Characterization of the L-Arginine/Nitric Oxide Pathway and Oxidative Stress in Pediatric Patients with Atopic Diseases.

INTRODUCTION: L-Arginine (Arg) is a semi-essential amino acid. Constitutive and inducible nitric oxide synthase (NOS) isoforms convert Arg to nitric oxide (NO), a potent vaso- and bronchodilator with multiple biological functions. Atopic dermatitis (AD) and bronchial asthma (BA) are atopic diseases affecting many children globally. Several studies analyzed NO in airways, yet the systemic synthesis of NO in AD and BA in children with BA, AD or both is elusive. METHODS: In a multicenter study, blood and urine were obtained from 130 of 302 participating children for the measurement of metabolites of the Arg/NO pathway (BA 31.5%; AD 5.4%; AD + BA 36.1%; attention deficit hyperactivity disorder (ADHD) 12.3%). In plasma and urine amino acids Arg and homoarginine (hArg), both substrates of NOS, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), both inhibitors of NOS, dimethylamine (DMA), and nitrite and nitrate, were measured by gas chromatography-mass spectrometry. Malondialdehyde (MDA) was measured in plasma and urine samples to evaluate possible effects of oxidative stress. RESULTS: There were no differences in the Arg/NO pathway between the groups of children with different atopic diseases. In comparison to children with ADHD, children with AD, BA or AD and BA had higher plasma nitrite (p < 0.001) and nitrate (p < 0.001) concentrations, suggesting higher systemic NO synthesis in AD and BA. Urinary excretion of DMA was also higher (p = 0.028) in AD and BA compared to patients with ADHD, suggesting elevated ADMA metabolization. DISCUSSION/CONCLUSION: The Arg/NO pathway is activated in atopic diseases independent of severity. Systemic NO synthesis is increased in children with an atopic disease. Plasma and urinary MDA levels did not differ between the groups, suggesting no effect of oxidative stress on the Arg/NO pathway in atopic diseases.

Association between habitual physical activity (HPA) and sleep quality in patients with cystic fibrosis.

PURPOSE: Sleep disturbances and poor sleep quality are known to be present in patients with CF. Regular physical activity plays an important role in the treatment of CF patients due to its positive influence on progression of disease and quality of life. The aim of this work is to create a home-based sleep and activity profile and to investigate the influence of habitual physical activity (HPA) on sleep quality in children, adolescents, and adults with CF. METHODS: A total of 109 CF patients (64 male, mean age 22.7 ± 12.0 years; mean ppFEV1 63.0 ± 26.7) were equipped with an actigraph for a home-based collection of data on sleep and activity over 4 weeks. RESULTS: Age, FEV1, and BMI affect sleep and activity in CF patients. Especially younger age and higher FEV1 show a great influence on certain aspects of sleep (SE, TST, TIB, WASO, # of awakenings) and activity and its different intensities. General HPA does not affect sleep, but there is a strong correlation between times spent in vigorous to very vigorous intensities and better sleep quality. CONCLUSION: Besides younger age and higher FEV1, daily activity in higher intensities influences sleeping behavior of CF patients in a positive way. Patients with poor sleep quality and sleep disturbances possibly benefit from an intensification of physical activity in the home environment. TRAIL REGISTRATION: number: 14-6117-BO (University Duisburg-Essen) and NCT03518697 (clinical trials).

Move-PCD-a multi-center longitudinal randomized controlled superiority trial on the effect of a 6-month individualized supported physical activity (PA) program on quality of life (QoL) in children, adolescents, and adults with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient's quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD. METHODS: To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23-7938; December 4, 2023). Recruitment start: March 2024. DISCUSSION: Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. STUDY PROTOCOL VERSION 10: Version 1.2; 12 June 2024.

Health-Related and Motor Performance-Related Fitness and Physical Activity Among Youth With Cystic Fibrosis.

Little is known about motor competence and the longitudinal development of motor performance among youth with cystic fibrosis (CF). In this study, we assessed aspects of motor performance in different age groups of young patients with CF and compared them with a healthy reference group of same aged children. We also examined the development of motor performance among different age groups of these children with CF, using The Deutscher Motorik Test (DMT) to assess attributes of health-related and motor performance-related fitness. We used an incremental ergometer cycle test to determine maximal exercise capacity (expressed as peak workload). We evaluated and recorded habitual physical activity (PA) as measured by the number of steps per day and the time spent in different PA intensities (expressed in metabolic equivalents). In total, 31 children and adolescents with CF agreed to participate (13 girls,18 boys) aged 6-17 years (M = 11.3, SD =3.3 years); they had a mean one second forced expiratory volume (expressed as a percentage of predicted value [% pred]) of 87.2% (SD = 22.3%). We found their values of health-related and motor performance-related fitness to be significantly lower (p < 0.05) than those of their healthy peer participants. In contrast to the reference group, participants with CF up to 14 years of age showed a linear improvement in these values and in their PA, followed by a plateau or even a nonsignificant decrease after age 14. These findings have important implications for the development and prescription of exercise programs for children with CF. Besides aerobic and strength exercises, we recommend that neuromuscular training be integrated into exercise programs to improve the coordinative abilities of youth with CF. More attention should be paid to vulnerable older adolescents to ensure their long-term motivation to maintain exercise participation.