substantially decreased during the study period (p-for-trend<0.001). However, while HITS declined among the fathers of asthmatic and non-asthmatic children as well as among the mothers of non-asthmatic ones (p-for-trend<0.001), it remained unchanged in the case of the mothers of asthmatic participants (p-for-trend 0.283). The mothers of asthmatic children consistently reported more HITS than those of non-asthmatic participants, while prevalence changes of current wheeze/asthma over the surveillance period were in complete agreement with changes in maternal HITS (cross-correlation coefficient 0.918 at zero-year lag) but not with paternal smoking behaviors. Overall and indoor smoking rates of school children's adult family members declined substantially during the 1998-2018 period in Greece. However, no such trend was noted among mothers of asthmatic children, while temporal changes in maternal indoor smoking rates occurred in parallel with those of childhood asthma prevalence.

Risk Factors for Asthma Development in Adult Patients in the Electronic Health Record: A Landmark Analysis from the Vanderbilt CardiOvascular and Multiple MetabOlic Disease in Obesity Resource (COMMODORE)

Obesity adversely impacts asthma prevalence, severity, morbidity, and therapeutic response. The increasing prevalence of obesity necessitates clarifying the role of obesity and metabolic dysregulation (MetD) in incident asthma.

The Asthma Risk Is Increased in Children with Severe Allergic Rhinitis.

Objective:The aim of the study was to evaluate the allergic rhinitis severity, to identify risk factors associated with asthma, and to determine the frequency of comorbid conditions in allergic rhinitis patients with positive skin prick test.Materials and Methods:Clinical characteristics of pediatric patients with allergic rhinitis were investigated. The frequency of comorbidities and risk factors for asthma development were investigated.Results:A total of 120 patients with a mean age of 13.05 ± 3.20 years were included in the study. Dermatophagoides pteronyssinus was the most common source of allergic sensitization (n = 78, 61.0%), whereas mild-persistent disease was the most common type of allergic rhinitis severity (n = 44, 36.6%). Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more common in patients with a moderate–severe course of allergic rhinitis than in the mild group (P = .006, P = .008, and P = .005, respectively). The most frequent comorbidity in children with allergic rhinitis was allergic conjunctivitis (71.7%). The incidence of asthma in those with moderate–severe allergic rhinitis was found to be significantly higher compared to those with mild disease severity (P = .009). Also, the multivariate analysis disclosed moderate–severe allergic rhinitis severity and persistent allergic rhinitis symptoms (OR: 3.822; 95% CI: 1.587–9.200; P =0.003 and OR: 0.333; 95% CI: 0.150–0.737; P =.007, respectively) as risk factors for asthma development.Conclusion:Sensitization to Dermatophagoides farinea, Dermatophagoides pteronyssinus, and Alternaria was more frequent in patients with moderate–severe allergic rhinitis course. Also, having moderate–severe allergic rhinitis severity and persistent allergic rhinitis symptoms are associated with the development of asthma. Awareness of the risk factors could prevent the progression and complications of allergic rhinitis in children.

Effect of Dermatophagoides pteronyssinus extract on the expression of genes involved in inflammation and tissue remodeling by peripheral blood mononuclear cells of allergic asthma patients

PurposeHouse dust mite allergy constitutes a risk factor for asthma development and is associated with a faster decline of lung function in allergic asthmatics (AAs).To evaluate the effect of Dermatophagoides pteronyssinus (Dp) allergens on the expression of genes involved in inflammation and tissue remodeling by peripheral blood mononuclear cells (PBMCs) isolated from the blood of AAs. Materials and methodsThe cells from AAs, allergic rhinitis without asthma patients (ARs), and healthy controls (HCs) were cultured in the presence of Dp, lipopolysaccharide (LPS), or without any stimulation. The expression of 84 genes was evaluated using a low-density microarray whereas, the quantitative expression analysis of selected genes was performed using a real-time polymerase chain reaction. The concentration of selected proteins in the cell culture supernatants was assessed using ELISA. ResultsStimulation of PBMCs with Dp and LPS resulted in a significant upregulation of 8 and 15 among 84 studied genes, respectively. The greatest upregulation was observed for CCL2 and CCL3 using Dp and LPS, respectively. In comparison with HCs, in AAs, significantly increased upregulation of CCL2 in response to Dp was found. The secretion of CCL2 and CCL3 by PBMCs reflected the pattern of gene expression at the mRNA level. The mean Dp-stimulated secretion of CCL2 by PBMCs of ARs was less than in AAs (p ​< ​0.01), both being notably greater than in the HCs (p ​< ​0.01). ConclusionRapid and potent upregulation of CCL2 expression by PBMCs in response to Dp may constitute an important contribution to the development of allergic asthma.

