Exercise-induced Bronchoconstriction In Asthmatic Children Research Articles

Leptin and exercise-induced bronchoconstriction in obese asthmatic children

Exercise-induced bronchoconstriction (EIB) in asthmatic children has been associated with obesity. Leptin, the proinflammatory adipokine, is typically increased in obesity, whereas cysteinyl leukotrienes (cysLTs) are the main inflammatory mediators implicated in the pathogenesis of EIB. The aim of this work was to study the possible impact of obesity on the severity of EIB in asthmatic children and the possible association with the adipokine leptin. The study included eighty pre-pubertal asthmatic children divided according to their body mass index (BMI) and response to exercise into four groups; obese exercise-responders (n=20), normal-weight exercise-responders (n=20), obese exercise non-responders (n=20), and normal-weight exercise non-responders (n=20). A baseline spirometry test and a standardized exercise challenge test (ECT) were performed. The severity of EIB was assessed by the maximum percentage fall in forced expiratory volume in 1 second (MF%FEV1) after exercise. The level of fasting serum leptin and the release of cysLTs during exercise were compared between the 4 groups. The MF%FEV1 during exercise was significantly greater in obese responder compared to normal-weight responder patients (p=0.004) and MF%FEV1 was positively correlated with cysLT release during exercise, BMI z-score, waist circumference and serum leptin. CysLT release during exercise was positively correlated with the level of serum leptin (r =0.514, p=0.001). This study reports that the severity of EIB is significantly greater in obese compared to normal-weight asthmatic children and suggests an association between leptin and airway hyperresponsiveness to exercise in obese asthmatic children through a mechanism related to cysLT release

The Visual Analog Scale detects exercise-induced bronchoconstriction in children with asthma

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and an important sign of uncontrolled asthma. The occurrence of EIB is insufficiently identified by the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT). This study aimed to (1) evaluate the Visual Analog Scale (VAS) for dyspnea as a tool to detect EIB in asthmatic children and (2) assess the value of combining (C-)ACT outcomes with VAS scores. Methods: We measured EIB in 75 asthmatic children (mean age 10.8 years) with a standardized exercise challenge test (ECT) performed in cold and dry air. Children and parents reported VAS dyspnea scores before and after the ECT. Asthma control was assessed by the (C-)ACT. Results: Changes in VAS scores (ΔVAS) of children and parents correlated moderately with fall in forced expiratory volume in 1 second (FEV1), respectively rs=0.57 (p < .001) and rs=0.58 (p < .001). At a ΔVAS cutoff value of ≥3 in children, sensitivity and specificity for EIB were 80% and 79% (AUC 0.82). Out of 38 children diagnosed with EIB, 37 had a (C-)ACT score of ≤19 and/or a ΔVAS of ≥3, corresponding with a sensitivity of 97% and a negative predictive value of 96%. Conclusion: This study shows that the VAS could be an effective additional tool for diagnosing EIB in children. A reported difference in VAS scores of ≥3 after a standardized ECT combined with low (C-)ACT scores was highly effective in detecting and excluding EIB.

Study of Serum Level of Lipoxin A4 in Exercise-Induced Bronchoconstriction in Asthmatic Children

