Steven R. Boas

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.

Very high-dose ergocalciferol is effective for correcting vitamin D deficiency in children and young adults with cystic fibrosis

Approximately 10-80% of patients with Cystic Fibrosis (CF) have vitamin D deficiency. Obtaining therapeutic vitamin D levels has been a challenge for CF care providers using current recommended high-dose oral ergocalciferol (400,000 IU over 2 months). The objective of this study was to evaluate the safety and efficacy of a 2-week, very high dose ergocalciferol (700,000 IU over 14 days) repletion strategy in children and young adults with CF. As part of a quality improvement initiative, a prospective cohort study was performed from January through May 2007. Phase I included identifying individuals with CF who were subtherapeutic in 25-OH D. In phase II, 50,000 IU of ergocalciferol was prescribed for a 14 day term and administered daily. During phase III, a post treatment 25-OH D level was obtained to determine improvement. Baseline demographics and clinical characteristics were obtained at study entry. Stratification of the post 25-OHD levels was defined. Eighteen individuals with CF participated in the study. The mean age was 17+/-5 years (range 6-25 years). One hundred percent were pancreatic insufficient and required pancreatic enzyme replacement. All 18 had 25-OHD levels less than 30 ng/mL pre-treatment. Seventeen of the 18 (94%) participants became therapeutic in the 2-week interval. No patients had values considered high abnormal (100-150 ng/mL) or toxic (>150 ng/mL). Mean change was noted at an increase of 37.3+/-22 ng/mL in the 2-week period (p<0.001). Pre and peripubertal individuals had a significantly greater increase in 25-OH D levels. The results of this study demonstrate that very high dosing of vitamin D using oral ergocalciferol over a 14 day period is an effective strategy in achieving therapeutic levels of 25-OH vitamin D in children and young adults with CF. We believe this regimen deserves further study.

Validity of self-assessment of sexual maturation in adolescent male patients with cystic fibrosis

PURPOSE Self-assessment of sexual maturity by healthy male adolescents has been found to correlate closely with physician ratings. Data are lacking, however, in adolescents with cystic fibrosis (CF), where an altered body image may affect self-assessment. Delayed sexual maturation occurs in many patients with CF, particularly those with severe disease. We hypothesized that self-assessment of sexual maturation by adolescents with CF would agree with physician ratings. METHODS Using Tanners standard photographs for pubic hair (PH) and genital (G) development, we compared self-assessment of sexual maturation to physician rating in 34 adolescent male patients with CF and 27 healthy male controls (C). RESULTS The two groups did not differ in age. All subjects were initially examined and Tanner-staged by a physician (SRB), and instructed in self-assessment using the Tanner photographs; they then performed a self-assessment. Scores by physician and subjects were assessed for inter-observer agreement by Kappa analysis. For the CF group, 29 of 34 PH assessments and 21 of 34 G assessments demonstrated exact inter-observer agreement between physician and subject ratings. The Kappa coefficient, kappa, (weighted for the degree of closeness between two observers) was 0.946 for PH and 0.840 for G and the C group, kappa was 0.905 for PH and 0.737 for G. Repeat analysis combining stages 3 and 4 PH and G development yielded higher inter-observer agreement in the CF group (33 of 34 PH assessments and 26 of 34 G assessments) and in the C group (24 of 27 PH assessments and 18 of 27 G assessments). CONCLUSIONS Self-assessment is a valid method to assess sexual maturity in clinical evaluation and as a research tool in the study of patients with CF.

Evolution of airway hyperresponsiveness in infants with severe congenital diaphragmatic hernia

