Vigorous Exercise Can Cause Abnormal Pulmonary Function in Healthy Adolescents.

RATIONALE: Although exercise-induced bronchoconstriction is more common in adolescents with asthma, it also manifests in healthy individuals without asthma. The steady-state exercise protocol is widely used and recommended by the American Thoracic Society (ATS) as a method to diagnose exercise-induced bronchoconstriction. Airway narrowing in response to exercise is thought to be related to airway wall dehydration secondary to hyperventilation. More rigorous exercise protocols may have a role in detecting exercise-induced bronchoconstriction in those who otherwise have a normal response to steady-state exercise challenge. OBJECTIVES: The objective of this study was to determine the effect of two different exercise protocols--a constant work rate protocol and a progressive ramp protocol--on pulmonary function testing in healthy adolescents. We hypothesized that vigorous exercise protocols would lead to reductions in lung function in healthy adolescents. METHODS: A total of 56 healthy adolescents (mean age, 15.2 ± 3.3 [SD] years) were recruited to perform two exercise protocols: constant work rate exercise test to evaluate for exercise-induced bronchoconstriction (as defined by ATS) and standardized progressive ramp protocol. Pulmonary function abnormalities were defined as a decline from baseline in FEV1 of greater than 10%. MEASUREMENTS AND MAIN RESULTS: Ten participants (17.8%) had a significant drop in FEV1. Among those with abnormal lung function after exercise, three (30%) were after the ATS test only, five (50%) were after the ramp test only, and two (20%) were after both ATS and ramp tests. CONCLUSION: Healthy adolescents demonstrate subtle bronchoconstriction after exercise. This exercise-induced bronchoconstriction may be detected in healthy adolescents via constant work rate or the progressive ramp protocol. In a clinical setting, ramp testing warrants consideration in adolescents suspected of having exercise-induced bronchoconstriction and who have normal responses to steady-state exercise testing.

Higher IL-6 and IL6:IGF Ratio in Patients with Barth Syndrome.

BACKGROUND: Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients. METHODS: Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was analyzed for two growth factors: IGF-1 (bound and free) and Growth Hormone (GH); and two inflammatory cytokines IL-6 and TNF-α using high-sensitivity enzyme-linked immunosorbent assays. RESULTS: The average IL-6 and IL6:IGF ratio levels were significantly higher in the BTHS (p = 0.046 and 0.02 respectively). As for GH, there was a significant group by age interaction (p = 0.01), such that GH was lower for BTHS patients under the age of 14.4 years and higher than controls after age 14.4 years. TNF-α levels were not significantly different, however, the TNF-α:GH was lower in BTHS patients than controls (p = 0.01). CONCLUSIONS: Comparison of two anabolic growth mediators, IGF and GH, and two catabolic cytokines, IL-6 and TNF-α, in BTHS patients and healthy age-matched controls demonstrated a potential imbalance in inflammatory cytokines and anabolic growth factors. Higher rates of IL-6 (all ages) and lower GH levels were observed in BTHS patients (under age 14.5) compared to controls. These findings may implicate inflammatory processes in the catabolic nature of Barth Syndrome pathology as well as provide a link to mitochondrial function. Furthermore, interactions between growth factors, testosterone and inflammatory mediators may explain some of the variability in cardiac and skeletal myopathies seen in Barth Syndrome.

Characterization of the asthmatic population of St. Vincent and the Grenadines: asthma severity levels and atopic sensitization.

BACKGROUND: The developing country of St. Vincent and the Grenadines (SVG) reported a 4.5-fold increase in wheezing incidence between 1986 and 2002. It is unknown whether aeroallergens play a significant role in asthma in SVG. OBJECTIVE: The objective of the study is to investigate the importance of aeroallergens and the association between age and persistence of asthma into adulthood. Methods. Subjects were recruited from the National Asthma Clinic. Asthma was diagnosed in 525 participants and severity levels assigned according to the National Heart, Lung, and Blood Institute guidelines. Participants were separated into three age groups [≤6 years (n=176), 7-18 years (n=164), and ≥19 years (n=185)]. Skin testing was performed on 171 participants to dust mite, cat, dog, cockroach, pollens, and mold. Age of asthma onset was obtained. RESULTS: Persistent asthma was diagnosed in 235 participants (44.8%) and increased with increasing age group (p<.0001). Atopy was identified in 121/171 (70.8%) participants and was significantly higher in persistent asthma (p<.004). A significant positive association was seen between atopy and age group (p<.0004) in participants with intermittent asthma but not in participants with persistent asthma. The most common allergen among the atopic participants was house dust mite (93.4%), followed by cockroach (47.9%). Adult participants reporting asthma onset in adulthood were less atopic than those whose asthma developed ≤18 years of age (p<.05). CONCLUSIONS: The predominance of asthma with atopy in SVG implicates a role for atopy in the sudden rise in asthma cases. This asthma characteristic and the increase in persistent asthma with age in SVG are similar to those reported in the developed countries.

Inhaled fluticasone and the hormonal and inflammatory response to brief exercise.

PURPOSE: Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men. METHODS: Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 µg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry. RESULTS: After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng·mL(-1) and were increased to 0.20 ng·mL(-1) in response to exercise. CONCLUSIONS: Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids.

Circulating T-regulatory cells, exercise and the elite adolescent swimmer.

