Long-term outcomes of early exposure to repeated general anaesthesia in children with cystic fibrosis (CF-GAIN): a multicentre, open-label, randomised controlled phase 4 trial.

BACKGROUND: Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. METHODS: This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. FINDINGS: At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. INTERPRETATION: Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. FUNDING: National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland.

Circadian variation in muscle force output in males using isokinetic, isometric dynamometry: can we observe this in multi-joint movements using the muscleLab force-velocity encoder and are they similar in peak and magnitude?

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (Trec, Tm) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s-1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, Trec and Tm were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for Trec and Tm at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (p < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

Region-Specific Phosphorylation Determines Neuroligin-3 Localization to Excitatory Versus Inhibitory Synapses.

BACKGROUND: Neuroligin-3 is a postsynaptic adhesion molecule involved in synapse development and function. It is implicated in rare, monogenic forms of autism, and its shedding is critical to the tumor microenvironment of gliomas. While other members of the neuroligin family exhibit synapse-type specificity in localization and function through distinct interactions with postsynaptic scaffold proteins, the specificity of neuroligin-3 synaptic localization remains largely unknown. METHODS: We investigated the synaptic localization of neuroligin-3 across regions in mouse and human brain samples after validating antibody specificity in knockout animals. We raised a phospho-specific neuroligin antibody and used phosphoproteomics, cell-based assays, and in utero CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) knockout and gene replacement to identify mechanisms that regulate neuroligin-3 localization to distinct synapse types. RESULTS: Neuroligin-3 exhibits region-dependent synapse specificity, largely localizing to excitatory synapses in cortical regions and inhibitory synapses in subcortical regions of the brain in both mice and humans. We identified specific phosphorylation of cortical neuroligin-3 at a key binding site for recruitment to inhibitory synapses, while subcortical neuroligin-3 remained unphosphorylated. In vitro, phosphomimetic mutation of that site disrupted neuroligin-3 association with the inhibitory postsynaptic scaffolding protein gephyrin. In vivo, phosphomimetic mutants of neuroligin-3 localized to excitatory postsynapses, while phospho-null mutants localized to inhibitory postsynapses. CONCLUSIONS: These data reveal an unexpected region-specific pattern of neuroligin-3 synapse specificity, as well as a phosphorylation-dependent mechanism that regulates its recruitment to either excitatory or inhibitory synapses. These findings add to our understanding of how neuroligin-3 is involved in conditions that may affect the balance of excitation and inhibition.

Rapid modeling of an ultra-rare epilepsy variant in wild-type mice by in utero prime editing.

Generating animal models for individual patients within clinically-useful timeframes holds great potential toward enabling personalized medicine approaches for genetic epilepsies. The ability to rapidly incorporate patient-specific genomic variants into model animals recapitulating elements of the patient's clinical manifestations would enable applications ranging from validation and characterization of pathogenic variants to personalized models for tailoring pharmacotherapy to individual patients. Here, we demonstrate generation of an animal model of an individual epilepsy patient with an ultra-rare variant of the NMDA receptor subunit GRIN2A, without the need for germline transmission and breeding. Using in utero prime editing in the brain of wild-type mice, our approach yielded high in vivo editing precision and induced frequent, spontaneous seizures which mirrored specific elements of the patient's clinical presentation. Leveraging the speed and versatility of this approach, we introduce PegAssist, a generalizable workflow to generate bedside-to-bench animal models of individual patients within weeks. The capability to produce individualized animal models rapidly and cost-effectively will reduce barriers to access for precision medicine, and will accelerate drug development by offering versatile in vivo platforms to identify compounds with efficacy against rare neurological conditions.

Enhancing Precision and Efficiency of Cas9-Mediated Knockin Through Combinatorial Fusions of DNA Repair Proteins.

Cas9 targets genomic loci with high specificity. For knockin with double-strand break repair, however, Cas9 often leads to unintended on-target knockout rather than intended edits. This imprecision is a barrier for direct in vivo editing where clonal selection is not feasible. In this study, we demonstrate a high-throughput workflow to comparatively assess on-target efficiency and precision of editing outcomes. Using this workflow, we screened combinations of donor DNA and Cas9 variants, as well as fusions to DNA repair proteins. This yielded novel high-performance double-strand break repair editing agents and combinatorial optimizations, yielding increases in knockin efficiency and precision. Cas9-RC, a novel fusion Cas9 flanked by eRad18 and CtIP[HE], increased knockin performance in vitro and in vivo in the developing mouse brain. Continued comparative assessment of editing efficiency and precision with this framework will further the development of high-performance editing agents for in vivo knockin and future genome therapeutics.

