Bronchial Hyperresponsiveness In Children Research Articles

Extended Nitric Oxide Analysis and Bronchial Hyperresponsiveness In Children With Asthma According To Atopy

Extended Nitric Oxide Analysis and Bronchial Hyperresponsiveness In Children With Asthma According To Atopy

小児の肺機能検査・気道過敏性検査

小児の肺機能検査・気道過敏性検査

Relationship between bronchial hyperresponsiveness and lung function in children age 5 and 6 with and without asthma

It is unknown whether wheezy children have bronchial hyperresponsiveness (BHR) or which lung function parameters are correlated with BHR in children. We evaluated the relationship between BHR parameters and the lung functions by minimizing the effects of age and height in asthmatic, non-asthmatic wheezers and healthy children. The subjects comprised of 154 children aged 5 and 6 years (78 males, 76 females), who were divided into three groups: asthmatics, non-asthmatic wheezers and healthy controls. Spirometry and a methacholine inhalation challenge by the oscillation method were performed. The age of the study cohort was 5.9 ± 0.2 years (mean ± standard deviation), and the height was 114.4 ± 5.3 cm. No significant differences in height, weight, body mass index or lung function were observed in the three groups. The minimal dose of methacholine to start bronchoconstriction, a parameter of bronchial sensitivity, was lower in asthmatics and non-asthmatic wheezers than that in controls. The speed of bronchoconstriction in response to methacholine, a parameter of bronchial reactivity, was strongly correlated with baseline respiratory resistance (Rrs cont) in all three groups. Our data suggest that it not possible to distinguish preschool children with asthma from non-asthmatic wheezers based on their bronchial sensitivity and that the baseline Rrs has a strong effect on the bronchial reactivity in children.

Serum Periostin Levels Correlate with Bronchial Hyperresponsiveness to Mannitol and Methacholine in Children with Asthma

Recently it has been found that periostin, a matricellular protein, is a highly inducible product of IL-4 or IL-13 in lung fibroblasts and is involved in fibrosis of bronchial asthma. Effects of serum periostin on bronchial hyperresponsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to address the relationship between serum periostin and BHR in children with asthma.

Immunotherapy – 2082. Long term prevention of asthma and rhinitis in children with atopic dermatitis four year after discontinuation of sublingual immunotherapy

Background Atopic Dermatitis is a disease with high prevalence in Italy (about 15% of the population). As known, Atopic Dermatitis is often associated with respiratory allergy to mite.We previously showed that sublingual immunotherapy (SLIT) to mite has a beneficial clinical effect in patients with allergic extrinsic Atopic Dermatititis (AD). To investigate the long term effects, we performed a 4-year follow up after the termination of SLIT. Methods 46 children with AD, aged 5-16 years and allergic to mite were re-assessed 4 years after discontinuation of a 2-year course of SLIT (or placebo). Methacholine provocation tests were carried out at baseline, after 2 years (when SLIT was stopped) and after 4 years. The development of asthma and rhinitis was assessed by clinical evaluations. Results The children who previously had received SLIT had significantly less asthma after 6 years as evaluated by clinical symptoms: odd ratio 3.73 (0.130 vs 0.511; P=0.02) as compared to the former placebo group. In addition, significantly less patients reported an increase in asthma scores P=0.003. A significant difference in bronchial methacholine responsiveness was found between the two groups (P=0.03), with an overall lower bronchial hyperreactivity in children who previously received active SLIT. Conclusions A 2-year course of SLIT to mite provided a long term clinical effect and prevented the development of asthma in children with allergic extrinsic form of Atopic Dermatitis.

Forced expiratory flow between 25% and 75% of vital capacity as a predictor for bronchial hyperresponsiveness in children with allergic rhinitis

