European Respiratory Society Statement on preschool wheezing disorders: updated definitions, knowledge gaps, and proposed future research directions.

Since the publication of the European Respiratory Society (ERS) Task Force reports on the management of preschool wheezing in 2008 and 2014, a large body of evidence has accumulated suggesting the clinical phenotypes that were proposed, episodic (viral) wheezing and multiple-trigger wheezing, do not relate to underlying airway pathology and may not help determine response to treatment. Specifically, using clinical phenotypes alone may no longer be appropriate, and new approaches that can be used to inform clinical care are needed for future research. This ERS Task Force reviewed the literature published after 2008 related to preschool wheezing and has suggested the criteria used to define wheezing disorders in preschool children should include age of diagnosis (0 to <6 years), confirmation of wheezing on at least one occasion, and more than one episode of wheezing ever.Furthermore, diagnosis and management may be improved by identifying treatable traits, including inflammatory biomarkers (blood eosinophils, aeroallergen sensitisation) associated with type-2 immunity and differential response to inhaled corticosteroids, lung function parameters, and airway infection. However, more comprehensive use of biomarkers/treatable traits in predicting the response to treatment requires prospective validation. There is evidence that specific genetic traits may help guide management, but these must be adequately tested. In addition, the Task Force identified an absence of caregiver-reported outcomes, caregiver/self-management options, and features that should prompt specialist referral for this age group. Priorities for future research include a focus on identifying i) mechanisms driving preschool wheezing, ii) biomarkers of treatable traits and efficacy of interventions in those without allergic sensitisation/eosinophilia, iii) the need to include both objective outcomes and caregiver-reported outcomes in clinical trials, iv) the need for a suitable action plan for children with preschool wheezing and v) a definition of severe/difficult-to-treat preschool wheezing.

Mental health, sleep, and respiratory health after initiating elexacaftor/tezacaftor/ivacaftor treatment in children with cystic fibrosis.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function but its effect on mental health and sleep remains poorly understood. We report on mental health, sleep, and respiratory health outcomes of adolescents with CF commenced on ETI therapy, and monitored the prevalence of neuropsychiatric issues through the coronavirus disease 2019 pandemic. METHODS: We conducted a prospective longitudinal study of 31 adolescents (aged 10-18 years) from July 2021 to October 2022. Data collected include demographics, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC) scores, and FEV1 percent predicted. Twenty of 31 adolescents had data before and after ETI initiation. Mean differences (MD) in mental health, sleep, and respiratory health pre- and post-ETI therapy commencement were estimated using paired t-tests. The prevalence and trajectories of anxiety, depression, and sleep disturbance were described between the ETI epochs, and over the pandemic period. RESULTS: FEV1 improved following ETI therapy commencement (MD, 95% confidence interval [CI]: 7.1% (4.7%-9.6%) whereas PHQ-9, GAD-7, PDSS, and SDSC scores did not change significantly. Ten percent of participants developed new-onset anxiety/depression concerns and 10% developed new sleep concerns following ETI initiation. CONCLUSION: This is the first prospective longitudinal study of mental health and sleep changes after ETI commencement in adolescents with CF. Although respiratory outcomes improved, ETI did not improve anxiety, depression or sleep.

Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children.

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

The longitudinal microbial and metabolic landscape of infant cystic fibrosis: the gut-lung axis.

BACKGROUND AND AIM: In cystic fibrosis, gastrointestinal dysfunction and lower airway infection occur early and are independently associated with poorer outcomes in childhood. This study aimed to define the relationship between the microbiota at each niche during the first 2 years of life, its association with growth and airway inflammation, and explanatory features in the metabolome. MATERIALS AND METHODS: 67 bronchoalveolar lavage fluid (BALF), 62 plasma and 105 stool samples were collected from 39 infants with cystic fibrosis between 0 and 24 months who were treated with prophylactic antibiotics. 16S rRNA amplicon and shotgun metagenomic sequencing were performed on BALF and stool samples, respectively; metabolomic analyses were performed on all sample types. Sequencing data from healthy age-matched infants were used as controls. RESULTS: Bacterial diversity increased over the first 2 years in both BALF and stool, and microbial maturation was delayed in comparison to healthy controls from the RESONANCE cohort. Correlations between their respective abundance in both sites suggest stool may serve as a noninvasive alternative for detecting BALF Pseudomonas and Veillonella. Multisite metabolomic analyses revealed age- and growth-related changes, associations with neutrophilic airway inflammation, and a set of core systemic metabolites. BALF Pseudomonas abundance was correlated with altered stool microbiome composition and systemic metabolite alterations, highlighting a complex gut-plasma-lung interplay and new targets with therapeutic potential. CONCLUSION: Exploration of the gut-lung microbiome and metabolome reveals diverse multisite interactions in cystic fibrosis that emerge in early life. Gut-lung metabolomic links with airway inflammation and Pseudomonas abundance warrant further investigation for clinical utility, particularly in non-expectorating patients.