Comparison of circulating fibrocytes from non-asthmatic patients with seasonal allergic rhinitis between in and out of pollen season samples

BackgroundAllergic rhinitis is a risk factor for asthma development. In asthma, fibroblast progenitors, fibrocytes, are increased in the blood and bronchial mucosa following allergen exposure. These cells may play a role in lower airways remodeling as observed in non-asthmatic subjects with allergic rhinitis.ObjectiveTo determine the influence of seasonal allergen exposure on blood circulating fibrocytes in allergic rhinitic subjects without asthma.MethodsNon-asthmatic subjects with seasonal allergic rhinitis had blood sampling at baseline and at the peak of rhinitis symptoms. Cells were stained for fibrocyte markers (CD34, CD45, CXCR4, collagen I) and analyzed by flow cytometry.ResultsData from 26 subjects (11M:15F) aged 29 ± 8 years were analysed. Compared to baseline, there was a significant decrease in blood fibrocytes during the pollen season in subjects sensitized to trees [median (25–75 percentile), 9.3 (6.4–20.7)% vs 7.0 (4.2–10.1)%, P = 0.007] and a significant increase in subjects sensitized to grass [12.7 (9.9–23.1)% vs 64.0 (57.6–73.6)%, P < 0.001] and ragweed [8.0 (7.4–10.8)% vs 48.2 (43.5–52.6)%, P < 0.001]. A significant decrease in CXCR4 mean fluorescence was also observed between the two visits [1814 (1261–2235) vs 1352 (814–1796) (arbitrary units), P = 0.02].Conclusions and clinical relevanceThese results contribute to document dynamic variations in blood fibrocytes’ activation and migration into the airways following natural exposure to allergens. These findings may help identify one of the potential factors involved in the development of asthma in allergic rhinitic subjects.

Nasopharyngeal metatranscriptome profiles of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study.

Bronchiolitis is not only the leading cause of hospitalisation in US infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. Our objectives were to identify metatranscriptome profiles of infant bronchiolitis, and to examine their relationship with the host transcriptome and subsequent asthma development. As part of a multicentre prospective cohort study of infants (age <1 year) hospitalised for bronchiolitis, we integrated virus and nasopharyngeal metatranscriptome (species-level taxonomy and function) data measured at hospitalisation. We applied network-based clustering approaches to identify metatranscriptome profiles. We then examined their association with the host transcriptome at hospitalisation and risk for developing asthma. We identified five metatranscriptome profiles of bronchiolitis (n=244): profile A: virusRSVmicrobiomecommensals; profile B: virusRSV/RV-Amicrobiome H.influenzae ; profile C: virusRSVmicrobiome S.pneumoniae ; profile D: virusRSVmicrobiome M.nonliquefaciens ; and profile E: virusRSV/RV-Cmicrobiome M.catarrhalis . Compared with profile A, profile B infants were characterised by a high proportion of eczema, Haemophilus influenzae abundance and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated T-helper 17 and downregulated type I interferon pathways (false discovery rate (FDR) <0.005), and significantly higher risk for developing asthma (17.9% versus 38.9%; adjusted OR 2.81, 95% CI 1.11-7.26). Likewise, profile C infants were characterised by a high proportion of parental asthma, Streptococcus pneumoniae dominance, and enriched glycerolipid and glycerophospholipid metabolism of the microbiome. These profile C infants had an upregulated RAGE signalling pathway (FDR <0.005) and higher risk of asthma (17.9% versus 35.6%; adjusted OR 2.49, 95% CI 1.10-5.87). Metatranscriptome and clustering analysis identified biologically distinct metatranscriptome profiles that have differential risks of asthma.