Purpose: Allergic rhinitis (AR) is regarded as a risk factor for asthma and bronchial hyperresponsiveness (BHR) is frequently observed in patients with AR. The purpose of this study is to analyze the characteristics of AR patients with BHR and identify factors that contribute to the incidence of BHR. Methods: The medical records of a total of 176 children with AR were analyzed retrospectively. All patients were evaluated by performing spirometry and a methacholine challenge test. Results: One hundred and fifty-five patients (88%) were classified as the BHR-negative group and 21 patients (12%) were classified as the BHR-positive group. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75 %predicted) was reduced, and total eosinphil counts, total immunoglobulin E (IgE) level, and serum specific IgE levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae were higher in the BHR-positive group compared to the BHR-negative group. However, FEF25-75 was the only statistically significant predictor for the presence of BHR on multivariate logistic regression analysis. The cutoff value to distinguish BHR-positive subjects obtained from a receiver operating characteristics curve of FEF25-75 was 88.4%. A higher frequency of BHR was found in the group with a FEF25-75 less than 88.4%, and the sensitivity, specificity, positive predictive value and negative predictive value were 57.1%, 80.6%, 28.6%, and 93.3%, respectively. Conclusion: Reduced FEF25-75 values in children with AR can be helpful in predicting BHR. Children with low FEF25-75 in spirometric tests should be followed closely for apparent onset of clinical symptoms of asthma. (Allergy Asthma Respir Dis 1?1):60-66, 2013)Allergy Asthma Respir Dis 1(1):60-66, 2013)

Chapter 15: Lessons learned from clinical trials of asthma

The preponderance of clinical data suggest that inhaled corticosteroids (ICSs) are the preferred therapy for the long-term management of asthma, whereas oral or parental corticosteroids and short-acting beta(2)-adrenergic agonists remain the mainstay treatment of acute exacerbations. Allergen and tobacco avoidance are tenets to the practice of allergy-immunology and are beneficial in the treatment of asthma. Failure to avoid animal danders or fungi to which a patient with asthma is allergic is a risk factor for a fatal attack. First introduced in the 1970s, ICSs are the mainstay of pharmacotherapy to control airway inflammation and bronchial hyperresponsiveness in children and adults with asthma. ICSs reduce symptoms, exacerbations, hospitalizations, and deaths while improving quality of life and lung function. When used in combination with an ICS, essentially all clinical trials have indicated that long-acting beta(2)-adrenergic agonists are effective and safe. Leukotriene modifiers (LTMs) are effective in the treatment of persistent asthma, exercise-induced asthma, and aspirin-induced asthma but, in general, are less efficacious than ICSs when used as monotherapy to control asthma symptoms. Nevertheless, some patients respond to LTMs better than ICSs so a personalized approach to asthma pharmacotherapy is recommended. Not only is conventional (subcutaneous) allergen immunotherapy effective in patients with allergic asthma, immunotherapy (subcutaneous or sublingual) administered for rhinoconjunctivitis in children has been shown to reduce the development of asthma.

525 Bronchial Hyperresponsiveness in Children with Suggestive Asthma Symptoms

BackgroundTo describe the accuracy of bronchial challenge tests (methacholine and manitol) to measure bronchial hyperresponsiveness in a group of pediatric patients with suggestive symptoms of asthma.MethodsWe selected 27 patients who attended consecutively to our outpatient clinic complaining of 1 or 2 symptoms of asthma. They showed a normal baseline spirometry and a negative bronchodilator test. All of them underwent unspecific bronchial provocation challenges. Methacholine was performed using the tidal volumen technique and a PC20 ≤ 8 mg/mL was considered positive. Dry-powder mannitol (Osmohale TM) was administered according to the manufacturer's recommendations and the challenge was considered positive if a PD15 ≤ 635 mg resulted. We performed both tests with an interval of at least 1 week. Asthma drugs were avoided during the 2 weeks previous to every challenge. Skin prick tests (SPT) to the most common aeroallergens were also performed.ResultsMean age was 9 (ranged 7–15) years, 18 (66.6%) children were male. Symptoms referred were: 14 (51.8%) cough, 10 (37%) seasonal cough or shortness of breath, 5 (18.51%) cough or shortness of breath due to physical exercise and 1 (3.7%) cough or wheezing related to respiratory infections. SPT were positive in 59.2% of the children. Eighteen (66.6%) out of 27 patients had bronchial hyperresponsiveness, and 10 (37.03%) were non atopic. All patients with a positive response to manitol showed also positivity to methacholine. Mean methacoline PC20 among responders was 0.64 ± 4.08 mg/mL. Manitol was performed in 16 children, and resulted positive in 8 cases (50%) with a mean PD15 of 146.8 ± 246.49 mg. In 2 (25%) out of 8 patients with negative manitol resulted a positive methacholine.ConclusionsMethacholine and manitol challenge tests detected bronchial hyperresponsiveness in more than a half of the studied children with suggestive asthma symptoms. Methacoline was more sensitive than manitol.