AbstractBackground: Asthma is a chronic lung disease character-ized by wheezy chest, resulting from allergic inflammation and hyperresponsivness of the bronchi to various stimuli. Exercise-induced broncho constriction is a common manifes-tation of asthma in children and adolescents, occurring in up to 90% of asthmatic children. Lipoxins are the first agents determined to be anti-inflammatory endogenous lipid mediators involved in the resolution of inflammation. Since there is defective lipoxin biosynthesis in patients with severe asthma, we hypothesized that Lipoxin A4 may be related to develop-ment of exercise induced bronchoconstriction.Aim of Study: It was to measure serum level of lipoxin A4 before and after exercise to evaluate its role in exercise induced bronchoconstriction in asthmatic children.Patients and Methods: The study was carried out on fifteen children with mild intermittent or mild persistant asthma with positive response to exercise challenge test and fifteen children with mild intermittent or mild persistant asthma with negative response to exercise challenge test who attended to the outpatient clinic of Chest and Allergic Diseases, Pediatric Department, Tanta University Hospital. Also it was carried on fifteen apparently healthy children with matched age and sex served as a control group. All studied children were subjected to full history taking, thorough clinical exam-ination, plain chest X-ray, pulmonary function tests (FEV 1and PEFR) by spirometer before and after exercise challenge test, eosinophilic count, serum Lipoxin A4 by ELISA before and immediately after exercise challenge test. Data was analyzed by using SPSS.Results: There was significant more decrease in serum Lipoxin A4 after exercise in asthmatic children with exercise induced bronchoconstriction as compared to asthmatic children without exercise induced bronchoconstriction. Regarding pulmonary function tests (FEV 1 and PEFR), there was signif-icant more decrease in FEV 1 after exercise in asthmatic children with exercise induced bronchoconstriction as com-pared to asthmatic children without exercise induced bron-choconstriction but, there was no significant difference between the asthmatic children with exercise induced bronchoconstric-tion and asthmatic children without exercise induced bron-choconstriction regarding the decrease in PEFR after exercise. And there was no statistical significant difference between subject's sex, age, residence nor BMI.Conclusion: There was inverse correlation between serum LXA4 levels and a reduction in FEV 1 after exercise in asth-matic children. The demonstration of lower levels of lipoxin A4 in association with exercise induced bronchoconstriction suggest that the development of exercise-induced bronchoc-onstriction in asthmatic children may be due to reduced endogenous lipoxin biosynthetic capability. This association not affected by ages and sex of patients.

Serum levels of periostin and exercise-induced bronchoconstriction in asthmatic children

BackgroundPeriostin is induced by IL-13 and has been studied as a biomarker of asthma. The present study explored the relationship between serum levels of periostin and exercise-induced bronchoconstriction (EIB) in asthmatic children. MethodsThe study population consisted of 86 children 6–15 years old divided into an asthmatic group (n = 56) and healthy controls (n = 30). We measured the levels of periostin in serum and performed pulmonary function tests including baseline measurements, post-bronchodilator inhalation tests, exercise bronchial provocation tests (BPTs), and mannitol BPTs. ResultsThe 56 asthmatic children were divided into four groups: asthmatics with positive exercise BPT and positive mannitol BPT (n = 30), asthmatics with positive exercise BPT but negative mannitol BPT (n = 7), asthmatics with negative exercise BPT but positive mannitol BPT (n = 10), and asthmatics with negative exercise BPT and negative mannitol BPT (n = 9). Serum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT (95.0 [75.0–104.0] vs. 79.0 [68.0–82.5] ng/mL, P = 0.008) and controls (74.0 [69.75–80.0] ng/mL, P < 0.001). Periostin levels were significantly correlated with both the maximum decrease in %FEV1 and mannitol PD15 value. ConclusionSerum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT and also greater than in healthy controls.

A comparison of the utilities of the fractional exhaled nitric oxide level and mannitol bronchial provocation test in terms of predicting exercise-induced bronchoconstriction in asthmatic children

A comparison of the utilities of the fractional exhaled nitric oxide level and mannitol bronchial provocation test in terms of predicting exercise-induced bronchoconstriction in asthmatic children

The Diagnostic Value of Impulse Oscillometry and Plethysmography for the Assessment of Exercise-Induced Bronchoconstriction in Asthmatic Children

Exercise-induced bronchoconstriction (EIB) is a key clinical problem for asthmatic children. Exercise challenge tests, used to confirm EIB, are time consuming and require patient cooperation. The a...

Reported Exercise-Related Respiratory Symptoms and Exercise-Induced Bronchoconstriction in Asthmatic Children.

