History Of Exercise-induced Bronchoconstriction Research Articles

Impact of Acute Exercise Challenge on Airway Dynamics in Children and Young Adults with Sickle Cell Anemia

Background Sickle cell anemia (SCA) complications such as frequent pain, chronic anemia, and acute and chronic organ damage lead to reduced physical functioning and cardiopulmonary fitness in affected individuals. Limited data support the safety of maximal cardiopulmonary exercise testing (CPET) in SCA, yet the safety of submaximal, longer-duration exercise at moderate to high intensity in SCA is unclear. The Sickle Cell Pro-Inflammatory Response to Interval Testing Study (SPRINTS) was a multicenter, prospective study that evaluated the impact of longer, submaximal exercise, which mimics the physical activity patterns of children better than CPET, on the acute inflammatory response and airway dynamics in children and young adults with SCA. In this analysis, we defined the effect of moderate to vigorous exercise on forced expiratory volume in 1 second (FEV1) and acute bronchoconstriction. We hypothesized the risk of exercise-induced bronchoconstriction (EIB) in children with SCA is greater than in controls. Methods SPRINTS was approved by the Lurie Children's central Institutional Review Board. Subjects 10-21 years old with hemoglobin (Hb) SS or S/β0 thalassemia and race-matched controls without SCA or sickle cell trait were enrolled across 4 institutions. Subjects were excluded for 1) inability to perform exercise, 2) receiving chronic transfusions, 3) history of exercise-related arrhythmia/syncope, 4) physician-diagnosed asthma, 5) history of EIB, or 6) history of cardiac disease precluding exercise testing. Participants performed maximal CPET on a cycle ergometer using a standardized Godfrey protocol. At least 2 weeks later, participants performed a controlled intensity interval test (CIIT) consisting of 8 bouts of constant workload cycling randomized to either 50% (moderate intensity) or 70% (vigorous intensity) of peak workload achieved during CPET. Exercise bouts were 2 min each with 1-min rest intervals between bouts. Spirometry was performed pre/post (5, 10, 15, and 30 min) CPET and CIIT. EIB was defined as a drop in FEV1 ≥10% from baseline to the lowest FEV1 recorded. Bivariable comparisons were performed, and logistic regression models analyzed the association between EIB and covariables (age, sex, SCA status, max workload, exercise intensity (CIIT only), baseline FEV1 % predicted, FEV1/FVC % predicted) using IBM ® SPSS ® Statistics. Results Available data from 64 subjects (48% F, 73% on hydroxyurea, mean 13.8±2.8 years) and 40 controls (45% F, mean 15.4±2.9 years) were analyzed. Baseline Hb (8.5±1.2 vs. 13±1.4 g/dL, p < 0.001) and maximal workload achieved during CPET (85±26 vs. 135±45 watts, p < 0.001) were lower in subjects vs. controls. The percentage of participants who completed CIIT did not differ between subjects and controls, and no respiratory-related adverse events, including need for bronchodilator therapy, occurred. At baseline, FEV1 and FEV1 % predicted and other parameters (FVC and FVC % predicted, MMEF and MMEF % predicted) were significantly lower in subjects vs. controls (Table 1). However, there was no between-group difference in baseline FEV1/FVC % predicted. Post-exercise, the percentage of participants who met criteria for EIB did not differ between subjects and controls after CPET (21 vs. 26%, p = 0.537) or CIIT (32 vs. 17%, p = 0.126). There was also no significant between-group difference in the greatest drop in FEV1 from baseline to any post-exercise timepoint (mean value or as % of baseline) after CPET or CIIT. In logistic regression models, SCA status, age, sex, maximal workload during CPET, exercise intensity (CIIT only), baseline FEV1 % predicted and FEV1/FVC % predicted were not associated with EIB after CPET or CIIT (Table 2). Conclusion Compared to controls, children and young adults with SCA and no history of asthma or EIB had lower baseline values on all spirometry parameters except FEV1/FVC % predicted. EIB was not more common in subjects with SCA vs. controls after maximal CPET or a submaximal exercise challenge of longer duration at moderate or vigorous intensity. No independent factors were associated with development of EIB after acute exercise. Despite concerns that undiagnosed lower airways disease in children with SCA is common, our results suggest the risk of EIB in SCA is low and underscore the safety of moderate to vigorous exercise toward developing evidence-based exercise guidelines in non-asthmatic children and young adults with SCA.