Nitric Oxide Synthase 2 Promoter Polymorphism Is a Risk Factor for Allergic Asthma in Children.

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

Air Pollution and Family Related Determinants of Asthma Onset and Persistent Wheezing in Children: Nationwide Case-Control Study

To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children.All Danish children born from 1997 to 2014 who were managed for asthma onset and persistent wheezing from the age of 1 year to 15 years by using a national registry based, matched case-control design.Children were managed in the Danish National Patient Register for the classification of asthma or persistent wheezing after hospital discharge, or with a minimum of 2 prescriptions for asthma medications. Information regarding concentration of air pollutants (several gases, aerosols, particular matter <2.5µm [PM2.5] and particular matter <10µm), parental asthma diagnoses and asthma medication prescriptions, maternal smoking habits, highest completed parental education, and parental income levels were collected and analyzed for hazard ratios (HRs).From 1997–2014, 3 192 785 children were included in the study, and 122 842 (3.84%) children developed asthma and/or persistent wheezing, with a mean age of development of 1.9 years. Maternal asthma had a higher risk than paternal asthma (adjusted HR): 1.72 (95% CI: 1.72 to 1.77) vs 1.51 (95% CI: 1.48 to 1.53)], but having 2 parents with asthma was associated with a 2.40-fold (2.34-fold to 2.47-fold) risk of childhood asthma. Maternal smoking during pregnancy (adjusted HR: 1.23 [1.18 to 1.28]) or quitting during pregnancy (HR: 1.20 [1.18 to 1.22]) increased the risk of childhood asthma. Exposures to PM2.5, particular matter <10µm, and nitrogen dioxide were also associated with development of asthma, with PM2.5 exposure being the most consistent. Higher parental income levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.85 [95% CI: 0.81 to 0.89) for the highest parental income level, compared with 1.04 (95% CI: 1.00 to 1.08) for the lowest parental income level]. Higher parental education levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.72 [95% CI: 0.69 to 0.75]) for the highest parental education level, compared with 0.98 [95% CI: 0.95 to 1.00] for the lowest parental education level).Parental history of asthma, higher levels of exposure to PM2.5, and maternal smoking during pregnancy all increase a child’s risk of developing asthma and persistent wheezing. High levels of parental educational attainment and income are associated with a lower risk of developing asthma and persistent wheezing in children.Strengths of this study include the use of a large database that covered 18 years. In this study, researchers did not analyze atopy, lung function, or inflammatory markers. A family history of asthma, tobacco exposure and environmental pollutants were confirmed as risk factors for asthma development. Smoking cessation campaigns and environmental strategies to decrease particulate matter exposure may reduce the number of children who develop asthma.

Lung sound analysis in infants with risk factors for asthma development.

Background and objectivesUsing a lung sound analysis, the prognosis of asthma was investigated in infants with risk factors for asthma development by a long‐term observation.MethodsA total of 268 infants were included (median age: 8 months old). The lung sound parameters (the ratio of the third and fourth area to the total area under the curve [A3/AT and B4/AT], and the ratio of power and frequency at 50% and 75% of the highest frequency [RPF50 and RPF75]) were evaluated at the first visit. At 3 years old, using a questionnaire, we examined the relationship between the lung sound parameters and risk factors of asthma development.ResultsAmong the 268 infants, 175 infants were in good health and 93 had a history of acute respiratory infection (ARI) within 7 days at the first visit. Among the 3‐ to 12‐month‐old infants with an ARI, the A3/AT, B4/AT values in those with a history of asthma/asthmatic bronchitis, atopic dermatitis, and atopy were smaller than in the infants without such histories. Among the 13‐ to 24‐month‐old infants with an ARI, the A3/AT and B4/AT values in those with a wheezing history were larger than in the infants without such a history.ConclusionsThe characteristics of the lung sounds in infants with risk factors for asthma development were demonstrated over long‐term follow‐up. Lung sound analyses may be useful for assessing the airway condition of infants.

Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFN-intermediate, B) clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high, C) clinicalseveremicrobiomemixedinflammationIFN-low, and D) clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6. Particularly, compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.

Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth.

Background: Early rhinovirus (RV) infection is a strong risk factor for asthma development. Airway remodeling factors play a key role in the progression of the asthmatic condition. We hypothesized that RV infection in young children elicits the secretion of growth factors implicated in airway remodeling and asthma progression.Methods: We examined the nasal airway production of remodeling factors in children ( ≤ 2 years old) hospitalized due to PCR-confirmed RV infection. Airway remodeling proteins included: MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, EGF, Angiopoietin-2, G-CSF, BMP-9, Endoglin, Endothelin-1, Leptin, FGF-1, Follistatin, HGF, HB-EGF, PLGF, VEGF-A, VEGF-C, VEGF-D, FGF-2, TGF-β1, TGF-β2, TGF-β3, PDGF AA, PDGF BB, SPARC, Periostin, OPN, and TGF-α.Results: A total of 43 young children comprising RV cases (n = 26) and uninfected controls (n = 17) were included. Early RV infection was linked to (1) enhanced production of several remodeling factors (e.g., HGF, TGFα), (2) lower MMP-9/TIMP-2 and MMP-2/TIMP-2 ratios, and (3) increased MMP-10/TIMP-1 ratios. We also found that relative to term infants, severely premature children had reduced MMP-9/TIMP-2 ratios at baseline.Conclusion: RV infection in young children elicits the airway secretion of growth factors implicated in angiogenesis, fibrosis, and extracellular matrix deposition. Our results highlight the potential of investigating virus-induced airway remodeling growth factors during early infancy to monitor and potentially prevent chronic progression of respiratory disorders in all ages.

CircARRDC3 contributes to interleukin‑13‑induced inflammatory cytokine and mucus production in nasal epithelial cells via the miR‑375/KLF4 axis.

Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa. It is a major risk factor for asthma development, and uncontrolled AR can lead to the worsening of asthma symptoms, which affects the quality of life and productivity of patients. Circular RNAs (circRNA) were reported to be involved in the pathogenesis of AR. The aim of the present study was to investigate the functional role of circRNA arrestin domain-containing 3 (circARRDC3) in AR progression. circARRDC3 knockdown suppressed the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and eotaxin and mucin 5AC (MUC5AC) in IL-13-induced nasal epithelial cells. Moreover, circARRDC3 silencing promoted viability and suppressed apoptosis in IL-13-induced NECs. circARRDC3 targeted microRNA (miR)-375 and negatively regulated its expression. miR-375 inhibition reversed the effects of circARRDC3 knockdown on GM-CSF, eotaxin and MUC5AC expression levels, cell viability and cell apoptosis. In addition, miR-375 inhibited krueppel-like factor 4 (KLF4) expression through direct interaction, and miR-375 overexpression inhibited GM-CSF, eotaxin and MUC5AC expression levels, and cell apoptosis, which was abolished following KLF4 overexpression. In addition, circARRDC3, miR-375 and KLF4 were all dysregulated in the nasal mucosa of patients with AR. miR-375 expression was negatively correlated with circARRDC3 and KLF4 expression, and circARRDC3 expression was positively correlated with KLF4 expression. In conclusion, circARRDC3 contributed to the development of AR by regulating the miR-375/KLF4 axis. These findings may provide novel insights into the pathogenesis of AR.

Impact of Air Pollution on Asthma Outcomes.

