Exercise Challenge In Patients Research Articles

Within-breath oscillometry for identifying exercise-induced bronchoconstriction in pediatric patients reporting symptoms with exercise.

Evaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced bronchoconstriction (EIB) in pediatric outpatients disclosing exercise-induced symptoms (EIS). To assess the response in impedance parameters following an exercise challenge in patients reporting EIS. Sixty-eight patients reporting EIS (34 asthmatics and 34 suspected of asthma, age mean = 10.8 years, range = 6.0-16.0) underwent an incremental treadmill exercise test. Spirometry was performed at baseline and 1, 5-, 10-, 15-, and 20-min post exercise. Oscillometry was performed at baseline and at 3- and 18-min post exercise. Bronchodilator response to 200 µg albuterol was then assessed. EIB was defined as a forced expiratory volume in 1 s (FEV1) fall ≥10% from baseline. Expiratory and inspiratory resistance (Rrs) and reactance (Xrs), their z-score (Ducharme et al. 2022), and their mean within-breath differences (ΔRrs = Rrsexp-Rrsinsp, ΔXrs = Xrsexp-Xrsinsp) were calculated. Receiver operating characteristic (ROC) curves and their areas (AUCs) were used to evaluate impedance parameters' performances in classifying EIB. Asthmatic patients developed EIB more frequently than those suspected of asthma [18/34 (52.9%) vs. 2/34 (5.9%), p < 0.001]. In the 20 subjects with EIB, Rrsinsp, Rrsexp, Xrsinsp, and Xrsexp peaked early (3'), and remained steady except for Xrsinsp, which recovered faster afterward. ΔXrs widened 18 min following the exercise and reversed sharply after bronchodilation (BD) (-1.81 ± 1.60 vs. -0.52 ± 0.80 cmH2O × s/L, p < 0.001). Cutoffs for EIB leading to the highest AUCs were a rise of 0.41 in z-score Rrsinsp (Se: 90.0%, Sp: 66.7%), and a fall of -0.64 in z-score Xrsinsp (Se: 90.0%, Sp: 75.0%). Accepting as having "positive" postexercise oscillometry changes those subjects who had both z-scores beyond respective cutoffs, sensitivity for EIB was 90.0% (18/20) and specificity, 83.3% (40/48). Oscillometry parameters and their within-breath differences changed markedly in pediatric patients presenting EIB and were restored after the bronchodilator. Strong agreement between z-scores of inspiratory oscillometry parameters and spirometry supports their clinical utility, though larger studies are required to validate these findings in a broader population.

Urinary excretion of 9α,11β-prostaglandin F2 and leukotriene E4 in patients with exercise-induced bronchoconstriction.

Increased levels of mast cell-derived eicosanoids, such as prostaglandin (PG) D2 and cysteinyl leukotrienes (CysLTs), have been reported in patients with exercise-induced bronchoconstriction (EIB), suggesting that mast cell activation is involved in the mechanism of EIB. However, it is still controversial since these results have not been reproduced in other studies. The aim of this study was to evaluate the role of PGD2 and LTE4 in adult asthma with EIB, as measuring urinary levels of their metabolites-9α,11β-PGF2 and LTE4 before and after an exercise challenge test. Eight patients with asthma and EIB and five normal controls without EIB were enrolled. Exercise challenge tests comprised of 6 min of treadmill exercise or free running were performed in all study subjects, and urine samples before and 1 h after the challenge were collected. Urinary levels of 9α,11β-PGF2 and LTE4 were measured by enzyme immunoassay (EIA). No significant differences were observed in 9α,11β-PGF2 and LTE4 levels before/after the exercise challenge between patients with EIB and normal controls. No significant increases in urinary levels of 9α,11β-PGF2 or LTE4 were detected during the exercise challenge in patients with EIB and normal controls. No significant correlations were observed between the percent decrease in forced expiratory volume in 1 s (FEV1) or percent changes in 9α,11β-PGF2 and LTE4 levels after the exercise challenge. Urinary 9α,11β-PGF2 and LTE4 levels did not increase after an exercise challenge in patients with EIB, suggesting that urinary excretion of 9α,11β-PGF2 and LTE4 may not be a good marker of mast cell activation in patients with EIB.

Exercise-induced ventricular re-polarisation changes in moderate congenital aortic valve stenosis.

Introduction Pressure overload increases in patients with moderate aortic valvular stenosis during exercise. In the absence of symptoms, it remains difficult, however, to discriminate patients for surgery based only on pressure overload. Other parameters, such as the dispersion of ventricular re-polarisation (d-QT), which reportedly increases with the transvalvular pressure gradient, have not been fully studied in this condition. To determine the pattern of QT and d-QT response to exercise testing in children with moderate aortic valve stenosis in order to evaluate the impact of pressure overload from an electrophysiological perspective. Materials and methods In all, 15 patients were compared with 15 controls paired for age (14.8±2.5 versus 14.2±1.5 years old) and gender (66.7% male). All the patients underwent exercise stress testing with 12-lead electrocardiograph recording. QT was measured from the onset of QRS to the apex (QTa) at rest, at peak exercise, and at 1 and 3 minutes upon recovery. QT was corrected using the Fridericia equation, and d-QT was calculated. Resting QTc was similar among the study groups, but increased significantly in study patients compared with the control group at maximal effort (p=0.004) and after 1 (p<0.001) and 3 (p<0.001) minutes of recovery. A significant association was identified between groups for d-QT (p=0.034), and post-hoc tests revealed a significant difference only at rest (p=0.001). Ventricular re-polarisation abnormalities can be unmasked and highlighted by the assessment of electrical re-polarisation during exercise challenge in patients with asymptomatic moderate aortic valve stenosis. Using QT response to exercise could be beneficial for better optimisation of risk stratification in these patients.