Effect of inspired air conditions on exercise-induced bronchoconstriction and urinary CC16 levels in athletes

Injury to the airway epithelium has been proposed as a key susceptibility factor for exercise-induced bronchoconstriction (EIB). Our goals were to establish whether airway epithelial cell injury occurs during EIB in athletes and whether inhalation of warm humid air inhibits this injury. Twenty-one young male athletes (10 with a history of EIB) performed two 8-min exercise tests near maximal aerobic capacity in cold dry (4°C, 37% relative humidity) and warm humid (25°C, 94% relative humidity) air on separate days. Postexercise changes in urinary CC16 were used as a biomarker of airway epithelial cell perturbation and injury. Bronchoconstriction occurred in eight athletes in the cold dry environment and was completely blocked by inhalation of warm humid air [maximal fall in forced expiratory volume in 1 s = 18.1 ± 2.1% (SD) in cold dry air and 1.7 ± 0.8% in warm humid air, P < 0.01]. Exercise caused an increase in urinary excretion of CC16 in all subjects (P < 0.001), but this rise in CC16 was blunted following inhalation of warm humid air [median CC16 increase pre- to postchallenge = 1.91 and 0.35 ng/μmol in cold dry and warm humid air, respectively, in athletes with EIB (P = 0.017) and 1.68 and 0.48 ng/μmol in cold dry and warm humid air, respectively, in athletes without EIB (P = 0.002)]. The results indicate that exercise hyperpnea transiently disrupts the airway epithelium of all athletes (not only in those with EIB) and that inhalation of warm moist air limits airway epithelial cell perturbation and injury.

Exercise increases exhaled breath condensate cysteinyl leukotriene concentration in asthmatic patients

Background. Although the importance of cysteinyl leukotrienes (Cys-LTs) in exercise-induced bronchoconstriction (EIB) is supported by various sources of evidence, how the concentration of these mediators change during the development of EIB has not been investigated. Objectives. Our goal was to determine the effect of exercise on the concentration of airway Cys-LT in asthmatic patients by measuring Cys-LT in exhaled breath condensate (EBC). Methods. Seventeen atopic asthmatic patients with a previous history of EIB and six healthy volunteers were studied. Before and two times within 10 minutes after exercise challenge, FEV1 was measured and EBC was collected for Cys-LT measurement. Exhaled nitric oxide level, a marker of airway inflammation, was also determined at baseline. Results. Baseline Cys-LT level was higher in the asthmatic group versus healthy subjects (168 pg/mL /112–223/ vs. 77 pg/mL /36–119/, p = .03). EBC Cys-LT concentration increased in all asthmatic patients post-exercise (n = 17, p = .03), with the increase significantly greater in patients developing exercise-induced bronchospasm (n = 7, p = .03), whereas no change was observed in healthy controls (p = .59). The exercise-induced fall in FEV1 in asthmatics was related to the increase in EBC Cys-LT concentration (r = −0.40, p = .03). Conclusions. Our study shows that Cys-LT concentration of EBC is elevated minutes after physical exercise in asthmatic patients and strongly supports the concept that the release of this mediator is involved in the development of EIB.