BackgroundUnlimited physical activity is one of the key issues of asthma control and management. We investigated how reliable reported exercise-related respiratory symptoms (ERRS) are in predicting exercise-induced bronchoconstriction (EIB) in asthmatic children.MethodsIn this prospective study, 179 asthmatic children aged 7 - 15 years were asked for specific questions on respiratory symptoms related to exercise and allocated into two groups according to whether they complained about symptoms. Group I (n = 134) consisted of children answering “yes” to one or more of the questions and group II (n = 45) consisted of children answering “no” to all of the questions.ResultsSixty-four of 179 children showed a positive exercise challenge test (ECT). There was no difference in the frequency of a positive test between children in group I (n = 48) and group II (n = 12) (P = 0.47). The sensitivity of a positive report for ERRS to predict a positive ECT was only 37%, with a specificity of 0.72.ConclusionAccording to current guidelines, the report or lack of ERRS has direct consequences on treatment decisions. However, the history of ERRS did not predict EIB and one-third of asthmatic children without complaints of ERRS developed EIB during the ECT. This raises the question of the need for objective measures of bronchial hyperresponsiveness (BHR) in pediatric asthma management.

Comparison of Non-Invasive Methods for Detecting Exercise-Induced Bronchoconstriction in Asthmatic Children

Comparison of Non-Invasive Methods for Detecting Exercise-Induced Bronchoconstriction in Asthmatic Children

The effect of body posture during medication inhalation on exercise induced bronchoconstriction in asthmatic children

RationaleInhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS) offers acute, but moderate protection against exercise induced bronchoconstriction (EIB). This study investigated whether inhaling a single dose of ICS in a forward leaning posture improves this protection against EIB. Methods32 Asthmatic children, 5–16 years, with EIB (Median fall in FEV1 or FEV0.5 30.9%) performed two exercise challenge tests (ECT's) with spirometry in a single blinded cross-over trial design. Children inhaled a single dose of 200 μg beclomethasone dipropionate (BDP) 4 h before the ECT, once in the standard posture and once with the neck extended in a forward leaning posture. Spirometry was also performed before the inhalation of the single dose of BDP. ResultsInhalation of BDP in both body postures provided similar protection against EIB (fall in FEV1 or FEV0.1 in standard posture 16.7%; in forward leaning posture 15.1%, p = 0.83). Inhaling ICS in a forward leaning posture significantly delayed EIB compared to inhaling in the standard posture (respectively 2.5 min ± 1.0 min vs. 1.6 min ± 0.8 min; difference 0.9 min (95CI 0.25; 1.44 min); p = 0.01). ConclusionInhalation of a single dose BDP in both the forward leaning posture and the standard posture provided effective and similar protection against EIB in asthmatic children, but the forward leaning posture resulted in a delay of EIB. RegisterNTR3432 (www.trialregister.nl).

Exhaled breath condensate annexin A5 levels in exercise-induced bronchoconstriction in asthma: A preliminary study

Background and objectiveThe pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma is incompletely understood. The role of exhaled breath condensate (EBC) annexin A5, which is an anti-inflammatory mediator, has not been investigated. The purpose of this study is to evaluate EBC annexin A5 levels in EIB in asthmatic children. MethodsTwo groups of children were enrolled in this study: asthmatic children with positive (n=11) and negative (n=7) responses to exercise. The levels of pre- and post-exercise EBC annexin A5 were determined with using enzyme-linked immunosorbent assay (ELISA). ResultsWe observed significant higher pre-exercise EBC annexin A5 levels in the challenge test negative children than in the challenge test positive children (p<0.05). No significant difference was observed in the post-exercise EBC annexin A5 levels between the groups (p>0.05). Also, no significant difference was observed between pre- and post-exercise EBC annexin A5 levels within each group (p>0.05). There was an inverse correlation between annexin A5 levels and a reduction in forced expiratory volume at one second percent (FEV1%) (p=0.009, r=−0.598). ConclusionsOur preliminary study showed that EBC annexin A5 may have a possible preventive role in EIB in asthma. Annexin A5 and related compounds may provide novel therapeutic approaches to the treatment of EIB in asthma.