Depressive Symptoms Are Associated with Soluble P-Selectin Reactivity to Acute Exercise in Heart Failure

To determine the effects of depressive symptom severity on the circulating soluble adhesion molecule response to an acute exercise challenge in patients with heart failure (HF) compared with control subjects. Thirty-eight male HF patients and 19 male control subjects (mean age +/- SEM: 55.5 +/- 1.9) completed the Beck Depression Inventory (BDI) before undergoing a moderate 20-minute bicycle exercise at approximately 65% to 70% VO(2peak). Plasma levels of the soluble adhesion molecules P-selectin (sP-selectin) (sCD62P) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined immediately before and after and 10 minutes after exercise. Higher BDI scores moderated greater increases in sP-selectin levels in response to exercise over time in HF patients as compared with control subjects [F(1.8/84.5) = 3.25, p = .05]. Post hoc testing revealed that in HF patients, but not in control subjects, higher BDI scores were significantly associated with greater increases in sP-selectin levels over time in response to exercise [BDI by exercise interaction: F(1.6/49.6) = 5.67, p = .010]. Also, in HF patients, but not in control subjects, higher BDI scores were associated with higher sP-selectin levels at pre-exercise and postexercise time points [main effect BDI: F(1/31) = 4.86, p = .035]. Our findings suggest that in male HF patients with increasing depressive symptom severity, levels of the adhesion molecule sP-selectin are higher before and after exercise and have greater increases in response to exercise. This could have implications for acute coronary syndromes associated with exercise and thereby may impact mortality.

Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction

The pathogenesis of exercise-induced bronchoconstriction (EIB) involves the release of mediators from several airway cells in response to exercise challenge, but the mechanism leading to airflow obstruction during EIB is incompletely understood. To evaluate the role of secreted mucin in the pathogenesis of EIB. Induced sputum was collected at baseline and 30 minutes after exercise challenge in patients with asthma with EIB. The expression of gel-forming mucins and epidermal growth factor receptor ligands were assessed by quantitative polymerase chain reaction. Secreted mucin 5AC (MUC5AC), the eicosanoids cysteinyl leukotrienes (cysLTs) and 15S-hydroxyeicosatetraenoic acid (15S-HETE), and tachykinins neurokinin A (NKA) and substance P (SP) were measured in induced sputum supernatant. Among the gel-forming mucins, MUC5AC was expressed at the highest level. The gene expression of MUC5AC increased after exercise challenge compared with baseline and was associated with EIB severity by regression analysis. The relative levels of MUC5AC in induced sputum increased from a geometric mean of 9.5 at baseline to 18.4 postexercise challenge. Associations between the levels of MUC5AC and cysLTs and between the levels of cysLTs and NKA postexercise challenge were identified by regression analysis. These data indicate that (1) the predominant gel-forming mucin expressed in induced sputum of patients with asthma with EIB is MUC5AC; (2) an increase in MUC5AC gene expression and release of MUC5AC protein occurs after exercise challenge; and (3) MUC5AC release may occur through the cysLT-associated activation of sensory airway nerves.

Exhaled Nitric Oxide and Airway Caliber during Exercise-Induced Bronchoconstriction

Data on the relationship between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (NO) in adult patients with asthma are controversial. It is unclear whether endogenous NO may act as either a protective or stimulatory factor in the airway response to exercise or whether changes in exhaled NO simply reflect acute narrowing of the airway. The aim of this study was to assess the changes in the fraction of exhaled nitric oxide (FE(NO)) before and after exercise challenge in patients with asthma and to analyze the relationship between FE(NO) and airway obstruction. Twenty-five non-smoking, steroid-naïve, atopic, adult patients with mild persistent asthma and 12 non-smoking, nonatopic, healthy subjects (control group) performed an exercise challenge on a cycloergometer, with monitored ventilation. FEV1 and FE(NO) were measured at baseline and 1, 5, 10, 15 and 20 minutes after the exercise challenge. Eleven of the asthmatic patients had exercise-induced bronchoconstriction (EIB group) and the remaining 14 did not (non-EIB group). Baseline FE(NO) was higher in the EIB and non-EIB asthmatic groups than in the control group. In the EIB group, FE(NO) was significantly lower 5, 10 and 15 minutes after exercise, and the changes in FE(NO) correlated with variation in FEV1 10 and 15 min after exercise. A significant correlation between baseline FE(NO) and maximal post-exercise decrease in FEV1 was found in asthmatic patients (EIB group). In conclusion, exhaled nitric oxide levels transiently decrease during exercise-induced bronchoconstriction in adult patients with asthma. Baseline FE(NO) might predict the airway obstruction resulting after exercise.