Mannitol and exercise challenge tests in asthmatic children

Bronchial hyperresponsiveness (BHR), a characteristic feature of asthma, can be assessed through standardized bronchial provocation tests (BPT). Exercise as a BPT is used in diagnosing and monitoring exercise induced bronchoconstriction (EIB). Recently a novel osmotic BPT has been developed, using dry powder mannitol. The aim of this study was to investigate the clinical utility of the mannitol challenge to identify asthmatic children with EIB. Thirty-three clinically stable children, aged 9-18 years, with a history of EIB, performed both mannitol and exercise provocation challenges. Data were composed of a cross tabulation comparing the reaction on exercise provocation challenge to mannitol challenge. Correlations between post-exercise fall in FEV1 and response-dose ratio (RDR) and PD1) of mannitol were calculated. Twenty-five children completed both tests. Pearson's correlation between log-transformed RDR for mannitol and post-exercise fall in FEV1 was r(p) = 0.666 (P < 0.001). There was no significant relationship between the log PD1) of mannitol and post-exercise fall in FEV1. Children on long acting bronchodilator agents (LABA) were significantly (P < 0.05) more likely to have a positive response on the mannitol challenge. Positive and negative predictive values of the mannitol challenge for EIB were 69% and 91%. Mannitol challenge appears to be a suitable alternative for an exercise provocation test to assess EIB in asthmatic children. Given the negative predictive value of 91%, it is especially useful to exclude EIB.

Efficacy and safety of a new pressurised metered-dose inhaler formulation of budesonide/formoterol in children with asthma: A superiority and therapeutic equivalence study

Aim: This paediatric asthma study evaluated the efficacy and safety of a novel hydrofluoroalkane pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol versus budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI). Methods: The study was a 12-week, multinational, double-blind trial involving children (aged 6–11 years) with symptomatic asthma on inhaled corticosteroids ( 375 – 1000 μ g / day ) , with a history of exercise-induced bronchoconstriction and peak expiratory flow (PEF) ⩾ 50 % of predicted. Patients were randomised (two inhalations twice daily) to budesonide pMDI 100 μ g , budesonide/formoterol DPI 80 / 4.5 μ g or budesonide/formoterol pMDI 80 / 4.5 μ g . The primary endpoint was change from baseline in morning PEF. Results: Overall, 622 patients were randomised. Increases in morning PEF with budesonide/formoterol pMDI and budesonide/formoterol DPI were therapeutically equivalent (29.5 versus 30.2 l/min, respectively; 95% confidence interval: - 6.0 to 4.6 ; P = 0.78 , also confirmed by per-protocol analysis). Improvements in secondary efficacy endpoints with both budesonide/formoterol formulations were not significantly different. Significantly greater improvement was achieved with budesonide/formoterol pMDI versus budesonide pMDI for morning PEF ( + 9.6 l/min; P < 0.001 ) and other lung function parameters. The safety profile of budesonide/formoterol pMDI was favourable and similar to that of budesonide/formoterol DPI and budesonide pMDI. Conclusion: Budesonide/formoterol, administered via the therapeutically equivalent hydrofluoroalkane pMDI or DPI, is an effective and well-tolerated treatment for children with asthma.

Exercise‐induced bronchoconstriction in children with atopic eczema

Non-specific bronchial hyper-responsiveness has been reported in most of the eczematous children even in the absence of asthmatic symptoms. We therefore investigated the occurrence of exercise-induced bronchoconstriction (EIB) in children with atopic eczema (AE) and the predictors of EIB. Fifty-five children referred to the paediatric clinic for AE and a control group of 17 healthy children were recruited. They all carried out a physical examination and skin prick test (SPT) both to inhalant and food allergens, prior to the exercise challenge test. Their parents filled a questionnaire on atopic diseases. They underwent exercise challenge test that consisted in free running for 6 min. Spirometric measurements were carried out before running and till 11 min after. Exercise challenge test was positive in 13 (23%) children with AE. None of the children in the control group had a positive exercise challenge test [OR (95% CI) = 1.31 (1.13-1.51); p = 0.030]. Sixteen (29%) eczematous children had a history of EIB. Such history was not reliable for identifying children who had a positive exercise test. Twenty-nine (52%) children with AE had asthma. Allergic rhinitis affected 33 (60%) of eczematous children and allergic conjunctivitis 28 (50%). EIB was not related to any history of asthma, allergic rhinitis, allergic conjunctivitis, severity of eczema or SPT results. Our study shows that EIB is common in children with AE. Our data also indicate that screening by medical history and physical examination is not a sensitive marker of EIB. This may explain why EIB is often ignored in eczematous children.

