Infants, children and adults born moderate-late preterm (after 30-36 weeks of pregnancy) are at increased risk of respiratory infections, wheezing and lower lung function leading to increased medication use and hospitalisation. Risk factors frequently present in this population are, at least in part, associated with (lack of) exposure to microbes and subsequent perturbations in microbiome and immune system development. This manuscript presents the protocol of the double-blinded randomised placebo-controlled PROTEA trial, which will demonstrate whether treatment with immunomodulatory bacterial lysates (OM-85) can reduce lower respiratory tract infections and wheeze in the first year of life. The follow-up PROTEA-2 trial will identify possible carry-over effects of OM-85 treatment and investigate the clinical effect of continued treatment in the second year of life. Infants included are otherwise healthy infants born after 30-36 weeks of gestation, excluding those small for gestational age (<3rd percentile). They are recruited shortly after birth in 22 medical centres in the Netherlands. Participants will take OM-85 or placebo starting from 6-10 weeks of life till age 1 year (PROTEA study) or 2 years (PROTEA-2 study) and are closely monitored regarding respiratory health through e-applications. Biological samples, lung function measurements and detailed information on covariates will be collected at ages 2, 6, 12 and 24 months. Biological samples will aid in estimating the impact of bacterial lysate administration on immune cell composition, activation and maturation, vaccination responses, and microbiome diversity and maturation. Participant recruitment started in March 2022.

Background: Recurrent wheezing (RW) is particularly prevalent in preschool-age children and is strongly associated with the future development of asthma. Objective: Because no meta-analysis of risk factors for RW comprehensively assess is needful. Methods: The research was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of English-language studies was performed across four medical literature data bases. Subgroup analyses, sensitivity analyses, and evaluations of publication bias were carried out. Multiple cohort studies were included. Stata software and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for data analysis; risk factors associated with positive results were discussed qualitatively. Results: A total of 15 cohort studies that covered 128,065 children were included. Some risk factors, including allergic rhinitis (odds ratio [OR] 4.16 [95% confidence interval {CI}, 1.06-16.33]), family history of asthma (OR 2.14 [95% CI, 1.24-3.69]), food allergy (OR 2.25 [95% CI, 1.73-2.93]), preterm (OR 1.87 [95% CI, 1.36-2.58]), male (OR 1.47 [95% CI, 1.17-1.84]), cesarean section (OR 1.36 [95% CI, 1.08-1.71]), environmental tobacco smoke (OR 2.15 [95% CI, 1.55-2.99]), got positive results. Conclusion: Risk factors for RW in preschool children were sought. This meta-analysis provides a new perspective theoretical basis for preventing childhood asthma.

To assess the association between gestational age at birth and the risk of growth failure and respiratory symptoms at 3 years of age.

Cohort study using the Japan Environment and Children's Study database.

A total of 86 158 singleton infants born without physical abnormalities at 32-41 weeks of gestation were enrolled between January 2011 and March 2014.

Growth failure (weight <10th percentile and height <10th percentile) and respiratory symptoms (asthma and wheezing) at 3 years of age.

Logistic regression analysis was used to evaluate the risk of growth failure and respiratory symptoms in the moderately preterm, late preterm and early term groups compared with the full-term group after adjusting for socioeconomic and perinatal factors. Multiple imputation was used to reduce the attrition bias related to missing data.

The respective adjusted ORs (95% CI) of growth failure and respiratory symptoms for the moderate preterm, late preterm and early term groups compared with the full-term group were as follows: weight <10th percentile, 2.29 (1.48-3.54), 1.43 (1.24-1.71) and 1.20 (1.12-1.28); height <10th percentile, 2.34 (1.59-3.45), 1.42 (1.25-1.60) and 1.15 (1.09-1.22); asthma, 1.63 (1.06-2.50), 1.21 (1.04-1.41) and 1.16 (1.09-1.23); and wheezing, 1.39 (1.02-1.90), 1.37 (1.25-1.51) and 1.11 (1.06-1.17).

Moderate preterm, late preterm and early term births were associated with a higher risk of growth failure and respiratory symptoms at 3 years of age than full-term births, with an inverse dose-response pattern.

