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Biomedical subjects

Timothy D Mickleborough

Publications and source records attributed to Timothy D Mickleborough.

12 recordsLinked to original sources
PubMed2006

Influence of menstrual cycle phase on pulmonary function in asthmatic athletes.

The main aim of this study was to investigate whether there is a relationship between menstrual cycle phase and exercise-induced bronchoconstriction (EIB) in female athletes with mild atopic asthma. Seven eumenorrheic subjects with regular 28-day menstrual cycles were exercised to volitional exhaustion on day 5 [mid-follicular (FOL)] and day 21 [mid-luteal (LUT)] of their menstrual cycle. Pulmonary function tests were conducted pre- and post-exercise. The maximal percentage decline in post-exercise forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow from 25 to 75% of forced vital capacity (FEF(25-75%)) was significantly greater (P<0.05) on day 21 (mid-LUT phase) (-17.35+/-2.32 and -26.28+/-6.04%, respectively), when salivary progesterone concentration was highest, compared to day 5 (mid-FOL phase) (-12.81+/-3.35 and -17.23+/-8.20%, respectively), when salivary progesterone concentration was lowest. The deterioration in the severity of EIB during the mid-LUT phase was accompanied by worsening asthma symptoms and increased bronchodilator use. There was a negative correlation between the percent change in pre- to post-exercise FEV(1) and salivary progesterone concentration. However, no such correlation was found between salivary estradiol and the percentage change in pre- to post-exercise FEV(1). This study has shown for the first time that menstrual cycle phase is an important determinant of the severity of EIB in female athletes with mild atopic asthma. Female asthmatic athletes may need to adjust their training and competition schedules to their menstrual cycle and to consider the potential negative effects of the LUT phase of the menstrual cycle on exercise performance.

Asthma↗
PubMed2006

The systemic inflammatory response to exercise in adults with cystic fibrosis.

Exercise is associated with release of inflammatory mediators in the circulation and there is evidence that the exercising muscles and tendons are sources of interleukin-6. Due to the catabolic effects of some cytokines, increased release in circulation might contribute to alterations in body composition in adults with cystic fibrosis. We hypothesised that exercise of moderate intensity would generate increased blood concentrations of some inflammatory mediators. We investigated the change in blood concentrations of interleukin-6, tumour necrosis factor alpha and their soluble receptors after a structured exercise (box stepping) of intensity similar to that encountered during activities of daily living in 12 adults with cystic fibrosis and mean (95% confidence interval) FEV1 55.6 (44.4, 66.8)% predicted, body mass index 23.0 (21.3, 24.6) kg/m2 and 12 healthy subjects. The increments post-exercise for all inflammatory mediators and lactate corrected for the work performed until voluntary exhaustion were greater for patients, while the total work was less for patients (all p<0.01). Daytime variability of the inflammatory mediators was assessed in eight patients and was less than the change due to exercise. We report greater increments in circulating concentrations of some cytokines with moderate exercise in adults with cystic fibrosis compared to healthy subjects.

Adult↗
PubMed2006

Chocolate milk as a post-exercise recovery aid.

Nine male, endurance-trained cyclists performed an interval workout followed by 4 h of recovery, and a subsequent endurance trial to exhaustion at 70% VO2max, on three separate days. Immediately following the first exercise bout and 2 h of recovery, subjects drank isovolumic amounts of chocolate milk, fluid replacement drink (FR), or carbohydrate replacement drink (CR), in a single-blind, randomized design. Carbohydrate content was equivalent for chocolate milk and CR. Time to exhaustion (TTE), average heart rate (HR), rating of perceived exertion (RPE), and total work (WT) for the endurance exercise were compared between trials. TTE and WT were significantly greater for chocolate milk and FR trials compared to CR trial. The results of this study suggest that chocolate milk is an effective recovery aid between two exhausting exercise bouts.

Adult↗
PubMed2006

Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma.