Effects of treatment dosage of whole-body cryotherapy upon post-match recovery of endocrine and biochemical markers in elite rugby league players: An experimental study.

Background and Aims: The use of whole-body cryotherapy (WBC) for athletic recovery is becoming increasingly popular despite the lack of evidence supporting the dosage parameters in its implementation. The aim of the current study was to investigate the dose-response effects of WBC following match-play in elite rugby league players. Methods: We observed endocrine (salivary cortisol and testosterone) and biochemical (creatine kinase) responses following three separate post-match recovery periods in elite rugby league players. Comparisons were made between a single exposure (3 min at -120°C to --135°C) of WBC to two consecutive exposures (2 × 3 min), to a control (no exposure) during the recovery trials. Recovery characteristics were measured 36 h prematch, immediately postmatch, and 60 h postmatch. Results: Cortisol concentrations remained unchanged in its pattern of response during the postmatch recovery periods across all WBC doses. Testosterone concentrations increased significantly (p < 0.0005) at 60 h, in the WBC2 trial. The Testosterone:Cortisol ratio increased significantly (p < 0.0005) at 60 h in the WBC2 trial, while during the WBC0 trial it did not recover to baseline levels. No significant effect on creatine kinase concentration was observed, although a statistical trend was shown in WBC2 for improved reduction of this marker at 60 h. Conclusions: These findings suggest that two, consecutive exposures to WBC immediately following fatiguing rugby league competition appear to stimulate an increase to the anabolic endocrine profile of participants by 60 h post-match, and may reduce the CK concentration. Coaches and athletes should consider the treatment dosage of WBC when used to optimize the desired response following a high-stress environment.

Brain capillary pericytes are metabolic sentinels that control blood flow through a KATP channel-dependent energy switch.

Despite the abundance of capillary thin-strand pericytes and their proximity to neurons and glia, little is known of the contributions of these cells to the control of brain hemodynamics. We demonstrate that the pharmacological activation of thin-strand pericyte KATP channels profoundly hyperpolarizes these cells, dilates upstream penetrating arterioles and arteriole-proximate capillaries, and increases capillary blood flow. Focal stimulation of pericytes with a KATP channel agonist is sufficient to evoke this response, mediated via KIR2.1 channel-dependent retrograde propagation of hyperpolarizing signals, whereas genetic inactivation of pericyte KATP channels eliminates these effects. Critically, we show that decreasing extracellular glucose to less than 1 mM or inhibiting glucose uptake by blocking GLUT1 transporters in vivo flips a mechanistic energy switch driving rapid KATP-mediated pericyte hyperpolarization to increase local blood flow. Together, our findings recast capillary pericytes as metabolic sentinels that respond to local energy deficits by increasing blood flow to neurons to prevent energetic shortfalls.

A machine learning analysis of drought and rural population change on the North American Great Plains since the 1970s.

Machine learning techniques have to date not been widely used in population-environment research, but represent a promising tool for identifying relationships between environmental variables and population outcomes. They may be particularly useful for instances where the nature of the relationship is not obvious or not easily detected using other methods, or where the relationship potentially varies across spatial scales within a given study unit. Machine learning techniques may also help the researcher identify the relative strength of influence of specific variables within a larger set of interacting ones, and so provide a useful methodological approach for exploratory research. In this study, we use machine learning techniques in the form of random forest and regression tree analyses to look for possible connections between drought and rural population loss on the North American Great Plains between 1970 and 2020. In doing so, we analyzed four decades of population count data (at county-size spatial scales), monthly climate data, and Palmer Drought Severity Index scores for Canada and the USA at multiple spatial scales (regional, sub-regional, national, and county/census division levels), along with county level irrigation data. We found that in some parts of Saskatchewan and the Dakotas - particularly those areas that fall within more temperate/less arid ecological sub-regions - drought conditions in the middle years of the 1970s had a significant association with rural population losses. A similar but weaker association was identified in a small cluster of North Dakota counties in the 1990s. Our models detected few links between drought and rural population loss in other decades or in other parts of the Great Plains. Based on R-squared results, models for US portions of the Plains generally exhibited stronger drought-population loss associations than did Canadian portions, and temperate ecological sub-regions exhibited stronger associations than did more arid sub-regions. Irrigation rates showed no significant influence on population loss. This article focuses on describing the methodological steps, considerations, and benefits of employing this type of machine learning approach to investigating connections between drought and rural population change. Supplementary Information: The online version contains supplementary material available at 10.1007/s11111-022-00399-9.