Cervical auscultation, commonly used by speech-language pathologists in some countries as an adjuvant to the clinical feeding evaluation, requires data on acoustic and perceptual profiles of swallowing sounds. Whilst these exists in adults and children, none currently exist for preterm neonates. Our study aims to establish the acoustic and perceptual parameters of swallowing sounds in preterm neonates. Swallowing sounds were recorded on a digital microphone during oral feeding observations. Acoustic parameters of duration, peak frequency, peak power and peak intensity were determined. Perceptual parameters heard pre, during and post-swallows were rated as 'present', 'absent', or 'cannot be determined'. Eighty preterm neonates (43 males; mean age = 33.4 weeks [SD 2.6]) from three Australian special care nurseries demonstrated mean swallow durations of < 1 s. The peak amplitude correlated with the number of medical co-morbidities (r = 0.24; 95%CI 0.03-0.45). Most preterm neonates have coordinated swallows that are loud, quick and completed in < 1 s. The perceptual parameters of a bolus transit sound was consistently present in all preterm neonates. One in five pre-term neonates have an uncoordinated swallow where wheeze, stridor or wet breath sounds were present post-swallow. Our study provides clinicians with acoustic and perceptual parameters to guide use of cervical auscultation in special care nurseries. Future studies should consider simultaneous instrumental assessment to ensure validity when using cervical auscultation to support diagnostic decision-making on swallowing coordination.

It is essential to embed patient and public perspectives into every stage of the research journey, including setting the future research agenda. The substantial gaps in our understanding of prematurity-associated lung disease presented a timely opportunity to determine the community's research priorities.

To conduct a priority setting partnership (PSP) to determine the top 10 research priorities for preterm lung health.

We undertook a modified James Lind Alliance methodology comprising three main stages: (1) an idea generating survey with open questions to ascertain the community's most important ideas for future preterm lung health research, (2) prioritisation survey to distill the main themes into a shortlist of 20 and (3) consensus workshop where participants were tasked with ranking their final top 10. This PSP is reflective of the view of preterm-born individuals, parents of preterm children and healthcare professionals in an Australian healthcare setting.

We collated 144 submissions from the idea generating survey from which 27 prioritisation themes were developed. From the 150 prioritisation survey responses, the 20 themes receiving the most votes were taken to the consensus workshop. Participants identified the following top 10: (1) lifelong impacts; (2) interventions, treatments or supports; (3) ongoing lung health follow-up; (4) diagnostic tools, resources and education for primary healthcare providers; (5) resources to inform and empower families; (6) relationship to physical health and developmental issues; (7) preventing and/or treating lung infections; (8) additional supports, resources and research for minority groups; (9) impact on mental well-being; and (10) likelihood of asthma diagnosis.

Priorities identified through the PSP will be invaluable in informing future research into prematurity-associated lung disease.

Background and Objectives: The prevalence of stunted children under 5 years in Indonesia is relatively high. Stunting is a significant risk factor for wheezing disorders. The asthma predictive index (API) identifies children with a recurrent wheezing disorder at risk of developing asthma during the first 3 years. However, the risk of developing asthma and its associated factors among stunted children has not been studied. This study aims to determine the asthma risk prevalence in stunted children via the API score and associated factors. Materials and Methods: This cross-sectional study was conducted at the Bandung District Health Center from October 2021 to January 2022. This study included stunted children aged 24-59 months living in Bandung District whose parents could answer the API and asthma risk factor questionnaires. Results: A total of 422 participants with an average age of 43.1 ± 9.7 months were included. Among the stunted children, 4.7% (20/422) met the positive API criteria, and 50.0% were malnourished (stunted-underweight). The participants with positive API results had a parental medical diagnosis of asthma (45%), eczema (10.0%), allergic rhinitis (20.0%), and wheezing apart from colds (40.0%) (p < 0.05). Significant risk factors for developing asthma in the participants with a positive API were dog ownership in the past 12 months and parents and siblings with allergic diseases. Conclusions: The asthma risk prevalence in stunted children was 4.7%. The associated risk factors included a history of allergic diseases in parents and siblings, as well as dog ownership; however, further investigation is needed.