Brief high intensity exercise induces peripheral leukocytosis possibly leading to a higher incidence of allergic symptoms in athletes undergoing excessive training. We studied the exercise-induced alternation of circulating Tregs and FoxP3+ Tregs due to acute intense swim exercise in elite swimmers (n = 22, 12 males, age = 15.4 yrs). Twelve had prior or current rhinitis or asthma and 10 had no current or prior allergy or asthma. Circulating Tregs increased significantly (p < .001) following exercise (pre = 133 +/- 11.2, post = 196 +/- 17.6) as did FoxP3+ cells (pre = 44, post = 64 cells/microl). Increases in Tregs and FoxP3+ Tregs occurred to the same extent in both groups of adolescent swimmers.

Exercise leukocyte profiles in healthy, type 1 diabetic, overweight, and asthmatic children.

Leukocytosis contributes to exercise-induced immune modulation, which is a mechanism of cardiovascular protection. However, this process is poorly defined in children. We therefore measured leukocytes in 45 healthy, 18 overweight, 16 type 1 diabetic, and 8 asthmatic children at pre, end-, and 30-min postexercise (30-min intermittent or 6-min continuous). In all groups, total leukocytes, neutrophils, lymphocytes, and monocytes increased at end-exercise, but returned to baseline by 30-min postexercise, including neutrophils, previously reported to remain elevated for at least some exercise formats. This highly preserved pattern indicates the importance of the adaptive response to physical stress across multiple health conditions.

The Pro- and Anti-Inflammatory Cytokine Response to Exercise in Adolescent Swimmers.

OBJECTIVE: Whether or not individuals with allergy and asthma experience different patterns of change in the balance of both pro- and anti-inflammatory mediators with acute exercise is not known. We hypothesized that adolescent swimmers with a clinical diagnosis of respiratory allergy would have an exaggerated proinflammatory response to laboratory exercise relative to a no-allergy comparison group. METHODS: Adolescent swimmers (17 with clinical symptoms of respiratory allergy (CSRA) and 17 in comparison group) completed the American Thoracic Society (ATS) exercise challenge on cycle ergometer. Blood was collected at baseline and immediately post-exercise. All study tests were conducted at the Institute for Clinical Translational Science at the University of California, Irvine. Circulating cytokines, growth factors, and adhesion molecules were measured using ELISAs including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, P-selectin, and immunoglobulin E (IgE). RESULTS: There was a trend toward higher resting levels of TNF-α in the CSRA group (P = 0.076). Exercise induced a significant increase in P-selectin and TGF-ß1 in both groups. TNF-α increased significantly (17%) in the comparison group (pre = 0.6, post = 0.7 pg/mL), but not in the CSRA group. IL-6 increased significantly in the CSRA group (pre = 0.7, post = 0.8 pg/mL), but not in the comparison group. Circulating levels of IL-4 and IL-10 were not altered immediately post-exercise in either group. CONCLUSIONS: A short bout of intense exercise increased inflammatory growth factors and adhesion molecules, namely TGF-ß1 and P-selectin, both of which are known to be involved in allergic airway diseases. Differences in resting IL-6 and TNF-α and exercise alterations in these cytokines may also contribute to allergic disease in adolescent elite swimmers.

Association of atopy to asthma severity and medication use in children.

The importance of aeroallergens as triggers for asthma is well recognized, but the relationship between asthma severity and atopic profiles in childhood has not been elucidated. This study assessed the relationship of allergen sensitization to asthma severity in a study of 114 asthmatic children followed for 8 weeks in three Southern California areas. Increased controller medication and beta-agonist use were positively associated with number of positive skin tests and allergy to mold and pollens. Mold was associated with increased asthma symptoms. Degree of atopy and reactivity to mold and pollens plays a significant role in asthma severity in asthmatic children.

Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry.

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.

Role of intradermal skin tests in the evaluation of clinically relevant respiratory allergy assessed using patient history and nasal challenges.

BACKGROUND: Skin testing, correlated with patient history, is the accepted method of identifying clinically relevant aeroallergen sensitivity. Traditionally, intradermal tests are believed to be more sensitive in identifying aeroallergen sensitivity than the epicutaneous and percutaneous methods. Therefore, many allergy practitioners use the epicutaneous or percutaneous method first and, if the results are negative, follow up with intradermal tests. OBJECTIVES: To compare the epicutaneous, percutaneous, and intradermal methods to determine their sensitivity to patient history and to evaluate the value of intradermal tests when epicutaneous and percutaneous test results are negative. METHODS: Participants were evaluated for rhinoconjunctivitis symptoms and then were skin tested using the prick and Multi-Test II (MTII) methods. Intradermal tests were performed when prick and MTII test results were negative to an aeroallergen. Participants with negative prick and MTII test results and corresponding positive intradermal test results underwent nasal challenges with evaluation by anterior rhinomanometry. RESULTS: Compared with patient history, average sensitivity for MTII was 77% and for the prick method was 62%. When MTII results were negative, 17% of intradermal tests corresponded with probable patient histories of allergy but none with positive nasal challenge results. Nasal challenge results were similar to those of the negative control group and significantly different from those of the positive control group (P < .001). CONCLUSIONS: The MTII tests are more sensitive and equally specific compared with the prick method. When MTII results are negative, positive intradermal test results are unlikely to identify clinically relevant aeroallergen sensitivity. Routine performance of intradermal tests when MTII results are negative is likely to be of low clinical yield.