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Objectives: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis.Methods: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1).Results: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17).Conclusions: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1. [ABSTRACT FROM AUTHOR]

Background: Increased maximal oxygen uptake (V̇O 2max ) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle "quality") and skeletal muscle size (muscle "quantity") are both proposed as potential causes for the lower V̇O 2max , although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O 2max to address this "quality" vs. "quantity" debate., Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size - muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O 2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t -tests and effect sizes (ES) identified differences between groups in V̇O 2max , once mCSA and TMV were controlled for., Results: V̇O 2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45)., Conclusions: A lower V̇O 2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle "quality" in CF (as muscle "quantity" is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tomlinson, Barker, Fulford, Wilson, Shelley, Oades and Williams.)

Purpose: The aim of this study was to describe the relationship between body size and oxygen uptake efficiency slope (OUES) in pediatric patients with cystic fibrosis (CF) and healthy controls (CON), to identify appropriate scaling procedures to adjust the influence of body size upon OUES., Methods: The OUES was derived using maximal and submaximal points from cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body mass (BM), and body surface area (BSA) using ratio-standard (Y/X) and allometric (Y/X) methods. Pearson's correlation coefficients were used to determine the relationship between body size and OUES., Results: When scaled using the ratio-standard method, OUES had a significant positive relationship with stature (r = 0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric exponents (b) for CF and CON were stature 3.00, BM 0.86, and BSA 1.40. A significant negative correlation was found between OUES and stature in the CF group when scaled allometrically (r = -0.37, P = 0.027). Nonsignificant (P > 0.05) correlations for the whole group were found between OUES and allometrically scaled BM (CF r = -0.25, CON, r = 0.15) and BSA (CF r = -0.27, CON r = 0.13)., Conclusions: Only allometric scaling of either BM or BSA, and not ratio-standard scaling, successfully eliminates the influence of body size upon OUES. Therefore, this enables a more direct comparison of the OUES between patients with CF and healthy controls.

Purpose: This study aimed to investigate the effects of mild-to-moderate cystic fibrosis (CF) on the pulmonary oxygen uptake (V˙O2) kinetics of seven pediatric patients (13.5 ± 2.8 yr) versus seven healthy matched controls (CON; 13.6 ± 2.4 yr). We hypothesized that CF would slow the V˙O2 kinetic response at the onset of moderate (MOD) and very heavy (VH) intensity cycling., Methods: Changes in breath-by-breath V˙O2, near-infrared spectroscopy-derived muscle deoxygenation ([HHb]) at the vastus lateralis muscle and thoracic bioelectrical impedance-derived heart rate (HR), stroke volume index, and cardiac index were measured during repeat transitions to MOD (90% of the gas exchange threshold) and VH (Δ60%) intensity cycling exercise., Results: During MOD, the phase II V˙O2 τ (P = 0.84, effect size [ES] = 0.11) and the overall mean response time (MRT) (P = 0.52, ES = 0.11) were not significantly slower in CF versus CON. However, during VH exercise, the phase II V˙O2 τ (P = 0.02, ES = 1.28) and MRT (P = 0.01, ES = 1.40) were significantly slower in CF. Cardiac function, central O2 delivery (stroke volume index and cardiac index), and muscle [HHb] kinetics were unaltered in CF. However, the arteriovenous O2 content difference ((Equation is included in full-text article.)) was reduced during VH at 30 s (P = 0.03, ES = 0.37), with a trend for reduced levels at 0 s (P = 0.07, ES = 0.25), 60 s (P = 0.05, ES = 0.28), and 120 s (P = 0.07, ES = 0.25) in CF. Furthermore, (Equation is included in full-text article.)significantly correlated with the VH phase II V˙O2 τ (r = -0.85, P = 0.02) and MRT (r = -0.79, P = 0.03) in CF only., Conclusion: Impairments in muscle oxidative metabolism during constant work rate exercise are intensity dependent in young people with mild-to-moderate CF. Specifically, V˙O2 kinetics are slowed during VH but not MOD cycling and appear to be mechanistically linked to impaired muscle O2 extraction and utilization.