Particulate matter (PM) and contaminants attached to PM can increase the risk of respiratory diseases. However, the health risk assessment of chlorinated paraffins (CPs), an emerging pollutant occupying a high proportion of persistent organic pollutants (POPs) in PM, remains scarce. This study aimed to evaluate the association between PM2.5-bound CPs and asthma, along with relative symptoms, in school-aged children and adolescents. A large sample size cross-sectional study (n = 131,304) was conducted in the Pearl River Delta (PRD). The results showed that increased quantiles of ∑CPs were associated with odds ratios (ORs) of 1.22 (95%CI: 1.20-1.25), 1.38 (95%CI: 1.35-1.41), 1.17 (95%CI: 1.15-1.19), 1.52 (95%CI: 1.48-1.56), 1.66 (95%CI: 1.61-1.71), and 1.33 (95%CI: 1.30-1.37) for ever diagnosed asthma, current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough, respectively. Additionally, C11-, C12-SCCPs and C14-, C17-MCCPs contributed the most positive weight to the risk of asthma and relative symptoms. These findings provide cutting-edged evidence for the health risk assessment of CPs, which is crucial for developing effective CPs management strategy.

As wildfire frequency and severity increases, smoke exposures will cause increasingly more adverse respiratory effects. While acute respiratory effects of smoke exposure have been documented in children, longer term sequelae are largely unstudied. Our objective here was to examine the association between gestational and postnatal exposure to wildfire smoke and prolonged use of prescription medication for respiratory conditions in early childhood. Using Merative MarketScan claims data, we created cohorts of term children born in western states between 1 January 2010-31 December 2014 followed for at least three years. Using NOAA Hazard Mapping System data, we determined the average number of days a week that >25% of the population in a metropolitan statistical area (MSA) was covered by smoke within each exposure period. The exposure periods were defined by trimester and two 12 week postnatal periods. Medication use was based on respiratory indication (upper respiratory, lower respiratory, or any respiratory condition) and categorized into outcomes of prolonged use (⩾30 d use) (PU) and multiple prolonged uses (at least two prolonged uses) (MPU). We used logistic regression models with random intercepts for MSAs adjusted for child sex, birth season, and birth year. Associations differed by exposure period and respiratory outcome, with elevated risk of MPU of lower respiratory medications following exposure in the third trimester and the first 12 postnatal weeks (RR 1.15, 95% CI 0.98, 1.35; RR 1.21, 95% CI 1.05, 1.40, respectively). Exposure in the third trimester was associated with an increase in MPU of any respiratory among males infants only (male RR 1.22, 95% CI 1.00, 1.50; female RR 0.93, 95% CI 0.66, 1.31). Through novel use of prescription claims data, this work identifies critical developmental windows in the 3rd trimester and first 12 postnatal weeks during which environmental inhalational disaster events may impact longer-term respiratory health.

Preterm birth (PTB) is a leading cause of neonatal mortality. However, evidence on mortality beyond the neonatal period is limited, especially in North America.

To examine associations of PTB with all-cause and cause-specific mortality from birth through 23 to 36 years of age.

This population-based matched cohort study of live births in Canada included individuals born between January 1, 1983, and December 31, 1996, and followed up until December 31, 2019. Data were analyzed from June 1, 2023, to April 30, 2024.

PTBs, between 24 and 37 weeks' gestation (with gestational age [GA]-specific subcategories of 24 to 27 weeks, 28 to 31 weeks, 32 to 33 weeks, and 34 to 36 weeks) compared with term births (37-41 weeks' gestation).

All-cause mortality and cause-specific mortality were the main outcomes. Risk differences (RDs) and risk ratios (RRs) were estimated for all-cause mortality using log-binomial regressions and hazard ratios were estimated for cause-specific mortality using Cox proportional hazards regression models (censoring individuals who died from other causes) within prespecified age intervals (ages 0-11 months and ages 1-5, 6-12, 13-17, 18-28, and 29-36 years). Observed confounding was accounted for using coarsened exact matching on baseline characteristics.