Infants born with severe congenital diaphragmatic hernia (DH) characteristically have pulmonary hypoplasia. Airway hyperresponsiveness during the first 4 weeks of life can be demonstrated in most of these neonates. Early postnatal pulmonary development in infants with severe DH has not been well characterized. We examined lung growth in patients with congenital DH by using the forced deflation method to study pulmonary function in 18 infants on mechanical ventilation who survived neonatal repair of their congenital DH. Thirteen infants without primary pulmonary pathology who required general anesthesia for other surgery served as controls. Infants were further divided according to age at the time of testing into early (age ≤ 7 days at time of testing) and late (age ≥ 29 days) groups, yielding four groups of subjects: early diaphragmatic hernia (EDH): n = 9; mean age, 4.2 days, range, 1–7 days; early controls (EC): n = 8; mean age, 3.1 days; range, 1–6 days; late diaphragmatic hernia (LDH): n = 11; mean age, 57.7 days, range, 28–120 days; and late controls (LC); n = 5; mean age, 52.2 days; range 32–90 days. All infants were studied once, with the exception of two infants with DH who were studied on two occasions at EDH and LDH stages. A marked reduction in weight‐corrected forced vital capacity (FVC) was seen in the EDH group (13.9 ± 3.9 ml/kg) as compared to the EC group (44.4 ± 4.9 ml/kg). During the ensuing 4 months of life, FVC in patients with LDH (24.5 ± 1.9 ml/kg) was much higher than FVC in patients with EDH (P < 0.05). These findings demonstrate the presence of pulmonary hypoplasia in the EDH group and suggest subsequent rapid postnatal lung growth. An index of rate, constant, MEF25/FVC, as compared with control groups was abnormally elevated in EDH subjects (1.87 ± 0.30/second vs 1.16 ± 0.32/second, P < 0.05), indicating significantly increased lower airway caliber relative to lung volume. The severe reduction of the rate constant in the LDH group (0.36 ± 0.05/second vs 0.73 ± 0.07/second, P < 0.05) suggests the development of lower airway obstruction. After the administration of a nebulized bronchodilator (BD), an increase in MEF25 (32.9%) in the EDH group was not significant, but an increase of 134.7% in the LDH group was significant (P < 0.05). Although the study utilized a cross‐sectional design with most of the infants in either the early or late group, present findings suggest that infants with EDH have lung restriction reflecting pulmonary hypoplasia. These infants developed lower airway obstruction and airway hyperresponsiveness with only mild fixed obstruction over the first 4 months of life. Pediatr Pulmonol. 1996; 22:295–304.

Hypertrophic osteoarthropathy in a child with follicular bronchiolitis.

Hypertrophic Osteoarthropathy (hoa) is a syndrome affecting the bones, soft tissue, and joints, often occurring in association with chronic pulmonary disorders. Radiography has traditionally been the imaging modality employed to confirm this diagnosis. However, radionuclide bone imaging provides a sensitive method for the detection of HOA and correlates well with the clinical manifestations. The authorss describe the case of a child with HOA in association with follicular bronchiolitis, a rare chronic pulmonary disorder, whose HOA was diagnosed by radionuclide imaging.

Airway function tests and vocal cord paralysis in lung transplant recipients

Maximum expiratory and inspiratory flow‐volume (MEFV, MIFV) curves, specific airway conductance (sGaw), and flexible fiberoptic laryngoscopy were examined in 8 pediatric lung transplant recipients with vocal cord paralysis (VCP). Six were heart‐lung (H‐L) and 2 double‐lung (D‐L) recipients, 7 had left VCP, and 1 had right VCP. Based on the pulmonary function tests (PFT), 2 subgroups could be distinguished in the 8 recipients with VCP. Group A (5/8 recipients; mean age, 13 ± 3.4 years; mean height, 144.3 ± 12.3 cm) had significantly reduced specific airway conductance (sGaw; < 2 SD from predicted) and normal MEF25, MEF50, peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), and %FEV1/forced vital capacity (FVC); this pattern suggested variable extrathoracic airway obstruction. PIF was normal in 4/5 and reduced in 1/5 of these recipients. Group B (3/8 recipients with VCP; mean age, 17 ± 2.4 years; mean height, 156.3 ± 12.0 cm) had significantly reduced sGaw, MEF25, MEF50, PEF, FEV1, and %FEV1/FVC, implying primarily small airway obstruction. These recipients had bronchiolitis obliterans. The results suggest that a pattern of reduced sGaw and normal MEFs, PEF, FEV1, and PIF should raise the possibility of VCP in patients after lung transplantation. sGaw is more sensitive than PIF and PEF in identifying airway obstruction due to VCP, and should be routinely included in the follow‐up evaluation of lung transplant recipients. Pediatr Pulmonol. 1997; 23:87–94.