S7 Adiposity and asthma, pulmonary function and atopy in 11-year old children: a birth cohort study

BackgroundResults of studies investigating the association between obesity and asthma, atopy and lung function have been inconsistent, in part due to the limitation of BMI in evaluating body adiposity.ObjectivesTo investigate...

Alpha‐nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children

The CHRNA 3 and 5 genes on chromosome 15 encode the alpha subunits of the nicotinic acetylcholine receptor, mediating airway cholinergic activity. Polymorphisms are associated with cigarette smoking, chronic obstructive pulmonary disease, and lung cancer. To determine possible associations between CHRNA 3/5 SNP rs8034191 and asthma or lung function in children in one local and one replicate multinational population, and assess if tobacco smoke modified the associations. The rs8034191 SNP genotyped in 551 children from the environment and childhood asthma (ECA) birth cohort study in Oslo, Norway, and in 516 families from six European centers [the Genetics of Asthma International Network (GAIN) study] was tested for genotypic or allelic associations to current or history of asthma, allergic sensitization (≥ one positive skin prick tests), bronchial hyperresponsiveness (BHR), and lung function (FEV(1%) of predicted and FEV(1) /FVC ratio over/ below the 5th percentile). Although the TT and CT genotypes at SNP rs 8034191 were overall significantly associated with BHR (OR = 3.9, 95% CI 1.5-10.0, p = 0.005), stratified analyses according to exposure to maternal smoking in-utero or indoor smoking at 10 yrs of age showed significant association (OR = 4.4, 95% CI 1.5-12.6, p = 0.006 and OR 5.6, 95% CI 1.7-18.5, p = 0.004, respectively) only in the non-exposed and not in exposed children. The SNP-BHR association was replicated in the non-tobacco-smoke-exposed subjects in one of the GAIN centers (BHR associated with the T allele (p = 0.034)), but not in the collated GAIN populations. Asthma, allergic sensitization, and lung function were not associated with the rs8034191 alleles. An interaction between tobacco smoke exposure and a CHRNA3/5 polymorphism was found for BHR in children, but CHRNA3/5 was not associated with asthma or lung function.

Forced expiratory flow between 25 and 75% of vital capacity might be a predictive factor for bronchial hyperreactivity in children with allergic rhinitis, asthma, or both

Allergic rhinitis and asthma are closely associated. Bronchial hyperreactivity (BHR) is a pathophysiological characteristic of asthma. Forced expiratory flow between 25 and 75% of vital capacity (FEF(25-75)) has been previously shown to be able to predict BHR in adult patients with allergic rhinitis. Therefore, the aim of this study was (i) to evaluate the presence of BHR in a large group of children with allergic rhinitis, asthma or both and (ii) to confirm whether FEF(25-75) might be related to BHR and may predict BHR also in a pediatric population. Nine hundred fifty children with allergic rhinitis (350), asthma (300), or both (300) were enrolled. Clinical examination, skin-prick test, spirometry, and methacholine challenge were performed in all patients. Severe BHR was quite frequent in allergic children, mainly in asthmatic patients. FEF(25-75) values were significantly related to BHR grade, mainly in children with rhinitis (r = 0.69). Impaired FEF(25-75) values (such as ≤65% of predicted) constituted a relevant predictive factor for severe BHR, mainly in children with rhinitis (odds ratio, 8.9). In conclusion, this pediatric study confirmed that impaired FEF(25-75) values might predict severe BHR in children, mainly in those with allergic rhinitis. Therefore, low FEF(25-75) values could suggest BHR in children.