Cystic fibrosis (CF) is a genetic condition affecting the respiratory and gastrointestinal systems, with patients experiencing problems maintaining weight, especially during rapid growth periods such as puberty. The aim of this case report was to monitor the effect of gastrostomy insertion and implementation of overnight supplemental feeding upon clinical outcomes, including body mass index (BMI), lung function (FEV 1 ), and exercise-related variables (maximal oxygen uptake [VO 2max ] and ventilatory efficiency [V E /VO 2 ]) in an 11-year-old female with CF Combined incremental and supramaximal exercise testing to exhaustion was performed at four time points: 3 months prior to the procedure (T1), 2 days prior to (T2), 4 months (T3), and 1 year following the procedure (T4). Improvements following gastrostomy insertion were observed at the 1 year follow-up with regards to BMI (+20%); whereas absolute VO 2max remained stable and lung function fluctuated throughout the period of observation. Declines in function with regards to body weight relative VO 2max (-16.3%) and oxygen uptake efficiency (+7.5%) were observed during this period. This case report is the first to consider exercise-related clinical outcomes in assessing the effect of implementing gastrostomy feeding in CF The varied direction and magnitude of the associations between variables shows that further investigations are required., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Purpose: This study aimed to document the matching of muscle O2 delivery to O2 use in young patients with cystic fibrosis (CF) from muscle deoxygenation (HHb) dynamics during ramp exercise., Methods: Ten patients with stable, mild-to-moderate CF (12.7 ± 2.8 yr) and 10 healthy controls (CON, 12.8 ± 2.8 yr) completed a combined ramp and supramaximal cycling test to determine maximal O2 uptake (V˙O2max). Changes in gas exchange and ventilation, HR, and m. vastus lateralis HHb (near-infrared spectroscopy) were assessed. Δ[HHb]-work rate and Δ[HHb]-V˙O2 profiles were normalized and fit using a sigmoid function., Results: Aerobic function was impaired in CF, indicated by very likely reduced fat-free mass-normalized V˙O2max (mean difference, ±90% confidence interval: -7.9 mL·kg·min, ±6.1), very likely lower V˙O2 gain (-1.44 mL·min·W, ±1.12), and a likely slower V˙O2 mean response time (11 s, ±13). An unclear effect was found upon the absolute and relative work rate (-14 W, ±44, and -0.7% peak power output, ±12.0, respectively) and the absolute and percentage (-0.10 L·min, ±0.43, and 3.3% V˙O2max, ±6.0) V˙O2 corresponding to 50% Δ[HHb] amplitude, respectively, between groups. However, arterial oxygen saturation (SpO2) was very likely lower in CF (-1%, ±1) and demonstrated moderate-to-very large relations with parameters of aerobic function., Conclusions: Young patients with mild-to-moderate CF present with impaired aerobic function during ramp incremental cycling exercise. Because the rate of fractional O2 extraction during ramp cycling exercise was not altered by CF, yet SpO2 was lower, the present findings support the notion of centrally mediated oxygen delivery to principally limit the aerobic function of pediatric patients with CF during ramp incremental cycling exercise.

Purpose: The purpose of this report was to evaluate the influence of 12 weeks of ivacaftor treatment on the aerobic function of 2 teenage patients with cystic fibrosis (CF; ΔF508/G551D) using a maximal cardiopulmonary exercise test., Summary of Key Points: One patient, with relatively mild disease, demonstrated no clinically meaningful changes in maximal oxygen uptake ((Equation is included in full-text article.)O2max). However, in the second case, with more established lung disease on imaging, (Equation is included in full-text article.)O2max improved by approximately 30%, an improvement out of proportion with early lung function changes. This improvement resulted from increased muscle oxygen delivery and extraction., Statement of Conclusions: Cardiopulmonary exercise testing can monitor the extent and cause(s) of change following interventions such as ivacaftor, with the potential to identify functional changes independent from spirometry indices., Recommendations for Clinical Practice: Cardiopulmonary exercise testing represents an important and comprehensive clinical assessment tool, and its use as an outcome measure in the functional assessment of patients with CF is encouraged.