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease.

Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary [bronchoalveolar lavage (BAL)] and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different from controls. We showed these endotypes are measurable in a clinical setting and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across pediatric wheeze and chronic suppurative lung disease that, if validated in future studies, have the potential to inform clinical management.

QuantiFERON Gold-In-Tube for the diagnosis of mycobacterial tuberculosis infection in children under 5 years of age: A systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis regarding the performance of QuantiFERON Gold-In-Tube in children have yielded contrasting results. Emerging data in children younger than 5 years of age necessitates a new analysis. METHODS: Systematic searches were conducted of MedLINE, EMBASE and Cochrane databases between 1998-2023. Pooled estimates of sensitivities and specificities of QFT-GIT compared to tuberculin skin test (TST) were calculated. The Kappa (k) coefficient was calculated for each study to determine the degree of congruence between TST and QFT-GIT results. Studies including patients co-infected with HIV or other immune compromising conditions or those treated with anti-tubercular treatment were excluded. RESULTS: Seventeen studies (4335 patients) were included in quantitative analysis. All studies were conducted in middle to high income countries. They were conducted across 14 countries and 4 studies in countries with high TB incidence. The pooled sensitivity, specificity and DOR were 0.45 (0.42-0.48), 0.96 (0.96-0.97) and 18.84 (7.33-48.41) respectively. The ability of QFT-GIT to discriminate with disease and no disease was "good" as demonstrated by a summary receiver operating characteristic curve with area under curve of 0.7812. The average Kappa (k) co-efficient was 0.501 with a wide variety of values between studies (0.167 to 0.800). CONCLUSION: The findings of this meta-analysis support the judicious use of QFT-GIT in children 5 years and under, with caution as a sole test to exclude Tuberculosis in this age group. The heterogeneity and methodological quality of diagnostic studies limits the generalisability of results.

Benchmarking single-cell hashtag oligo demultiplexing methods.

Sample multiplexing is often used to reduce cost and limit batch effects in single-cell RNA sequencing (scRNA-seq) experiments. A commonly used multiplexing technique involves tagging cells prior to pooling with a hashtag oligo (HTO) that can be sequenced along with the cells' RNA to determine their sample of origin. Several tools have been developed to demultiplex HTO sequencing data and assign cells to samples. In this study, we critically assess the performance of seven HTO demultiplexing tools: hashedDrops, HTODemux, GMM-Demux, demuxmix, deMULTIplex, BFF (bimodal flexible fitting) and HashSolo. The comparison uses data sets where each sample has also been demultiplexed using genetic variants from the RNA, enabling comparison of HTO demultiplexing techniques against complementary data from the genetic 'ground truth'. We find that all methods perform similarly where HTO labelling is of high quality, but methods that assume a bimodal count distribution perform poorly on lower quality data. We also suggest heuristic approaches for assessing the quality of HTO counts in an scRNA-seq experiment.

Wearing masks as a protective measure for children against traffic-related air pollution: A comparison of perceptions between school children and their caregivers in Ho Chi Minh City, Vietnam.

BACKGROUND: Traffic-related air pollution (TRAP) problems are unlikely to be solved in the short term, making it imperative to educate children on protective measures to mitigate the negative impact on their health. Children and their caregivers may hold differing views on wearing a face mask as a safeguard against air pollution. While many studies have focused on predicting children's health-protective behaviours against air pollution, few have explored the differences in perceptions between children and their caregivers. OBJECTIVES: To examine this, we conducted a study that compared the health beliefs of two generations and evaluated the factors that influence the use of masks by children to reduce air pollution exposure. METHODS: The study was conducted in 24 secondary schools and involved 8420 children aged 13-14 and their caregivers. We used a Health Belief Model (HBM)-based instrument containing 17-item self-administered health beliefs questionnaires to gather data. The results were analysed using hierarchical logistic regression to determine the probability of children frequently wearing masks to protect against TRAP. RESULTS: Our study showed both children and caregivers recognised that several factors could influence mask-wearing among children: discomfort or difficulty breathing while wearing a mask and forgetting to bring a mask when going outside; perceived threats of the poor quality of air and children's respiratory health problems; and cues to mask use (i.e., seeing most of their friends wearing facemasks and ease of finding masks in local stores). However, only children were significantly concerned with public perception of their appearance while wearing a mask. Females were more likely to wear masks, and caregivers with higher levels of education were more likely to encourage their children to wear masks. Children who commuted to schools by walking, biking, or motorbiking were also more accepting of mask-wearing than those who travelled by car or bus. CONCLUSIONS: Children and their caregivers hold different perceptions of wearing masks to protect against air pollution. Children are more susceptible to social judgements regarding their appearance when wearing a mask.

Infant food allergy phenotypes and association with lung function deficits and asthma at age 6 years: a population-based, prospective cohort study in Australia.

BACKGROUND: Food allergy is considered a precursor to asthma in the context of the atopic march, but the relationship between infant food allergy phenotypes and lung function and asthma in childhood is unclear. We aimed to examine the association between food sensitisation and challenge-confirmed food allergy in infancy, as well as persistent and resolved food allergy up to age 6 years, and the risk of lung function deficits and asthma at age 6 years. METHODS: The longitudinal, population-based HealthNuts cohort study in Melbourne, VIC, Australia, recruited 5276 infants children aged 1 year who attended council-run immunisation sessions between Sept 28, 2007, and Aug 5, 2011. At age 1 year, all children completed skin prick testing to four food allergens (egg, peanut, sesame, and either shrimp or cow's milk) and an oral food challenge (egg, peanut, and sesame) at the Royal Children's Hospital in Melbourne. Parents completed questionnaires about their infant's allergy history, demographic characteristics, and environmental exposures. At age 6 years, children were invited for a health assessment that included skin prick testing for ten foods (milk, egg, peanut, wheat, sesame, soy, shrimp, cashew, almond, and hazelnut) and eight aeroallergens (alternaria, cladasporum, house dust mite, cat hair, dog hair, bermuda grass, rye grass, and birch mix), oral food challenges, and lung function testing by spirometry. Questionnaires completed by parents (different to those completed at age 1 year) captured the child's allergy and respiratory history and demographics. We investigated associations between food allergy phenotypes (food-sensitised tolerance or food allergy; and ever, transient, persistent, or late-onset food allergy), lung function spirometry measures (forced expiratory volume in 1 sec [FEV1] and forced vital capacity [FVC] z-scores, FEV1/FVC ratio, forced expiratory flow at 25% and 75% of the pulmonary volume [FEF25-75%], and bronchodilator responsiveness), and asthma using regression methods. Only children with complete data on the exposure, outcome, and confounders were included in models. Infants without food sensitisation or food allergy at age 1 year and 6 years served as the reference group. FINDINGS: Of 5276 participants, 3233 completed the health assessment at age 6 years and were included in this analysis. Food allergy, but not food-sensitised tolerance, at age 1 year was associated with reduced FEV1 and FVC (aß -0·19 [95% CI -0·32 to -0·06] and -0·17 [-0·31 to -0·04], respectively) at age 6 years. Transient egg allergy was associated with reduced FEV1 and FVC compared with never having egg allergy (-0·18 [95% CI -0·33 to -0·03] and -0·15 [-0·31 to 0·00], respectively), whereas persistent egg allergy was not (FEV1 -0·09 [-0·48 to 0·31]; FVC -0·20 [-0·62 to 0·21]). Transient peanut allergy was associated with reduced FEV1 and FVC (FEV1 aß -0·37 [-0·79 to 0·04] and FVC aß -0·55 [-0·98 to -0·12]), in addition to persistent peanut allergy (FEV1 aß -0·30 [-0·54 to -0·06] and FVC aß-0·30 [-0·55 to -0·05]), and late-onset peanut allergy (FEV1 aß -0·62 [-1·06 to -0·18] and FVC aß-0·49 [-0·96 to -0·03]). Estimates suggested that food-sensitised tolerance and food allergy were associated with reduced FEF25-75%, although some estimates were imprecise. Food allergy phenotypes were not associated with an FEV1/FVC ratio. Late-onset peanut allergy was the only allergy phenotype that was possibly associated with increased risk of bronchodilator responsiveness (2·95 [95% CI 0·77 to 11·38]). 430 (13·7%) of 3135 children were diagnosed with asthma before age 6 years (95% CI 12·5-15·0). Both food-sensitised tolerance and food allergy at age 1 year were associated with increased asthma risk at age 6 years (adjusted odds ratio 1·97 [95% CI 1·23 to 3·15] and 3·69 [2·81 to 4·85], respectively). Persistent and late-onset peanut allergy were associated with higher asthma risk (3·87 [2·39 to 6·26] and 5·06 [2·15 to 11·90], respectively). INTERPRETATION: Food allergy in infancy, whether it resolves or not, is associated with lung function deficits and asthma at age 6 years. Follow-up studies of interventions to prevent food allergy present an opportunity to examine whether preventing these food allergies improves respiratory health. FUNDING: National Health & Medical Research Council of Australia, Ilhan Food Allergy Foundation, AnaphylaxiStop, the Charles and Sylvia Viertel Medical Research Foundation, the Victorian Government's Operational Infrastructure Support Program.

Telehealth use in Australian cystic fibrosis centers: Clinician experiences.

BACKGROUND: Telehealth has been rapidly adopted by cystic fibrosis (CF) centers and ongoing use in routine CF care is endorsed by CF consumers. However, data describing CF clinician perceptions regarding telehealth are scarce. We aimed to describe clinician experiences and attitudes towards telehealth in CF care among health professionals across Australia. METHODS: CF multidisciplinary health professionals from all CF clinics in Australia were sent an anonymous electronic survey. RESULTS: Eighty-five responses were received representing 15 of 23 (65%) centers. Most clinicians reported using telehealth for routine clinic visits, and a range of other clinical encounters (69.9%). Telehealth was widely perceived as acceptable (91.8%), and clinicians were comfortable/very comfortable (81.2%) integrating telehealth into future CF care. Despite this, 64.1% of respondents considered telehealth clinics to be much worse than face-to-face clinics and 57.5% reported quality of care was somewhat/much worse using telehealth. Home spirometry was available in 73.7% of centers, however, only 26.7% of clinics could provide spirometers for >75% eligible patients. Growth and microbiology assessments were often missed in telehealth clinics and 75.7% reported a technical issue had prevented a telehealth consultation from occurring. CONCLUSIONS: Telehealth for CF in Australia is considered feasible and acceptable by CF clinicians, although use of telehealth varies widely between centers. Concerns exist around the impact of telehealth on health outcomes, especially given core assessments are frequently omitted. Guidelines may help ensure the benefits of telehealth are realized for people with CF without compromising the standard of care.

Substrate-dependent metabolomic signatures of myeloperoxidase activity in airway epithelial cells: Implications for early cystic fibrosis lung disease.

Myeloperoxidase (MPO) is released by neutrophils in inflamed tissues. MPO oxidizes chloride, bromide, and thiocyanate to produce hypochlorous acid (HOCl), hypobromous acid (HOBr), and hypothiocyanous acid (HOSCN), respectively. These oxidants are toxic to pathogens, but may also react with host cells to elicit biological activity and potential toxicity. In cystic fibrosis (CF) and related diseases, increased neutrophil inflammation leads to increased airway MPO and airway epithelial cell (AEC) exposure to its oxidants. In this study, we investigated how equal dose-rate exposures of MPO-derived oxidants differentially impact the metabolome of human AECs (BEAS-2B cells). We utilized enzymatic oxidant production with rate-limiting glucose oxidase (GOX) coupled to MPO, and chloride, bromide (Br-), or thiocyanate (SCN-) as substrates. AECs exposed to GOX/MPO/SCN- (favoring HOSCN) were viable after 24 h, while exposure to GOX/MPO (favoring HOCl) or GOX/MPO/Br- (favoring HOBr) developed cytotoxicity after 6 h. Cell glutathione and peroxiredoxin-3 oxidation were insufficient to explain these differences. However, untargeted metabolomics revealed GOX/MPO and GOX/MPO/Br- diverged significantly from GOX/MPO/SCN- for dozens of metabolites. We noted methionine sulfoxide and dehydromethionine were significantly increased in GOX/MPO- or GOX/MPO/Br--treated cells, and analyzed them as potential biomarkers of lung damage in bronchoalveolar lavage fluid from 5-year-olds with CF (n = 27). Both metabolites were associated with increasing bronchiectasis, neutrophils, and MPO activity. This suggests MPO production of HOCl and/or HOBr may contribute to inflammatory lung damage in early CF. In summary, our in vitro model enabled unbiased identification of exposure-specific metabolite products which may serve as biomarkers of lung damage in vivo. Continued research with this exposure model may yield additional oxidant-specific biomarkers and reveal explicit mechanisms of oxidant byproduct formation and cellular redox signaling.

Telehealth in Cystic Fibrosis. A systematic review incorporating a novel scoring system and expert weighting to identify a 'top 10 manuscripts' to inform future best practices implementation.

The ongoing development and integration of telehealth within CF care has been accelerated in response to the Covid-19 pandemic, with many centres publishing their experiences. Now, as the restrictions of the pandemic ease, the use of telehealth appears to be waning, with many centres returning to routine traditional face-to-face services. For most, telehealth is not integrated into clinical care models, and there is a lack of guidance on how to integrate such a service into clinical care. The aims of this systematic review were to first identify manuscripts which may inform best CF telehealth practices, and second, to analyse these finding to determine how the CF community may use telehealth to improve care for patients, families, and Multidisciplinary Teams into the future. To achieve this, the PRISMA review methodology was utilised, in combination with a modified novel scoring system that consolidates expert weighting from key CF stakeholders, allowing for the manuscripts to be placed in a hierarchy in accordance with their scientific robustness. From the 39 found manuscripts, the top ten are presented and further analysed. The top ten manuscripts are exemplars of where telehealth is used effectively within CF care at this time, and demonstrate specific use cases of its potential best practices. However, there is a lack of guidance for implementation and clinical decision making, which remains an area for improvement. Thus, it is suggested that further work explores and provides guidance for standardised implementation into CF clinical practice.

Gut microbiota maturity mediates the protective effect of siblings on food allergy.

BACKGROUND: The mechanisms underlying the protective effect of older siblings on allergic disease remain unclear but may relate to the infant gut microbiota. OBJECTIVE: We sought to investigate whether having older siblings decreases the risk of IgE-mediated food allergy by accelerating the maturation of the infant gut microbiota. METHODS: In a birth cohort assembled using an unselected antenatal sampling frame (n = 1074), fecal samples were collected at 1 month, 6 months, and 1 year, and food allergy status at 1 year was determined by skin prick test and in-hospital food challenge. We used 16S rRNA gene amplicon sequencing to derive amplicon sequence variants. Among a random subcohort (n = 323), microbiota-by-age z scores at each time point were calculated using fecal amplicon sequence variants to represent the gut microbiota maturation over the first year of life. RESULTS: A greater number of siblings was associated with a higher microbiota-by-age z score at age 1 year (ß  = 0.15 per an additional sibling; 95% CI, 0.05-0.24; P = .003), which was in turn associated with decreased odds of food allergy (odds ratio, 0.45; 95% CI, 0.33-0.61; P < .001). Microbiota-by-age z scores mediated 63% of the protective effect of siblings. Analogous associations were not observed at younger ages. CONCLUSIONS: The protective effect of older siblings on the risk of developing IgE-mediated food allergy during infancy is substantially mediated by advanced maturation of the gut microbiota at age 1 year.

Virtual monitoring in CF - the importance of continuous monitoring in a multi-organ chronic condition.

Cystic Fibrosis (CF) is a chronic life-limiting condition that affects multiple organs within the body. Patients must adhere to strict medication regimens, physiotherapy, diet, and attend regular clinic appointments to manage their condition effectively. This necessary but burdensome requirement has prompted investigations into how different digital health technologies can enhance current care by providing the opportunity to virtually monitor patients. This review explores how virtual monitoring has been harnessed for assessment or performance of physiotherapy/exercise, diet/nutrition, symptom monitoring, medication adherence, and wellbeing/mental-health in people with CF. This review will also briefly discuss the potential future of CF virtual monitoring and some common barriers to its current adoption and implementation within CF. Due to the multifaceted nature of CF, it is anticipated that this review will be relevant to not only the CF community, but also those investigating and developing digital health solutions for the management of other chronic diseases.