Serum Periostin Levels Correlates with Exercise-Induced Bronchoconstriction in Asthmatic Children

The significance of periostin as a biomarker of TH2-induced airway inflammation, and as a measure of the response to TH2-targeted therapy, has recently been emphasized. The aim of our present study was to explore the relationship between serum periostin levels and exercise-induced bronchoconstriction (EIB) in asthmatic children.

Plasma secreted phospholipase A2 in asthmatic children: correlation with leptin levels and exercise induced bronchoconstriction

Purpose: Dysregulated cysteinyl leukotriene (CysLT) synthesis is prominent in exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 (sPLA2) plays a key regulatory role in the biosynthesis of CysLTs. We previously found that serum leptin levels correlate with (EIB) in children with asthma. The aim of this study was to address the relationship between plasma sPLA2/leptin levels and EIB. Methods: Sixty-seven prepubertal children between the ages of 6 and 10 years were included in the study. They were asthmatics with EIB (n= 25), asthmatics without EIB (n= 21), and healthy subjects (n= 21). We measured the plasma sPLA2 and leptin levels. We also performed pulmonary function tests at baseline, after bronchodilator inhalation, and after exercise. Results: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in those without and control subjects. In addition, sPLA2 levels were significantly correlated with body mass index (Speraman correlation coefficient r= 0.343, P= 0.023) and leptin levels (partial correlation coefficient r= 318, P= 0.033). The maximum decrease in % forced expiratory volume in 1 second after exercise was significantly correlated with both PLA2 levels (r= 0.301, P= 0.041) and leptin levels (r= 0.346, P= 0.018). Conclusion: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in asthmatics without EIB and control subjects. In addition, sPLA2 levels were significantly correlated with leptin levels and EIB in asthmatic children. (Allergy Asthma Respir Dis 2015;3:99-104)

Exercise-induced Bronchoconstriction

The invitation by the editor, Rafeul Alam, to guest edit this issue on exercise-induced bronchoconstriction (EIB) allowed me to bring together investigators from physiology to cellular biology of EIB. The preface contains information on how some of the contributors came together and identifies some conferences that helped broaden the scientific research in EIB in asthmatic children to include healthy elite athletes. The contributors come from Australia, Canada, Denmark, England, France, Israel, Sweden, Netherlands, and the United States and trained in pediatric, respiratory, and sports medicine and science. Most have either obtained a doctoral degree in EIB or supervised one. My first encounter with EIB was at Royal Prince Alfred Hospital, in Sydney, in 1968. In January 1970 I started research in EIB with Simon Godfrey in the Department of Paediatrics at the Brompton Hospital in London. Over the next 3 years, under Simon’s enthusiastic guidance, a group of us carried out many studies on various aspects of EIB. In 1968 Ken Fitch from Perth, Australia observed severe EIB when supervising an exercise test on an 18-year-old asthmatic Olympic swimmer, who 3 months later won an Olympic Gold Medal in Mexico. This induced Ken to do his MD in EIB. Both Simon and Ken’s laboratories were coincidentally investigating the effect of different forms of exercise to provoke EIB. In 1971, both laboratories reported running as the most provocative exercise. Being ahead of their time, Ken and Simon wrote an article in 1976 on the topic of Asthma and Athletic Performance. They now celebrate the 50 years of research since the modern description of EIB in children by R.S. Jones of Liverpool, United Kingdom, in 1962. In 1973 Simon moved to the Hammersmith Hospital and later, in 1977, to Israel, where he continued his studies, among many others, on refractoriness and EIB. The article by Larsson and coworkers discusses these early studies and presents a new hypothesis to explain refractoriness following EIB.

Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction.

Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against EIB in asthmatic children. 31 Mild asthmatic children not currently treated with inhaled corticosteroids, 5-16 years, with EIB (fall in FEV0.5/1 ≥ 13%) were included in a prospective intervention study. They performed two ECT's within 2 weeks. Four hours before the second test children inhaled 200 μg beclomethasone-dipropionate (BDP) with a breath-actuated inhaler (BAI). The median fall in FEV0.5/1 after 200 μg BDP was significantly reduced from 30.9% at baseline to 16.0% (P < 0.001). Twenty children (64.5%) showed a good response to 200 μg BDP (≥ 50% decrease in fall of FEV0.5/1), while 8 children showed a moderate response (25-50%), and three children showed no response at all (< 25%). A low single dose ICS offers acute protection against EIB in the majority of asthmatic children not currently treated with inhaled corticosteroids.

Bronchial and alveolar nitric oxide in exercise‐induced bronchoconstriction in asthmatic children

Epidemiological studies have shown an association between the severity of exercise-induced bronchoconstriction (EIB) and fractional exhaled nitric oxide at the flow of 50 mL/s (FeNO(50)). However, no study has assessed the correlation between alveolar production (C(alv)) and bronchial flux (J(NO)) of nitric oxide (NO) and EIB in asthmatic children. To identify the relationship between severity of EIB and bronchial or alveolar nitric oxide. Our group included 36 allergic children with intermittent asthma. The EIB was determined by a standard exercise challenge and the severity was expressed as the maximum change in percentage from the baseline value of lung function (ΔFEV(1)%, ΔFEF(25-75)%) after exercising. A chemiluminescence analyser at multiple flows was used to calculate FeNO(50), J(NO) and C(alv,) which reflect large airways, J(NO) and alveolar concentration of NO respectively. Sixteen (44.4%) children presented a ∆FEV(1) ≥ 10%, eight (22.2%) had ∆FEV(1) ≥ 15% and nine (25%) children had a ∆FEF(25-75) ≥ 26%. A significant correlation was observed between severity of EIB and FeNO(50) , J(NO) and C(alv.) EIB was significantly more severe in children sensitive to indoor allergens compared with outdoor allergens only (P = 0.014); those children showed also higher levels of C(alv) (P = 0.003) and of J(NO) (P = 0.044). Our results suggest that inflammation is present in the central and peripheral airways and that it is associated with the severity of EIB. Clinicaltrials.gov NCT00952835.

Exhaled breath temperature and exercise‐induced bronchoconstriction in asthmatic children

It has been hypothesized that exhaled breath temperature (EBT) is related to the degree of airway inflammation/remodeling in asthma. The purpose of this study was to evaluate the relationship between the level of airway response to exercise and EBT in a group of controlled or partly controlled asthmatic children. Fifty asthmatic children underwent measurements of EBT before and after a standardized exercise test. EBT was 32.92 ± 1.13 and 33.35 ± 0.95°C before and after exercise, respectively (P < 0.001). The % decrease in FEV(1) was significantly correlated with the increase in EBT (r = 0.44, P = 0.0013), being r = 0.49 (P < 0.005) in the children who were not receiving regular inhaled corticosteroids (ICS) and 0.37 (n.s.) in those who were. This study further supports the hypothesis that EBT can be considered a potential composite tool for monitoring asthma.

The Pathobiologic Effect of Montelukast and Inhaled Budesonide on Exercise-induced Bronchoconstriction in Children

RATIONALE: Exercise-induced bronchoconstriction (EIB) is a common condition. However, the pathogenesis and proper treatment regimen are still controversial. The aim of this study was to compare the pathobiologic effect of oral montelukast and inhaled budesonide on EIB in asthmatic children.

Nitric Oxide Correlates with Exercise-Induced Bronchoconstriction in Asthmatic Children

P<0.001; r, partial correlation coefficient adjusted for age and height). The cutoff value for predic- tion of significant EIB was 20 ppb, and the overall sensitivity, specificity, positive predictive value, and negative predictive values were 61.3%, 80.0%, 57.6%, and 82.4%, respectively. The area under the receiver operating characteristic curve was 0.767 (95% confidence interval, 0.661 to 0.874). Conclusion:Baseline eNO levels correlate with the post-exercise decrease of forced expiratory volume in 1 second, suggesting that eNO may be a tool in the prediction of EIB. (Pediatr Allergy Respir Dis(Korea) 2011;21:99-107)

Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma

Epidemiological studies have established a relationship between low levels of serum vitamin D and reduced lung function in healthy adults, and asthma onset and severity in children. However, no study has examined the relationship between vitamin D levels and exercise-induced bronchoconstriction in asthmatic children. We evaluated the relationship between 25-hydroxyvitamin D concentrations and baseline forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and change in FEV1 (ΔFEV1) after a standardised exercise challenge in 45 children with intermittent asthma. Only 11% of the children had desirable serum vitamin D levels (at least 30-40 ng·mL(-1)). A positive correlation was found between serum 25-hydroxyvitamin D and both FVC (r=0.34; p=0.037) and FEV1 (r=0.32; p=0.037). Subjects with a positive response to the exercise challenge (ΔFEV1≥10%) presented lower serum levels of 25-hydroxyvitamin D than children with a negative challenge (mean±sd 16.2±5.2 versus 23.4±7.0 ng·mL(-1), respectively; p=0.001). Our results indicate that hypovitaminosis D is frequent in asthmatic children who live in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced lung function and increased reactivity to exercise.

Exercise-Induced Bronchoconstriction in Asthmatic Children

The aim of this article is to critically review the efficacy and safety data from randomized controlled trials (RCTs) using inhaled corticosteroids (ICSs), long- or short-acting beta(2)-adrenoceptor agonists (LABAs, SABAs), parasympatholytics and oral leukotriene receptor antagonists in the management of exercise-induced bronchoconstriction (EIB) in children with persistent asthma (EIA). The studies with sufficient information on patient characteristics and outcomes were chosen using a MEDLINE search. Results from the individual searches were combined and repeated. Studies were also found by reviewing the reference lists of the articles not included in this review. Studies focusing solely on individuals with asthma and other allergic co-morbidities (i.e. a degree of bronchial reversibility) were considered in this review. To make the paper evidence-based, the design and the quality of different studies were assessed employing the Sign criteria (evidence level [EL] and grades of recommendation [GR]). No additional statistical analyses were performed. Most of studies included paediatric patients with underlying EIA. We need to distinguish children with recurrent asthma symptoms in whom EIB is also present (patients with EIA) from asthmatic subjects whose symptoms appear only as a result of exercise (patients with EIB). Further controller treatment is indicated in patients with EIA and further reliever treatment in patients with EIB. ICSs are the first-choice controller drugs for EIA in children with persistent asthma (Sign grade of recommendation [GR]:A). In children with EIA without complete control with ICSs, SABAs (GR:A), leukotriene receptor antagonists (LTRAs) [GR:A] or LABAs (GR:A) may be added to gain control. Treatment with relievers such as SABAs (GR:A), parasympatholytics (GR:B) or, eventually, LABAs (GR:A), administered 10-15 minutes before exercise is the most preferable method of preventing EIB symptoms in children; however, not as monotherapy in children with EIA. The disadvantages and controversy relating to inhaled beta(2)-adrenoceptor agonist use lie in the development of tolerance to their effect when they are used on a regular basis, and the possibility of a resulting underuse of ICSs in patients with EIA. Researchers and guidelines recommend that if any patient requires treatment with a beta(2)-adrenoceptor agonist more than twice weekly, a low dose of ICSs should be administered. Inhaled parasympatholytics may be effective as preventive relievers in some children with EIB or EIA, especially among those with increased vagal activity. LTRAs have a well balanced efficacy-safety profile in preventing the occurrence of EIB symptoms in children. Compared with LABAs, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue SABA therapy in persistent asthmatic patients with EIA. A disadvantage of LTRAs is a non-response phenomenon. There are still insufficient data on the efficacy-safety profiles of ICS/LABA combination drugs in the treatment of EIA in children to recommend this treatment without caution. Safety profiles of inhaled SABAs, anticholinergics and montelukast in approved dosages seem sufficient enough to recommend use of these drugs in the prevention of EIB symptoms in children. Many researchers agree that treatment of EIA in children should always be individualized.