Background: The reproducibility of cardiopulmonary exercise testing (CPET) has not been established in young cystic fibrosis (CF) patients using a valid protocol., Methods: Thirteen 7-18 year olds completed three CPETs, separated by 48 h and 4-6 weeks. CPET involved a ramp-incremental cycling test with supramaximal verification., Results: Maximal oxygen uptake was repeatedly determined with no learning effect and typical errors expressed as a coefficient of variation (TE(CV%)) of 9.3% (48 h) and 13.3% (4-6 weeks). The reproducibility of additional parameters of aerobic function [gas exchange threshold (TE(CV%): 11.2%, 16.8%); VO2 mean response time (TE(CV%): 37.8%, 89.4%); VO2 gain (TE(CV%): 17.4%, 24.5%)] and clinical utility [e.g. SaO2% (TE(CV%): 2.2%, 3.1%); ventilatory drive (V(E)/VCO2-slope) (TE(CV%): 7.8%, 17.7%)] was also established over the short- and the medium-term, respectively., Conclusion: These results establish limits of variability to determine meaningful changes over the short- and the medium-term for CPET outcomes in young CF patients., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Exercise testing is a valuable prognostic tool and exercise training has many health benefits in cystic fibrosis (CF). The objective of this study was to survey the provision of exercise testing and training in UK CF clinics., Methods: A three-page questionnaire was used to determine the extent of, scope and importance assigned to exercise testing and training., Results: Data from returned questionnaires showed that 38.9% of paediatric and 27.8% of adult patients had performed an exercise test in the preceding 12 months, most as part of an annual review process. Pulmonary rehabilitation programmes were accessible in only 31.3% of clinics, and only 26.0% provide exercise training programmes. When assigning importance for exercise testing on a scale from 1 'not important' to 5 'very important', the mean and median respondent scores were 3.5 and 4.0, respectively, and for the importance of training were 4.0 and 4.0, respectively., Conclusions: Despite the level of importance given to exercise testing and training by healthcare providers, exercise is underused as either an assessment tool or therapeutic intervention in the healthcare of patients with CF in the UK., (Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Many problems may arise within the gastrointestinal tract of patients with cystic fibrosis. We report a new cause of subacute intestinal obstruction due to a fibrotic stricture of the ascending colon in a child with cystic fibrosis. Treatment was with a right hemicolectomy. There has been no recurrence after nine months follow-up. Recent similar cases suggest that this new pathology is linked to the use of enteric-coated high-strength pancreatin microspheres.

Objective: To assess the usefulness of a hypoxic challenge in a laboratory at sea level in predicting acute desaturation at altitude in children with lung disease., Design: Comparison of responses to hypoxic challenge in different settings., Subjects: 22 children (12 boys) aged 11 to 16 years with cystic fibrosis in whom the mean forced expiratory volume in one second was 64% (range 24-100%)., Setting: Lung function laboratory, the Alps, and aboard commercial jet aircraft., Main Outcome Measures: Spirometric lung function at sea level and finger probe oximetry with air and 15% oxygen. Oximetry during high altitude flight and on a mountain at altitude of 1800 m., Results: Significant desaturation (range 0 to 12%) occurred with all hypoxic challenges (P < 0.002). The best predictor of hypoxic response from a single reading was the laboratory test (r2 = 76% for flight and r2 = 47% for mountain altitude), but the mean errors of prediction were not clinically significantly different. In six children who showed the greatest desaturation the laboratory test overestimated desaturation, but other predictors underestimated desaturation in three by up to 5%., Conclusions: The laboratory hypoxic challenge directly predicted the worst case of desaturation during flight and at equivalent high altitude. Spirometry and baseline oxygen saturations may underestimate individual hypoxic response. The test may have wider applications to other patients with stable chronic lung diseases, particularly in determining who needs supplementary oxygen during air travel and who should be advised against holidays at high altitude.

The 2-cell stage of mouse embryogenesis is characterized by two phases of alpha-amanitin-sensitive polypeptide synthetic activity, which appear to mark the first major expression of the embryonic genome, as assessed by examination of in vitro translates of mRNA. Using populations of embryos synchronized to the first cleavage division, we have established that DNA replication takes place over the period 1 to 5.5 h after the first cleavage division; the two bursts of putative transcription take place before and immediately after DNA replication, and the translation products are detectable in each case within 3-4 h. In addition, we have shown that suppression of cytokinesis and the second round of DNA replication does not affect synthesis of the alpha-amanitin-sensitive polypeptides, and that neither DNA replication nor the loss of maternal mRNA that take place during the 2-cell stage are dependent upon synthesis of the alpha-amanitin-sensitive polypeptides.