Prevalence of asthma and bronchial hyperreactivity in Danish schoolchildren: no change over 10 years

To describe the point prevalence of current physician-diagnosed asthma and bronchial hyperreactivity (BHR) in 2001 among unselected Danish schoolchildren aged 6-17 years, compared with the prevalence from a similar study from 1990 to 1991. Cross-sectional study using parental questionnaire on asthma and respiratory symptoms combined with a 6-min free running test with peak expiratory flow rate (PEFR) measurement (n = 1051, response rate 89.3%). Results were compared with those of a similar study in the same area from 1990 to 1991. Main outcome measures were current physician-diagnosed asthma or BHR in children without physician-diagnosed asthma measured by either a decrease in lung function after standardized running test and/or variability in PEFR on home monitoring. The prevalence of current physician-diagnosed asthma was 4.0% [95% confidence interval (CI) 2.7-5.3%] in 1990-1991 and 3.6% (95% CI 2.4-4.8%) in 2001. The prevalence of BHR was 3.2% (95% CI 2.0-4.4%) in 1990-1991 and 2.0% (95% CI 1.1-2.9%) in 2001. The combined prevalence was 7.2% (95% CI 5.4-8.9%) in 1990-1991 and 5.6% (95% CI 4.2-7.1%) in 2001. The point prevalence of current physician-diagnosed asthma and BHR among unselected Danish schoolchildren aged 6-17 years was unchanged over 10 years between 1990-1991 and 2001.

Hiperrespuesta bronquial a la metacolina en niños menores de 4 años con bronquitis de repetición

Objective To evaluate bronchial hyperresponsiveness in children under 4 years of age with recurrent wheezing bronchitis, and to determine if its presence or absence can predict the subsequent progression to a transient or persistent wheezing bronchitis phenotype. Population and methods A bronchial challenge test was performed with methacholine using a modified tidal volume method, without sedation in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress. Results A total of 63 patients and 16 controls were studied (mean age 23.9 vs. 25.2 months). The PCw was lower than the control group (≤4 mg/ml) in 43 (68%) children from the bronchitis group ( P<0.001). No significant adverse effects were observed on performing the test. After a mean follow up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent and frequent wheezing ( P=0.63). Conclusions A high percentage of children under 4 years of age affected by wheezing bronchitis had a bronchial hyperresponse. The subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.

Methacholine is more sensitive than mannitol for evaluation of bronchial hyperresponsiveness in children with asthma

Methacholine is more sensitive than mannitol for evaluation of bronchial hyperresponsiveness in children with asthma

Effects of swimming on spirometric parameters and bronchial hyperresponsiveness in children and adolescents with moderate persistent atopic asthma

To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clínicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test--provocative concentration of methacholine causing a 20% fall in FEV1 (PC₂₀)--before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. Significant increases in PC₂₀ (pre-training, 0.31±0.25; post-training, 0.63±0.78; p = 0.008), MIP (pre-training, 67.08±17.13 cm H₂O; post-training 79.46±18.66; p < 0.001), and MEP (pre-training, 71.69±20.01 cm H₂O; post-training, 78.92±21.45 cm H₂O; p < 0.001) were found in the swimming group. Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC₂₀ values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall.

Bronchial Hyperresponsiveness to Methacholine in Children Under 4 Years with Recurrent Bronchitis

Objective To evaluate bronchial hyperresponsiveness in children under 4 years old with recurrent wheezing bronchitis, and to determine if its presence or absence can predict subsequent progression to a transient or persistent wheezing bronchitis phenotype. Population and methods A bronchial challenge test was performed with methacholine using a modified tidal volume method without sedation, in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress. Results A total of 63 patients and 16 controls were studied (mean age 23.9 compared to 25.2 months). The PCw in 43 (68%) children from the bronchitis group was lower than the control group (≤4 mg/mL), ( P<.001). No significant adverse effects were observed on performing the test. After a mean follow-up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent or frequent wheezing ( P=.63). Conclusions A high percentage of children under 4 years old with wheezing bronchitis had a bronchial hyperresponse. Subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.

Can the Use of HEPA Cleaners in Homes of Asthmatic Children and Adolescents Sensitized to Cat and Dog Allergens Decrease Bronchial Hyperresponsiveness and Allergen Contents in Solid Dust?

