Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis.

Exercise can stimulate catabolic inflammatory cytokines even in healthy children. For patients with cystic fibrosis (CF), this may be problematic because CF is characterized by increased inflammation and suppressed growth. We examined fitness and the response to brief exercise of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 +/- 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 +/- 0.5 yr of age, NS). Subjects performed brief intermittent, constant work rate protocol (scaled to each individual's exercise capacity) with blood and urine sampling. Peak V O(2) was correlated with IGF-I (r = 0.68, p < 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p < 0.05) and IGF-I was 47% lower than in control subjects (p < 0.05). Post hoc analysis revealed a progressive increase in the IL-6 response to exercise, with the lowest increase observed in control subjects (11.8 +/- 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 +/- 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 +/- 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-alpha. Exercise also significantly increased IGFBP-1 in both control subjects and subjects with CF. Brief exercise can increase even chronically elevated inflammatory mediators in CF, and this response may be attenuated by ibuprofen.

Junctional epidermolysis bullosa associated with congenital localized absence of skin, and pyloric atresia in two newborn siblings.

Congenital localized absence of the skin has been observed in various subsets of inherited epidermolysis bullosa (EB). Pyloric atresia is a rare disorder that has been seen in association with EB. Ureterovesical junction obstruction is a condition unique to the association between pyloric atresia and EB. The authors describe 2 premature male siblings with pyloric atresia, congenital localized absence of the skin, urinary obstruction, and EB at birth. Electron microscopic study of the biopsy specimen from the first sibling revealed characteristic findings of EB simplex. However, prenatal diagnosis of the next sibling was made by integrin B4 mutations and the electron microscopic study of the biopsy specimen after delivery confirmed junctional EB (JEB). These cases emphasize this unusual combination of defects and limitations of electron microscopy.

Muscle size and cardiorespiratory response to exercise in cystic fibrosis.

The mechanism responsible for diminished exercise performance in cystic fibrosis (CF) is not clear. We hypothesized that reduced muscle size, rather than an intrinsic muscle defect, was the primary factor in such diminished exercise performance. Twenty-two subjects with CF (14 females and eight males, aged 6.5 to 17.7 yr, with FEV(1) of 46% to 111% predicted) participated in a study of this hypothesis, and were compared with healthy children tested in the same laboratory. Muscle size was estimated from midthigh muscle cross-sectional area (CSA) obtained by magnetic resonance imaging, and fitness was determined by progressive cycle ergometer exercise testing with breath-by-breath measurements of gas exchange. Peak oxygen consumption (V O(2)) was reduced in CF subjects (956 +/- 81 [mean +/- SEM] ml/min, as compared with 1,473 +/- 54 ml/min in controls; p < 0.00001). Surprisingly, CF subjects had a lower peak V O(2) per CSA (mean for CF subjects 70 +/- 3% predicted, p < 0.0001) than did controls, whereas muscle CSA in CF subjects was not significantly smaller than in controls. The scaling parameters of peak V O(2) and muscle CSA did not differ significantly between healthy controls (0.80 +/- 0.16) and CF subjects (1.03 +/- 0.12). Indexes of aerobic function that are less effort-dependent than peak V O(2) were also lower in the CF subjects (e.g., the slope of V O(2) versus work rate [WR] (DeltaV O(2)/DeltaWR) was 68 +/- 2% predicted; p < 0.005). The study data did not support the initial hypothesis, and suggest a muscle-related abnormality in oxygen metabolism in patients with CF.