Hyperresponsiveness In Asthmatic Children Research Articles

Combined assessment of serum periostin, YKL-40, and bronchial hyperresponsiveness in asthmatic children

Serum level of periostin has been studied as a biomarker for type 2 inflammation in asthma patients. In addition, serum levels of human chitinase-3-like protein 1 (YKL40) have been found to be related to asthma severity and airway remodeling. We explored the relationship between serum periostin, YKL-40, and bronchial hyperresponsiveness (BHR) in asthmatic children.

Enhanced airway hyperresponsiveness in asthmatic children and mice with A(H1N1)pdm09 infection.

BackgroundSevere asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic (A(H1N1)pdm09) in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. In this study, airway hyperresponsiveness (AHR) was measured in pediatric asthma patients infected with A(H1N1)pdm09. We also evaluated AHR in asthmatic mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison.MethodsAHRs in asthmatic children were defined as the provocative acetylcholine concentration causing a 20% reduction in forced expiratory volume in 1 s (PC20). To investigate the pathophysiology using animal models, BALB/c mice aged 6‐8 weeks were sensitized and challenged with ovalbumin. Either mouse‐adapted A(H1N1)pdm09, seasonal H1N1 virus (1 × 105 pfu/20 μl), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation.ResultsAHRs in the children with bronchial asthma were temporarily increased, and alleviated by 3 months after discharge. AHR was significantly enhanced in A(H1N1)pdm09‐infected asthmatic mice compared to that in seasonal H1N1‐infected mice (p < .001), peaking at 7 days postinfection and then becoming similar to control levels by 10 days postinfection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09‐infected mice at 7 days postinfection than at 10 days postinfection.ConclusionOur results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.

Elevated Th17 cell frequencies and Th17/Treg ratio are associated with airway hyperresponsiveness in asthmatic children

Introduction: The elevation of T helper (Th)17 cell frequencies and the imbalance of Th17/regulatory T (Treg) cells occur in asthma pathogenesis. Airway hyperresponsiveness (AHR) is a cardinal feature of asthma, and Th17 responses can promote AHR. We hypothesized that changes in Th17 cells and the Th17/Treg ratio correlate with AHR in asthmatic children.Methods: Twenty asthmatic children and twenty healthy children were included in the study. The peak expiratory flow (PEF) % pred, forced expiratory volume in 1 s (FEV1) % pred and the FEV1/forced vital capacity (FVC) ratio were measured in all subjects. Methacholine challenge test (MCT) was performed in asthmatic children. Flow cytometric analysis was used to determine the proportions of Th17 and Treg cells in peripheral blood mononuclear cells. ELISA was used to assess serum levels of interleukin (IL)-17A and IL-10.Results: Th17 cell frequencies (2.272 ± 0.207% in asthmatics, 1.193 ± 0.131% in controls, P < 0.01) and Th17/Treg ratios (0.371 ± 0.0387 in asthmatics, 0.183 ± 0.020 in controls, P < 0.01) were significantly increased in asthmatic children compared to controls. In asthmatic children, the MCT grade had positive correlations with the Th17 cell frequencies [r = 0.718, P < 0.01], serum IL-17A level [r = 0.753, P < 0.01] and Th17/Treg ratio [r = 0.721, P < 0.01], while the log10PD20-FEV1 value was negatively correlated with the Th17 cell frequencies [r = −0.654, P < 0.01], serum IL-17A level [r = −0.652, P < 0.01] and Th17/Treg ratio [r = −0.625, P < 0.01].Conclusion: Th17 cell, IL-17A and Th17/Treg ratio were positively correlated with AHR in asthmatic children. It may be helpful to monitor Th17 cells and the Th17/Treg ratio as indicators of AHR in clinical practice.

Elevation of Th17 and Th17/ Treg Ratio is Associated with Airway Hyperresponsiveness in Asthmatic Children

Elevation of Th17 and Th17/ Treg Ratio is Associated with Airway Hyperresponsiveness in Asthmatic Children

An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction.

BackgroundMannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction.MethodsPatients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 μg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14).ResultsOf 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067).ConclusionShort-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

Relationships Between The New Biomarkers Induced By Interleukin-13 and Bronchial Hyperresponsiveness In Asthmatic Children: Periostin and Squamous Cell Carcinoma-Related Antigens

Relationships Between The New Biomarkers Induced By Interleukin-13 and Bronchial Hyperresponsiveness In Asthmatic Children: Periostin and Squamous Cell Carcinoma-Related Antigens

Does The Sinusitis Affect Bronchial Hyperresponsiveness In Asthmatic Children ?

278 Psycho Social Stresses and Asthma Morbidity In Children Dr. Ejaz Yousef, MD, FAAAI; Marshfield Clinic, Marshfield, WI; Marshfield Clinic, MARSHFIELD, WI. RATIONALE: The purpose of this review is to investigate the influence of psycho-social stress on asthma morbidity in children. METHODS: Data on 56 asthmatic children aged 5-18 years were collected. Subjects were examined for the influence of psychological stresses (AHDH, Anxiety, Depression) and social factors (parental divorce, poor school performance, chronic illness in the family and any other stress in the family). The study subjects were divided into two groups. Group A (N5 30) comprised of children without personal or family history of psychosocial stress. Subjects in Group B (N5 26) had 2 or more background psychosocial stressors. RESULTS: Group A: Average asthma related hospital admission rate for group Awas 2 ER/Urgent care visits/year. 10 subjects had >2 courses of systemic steroids/year. Average asthma related missed school days/parental job time in the group was 4 days/year. Non compliance with asthma medications/care plan was found in 11 subjects Group B: Average hospital admission rate for group B was > 1.5 /year/subject.16 Subjects had >2 ER/Urgent care visits/year. 17 subjects had >2 courses of systemic steroids /year. Average missed school /parental job time in group was 9 days/ year. 16 subjects in Group were found to be non-compliant with medication/asthma care plan. CONCLUSIONS: These data suggest that psychosocial stressors may act as risk factors for asthma morbidity. Further research is needed to characterize the relationship with stress at multiple levels to more fully understand and address asthma morbidity in children.

Possible control of paternal imprinting of polymorphisms of the ADAM33 gene by epigenetic mechanisms and association with level of airway hyperresponsiveness in asthmatic children

ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.

Comparison of mannitol, methacholine and exercise challenge test to evaluate bronchial hyperresponsiveness in asthmatic children

To compare the effect of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP; 400μ g/d) with that of chlorofluorocarbon (CFC) BDP (800 μg/d) on asthma health-related quality of life in a 12-week, parallel-group, multicenter study.HFA-BDP is a new CFC-free preparation of BDP, which was developed as a result of CFCs being phased out from metered dose inhalers.Following 7 to 12 days of prednisone, 30 mg/d, 347 adults with moderate asthma were randomized to receive either 400μ g/d HFA-BDP, 800 μg/d CFC-BDP, or HFA placebo for 12 weeks (all other oral and inhaled steroids were withdrawn). Patients completed the Asthma Quality of Life Questionnaire (AQLQ), and clinical asthma status was measured at the end of a run-in period, at randomization (after oral steroid treatment), and at the end of the study treatment.Sixty-one patients withdrew, 43 due to worsening asthma (33 placebo; 5 HFA-BDP; 5 CFC-BDP). There was a deterioration in the AQLQ score (− 0.81) in the placebo group, and the difference between this and the stability observed in both the HFA-BDP group (+ 0.13) and the CFC-BDP group (− 0.03) was statistically significant (p ≤ 0.003). The difference between the two active treatments was not significant (p = 0.290). The calculated number of patients who needed to be treated in order to see a benefit in one patient (with the placebo as the standard treatment) was 2.4 for HFA-BDP and 3.0 for CFC-BDP. Only weak to moderate correlations were observed between changes in AQLQ scores and between asthma clinical status measures.HFA-BDP (400μ g/d) was as effective as CFC-BDP (800 μg/d) in sustaining improvements in asthma quality of life following withdrawal of 7 to 12 days of prednisone treatment in moderate asthma.