Post-exercise response to albuterol after addition of montelukast or salmeterol to inhaled fluticasone

Rationale To compare the bronchodilator response to albuterol after a standard exercise challenge in patients receiving montelukast (M) or salmeterol (S) added to low-dose fluticasone (F). Methods Randomized, double-blind multicenter study. Patients with asthma (N=91, ages 15–60) receiving F (110 μg twice daily) who remained symptomatic and had a history of exercise-induced bronchoconstriction (EIB) were randomized to addition of M (10 mg) or S (42 μg BID) for 4 weeks. At weeks 1 and 4, patients exercised on a treadmill for 6 minutes at near-maximum heart rate; at 15 and 45 minutes after exercise, patients received 180 μg albuterol by inhalation. Serial spirometry was performed both before and after albuterol administration. FEV 1 was expressed as the percent change from pre-exercise baseline. Results Baseline pre-exercise FEV 1 percent predicted was 81.3 ± 1.5% in the M+F group and 78.9 ± 1.7% in the S+F group. Before treatment, patients in both groups had a significant increase in FEV 1 in response to post-exercise albuterol (M+F: 11.9 ± 1.2%; S+F: 14.5 ± 1.6%). After 4 weeks, only S+F perceptibly improved pre-exercise FEV 1 (7.5 ± 1.1% versus 2.1 ± 1.1%, p<0.001). However, patients treated with M+F retained response to post-exercise albuterol, whereas those treated with S+F had a decreased response (11.0 ± 0.9% and 5.4 ± 0.9%, respectively). Maximum FEV 1 percent predicted after albuterol was 92.1 ± 1.8% in the M+F group and 90.9 ± 1.9% in the S+F group. Results at Week 1 and after a second albuterol rescue were consistent with those seen at Week 4. Conclusions The rescue response to albuterol after EIB in patients taking fluticasone is preserved with addition of montelukast but is significantly diminished with addition of salmeterol.

Exercise-induced bronchoconstriction depends on exercise load

Exercise-induced bronchoconstriction (EIB) is often used as a measure of bronchial hyperresponsiveness and employed in epidemiological studies. Different tests are used, including free running tests with poor standardization of exercise load. The present study aimed to assess the role of exercise load in relationship to level of EIB.Methods: 20 asthmatic children, 9–17 years old with a history of EIB, underwent two treadmill test with 85% and 95% exercise load. The children ran with increasing speed for the first 2 min until reaching a heart rate of 85% or 95% of calculated maximum (220–age) and maintained this speed for the last 4 min. Lung function was measured before running, and 0, 3, 6, 10 and 15 min after the run. Borg scale for perceived exertion was employed for children's self-evaluation of exercise load.Results: Peak heart rate, mean Borg score during 85% exercise load was 178·7/13·6 and during 95% was 194·3/18·2 (P<0·001). Maximum fall in FEV1after 85% exercise load was 8·84%vs. 25·11% after 95% (P<0·001). Nine subjects (40%) fell ≥10% in FEV1after 85% exercise loadvs. 20 subjects (100%) after 95% exercise load. EIB from the 95% exercise load test had markedly higher correlation with serum ECP (r=0·77, P<0·001).Conclusion: Exercise load is essential for the interpretation of EIB, and strict standardization of exercise tests should be undertaken. The EIB from the high exercise load tests seemed better correlated to inflammatory activity than the low exercise load test.