Of 4 998 560 births (54.2% male), 6.9% were born preterm (with GA-specific subcategories of 0.3% born at 24-27 weeks, 0.6% at 28-31 weeks, 0.8% at 32-33 weeks, and 5.1% at 34-36 weeks). During a median of 29 years of follow-up, 72 662 individuals died (14 312 born preterm and 58 350 at term). PTB was associated with an increased risk of death in all age intervals, with the highest RDs and RRs from birth through infancy (ages 0-11 months) (RD, 2.29% [95% CI, 2.23%-2.35%]; RR, 11.61 [95% CI, 11.09-12.15]) and in early childhood (ages 1-5 years) (RD, 0.34% [95% CI, 0.31%-0.36%]; RR, 2.79 [95% CI, 2.61-2.98]) and the lowest RDs and RRs among those between ages 18 and 28 years (RD, 0.07% [95% CI, 0.04%-0.10%]; RR, 1.13 [95% CI, 1.07-1.19]). We identified increased risks of mortality associated with several causes, including respiratory, circulatory, and digestive system disorders; nervous system, endocrine, and infectious diseases; cancers; congenital malformations; and conditions originating in the perinatal period. No associations were found for external causes of deaths. Associations by GA categories suggested lower risks with higher GA.

The findings of this population-based matched cohort study suggest that individuals born preterm were at an increased risk of death from birth until their third and fourth decades of life, with higher risks as GA decreased. Some of these associations may have been partly due to underlying health determinants that affected PTB and mortality. These findings suggest that PTB should be recognized as a risk factor for mortality and could inform preventive strategies.

Moderate-late preterm-born infants experience more frequent and severe respiratory tract infections and wheezing compared to term-born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. Until now, moderate-late preterm infants are underrepresented in research and mechanisms underlying their morbidity are largely unknown, although they represent 80% of all preterm-born infants. In order to protect these infants effectively, it is essential to understand the role of the immune system in early life respiratory health and to identify strategies to optimize immune development and respiratory health. This review elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm-born infants, exploring their impact on the immune system and microbiome. Factors discussed are early life antibiotic use, birth mode, feeding type and living environment. Further, differences in adaptive and innate immune maturation between term and preterm infants are discussed, as well as differences in local immune reactions in the lungs. Finally, preventative strategies are being explored, including microbiota transplantation, immune modulation (through pre-, pro-, syn- and postbiotics, bacterial lysates, vaccinations, and monoclonal antibodies) and antibiotic prophylaxis.

Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function.

We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV1) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Standardised mean differences in FEV1 and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies' FEV1 effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework.

We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV1 than controls (-0.58 sd, 95% CI -0.69- -0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4-3.4) for abnormal outcome, with high certainty of evidence. FEV1 was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R2=36-96%).

This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence.

Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing.

A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression.

Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers.

Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Both interpregnancy intervals (IPI) and environmental factors might contribute to low birth weight (LBW). However, the extent to which air pollution influences the effect of IPIs on LBW remains unclear. We aimed to investigate whether IPI and air pollution jointly affect LBW.

A retrospective cohort study was designed in this study. The data of birth records was collected from the Jiangsu Maternal Child Information System, covering January 2020 to June 2021 in Nantong city, China. IPI was defined as the duration between the delivery date for last live birth and date of LMP for the subsequent birth. The maternal exposure to ambient air pollutants during pregnancy-including particulate matter (PM) with an aerodynamic diameter of ≤ 2.5 μm (PM2.5), PM10, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)-was estimated using a hybrid kriging-LUR-RF model. A novel air pollution score was proposed, assessing combined exposure to five pollutants (excluding CO) by summing their concentrations, weighted by LBW regression coefficients. Multivariate logistic regression models were used to estimate the effects of IPI, air pollution and their interactions on LBW. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP) and synergy index (S) were utilized to assess the additive interaction.

Among 10, 512 singleton live births, the LBW rate was 3.7%. The IPI-LBW risk curve exhibited an L-shaped pattern. The odds ratios (ORs) for LBW for each interquartile range increase in PM2.5, PM10, O3 and the air pollution score were 1.16 (95% CI: 1.01-1.32), 1.30 (1.06-1.59), 1.22 (1.06-1.41), and 1.32 (1.10-1.60) during the entire pregnancy, respectively. An additive interaction between IPI and PM2.5 was noted during the first trimester. Compared to records with normal IPI and low PM2.5 exposure, those with short IPI and high PM2.5 exposure had the highest risk of LBW (relative risk = 3.53, 95% CI: 1.85-6.49, first trimester).

