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.
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-␣ (TNF-␣ ), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 Ϯ 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 Ϯ 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 O 2 was correlated with IGF-I (r ϭ 0.68, p Ͻ 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p Ͻ 0.05) and IGF-I was 47% lower than in control subjects (p Ͻ 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 Ϯ 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 Ϯ 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 Ϯ 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-␣ . 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.
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-␣ (TNF-␣), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 Ϯ 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 Ϯ 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 O 2 was correlated with IGF-I (r ϭ 0.68, p Ͻ 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p Ͻ 0.05) and IGF-I was 47% lower than in control subjects (p Ͻ 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 Ϯ 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 Ϯ 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 Ϯ 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-␣. 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.
Background: Peripheral airway impairment (PAI) has been shown to have a close association to risk of uncontrolled asthma in children. However, clear methods have not been established for the clinician to select impulse oscillometry (IOS) reference equations best suited for their population. Our study aimed to develop a practical external validation analytic approach for the clinician to determine which of the available reference equations best predicts uncontrolled asthma for their patients.Methods: This is a post hoc analyses of data collected at baseline in a randomized controlled study that occurred from March 2016 to 2018. The study population consisted of 227 children, ages 4−18 years, with moderate to severe asthma.Discrimination and calibration predictive performance of available and suitable IOS equations were assessed by using uncontrolled asthma as the criterion outcome.Discrimination statistics of accuracy, sensitivity, and specificity served as the primary performance indicators. Rank scores were determined by the number of acceptable limit thresholds met for these measures (≥60%, ≥50%, and ≥60%, respectively) across IOS metrics (R5, R5-R20, AX, and X5) resulting in a total possible score of 12.Results: External validity assessment determined the rank order of best to worst equations as being Gochicoa-Rangel (rank score = 10) > Nowowiejska (rank score = 9) > Assumapcao (rank score = 6) > Amra (rank score = 2). Gochicoa-Rangel reference equations provided the best option for universal application with accuracy of 73.1%, 72.2%, 76.7%, and 66.2% for R5, R5-R20, AX, and X5, respectively.Conclusions: External validation, particularly discrimination in asthmatic children, offers the clinician a practical approach to selecting the most suitable predictive equations for their patients.
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