BACKGROUND: Previous research has demonstrated that fish oil supplementation has a protective effect on exercise-induced bronchoconstriction (EIB) in elite athletes, which may be attributed to its antiinflammatory properties. Since EIB in asthma involves proinflammatory mediator release, it is feasible that fish oil supplementation may reduce the severity of EIB in asthmatic subjects. STUDY OBJECTIVES: To determine the efficacy of fish oil supplementation on severity of EIB in subjects with asthma. DESIGN: Randomized, double-blind, crossover study. SETTING: Lung function and exercise testing in a university research laboratory. PATIENTS AND MEASUREMENTS: Sixteen asthmatic patients with documented EIB entered the study on their normal diet and then received either fish oil capsules containing 3.2 g of eicosapentaenoic acid and 2.0 g of docohexaenoic acid (fish oil diet, n = 8) or placebo capsules (placebo diet, n = 8) daily for 3 weeks. At the beginning of the study (normal diet) and at the end of each treatment phase, the following pre-exercise and postexercise measures were assessed: (1) pulmonary function; (2) induced sputum differential cell count percentage and proinflammatory eicosanoid metabolite (leukotriene C4 [LTC4]-leukotriene E4 [LTE4] and prostaglandin D2 [PGD2]) and cytokine (interleukin [IL]-1beta and tumor necrosis factor [TNF]-alpha) concentrations; and (3) eicosanoid metabolites leukotriene B4 (LTB4) and leukotriene B5 (LTB(5)) generation from activated polymorphonuclear leukocytes (PMNLs). RESULTS: On the normal and placebo diet, subjects exhibited EIB. However, the fish oil diet improved pulmonary function to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use. Induced sputum differential cell count percentage and concentrations of LTC4-LTE4, PGD2, IL-1beta, and TNF-alpha were significantly reduced before and following exercise on the fish oil diet compared to the normal and placebo diets. There was a significant reduction in LTB4 and a significant increase in LTB5 generation from activated PMNLs on the fish oil diet compared to the normal and placebo diets. CONCLUSION: Our data suggest that fish oil supplementation may represent a potentially beneficial nonpharmacologic intervention for asthmatic subjects with EIB.

Adult↗
PubMed2005

Comparison of the properties of rare variants of alpha1-proteinase inhibitor expressed in COS-1 cells and assessment of their potential as risk factors in human disease.

Among the more than 75 known variants of alpha(1)-proteinase inhibitor, a sub-population of rare, point mutations causing single amino acid replacements have been identified and classified as "at risk" alleles for development of pulmonary disease. In most cases, it is not clear how the amino acid replacements typical of these variants change the properties of the inhibitor to increase risk of disease in the affected individuals. To begin to address this question, we mutagenized a wild type alpha(1)-proteinase inhibitor cDNA to encode a panel of eight different point mutants reported to be associated with increased risk for development of pulmonary disease. These variants were then expressed in COS-l cells transiently transfected with plasmids containing the altered cDNAs. The effects of the mutations on the rates of secretion, cellular location, intracellular degradation, activity, stability, and tendency to aggregate were determined. Results of these studies show that, in some cases, the mutations affect the rate of secretion, the activity or both of these properties of alpha(1)-proteinase inhibitor in a manner consistent with its designation as an "at-risk" allele. In other cases, the mutations do not significantly change the properties of the inhibitor, suggesting that these may be normal variants and that their expression may not increase the risk of disease.

Amino Acid Substitution↗
PubMed2005

Dietary omega-3 polyunsaturated fatty acid supplementation and airway hyperresponsiveness in asthma.

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.

Asthma↗
PubMed2005

Dietary salt, airway inflammation, and diffusion capacity in exercise-induced asthma.

PURPOSE: Recent studies have supported a role for dietary salt as a modifier of the severity of exercise-induced asthma. The main aim of this study was to demarcate a possible mechanism by which dietary salt modification may alter exercise-induced airway narrowing in asthmatic patients. METHODS: Twenty-four patients participated in a randomized, double-blind crossover study. Subjects entered the study on their normal salt diet (NSD) and were then placed on either a low-salt diet (LSD) or high-salt diet (HSD) for 2 wk with a 1-wk washout period occurring between diets. Pre- and postexercise spirometry, pulmonary diffusion capacity (DLCO) and its subdivisions, and induced sputum were obtained on the NSD and at the end of each 2-wk treatment period (LSD and HSD). RESULTS: FEV1 decreased by 7.9 +/- 2.8% on LSD, 18.3 +/- 4.0% on NSD, and 27.4 +/- 3.2% on HSD at 20 min postexercise. The NSD and HSD induced significant reductions (P < 0.05) in DLCO and its subdivisions. However, postexercise pulmonary capillary blood volume significantly increased (P < 0.05) by 6.3 and 9.6 mL on NSD and HSD, respectively, compared with baseline values, with no significant change (P > 0.05) being observed on LSD. Postexercise-induced sputum neutrophil and eosinophil differential cell counts and induced sputum supernatant concentration of eosinophil cationic protein, interleukin (IL)-1beta, IL-8, leukotriene (LT) C(4)-E(4), LTB(4), and prostaglandin D(2) were significantly elevated (P < 0.05) on NSD and HSD compared with LSD. CONCLUSION: Our findings indicate that dietary salt loading enhances airway inflammation following exercise in asthmatic subjects, and that small salt-dependent changes in vascular volume and microvascular pressure might have substantial effects on airway function following exercise in the face of mediator-induced increased vascular permeability.

Adult↗
PubMed2004

Omega-3 Fatty acids and airway hyperresponsiveness in asthma.

Despite the progress that has been made in the treatment of asthma, the prevalence and burden of this disease has continued to increase. Exercise is a powerful trigger of asthma symptoms and reversible airflow obstruction and may result in the avoidance of physical activity by patients with asthma, resulting in detrimental consequences to their health. Approximately 90% of patients with asthma are hyperresponsive to exercise and experience exercise-induced bronchoconstriction (EIB). While pharmacologic treatment of asthma is usually highly effective, medications often have significant side-effects or exhibit tachyphylaxis. Alternative therapies for treatment (complementary medicine) that reduce the dose requirements of pharmacologic interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may be the consumption of a proinflammatory diet. In the typical Western diet, 20- to 25-fold more omega- 6 polyunsaturated fatty acids (PUFA) than omega-3 PUFA are consumed, which causes the release of proinflammatory arachidonic acid metabolites (leukotrienes and prostanoids). This review analyzes the existing literature on omega-3 PUFA supplementation as a potential modifier of airway hyperresponsiveness in asthma and includes studies concerning the efficacy of omega-3 PUFA supplementation in EIB. While clinical data evaluating the effect of omega-3 PUFA supplementation in asthma has been equivocal, it has recently been shown that pharmaceutical-grade fish oil (omega-3 PUFA) supplementation reduces airway hyperresponsiveness after exercise, medication use, and proinflammatory mediator generation in nonatopic elite athletes with EIB. These findings are provocative and suggest that dietary omega-3 PUFA supplementation may be a viable treatment modality and/or adjunct therapy in airway hyperresponsiveness. Further studies are needed to confirm these results and understand their mechanism of action.

Airway Resistance↗
PubMed2004

Dietary salt intake as a potential modifier of airway responsiveness in bronchial asthma.

While pharmacologic treatment of chronic asthma is usually highly effective, medications often have significant side-effects or exhibit tachyphylaxis. Alternative and/or complementary treatments that reduce dependence on pharmacologic medications are of interest in reducing the severity of asthma. This review analyzes the literature that has evaluated dietary salt intake as a potential modifier of the severity of asthma and airway responsiveness. High dietary intakes of salt, greater than 9 g/d, are common in Western civilizations, as is asthma. The question is whether reducing dietary salt intake potentially would improve pulmonary function and airway responsiveness in individuals with asthma. This review details the existing studies in this regard and includes the studies that have evaluated dietary salt on the severity of exercise-induced asthma (exercise-induced bronchoconstriction [E1B]). From a critical analysis of the existing literature, the data that support a role for dietary salt reduction for reducing severity of asthma and airway responsiveness in individuals with asthma is considered encouraging but not clinically convincing. The existing studies have suffered from a variety of experimental and population limitations. In contrast, the data from studies that have altered dietary salt and evaluated severity of EIB in nonatopic individuals is much more convincing. In each study so far, lowering dietary salt has reduced the severity of EIB to subclinical levels. Correspondingly, the supplementing of diets to higher than normal salt intake increased EIB significantly. This review concludes that the data are sufficient to warrant a clinical trial that is properly controlled and randomized to further investigate the influence of dietary salt intake on pulmonary function, airway responsiveness, symptoms, quality of life, and medication requirements in asthma and EIB.

Airway Resistance↗
PubMed2003

Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes.

In elite athletes, exercise-induced bronchoconstriction (EIB) may respond to dietary modification, thereby reducing the need for pharmacologic treatment. Ten elite athletes with EIB and 10 elite athletes without EIB (control subjects) participated in a randomized, double-blind crossover study. Subjects entered the study on their normal diet, and then received either fish oil capsules containing 3.2 g eicosapentaenoic acid and 2.2 g docohexaenoic acid (n-3 polyunsaturated fatty acid [PUFA] diet; n = 5) or placebo capsules containing olive oil (placebo diet; n = 5) taken daily for 3 weeks. Diet had no effect on preexercise pulmonary function in either group or on postexercise pulmonary function in control subjects. However, in subjects with EIB, the n-3 PUFA diet improved postexercise pulmonary function compared with the normal and placebo diets. FEV1 decreased by 3 +/- 2% on n-3 PUFA diet, 14.5 +/- 5% on placebo diet, and 17.3 +/- 6% on normal diet at 15 minutes postexercise. Leukotriene (LT)E4, 9alpha, 11beta-prostaglandin F2, LTB4, tumor necrosis factor-alpha, and interleukin-1beta, all significantly decreased on the n-3 PUFA diet compared with normal and placebo diets and after the exercise challenge. These data suggest that dietary fish oil supplementation has a markedly protective effect in suppressing EIB in elite athletes, and this may be attributed to their antiinflammatory properties.

Adult↗
PubMed2003

The oxygen uptake response running to exhaustion at peak treadmill speed.

PURPOSE: Peak treadmill speed (V(max)), which is the final speed reached and sustained for a minute during a speed-incremented continuous maximal oxygen uptake ([OV0312]O(2max)) test, is an effective predictor of endurance performance. This study assesses the reliability of V(max) and [OV0312]O(2max), and examines the oxygen uptake response while running to exhaustion at V(max). METHODS: Eleven recreationally active runners completed two speed-incremented [OV0312]O(2max) tests (test 1 and test 2) to determine [OV0312]O(2max) and V(max). In addition, the subjects completed a constant speed test (test 3) at V(max) to determine time to exhaustion (T(max)). RESULTS: No significant differences existed between test 1 and test 2 for [OV0312]O(2max) (P = 0.68) and V(max) (P = 0.10). Means (+/- SD) for [OV0312]O(2max) and V(max) were 51.1 +/- 5.8 mL.kg-1.min-1 and 17.4 +/- 1.3 km.h-1, respectively; 95% limits of agreement for V(max) were -0.1 +/- 1.4 km.h-1. However, as heteroscedasticity was present in the [OV0312]O(2max) test data, 95% ratio limits of agreement were reported (1.01 *// 1.08). During test 3, 6 of the 11 subjects attained an oxygen uptake equivalent to their previously recorded [OV0312]O(2max). The time to attain [OV0312]O(2max) was 155.0 +/- 48.0 s, which represented 66.5% of T(max) (237.0 +/- 35.0 s). Although 5 of the 11 subjects did not attain an oxygen uptake response equivalent to that previously recorded, no significant difference existed between the oxygen uptakes for the three tests (P = 0.52). CONCLUSION: The results of this study indicate that V(max) and [OV0312]O(2max) attained during a speed incremented maximal oxygen uptake test were reliable. However, while running at V(max), not all the subjects attained an oxygen uptake response equivalent to that previously recorded during incremental tests 1 and 2.

Adult↗