Change of bronchial hyperresponsiveness in asthmatic children

Bronchial hyperresponsiveness (BHR) is a factor in predicting bronchial asthma independently of inflammation markers. The aims were to determine the frequency and important predictive facts of BHR and the effect of prophylaxis by Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) on BHR in asthmatic children. BHR in 106 children was evaluated by the bronchoprovocation test with methacholine. The prevalence rate of symptomatic BHR is 18% for crucial point of PC20 = 4.1 +/- 3.03 mg/ml and PD20 = 3.22 +/- 2.59 micromol methacholine. On average asthmatic children express moderate BHR, which persists even two years after administering prophylaxis. After two years bronchial reactivity is significantly smaller, the change of FEV1 is significantly smaller, the velocity of change of slope dose response curve (sDRC) is faster and the provocative concentration of methacholine that causes wheezing is 2-3 times lower. A mild sDRC shows milder bronchoconstriction after two years. The fast change of bronchial reactivity in 41% of asthmatic children is contributed to aero-pollution with sulfur dioxide and/or, possible insufficient and/or inadequate treatment during two years of administering prophylaxis. A simultaneous effect of allergens from home environment and grass and tree pollens and of excessive aero-pollution on children's airways is important in the onset of symptomatic BHR. After two years of treatment by GINA and NAEPP children do not show asthma symptoms or show mild asthma symptoms, however bronchial sensitivity remains unchanged. Optimal duration of anti-inflammatory treatment in asthmatic children who show moderate bronchial hyperresponsiveness should be longer than two years.

Do epigenetic mechanisms control paternal imprinting of polymorphisms of gene ADAM33 and the association with level of airway hyperresponsiveness in asthmatic children?

Do epigenetic mechanisms control paternal imprinting of polymorphisms of gene ADAM33 and the association with level of airway hyperresponsiveness in asthmatic children?

Effect of Age on Relationship Between Exhaled Nitric Oxide and Airway Hyperresponsiveness in Asthmatic Children

Numerous studies have examined the relationship between the fractional concentration of exhaled nitric oxide (Feno) and airway hyperresponsiveness (AHR). Our objective was to determine the effects of age on the relationship between Feno and AHR in asthmatic children. AHR was examined in 267 asthmatic patients (age range, 5 to 20 years). A challenge test was performed using acetylcholine chloride (Ach). We determined the provocative concentration of Ach producing a 20% decrease in FEV(1) from baseline (PC(20)). Feno was examined using the recommended online method before the Ach challenge test. In children < 12 years of age (range, 5 to 11 years), decreasing AHR (PC(20)) was significantly related to higher Feno (r = -0.43; beta = -0.28; p < 0.001). In adolescents >or= 12 years of age (range, 12 to 20 years), decreasing PC(20) was associated with peripheral airway obstruction (FEV(1): r = 0.32; beta = 5.5; p = 0.002; forced expiratory flow at 50% of the FVC: r = 0.24; beta=8.4; p = 0.006; and forced expiratory flow at 25% of FVC: r = 0.28; beta=11.4; p = 0.002). AHR and Feno were weakly related (r = -0.18; beta = -0.14; p = 0.02). In children with asthma, AHR is associated with airway inflammation. AHR in children with asthma may consist of variable components mainly reflecting airway inflammation. In contrast, in adolescents with asthma, AHR is associated with airway structural changes and weakly with airway inflammation. AHR in adolescents with asthma may consist of chronic components mainly reflecting airway remodeling.

Determinants of lung function and airway hyperresponsiveness in asthmatic children

Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment. We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA). The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0.25% lower per year of delay from diagnosis until treatment (p=0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking. In the secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV(1)% pred was inversely related to having asthmatic siblings (-7.9%; p<0.0001), asthma diagnosis (-2.7%; p=0.0007), smoking (-3.5%; p=0.0027), and positive allergy skin prick test (-0.47% per test; p=0.012), while positively related to being of female gender (1.8%; p=0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; p<0.0001). These data suggest that lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma.

A Chinese herbal decoction, Ding Chuan Tang, improves airway hyper-responsiveness in asthmatic children and adolescents,

A Chinese herbal decoction, Ding Chuan Tang, improves airway hyper-responsiveness in asthmatic children and adolescents,

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.