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis.

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life. METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017. RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score. CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.

Are rugby league players involved in more tackles than normal, prior to an injury sustained during a tackle event?

Rugby league has a relatively high injury risk, with the tackle having the greatest injury propensity. The number of tackles players engage in, prior to injurious tackles may influence injury risk, which has yet to be investigated. Therefore, this study investigated if rugby league players are involved in more tackles (as either tackler or ball carrier) (i) in the 10 minutes, or (ii) 1-min periods prior to an injurious tackle-event, (iii) differences for ball carriers vs. tacklers, and (iv) forwards vs. backs. Video analysis was utilised to quantify the number and rate of tackles in the 10-min periods prior to 61 tackle-related injuries. One thousand two hundred and eighty 10-min periods where players were not injured, were used as matched-controls. Generalized mixed linear models were used to analyse mean total and rate for tackles. Injured players were involved in significantly fewer tackles during the 10-min period, yet significantly more tackles during the final minute prior to the injurious tackle-event, compared to non-injured players. There were no differences between ball carriers vs. tacklers during the 10-min period. Both injured position groups were involved in significantly more tackles in the final minute. Additional match data sources are needed to further inform injury preventive strategies of tackle events.

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4.

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

Reducing asthma hospitalisations in at-risk children: A systematic review.

AIM: To identify interventions that reduce hospitalisations and improve related outcomes in children at risk of asthma hospital admissions. METHODS: Medline, Embase, Pubmed and Cochrane Library search from January 2002 to April 2020. INCLUSION CRITERIA: randomised controlled trials of any intervention for children with asthma who are at risk of hospitalisations. OUTCOMES: hospitalisation (primary outcome), rescue oral corticosteroid use, school absences, quality of life and cost-effectiveness. RESULTS: Twelve randomised controlled trials were conducted with 2719 participants. Due to heterogeneity of interventions and reporting of outcomes, a meta-analysis was not conducted. Multi-modal interventions comprising caregiver education, reduction of home environmental allergens and regular follow-up reduced hospitalisations, rescue corticosteroid use and improved quality of life. Cost-effectiveness was not reported. Three studies scored an overall low risk of bias, and nine had some concerns. CONCLUSION: Multi-modal interventions can be effective in reducing hospitalisations, rescue oral corticosteroid use and quality of life but cost-effectiveness is unknown.

Coaches, parents, or peers: Who has the greatest influence on sports participants' life skills development?

This study investigated the relationships between the coach, parent, and peer motivational climate and participants' life skills development in youth sport. In total, 308 participants (Mage = 14.67, SD = 2.20) completed a survey assessing the motivational climate (mastery and ego) and their life skills development in sport (teamwork, goal setting, social skills, emotional skills, problem solving and decision making, leadership, time management, and interpersonal communication). Multiple regression analyses found that a peer-created mastery-climate had the strongest positive associations with all eight life skills and total life skills. Coach and parent mastery-oriented climates were also positively related to five of the life skills and total life skills. A parent-created ego-climate had the strongest negative association with all life skills except for goal setting; whereas, a coach-created ego-climate was negatively related to three life skills and total life skills. Contrary to expectations, a peer-created ego-climate was positively associated with three life skills and total life skills. In practice, these novel results suggest that peers have the greatest positive influence on participants' life skills development in sport and all three social agents should be encouraged to create a mastery-climate to help promote participants' life skills development.

E-Learning in Teaching Emergency Disaster Response Among Undergraduate Medical Students in Malaysia.