Sulser C, Schulz G, Wagner P, et al. Int Arch Allergy Immunol. 2009;148(1):23–30PURPOSE OF THE STUDY. Because pet allergies are associated with asthma, the authors investigated whether high-efficiency particulate-arresting (HEPA) filtration had any effect on reducing indoor allergens and bronchial hyperreactivity in children with asthma who were sensitized to cat and dog.STUDY POPULATION. A total of 30 children with asthma (age: 6–17 years) who were sensitized and exposed to cat and/or dog allergen(s) at home completed the study. The children did not have dust mite or mold sensitivities, and those being treated for asthma stayed on treatment throughout this time.METHODS. This was a randomized, controlled trial in which the children were assigned to 1 of 2 groups. For 12 months, 1 group was exposed to HEPA air cleaners that were placed in the living room and bedroom, and the other group was exposed to paper sham filters. Filters were on for >50% of the time. Pulmonary function testing and cold-air challenges were performed at baseline, 6 months, and 12 months into the study. Serum eosinophil cationic protein, specific immunoglobulin E to several aeroallergens, current medications, and clinical symptoms (nighttime awakenings, physical exercise symptoms, breathing limitations, and nasal stuffiness) were assessed. The amounts of cat (Fel d 1) and dog (Can f 1) allergens in the filters and bulk dust samples were also collected.RESULTS. Forced expiratory volume in 1 second at baseline lung function improved in the entire study population (median: 90% at initial visit, 98% at 6 months, and 95% at 12 months; P < .01). However, there was no significant change in eosinophil cationic protein, use of medication, or quality of life for the 2 groups. Although after 12 months there seemed to be a trend for a decrease in change in forced expiratory volume in 1 second after cold-air challenge in the active group (8.1%–5.4%) versus the sham group (4.3%–8.2%), the difference was not statistically significant (P = .336). Active filters retained higher amounts of cat and dog allergens in their main filter devices, compared with sham filters.CONCLUSIONS. Although HEPA air cleaners were able to retain airborne pet allergens, they had no significant effect on bronchial hyperreactivity.REVIEWER COMMENTS. High-efficiency air filtration is often recommended to patients with asthma with known allergenic sensitivities, to reduce exposure to indoor pet allergens (which are ∼5 μm in size). HEPA filtration can filter out particles as small as 0.3 μm with up to 99.97% efficiency. This study did not find a significant effect of HEPA filtration on bronchial hyperreactivity after 1 year of use, but there seemed to be a trend toward improvement in bronchial hyperreactivity. Although this study revealed a very limited role for HEPA use in asthma therapy, future studies should evaluate whether HEPA filtration may help prevent or delay the development of asthma in younger children with atopy who are at increased risk of developing asthma.

Bronchial hyperreactivity in non‐atopic children with asthma and reflux: Effect of anti‐reflux treatment

The prevalence of bronchial hyperreactivity (BHR) or the effect of anti-reflux treatment on BHR in children with asthma and gastroesophageal reflux disease (GERD) is not known. Thirty non-atopic children with persistent asthma were studied. Extended esophageal pH monitoring was used to diagnose GERD and methacholine challenge test (MCT) was used as a marker of BHR and performed before and 2 years after anti-GERD treatment. Of the 21 patients positive for GERD (group A), 15 had positive MCT suggesting BHR. Of the 9 patients negative for GERD (group B), 5 had positive MCT. On repeat testing 2 years later, 11/15 group A patients and 3/5 group B patients tested negative for BHR. Group A patients were receiving fewer asthma medications and experienced fewer exacerbations than Group B patients. BHR is prevalent in children with asthma and GERD and improves with anti-GERD treatment.

The Effects of Inhaled Fluticasone and Pranlukast on Bronchial Hyperreactivity in Children with Asthma

Background: Guidelines recommend inhaled corticosteroids and leukotriene modifiers as daily therapies to control asthma in children. However, few studies have compared the effects of these drugs on bronchial hyperreactivity in children with asthma.Methods: The effects of inhaled fluticasone and pranlukast on bronchial hyperreactivity in 42 patients aged 7–15 years with mild persistent asthma (24 treated with inhaled fluticasone and 18 with pranlukast), who had experienced no asthma exacerbations after these treatments started, were studied. At the start of and after 6 and 18 months of treatment, bronchial hyperreactivity (PC20: provocative concentration of methacholine causing a 20% fall in FEV1) was assessed with methacholine.Results: Geometric averages of PC20 in patients treated with inhaled fluticasone were 385.2 μg/mL at the start, 2271.8 μg/mL after 6 months, and 4181.0 μg/mL after 18 months of treatment, whereas those patients treated with pranlukast were 415.8 μg/mL, 792.2 μg/mL, and 2105.1 μg/mL,...

Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.