Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention.

BACKGROUND: Impaired respiratory and intestinal microbiome composition is linked to cystic fibrosis lung disease severity. In people with cystic fibrosis (pwCF), regular exercise is recommended to delay disease progression and preserve a stable lung function. An optimal nutritional status is vital for best clinical outcomes. Our study investigated whether regular and monitored exercise and nutritional support promotes CF microbiome health. METHODS: A personalized nutrition and exercise program promoted nutritional intake and physical fitness in 18 pwCF for 12 months. Throughout the study, patients performed strength and endurance training monitored by a sports scientist via an internet platform. After three months, food supplementation with Lactobacillus rhamnosus LGG was introduced. Nutritional status and physical fitness were assessed before the study started, after three and nine months. Sputum and stool were collected, and microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: Sputum and stool microbiome composition remained stable and highly specific to each patient during the study period. Disease-associated pathogens dominated sputum composition. Lung disease severity and recent antibiotic treatment had the highest impact on taxonomic composition in stool and sputum microbiome. Strikingly, the long-term antibiotic treatment burden had only a minor influence. CONCLUSION: Despite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient. Dominant pathogens drove the composition and functionality of the microbiome. Further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of pwCF.

Prediction and prevention of allergic rhinitis: A birth cohort study of 20 years.

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases, usually starting in the first 2 decades of life. Information on predictors, risk, and protective factors is missing because of a lack of long-term prospective studies. OBJECTIVE: Our aim was to examine early-life environmental and lifestyle determinants for AR up to age 20 years. METHODS: In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated at 19 time points. A Cox regression model examined the associations between 41 independent early-life factors and onset of AR (as the primary outcome), including sensitization against aeroallergens and the secondary outcomes of nonallergic rhinitis and AR plus asthma. RESULTS: Two hundred ninety subjects had AR within 13,179 person years observed. The risk of AR was higher with a parental history of AR (adjusted hazard ratio [aHR], 2.49; 95% CI, 1.93-3.21), urticaria (aHR, 1.32; 95% CI, 1.00-1.74), or asthma (aHR, 1.29; 95% CI, 0.95-1.75). Early allergic sensitization (aHR, 4.53; 95% CI, 3.25-6.32), eczema within the first 3 years of life (aHR, 1.83; 95% CI, 1.38-2.42), male sex (aHR, 1.28; 95% CI, 1.02-1.61), and birthday in summer or autumn (aHR, 1.26; 95% CI, 1.00-1.58) were independent predictors of AR up to age 20 years. None of the other socioeconomic, environmental, lifestyle, pregnancy, and birth-related factors were associated with AR. CONCLUSION: Only nonmodifiable factors, particularly early allergic sensitization or eczema and parental AR, predicted AR up to age 20 years. No modifiable aspects of early-life environment or lifestyle were identified as targets for primary prevention.

Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS.

BACKGROUND: The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population-based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow-up data from two decades of a birth cohort study. METHODS: In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population-based MAS birth cohort study. The sample was purposely risk-enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow-up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema. RESULTS: Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0-22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3-9.0%) of those with non-allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7-16.2%) vs. 11.6% (95% CI, 8.9-14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2-28.5%) vs. 20.1% (95% CI, 16.6-24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre-puberty to adulthood. CONCLUSION: Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.

Early-life determinants of asthma from birth to age 20 years: a German birth cohort study.

BACKGROUND: The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. OBJECTIVE: We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. METHODS: In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). RESULTS: Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. CONCLUSION: Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

Feasibility and implementation of a personalized, web-based exercise intervention for people with cystic fibrosis for 1 year.

BACKGROUND: Regular participation in exercise is important for people with cystic fibrosis (CF). Therefore, we implemented a personalized, web-based exercise intervention over the course of one year for people with CF. The aims were to investigate the feasibility of the intervention and to evaluate changes in exercise participation, lung function, and exercise capacity. METHODS: In total, 11/17 participants [aged 12-52 years; FEV1%pred. 72.3 (SD: 17.3)] were included in the final data analysis. Every week, the participants received an individual training recommendation at the start and uploaded their training report on our website at the end of each week. The number of training minutes and sessions performed were analyzed over 13 four-week training sections. The participation in exercise (physical activity questionnaire), lung function and exercise capacity were assessed at baseline (T0), after 12 weeks (T1) and after 52 weeks (T2). RESULTS: A training duration of 178 min (SD: 75.5) and 3.3 (SD: 0.89) training sessions could be achieved weekly. In the first four-week training section, the participants performed 137.31 (SD: 95.7) minutes of training, with an increase of 42% in the third training section (195.01, SD: 134.99). Minutes of training reported on the questionnaire increased by 39.7% from T0 (179.38 min, SD: 120.9) to T1 (250.63 min, SD: 124.1) but decreased at T2 (166.88, SD: 155.4). There were slight decreases in lung function (FEV1 - 3.9%pred.; FVC - 1.9%pred.) and slight increases in exercise capacity (VO2peak + 1.5 ml/min/kg; six-minute-walk-test-distance + 26 m). Noticeably, five participants experienced deteriorations in their FEV1 of more than 5% but simultaneously experienced improvements in the parameters of exercise capacity of more than 5% throughout the year. CONCLUSIONS: The web-based concept was feasible for the participants over the course of a year and supported exercise participation. The improvement in exercise capacity due to increased exercise participation over a prolonged period of time, despite a decrease in lung function, should be further investigated. Finally, if integrated into usual care, this approach could facilitate the prescription of regular personalized exercise and promote exercise participation in the daily lives of people with CF.