The study demonstrates a synergistic effect of interpregnancy interval and air pollution on LBW, indicating that rational birth spacing and air pollution control can jointly improve LBW outcomes.

Moderate-to-late preterm infants constitute the majority within the preterm infant population. Most research on preterm infants has focused on very preterm children, often treating moderate-to-late preterm infants as similar to full-term infants. Our objective was to compare clinical, respiratory, cardio-metabolic and neurodevelopmental outcomes in adolescents aged 12-15 years born moderate and late preterm with a control group of the same age born full-term.

Observational cross-sectional study, comparing moderate-to-late preterm (32-36+6 weeks' gestational age) with full-term adolescents (37-41+6 weeks' gestational age; 75 each group). Perinatal and neonatal history were collected as well as data on respiratory evolution (ISAAC questionnaire for asthma symptoms for adolescents 13-14 years), anthropometric values, learning difficulties, behavioral test (screening questionnaire for high-performance autism spectrum disorder and evaluation test for attention deficit hyperactivity disorder), skin prick test, pulmonary function test, echocardiogram and blood pressure. A blood test with metabolic profile was conducted.

Moderate-to-late preterm adolescents had more current asthma [p = 0.008, OR3 (95% CI 1.26-7.14)] and longer duration of combined treatments to control asthma (inhaled corticosteroids and anti-leukotrienes; p = 0.048). Forced vital capacity <80% was detected more often in moderate-to-late preterm patients (p = 0.013). When assessing right ventricle, moderate-to-late preterm adolescents showed better tricuspid annular plane systolic excursion z-score (p = 0.003), shortening fraction (p < 0.001) and E/A ratio z-score (p = 0.002). Regarding left ventricular assessment, moderate-to-late preterm group had smaller ventricle diastolic diameter (p = 0.04) and lower posterior wall z-score values (p = 0.037). They also showed a better S'wave z-score (p = 0.027), E wave (p = 0.005), E/A ratio (p = 0.003) and a higher septal myocardial performance index z-score (p = 0.025). Moderate-to-late preterm adolescents presented lower weight z-score (p = 0.039), body mass index z-score (p = 0.013), Waterlow weight index (p = 0.006) and higher undernutrition index [p = 0.04; OR 1.4 (95% CI 1-1.9)]. Although there were no differences in neurodevelopmental survey or behavioral tests.

Our findings underscore the importance of extended follow-up for this predominant group of premature infants to identify potential respiratory, cardiac and anthropometric issues that may emerge in the future.

Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes.

Investigating asthma as an effect modifier between adverse birth outcomes and neurodevelopmental disabilities (NDDs) across different races is crucial for tailored interventions and understanding variable susceptibility among diverse populations.

Data were collected through the National Survey of Children's Health. This cross-sectional study included 131,774 children aged 0 to 17 years. Study exposures comprised adverse birth outcomes including preterm birth and low birth weight. Weighted prevalence estimates and odds ratios with 95% confidence intervals (CIs) among children with and without adverse birth outcomes were calculated for NDDs including attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, seizure, and several others including behavior problems. Adjusted odds ratios were stratified by asthma status and separate interactions were assessed for each outcome.

Of 131,774 participants, 10,227 were born low birth weight (9.12%; 95% CI: 8.77% to 9.49%), 14,058 were born preterm (11.35%; 95% CI: 10.94% to 11.76%), and 16,166 participants had asthma (11.97%; 95% CI: 11.58% to 12.37%). There were 68,100 males (51.11%), 63,674 females (48.89%), 102,061 non-Hispanic Whites (NHW) (66.92%), 8,672 non-Hispanic Blacks (NHB) (13.97%), and 21,041 participants (19.11%) categorized as other. NHB children with adverse birth outcomes had higher prevalence of several NDDs compared to NHW children.