Introduction: Teaching disaster response medicine (DRM) to medical students requires considerable resources. We evaluate the effectiveness of e-learning in teaching emergency disaster response (ELITE-DR), a novel initiative, in educating medical students of the cognitive aspect of DRM. Methods: A prospective cross-sectional study among pre-clinical year medical students was carried out to determine their knowledge on DRM and perception regarding the ELITE-DR initiative using a validated online questionnaire. A three-part self-learning video covering the principles and medical management of DRM were distributed before answering the questionnaire served as the training. Results: A total of 168 students participated in the study. Their overall knowledge showed a significant increase in between pre-and-post-interventions. Recall and simple decision-making knowledge aspects were better than complex decision-making knowledge. It appeared that participants assimilate knowledge better from visual rather than audio stimuli. Participants with high perception-scores demonstrated better knowledge-scores. However, e-learning was not preferred as a substitute for face-to-face (F2F) teaching. Conclusion: ELITE-DR shows promise in teaching DRM. Simple recall and comprehension levels of knowledge were well-served through this technique. However, for more complex decision-making knowledge, a different approach might be required. ELITE-DR offers flexibility, accessibility, and personalized learning. The content presentation is improved by using several different visual stimuli. This approach is useful for cognitive aspect learning, but it should not replace standard F2F teaching.

COVID-19 and complicated bacterial pneumonia in children.

Social distancing measures instituted due to #SARSCoV2 have dramatically reduced paediatric thoracic empyema cases in Australia https://bit.ly/3akG98M.

The sensitivity of countermovement jump, creatine kinase and urine osmolality to 90-min of competitive match-play in elite English Championship football players 48-h post-match.

Purpose: Examine changes from 90-minutes of competitive match-play in countermovement jump (CMJ), creatine kinase (CK) and urine osmolality (Uosm) in elite football players over a season and their association to match external load.Methods: Eighteen footballers participated. CMJ, CK and Uosm were collected 24-h pre-match and 48-h post-match. Match-performance data was examined using Prozone®.Results: Post-match CK concentrations increased 49% (ES:0.66), while CMJ flight-time (FT), flight-time:contraction time ratio (FT:CT), take-off velocity (TV) and average power (AP) decreased 2.4-7.4% post-match (ES:0.39-0.63). CMJ height post-match reduced 4.2% (ES:0.35). CMJ FT and AP showed associations with high intensity distance covered (HID), high intensity number (HIN), explosive sprints (EXS) and medium intensity accelerations (r= -0.395 to -0.496). Changes in CMJ FT also displayed associations to total sprint distance (TSD), total sprint number (TSN) and medium intensity decelerations (r = -0.395-0.446). Increases in CMJ CT were associated with HIN (r=0.39), and CMJ AF with HIN, EXS and medium accelations/decelerations (r= -0.397 to 0.459) completed during the match.Conclusion: CMJ outputs from the push-off phase and countermovement phase were sensitive to change in neuromuscular fatigue. CK concentrations were sensitive to the match-play demands. This helps practitioners determine player readiness and has implications for individual recovery strategies.

Sleep and the athlete: narrative review and 2021 expert consensus recommendations.

Elite athletes are particularly susceptible to sleep inadequacies, characterised by habitual short sleep (<7 hours/night) and poor sleep quality (eg, sleep fragmentation). Athletic performance is reduced by a night or more without sleep, but the influence on performance of partial sleep restriction over 1-3 nights, a more real-world scenario, remains unclear. Studies investigating sleep in athletes often suffer from inadequate experimental control, a lack of females and questions concerning the validity of the chosen sleep assessment tools. Research only scratches the surface on how sleep influences athlete health. Studies in the wider population show that habitually sleeping <7 hours/night increases susceptibility to respiratory infection. Fortunately, much is known about the salient risk factors for sleep inadequacy in athletes, enabling targeted interventions. For example, athlete sleep is influenced by sport-specific factors (relating to training, travel and competition) and non-sport factors (eg, female gender, stress and anxiety). This expert consensus culminates with a sleep toolbox for practitioners (eg, covering sleep education and screening) to mitigate these risk factors and optimise athlete sleep. A one-size-fits-all approach to athlete sleep recommendations (eg, 7-9 hours/night) is unlikely ideal for health and performance. We recommend an individualised approach that should consider the athlete's perceived sleep needs. Research is needed into the benefits of napping and sleep extension (eg, banking sleep).

Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort.

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.