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.

Deletion polymorphisms in the angiotensin converting enzyme gene are associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease.

Angiotensin converting enzyme (ACE) plays an important role in the pathogenesis of pulmonary hypertension. In this study we determined whether the deletion (D)/insertion (I) polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease (COPD). ACE genotypes were determined in 19 patients with COPD. All patients underwent right heart catheterization followed by a constant-load exercise test while breathing room air or oxygen. Subgroups were created of seven patients with the II genotype, six with the ID genotype, and six with the DD genotype who were well-matched with respect to age, blood gas data at rest or after exercise, baseline lung function, results of incremental exercise testing, and hemodynamic data at rest. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (Rpv) at rest in the three subgrpoups did not differ significantly during breathing of either room air or oxygen. However, the Ppa after exercise challenge in patients with the DD genotype (55.7 +/- 4.9 mm Hg [mean +/- SD]) was significantly higher than in patients with the II genotype (42.6 +/- 7.1 mm Hg, p = 0.008). The Rpv after exercise in patients with the DD genotype was also significantly higher than in patients with the ID and II genotypes. During breathing of oxygen to diminish acute hypoxic pulmonary vasoconstriction, the Ppa in patients with the DD genotype (52.3 +/- 3.1 mm Hg) was higher than in patients with the ID genotype (40.5 +/- 5.9 mm Hg, p = 0.0049) or the II genotype (37.7 +/- 5.9 mm Hg, p = 0.0027). In addition, the Rpv in patients with the DD genotype was higher than in patients with the ID and II genotypes. These results suggest that D-I polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with COPD. However, the number of patients in this study was very small for a genetic association study, and our results should be examined in larger studies.

Exercise challenge in patients with asthma whose peak expiratory flow values are controlled within the green zone

Recent guidelines for the management of asthma recommend that peak expiratory flow (PEF) should be measured to monitor the level of airflow limitation and to maintain PEF values within the green zone (80–100% of the patient's highest PEF value). Because no studies have evaluated the efficacy of PEF zone management on the basis of patients' physical activity, we studied the appearance of exercise-induced asthma (EIA) using treadmill exercise challenging in asthma patients whose PEF values had been maintained in the green zone for at least 3 months. Exercise-induced asthma was induced in nine of 44 (20.5%) asthma patients. The acetylcholine concentration required to cause a 20% fall in forced expiratory volume in 1 s (log PC20) was significantly lower in patients with EIA (2.39 ± 0.21 μg/mL) compared with patients without EIA (3.22 ± 0.12 μg/mL; P < 0.03). These results suggest that PEF green zone management alone does not ensure the ability to perform vigorous physical activity, especially in patients whose airway reactivity remains enhanced. Therefore, airway reactivity should be considered for asthma management.

Summary of Clinical Trials with Zafirlukast

Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT) receptor antagonist. In humans, zafirlukast antagonized the effects of exogenously administered LTD4 and cysLTs released endogenously in response to physical and chemical stimuli. Zafirlukast antagonized LTD4-induced bronchoconstriction, with effects still evident 12 h after drug administration. In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen or exercise challenge in patients with asthma. In multicenter trials in patients with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as-needed beta-agonist use, and improved pulmonary function without increasing the number of adverse events. Zafirlukast also exhibited evidence of an anti-inflammatory effect in the lung in preliminary studies involving segmental antigen challenge. The results from these clinical trials demonstrate that zafirlukast is effective and safe for the prophylactic treatment of asthma. Calhoun WJ. Summary of clinical trials with zafirlukast.

Real and Pseudo Late Asthmatic Reactions after Submaximal Exercise Challenge in Patients with Bronchial Asthma : A New Definition for Late Asthmatic Responses after Exercise Challenge

The late asthmatic reaction after exercise challenge remains a controversial issue. In this study, 21 patients recorded peak expiratory flow rate (PEFR) on two control days without performing exercise. There was no difference between both control days when PEFR at 1 h was compared with baseline PEFR and when PEFR at 4 to 13 hours was compared with baseline PEFR. After analyzing variation coefficients of baseline PEFR on a control day and exercise day, PEFR was not allowed to differ more than 15.3 percent in the same patient when comparing exercise day and control day for the late fall in PEFR in the study. In 17 of 81 patients, a late asthmatic reaction after exercise challenge was present when PEFR fall was ≥20 percent compared with baseline PEFR value. In eight of the 17 patients, a real late asthmatic reaction to exercise challenge was present with a PEFR fall ≥20 percent on at least three successive time points and who had a PEFR fall ≥20 percent compared with corresponding clocktime on a control day. The late asthmatic reaction to exercise challenge is characterized not as a nonspecific epiphenomenon, but as a fall in PEFR of ≥20 percent compared with baseline PEFR value and with corresponding clocktime on a control day on at least three successive time points. Graphic illustration of airway responses following exercises may facilitate the detection of a late asthmatic response.