Asthma was not shown to be an effect modifier of the association between adverse birth outcomes and NDDs. Nevertheless, these results suggest that NDDs are more prevalent within US children with adverse birth outcomes, with higher rates among NHB compared to NHW children. These findings support screening for NDDs in pediatric health care settings among patients with adverse birth outcomes, particularly among those from ethnic minority backgrounds.

Supplemental O2 (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O2), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O2 during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O2. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O2 and these data highlight the importance of neonatal sex in understanding airway disease.

Microbiota in early life is closely associated with the health of infants, especially premature ones. Probiotics are important drivers of gut microbiota development in preterm infants; however, there is no consensus regarding the characteristics of specific microbiota in preterm infants receiving probiotics. In this study, we performed a meta-analysis of 5 microbiome data sets (1816 stool samples from 706 preterm infants) to compare the gut microbiota of preterm infants exposed to probiotics with that of preterm infants not exposed to probiotics across populations. Despite study-specific variations, we found consistent differences in gut microbial composition and predicted functional pathways between the control and probiotic groups across different cohorts of preterm infants. The enrichment of Acinetobacter, Bifidobacterium, and Lactobacillus spp and the depletion of the potentially pathogenic bacteria Finegoldia, Veillonella, and Klebsiella spp. were the most consistent changes in the gut microbiota of preterm infants supplemented with probiotics. Probiotics drove microbiome transition into multiple preterm gut community types, and notably, preterm gut community type 3 had the highest α-diversity, with enrichment of Bifidobacterium and Bacteroides spp. At the functional level, the major predicted microbial pathways involved in peptidoglycan biosynthesis consistently increased in preterm infants supplemented with probiotics; in contrast, the crucial pathways associated with heme biosynthesis consistently decreased. Interestingly, Bifidobacterium sp. rather than Lactobacillus sp. gradually became dominant in gut microbiota of preterm infants using mixed probiotics, although both probiotic strains were administered at the same dosage. Taken together, our meta-analysis suggests that probiotics contribute to reshaping the microbial ecosystem of preterm infants at both the taxonomic and functional levels of the bacterial community. More standardized and relevant studies may contribute to better understanding the crosstalk among probiotics, the gut microbiota, and subsequent disease risk, which could help to give timely nutritional feeding guidance to preterm infants. This systematic review and meta-analysis was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) as CRD42023447901.

Not all wheeze is "asthma" in those born very preterm. Further work is needed to better understand the aetiology of prematurity-associated lung disease and the best treatments for this population. https://bit.ly/3Tko3vi.

Respiratory disease is one of the most common complications of preterm birth. Survivors of prematurity have increased risks of morbidities and mortalities independent of prematurity, and frequently require multiple medications, home respiratory support, and subspecialty care to maintain health. Although advances in neonatal and pulmonary care have improved overall survival, earlier gestational age, lower birth weight, chorioamnionitis and late onset sepsis continue to be major factors in the development of bronchopulmonary dysplasia. These early life events associated with prematurity can have respiratory consequences that persist into adulthood. Furthermore, after initial hospital discharge, air pollution, respiratory tract infections and socioeconomic status may modify lung growth trajectories and influence respiratory outcomes in later life. Given that the incidence of respiratory disease associated with prematurity remains stable or increased, there is a need for pediatric and adult providers to be familiar with the natural history, manifestations, and common complications of disease.

Childhood bronchial asthma (BA) is a chronic inflammatory respiratory disease. Nutritional conditions, including zinc deficiency, can affect such allergic disorders.

To outline the difference in serum zinc levels between asthmatic children and healthy controls.

A cross-sectional study was carried out at Children's Hospital, Cairo University, investigating serum zinc levels in children with BA (n = 40) and healthy children (n = 21). Other markers included serum ferritin, iron, hemoglobin (Hb), and immunoglobulin E (IgE) levels. Independent t-tests and Mann-Whinny tests were used for comparisons. The Kruskal-Wallis test was applied to compare serum ferritin and IgE levels with regard to asthma severity. Spearman's rank correlation was performed to explore the relationship between serum ferritin levels and both iron and Hb levels in asthmatic children.