Different IL‐5 and IFN‐γ Production from Peripheral Blood T‐Cell Subsets in Atopic and Nonatopic Asthmatic Children

Defective Th1 and enhanced Th2‐type cytokine responses have been implicated in the development of atopic disease. However, the immunopathology of nonatopic asthma, especially in children, remains unclear, and there have been few studies to compare the cytokine profile in peripheral blood T‐cell subsets between atopic and nonatopic asthmatic children. To document whether atopic asthmatic children have a cytokine imbalance and to compare the cytokine profile between atopic and nonatopic asthmatic children, we investigated the interleukin (IL)‐5‐producing and interferon (IFN)‐γ‐producing T‐cell subsets from peripheral blood mononuclear cells (PBMC). The percentages of IFN‐γ‐producing CD4+ and CD8+ T cells from atopic asthmatic children were decreased, but those in nonatopic asthmatic children were not decreased. In both groups of asthmatic children, the percentages of IFN‐γ‐producing CD4+ T cells were inversely correlated with the peripheral blood eosinophils and had a significant correlation with airway responsiveness (PC20). Thus, we found that the mechanism underlying allergic inflammation of nonatopic asthma is not simple a Th1/Th2 cytokine imbalance. Considering the inverse relationship between IFN‐γ‐producing CD4+ T cells and eosinophilia or airway hyperresponsiveness, IFN‐γ from CD4+ T cells may play an important role in allergic inflammation and airway hyperresponsiveness in asthmatic children.

Allergic sensitization but not allergic rhinitis influences bronchial hyperresponsiveness in asthmatic children

Allergic sensitization but not allergic rhinitis influences bronchial hyperresponsiveness in asthmatic children

Improvement of bronchial hyperresponsiveness in asthmatic children treated for concomitant sinusitis.

There appears to be an association between sinusitis and asthma. The effect on bronchial hyperresponsiveness of clinical therapy for sinusitis in children may help to decipher whether sinusitis and asthma are independent manifestations of the same disease. To evaluate the effect of clinical treatment for sinusitis in patients with rhinitis and/or asthma on symptoms and on bronchial hyperresponsiveness to methacholine. Open label, randomized, non-treatment control in a teaching hospital in São Paulo, Brazil. Forty-six atopic and 20 normal children were studied. The atopic children consisted of 18 with allergic rhinitis (12 without sinusitis and 6 with sinusitis), and 28 children with rhinitis with asthma (13 with normal sinus radiographs and 15 with complete opacification of the maxillary sinuses). Methacholine PC20 was determined before and 30 days after treatment with nasal saline, sulfamethoxazole-trimethoprim, antihistamine/decongestant, and five days of prednisone. Sinus radiographs were also repeated. The only patients with increase in methacholine PC20 were patients with rhinitis and asthma with opacified maxillary sinuses at entry and who at 30 days had normal sinus radiographs (P < .05). In this study, children with allergic rhinitis and sinusitis with asthma improved their bronchial hyperresponsiveness to methacholine and decreased their symptoms with appropriate response of their sinuses to clinical therapy.

Peak expiratory flow variation and bronchial hyperresponsiveness in asthmatic children during periods of antigen avoidance and reexposure.

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables.

THE EFFECTS OF DISODIUM CROMOGLYCATE ON BRONCHIAL HYPERRESPONSIVENESS IN CHILDREN WITH ASTHMA

We studied the effects of disodium cromoglycate (DSCG) on bronchial hyperresponsiveness in 38 mild asthmatic children. The subjects were divided into two groups; patients of group D inhaled 20mg of DSCG 3 times daily and group C had no prophylactic drugs. Acetylcholine inhalation challenge test was performed repeatedly before and after 3 months of treatment (10 cases in group D and 14 cases in group C), 6 months (7 in group D, 5 in group C) and 12 months (15 in group D, 10 in group C). Respiratory threshold of acetylcholine (RT-Ach) did not significantly change after 3 months of treatment and slightly increased after 6 months of treatment in both groups. After 12 months of treatment, RT-Ach significantly increased in group D, but did not change in group C. We concluded that long-term use of DSCG decreased the bronchial hyperresponsiveness in asthmatic children. The number of eosinophils in peripheral blood significantly decreased after 1 year of treatment only in group D. From this results, we guess that DSCG might have the effect on eosinophils contributing to the inflammatory process of asthma and protect against the increase of bronchial hyperresponsiveness.