Asthma is a chronic respiratory disease characterized by variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Evidence suggests that air pollution has a negative impact on asthma outcomes in both adult and pediatric populations. The aim of this review is to summarize the current knowledge on the effect of various outdoor and indoor pollutants on asthma outcomes, their burden on its management, as well as to highlight the measures that could result in improved asthma outcomes. Traffic-related air pollution, nitrogen dioxide and second-hand smoking (SHS) exposures represent significant risk factors for asthma development in children. Nevertheless, a causal relation between air pollution and development of adult asthma is not clearly established. Exposure to outdoor pollutants can induce asthma symptoms, exacerbations and decreases in lung function. Active tobacco smoking is associated with poorer asthma control, while exposure to SHS increases the risk of asthma exacerbations, respiratory symptoms and healthcare utilization. Other indoor pollutants such as heating sources and molds can also negatively impact the course of asthma. Global measures, that aim to reduce exposure to air pollutants, are highly needed in order to improve the outcomes and management of adult and pediatric asthma in addition to the existing guidelines.

Early-life heterologous rhinovirus infections induce an exaggerated asthma-like phenotype

Early-life wheezing-associated respiratory tract infection by rhinovirus (RV) is a risk factor for asthma development. Infants are infected with many different RV strains per year. We previously showed that RV infection of 6-day-old BALB/c mice induces a mucous metaplasia phenotype that is dependent on type 2 innate lymphoid cells (ILC2s). We hypothesized that early-life RV infection alters the response to subsequent heterologous infection, inducing an exaggerated asthma-like phenotype. Wild-type BALB/c mice and Rorafl/flIl7rcre mice lacking ILC2s were treated as follows: (1) sham on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 plus RV-A2 on day 13, and (4) RV-A1B on day 6 plus RV-A2 on day 13. Mice infected with RV-A1B at day 6 and sham at day 13 showed an increased number of bronchoalveolar lavage eosinophils and increased expression of IL-13 mRNA but not expression of IFN-γ mRNA (which is indicative of a type 2 immune response), whereas mice infected with sham on day 6 and RV-A2 on day 13 of life demonstrated increased IFN-γ expression (which is a mature antiviral response). In contrast, mice infected with RV-A1B on day 6 before RV-A2 infection on day 13 showed increased expression of IL-13, IL-5, Gob5, Muc5b, and Muc5ac mRNA; increased numbers of eosinophils and IL-13-producing ILC2s; and exaggerated mucus metaplasia and airway hyperresponsiveness. Compared with Rorafl/fl mice, Rorafl/flIl7rcre mice showed complete suppression of bronchoalveolar lavage eosinophils and mucous metaplasia. Early-life RV infection alters the response to subsequent heterologous infection, inducing an intensified asthma-like phenotype that is dependent on ILC2s.

Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells.

One of the major risk factors for asthma development is exposure to environmental allergens. House dust mites (HDM) can induce DNA damage, resulting in asthma. Resveratrol (RES) produced by several plants, has anti-apoptotic properties and may affect a variety of biological processes. The aim of the present study was to investigate the protective role of RES against apoptosis in bronchial epithelial cells. C57BL/6J mice treated with HDM exhibited high levels of cell apoptosis, while RES significantly reversed this process. Induced DNA damage was more severe in the HDM group vs. the HDM combined with RES group. This result was confirmed by immunostaining and western blot analysis of the protein expression of the DNA damage-related gene γH2AX, which was highly induced by HDM. In addition, treatment with RES protected bronchial epithelial cells exposed to HDM from DNA damage. RES decreases reactive oxygen species levels to inhibit oxidative DNA damage in bronchial epithelial cells. Furthermore, compared with the HDM group, induced cell apoptosis could be attenuated by RES in the group of combined treatment with RES and HDM. A DNA repair inhibitor augmented DNA damage and apoptosis in bronchial epithelial cells, whereas RES significantly attenuated cell apoptosis through inhibiting DNA damage.

Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation.

Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status. Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn-297 IgG glycosylation was analysed in maternal and offspring serum. When mothers and offspring were sensitized to the same allergen (OVA-OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS-OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro-inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn-297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro-inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies.