Patricia A. Nixon

The Prognostic Value of Exercise Testing in Patients with Cystic Fibrosis

BACKGROUND Previous studies have shown female sex, impaired pulmonary function, older age, malnutrition, and colonization of the respiratory tract with Pseudomonas cepacia to be associated with a poor prognosis in patients with cystic fibrosis. We sought to determine the prognostic value of exercise testing in addition to the other prognostic factors. METHODS A total of 109 patients with cystic fibrosis, 7 to 35 years old, underwent pulmonary-function and exercise testing in the late 1970s. They were followed for eight years to determine the factors associated with subsequent mortality. Survival rates were calculated with standard life-table methods. Cox proportional-hazards regression models were used to determine crude relative risks of mortality and relative risks adjusted for age, sex, body-mass index, forced expiratory volume in one second (FEV1) end-tidal partial pressure of carbon dioxide (PCO2) at peak exercise, and oxygen consumption at peak exercise (VO2 peak). RESULTS Patients with the highest levels of aerobic fitness (VO2 peak, > or = 82 percent of predicted) had a survival rate of 83 percent at eight years, as compared with rates of 51 percent and 28 percent for patients with middle (VO2 peak, 59 to 81 percent of predicted) and lowest (VO2 peak, < or = 58 percent of predicted) levels of fitness, respectively. After adjustment for other risk factors, patients with higher levels of aerobic fitness were more than three times as likely to survive than patients with lower levels of fitness. Colonization with P. cepacia was associated with a risk of dying that was increased fivefold. Age, sex, body-mass index, FEV1, and end-tidal PCO2 at peak exercise were not independently correlated with mortality. CONCLUSIONS Higher levels of aerobic fitness in patients with cystic fibrosis are associated with a significantly lower risk of dying. Although better aerobic fitness may simply be a marker for less severe illness, measurement of VO2 peak appears to be valuable for predicting prognosis. Further research is warranted to determine whether improving aerobic fitness through exercise programs will result in a better prognosis.

Clinical Stress Testing in the Pediatric Age Group A Statement From the American Heart Association Council on Cardiovascular Disease in the Young, Committee on Atherosclerosis, Hypertension, and Obesity in Youth

This statement is an updated report of the American Heart Associations previous publications on exercise in children. In this statement, exercise laboratory requirements for environment, equipment, staffing, and procedures are presented. Indications and contraindications to stress testing are discussed, as are types of testing protocols and the use of pharmacological stress protocols. Current stress laboratory practices are reviewed on the basis of a survey of pediatric cardiology training programs.

A six-minute walk test for assessing exercise tolerance in severely ill children

OBJECTIVES The primary objective of this study was to compare exercise tolerance, heart rate, and oxyhemoglobin saturation (Sao2) between a traditional progressive maximal exercise test and a self-paced, 6-minute walk test in severely ill children. STUDY DESIGN Seventeen patients (9 to 19 years of age) performed a progressive maximal exercise test on a cycle ergometer and a self-paced, 6-minute walk test as part of the evaluation for possible heart, lung, or combined heart and lung transplantation. Physical work capacity and peak oxygen uptake were measured during the progressive cycle test. The walk test was performed in a hospital corridor, with patients trying to cover as much distance as possible in 6 minutes at their own pace. Oxyhemoglobin saturation and heart rate were monitored continuously by pulse oximetry and compared between the two tests. RESULTS The distance walked in 6 minutes correlated with peak oxygen uptake (r = 0.70, p < 0.01) and physical work capacity (r = 0.64, p < 0.005). The minimum (Min) Sao2 on the bike test correlated significantly with Min Sao2 on the walk test (r = 0.82, p < 0.001), with 11 of 17 patients having a lower Min Sao2 on the walk test than the bike test (mean Min Sao2, 84% and 86%, respectively). The peak heart rate did not correlate significantly between the bike and walk tests (r = 0.25), although significantly lower (p < 0.01) values were observed on the walk (148 beats/min) than bike (169 beats/min) test. CONCLUSIONS The results suggest that the 6-minute self-paced walk test may provide an alternative method for assessing functional capacity in severely ill children, and that Sao2 measured during progressive exercise testing on a cycle ergometer may not reflect the degree of oxyhemoglobin desaturation during self-paced walking in some patients with severe cardiopulmonary disease.

Habitual physical activity in children and adolescents with cystic fibrosis.

PURPOSE This study was conducted to: 1) measure total physical activity levels, including the intensities of the various types of activities, in children and adolescents with CF compared with non-CF healthy control subjects; and 2) determine whether vigorous activity level was related to aerobic fitness and disease status in patients with CF. METHODS Thirty patients with CF (18 male, 12 female) and 30 control subjects (17 male, 13 female), 7-17 yr old, participated in this study. Habitual physical activity was measured using Kriskas Modifiable Activity Questionnaire (MAQ) and the past years average of total hours, MET-hours, and vigorous (VIG) hours (>6 METs) of activity per week were determined. Aerobic fitness was determined from peak oxygen uptake (VO2peak) obtained via maximal exercise testing on a cycle ergometer. Standard spirometry was used to measure pulmonary function. Body mass index (BMI) was determined from height and weight measurements. RESULTS The CF and control groups were similar in age and gender distribution, but the patients were smaller (BMI, 98 vs 112% of predicted) and less aerobically fit (36.5 vs 41.4 mL x kg(-1) x min(-1)). Total and MET-hours of physical activity did not differ between groups; however, the CF group participated in significantly fewer hours of vigorous activities than the control group (2 vs 3.7 h x wk(-1)). In patients with worse lung disease, VIG-h x wk(-1) were significantly related to VO2peak (r = 0.83). CONCLUSION These results suggest that children with CF engage in less vigorous physical activities than their healthy non-CF peers, despite having good lung function. In view of the progressive nature of the disease, and the association between aerobic fitness and vigorous activity, patients should be encouraged to engage in more vigorous activities that promote aerobic fitness and may ultimately have an impact on survival.

Follow-up of a Randomized, Placebo-Controlled Trial of Dexamethasone to Decrease the Duration of Ventilator Dependency in Very Low Birth Weight Infants: Neurodevelopmental Outcomes at 4 to 11 Years of Age

OBJECTIVE. High doses of dexamethasone reduce the risk of chronic lung disease among premature infants but may increase the risk of developmental impairments. The objective of this study was to compare developmental outcomes beyond infancy for children who, as neonates, participated in a randomized trial of dexamethasone. PATIENTS AND METHODS. One hundred eighteen children with birth weights <1500 g were randomly assigned at 15 to 25 days of life to a 42-day tapering course of dexamethasone or placebo. All 95 survivors were assessed by using standardized measures of developmental outcome at least once at or beyond 1 year of age, and 84 were examined at 4 to 11 years. For this follow-up study, the outcome of primary interest was death or major neurodevelopmental impairment, which was defined as cerebral palsy, cognitive impairment, or blindness. RESULTS. On the basis of each childs most recent follow-up, the rates of major neurodevelopmental impairments were 40% for the dexamethasone group and 20% for the placebo group. The higher impairment rate for the dexamethasone group was mainly attributed to a higher prevalence of cerebral palsy. Rates of the composite outcome of death or major neurodevelopmental impairment were 47% and 41%, respectively. CONCLUSION. A 42-day tapering course of dexamethasone, which was shown previously to decrease the risk of chronic lung disease in very low birth weight infants, does not increase the risk of the composite outcome of death or major neurodevelopmental impairment.

Factors limiting anaerobic performance in adolescent males with cystic fibrosis

Forty-one adolescent males (11.1-18.3 yr) with cystic fibrosis (CF) and 37 healthy adolescent males (11.1-17.9 yr) performed a Wingate Anaerobic Test (WAnT). The group with CF was subdivided by sexual maturity, nutritional status, and degree of airway obstruction. The subjects with CF had lower absolute power outputs than the healthy controls [mean power in Watts (mean +/- SD): 350.2 +/- 135.9 vs 424.5 +/- 120.4, P < 0.001; peak power: 525.2 +/- 178.4 vs 665.9 +/- 191.3, P < 0.001). When absolute power was corrected for lean body mass, the subjects with CF had lower power outputs than the healthy controls (mean power in W.kg-1: 8.9 +/- 1.7 vs 9.6 +/- 0.9, P < 0.05; peak power: 13.4 +/- 2.1 vs 15.0 +/- 1.6, P < 0.05). The subgroup with CF with a higher body mass index (BMI > 17.5 kg.m-2) had higher peak and mean power output than subjects with CF with a lower BMI in both absolute power and when power was expressed per lean body mass. When sexual maturation was considered, subjects with CF with salivary testosterone greater than 4.0 ng.dl-1 had a higher mean and peak power in both absolute terms and relative to lean body mass than subjects with CF with salivary testosterone less than 4.0 ng.dl-1. Multiple regression analysis indicated that the nutritional factor accounted for 70%-80% of the variability in power output in the subjects with CF, while testosterone accounted for 10% of the variability. Pulmonary function was not a significant independent correlate of anaerobic power. Our results suggest that nutritional status, and to a lesser extent maturational factors, may play a more important role than pulmonary function in determining anaerobic fitness in male adolescents with CF.

Effects of anaerobic exercise on the immune system in eight- to seventeen-year-old trained and untrained boys

OBJECTIVES To determine the immunologic response to a brief bout of intense exercise in children and to determine the effects of prolonged activity and maturation level of the subjects on this response. STUDY DESIGN We determined counts of leukocytes and their subsets, counts of lymphocytes and their subsets, and natural killer (NK) cell activity and cell number before and 3 and 60 minutes after a Wingate anaerobic test (WAnT) in 16 male swimmers (9 to 17 years of age) and 17 male nonswimmers (9 to 17 years of age). Subjects were also categorized by pubertal status based on Tanner staging and by level of physical activity. The Student t test and analysis of variance were used to determine statistical significance, with values expressed as mean +/- SEM. RESULTS Three minutes after the WAnT, all children had increases in leukocytes (28%), lymphocytes (43%), and NK cells (395%) (p < 0.01). Swimmers had less baseline NK cell activity (54 +/- 6 cytolytic units) than nonswimmers (87 +/- 10 cytolytic units) after the WAnT (p < 0.01), although both groups showed an increase to similar levels of NK activity 3 minutes after exercise. Pubertal effects on these responses were not significant. CONCLUSIONS Our results demonstrate transient leukocytosis, lymphocytosis, and increases in NK cell number and activity in 8- to 17-year-old boys after a brief bout of intense exercise. Formal athletic training appears to be associated with a lower baseline NK cell activity, and yet such activity is still within the normal range for this age group. Further investigations are necessary to determine the impact of such training on overall health and the ability to fight infection.

Adiposity in Adolescent Offspring Born Prematurely to Mothers with Preeclampsia

OBJECTIVE To evaluate the relationship between maternal preeclampsia resulting in premature delivery and adiposity in the offspring during adolescence. STUDY DESIGN The 172 study participants were 14 years old and had very low birth weight. We compared height, weight, body mass index (BMI), percent fat, waist circumference, and triceps and subscapular skin fold thicknesses between those born prematurely secondary to preeclampsia (n = 51; 22 male) and those born prematurely after normotensive pregnancies (n = 121; 55 male). Multiple linear regression analysis was used to adjust for potential confounders (maternal BMI, antenatal steroid exposure, and race) and to evaluate potential explanatory variables (fetal, infancy, and childhood weight gain, and caloric intake, level of fitness, and physical activity at 14 years). RESULTS When adjusted for potential prenatal confounders (antenatal steroid exposure and race), adolescent male offspring of preeclamptic pregnancies had higher BMI (4.0 kg/m(2) [1.5, 6.6]) (mean difference [95% CI]), waist circumference (11.8 cm [3.8, 19.7]), triceps (4.6 mm [0.6, 8.6]) and subscapular skinfold thicknesses (6.2 mm [1.5, 10.9]), and percent body fat (4.1% [-0.1, 8.3]). Adjusting for infancy and childhood weight gain attenuated these group differences. There were no group differences among females. CONCLUSION Male adolescent offspring born prematurely of women with preeclampsia have higher measures of adiposity than those born prematurely of normotensive pregnancies.

Follow-up of a Randomized, Placebo-Controlled Trial of Postnatal Dexamethasone: Blood Pressure and Anthropometric Measurements at School Age

OBJECTIVE. The purpose of this work was to evaluate the effects of a 42-day tapering course of dexamethasone on blood pressure and anthropometric measurements in school-age children who were born with very low birth weight. METHODS. Sixty-eight children, who as neonates participated in a randomized placebo-controlled trial of a 42-day tapering course of dexamethasone (n = 38, dexamethasone; n = 30, placebo) to facilitate weaning from the ventilator, were seen at a median of 9 years of age. Participants underwent measurements of systolic blood pressure, diastolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, and weight. Mann-Whitney U tests were used to compare groups, and Spearman coefficients were used to examine correlations between variables. RESULTS. Comparing dexamethasone- and placebo-treated children, we found no differences in systolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, weight, or body mass index. Twenty-nine percent of all subjects had systolic blood pressure and/or diastolic blood pressure ≥90th percentile for age and gender. Thirty percent of all subjects had body mass index ≥85th percentile for age and gender. CONCLUSIONS. In a group of preterm very low birth-weight infants at high risk for chronic lung disease, we found no effects of dexamethasone on blood pressure or anthropometric measurements at 8 to 11 years of age. Of concern is that a high proportion in this sample had blood pressure ≥90th percentile and/or body mass index ≥85th percentile.

The renin–angiotensin–aldosterone system in adolescent offspring born prematurely to mothers with preeclampsia

Hypothesis/introduction: Preeclampsia is associated with alterations in the maternal renin–angiotensin–aldosterone system (RAAS), increased blood pressure (BP), and cardiovascular risk in the offspring. We hypothesized that preeclampsia is associated with alterations in the RAAS in the offspring that persist into adolescence. Materials and methods: We compared components of the circulating (n = 111) and renal (n = 160) RAAS in adolescents born prematurely with very low birth weight (VLBW) of preeclamptic (PreE) and normotensive (NoHTN) pregnancies. Multivariable linear regression was used to evaluate potential confounding and intermediate variables. Analyses were stratified by sex. Results: Adjusting for race and antenatal steroid exposure, male offspring of PreE mothers had higher circulating aldosterone than those of NoHTN mothers (adjusted mean difference = 109; 95% confidence limits: −9, 227 pmol/L). Further adjustment for current BMI attenuated this difference (adjusted mean difference: 93; 95% confidence limits: −30, 215 pmol/L). Conclusion: Among male preterm VLBW infants, maternal preeclampsia is associated with increased circulating aldosterone level in adolescence, which appears to be mediated in part by higher BMI.