Children with BA had higher levels of zinc, yet the difference was not significant (P = 0.115). Serum ferritin and IgE levels were significantly higher in asthmatic children (P = 0.006 and 0.001, respectively), yet their levels did not differ significantly by severity (P = 0.623 and 0.126, respectively). There was a nonsignificant weak correlation between serum ferritin levels and both serum iron and Hb levels.

Serum zinc levels do not seem to differ between asthmatic children and healthy children. Serum ferritin levels may be a marker of asthma control. Serum IgE levels are not markers of asthma severity.

Schools are in a unique position to address social determinants of health (SDOHs) in pediatric asthma management because of their potential to provide resources and facilitate collaboration with health care providers and services for children at risk within their community. SDOHs include economic factors, educational attainment and health literacy, neighborhood factors and the built environment, social and community aspects including discrimination and racism, and health care access and quality. These factors have a significant impact on asthma health in children, and certain populations such as minoritzed populations and those living in high-poverty environments have been shown to be at greater risk for adverse effects of SDOHs on asthma outcomes. School-based asthma programs address several SDOHs including health literacy, the built environment, and health care quality and access and have been shown to improve asthma outcomes. Key components include connection between the school and the health care team, self-management education, and directly observed therapy. School nurses play a key role in directing and managing effective programs because they can evaluate and support a student's health while considering the effect of SDOHs at interpersonal, institutional, community, and policy levels.

Pakistan is one of most vulnerable low- and middle-income countries with 29 million adult active tobacco users. Smoking cessation services are lacking as the tobacco control initiatives have largely failed to address the smoking endemic. Over the last 5 years, Pakistan has witnessed the use of innovative tobacco harm reduction (THR) products such as e-cigarettes and nicotine pouches. However, their use remains limited. THR products are imported legally as consumer goods and are taxable. The lack of sufficient data for THR and its application is a challenge in gauging their effectiveness in assisting smokers quit combustible smoking. Evidence-based studies can help in measuring the effectiveness of e-cigarettes and nicotine pouches as smoking cessation aids.

Keeping in view the study objectives, a sample size of 600 participants will be sufficient to assess the effectiveness of e-cigarettes and nicotine pouches for smoking cessation in Pakistan. Of these, 200 participants each will receive e-cigarettes and nicotine pouches along with basic care counselling, while the remaining 200 participants will only receive basic care counselling for 48 weeks. The association of participants' characteristics with smoking and health status will be based on the bivariate and multivariate analysis. The simple t-test and variance analysis will assess the differences in intervention indicators between the control and treatment groups. For the inferential analysis, the average treatment impact will be based on the quasi-experimental techniques such as difference in difference (DID) or propensity score matching (PMS).

The study will evaluate the participants at the baseline as they decide the quit date. After every 12 weeks, a follow-up survey with the participants will be conducted. Results are anticipated to inform the public, decision-makers, and researchers about the effects of using e-cigarettes and nicotine pouches in the short- and medium-term periods. Critically, the potential of e-cigarettes and other alternative nicotine delivery systems as smoking cessation aid will be assessed.

ClinicalTrials.gov NCT05715164 . Registered on February 6, 2023.

Protocol version 1.0, 14-12-2022 Trial in progress and not yet recruiting participants. Estimated primary data collection date-April 2024.

Supplemental O2 remains a necessary intervention for many premature infants (<34 wk gestation). Even moderate hyperoxia (<60% O2) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contributes to impaired bronchodilation and remodeling (proliferation, altered extracellular matrix). Understanding mechanisms by which O2 initiates long-term airway changes in prematurity is critical for therapeutic advancements for wheezing disorders and asthma in babies and children. Immature or dysfunctional antioxidant systems in the underdeveloped lungs of premature infants thereby heightens susceptibility to oxidative stress from O2. The novel gasotransmitter hydrogen sulfide (H2S) is involved in antioxidant defense and has vasodilatory effects with oxidative stress. We previously showed that exogenous H2S exhibits bronchodilatory effects in human developing airway in the context of hyperoxia exposure. Here, we proposed that exogenous H2S would attenuate effects of O2 on airway contractility, thickness, and remodeling in mice exposed to hyperoxia during the neonatal period. Using functional [flexiVent; precision-cut lung slices (PCLS)] and structural (histology; immunofluorescence) analyses, we show that H2S donors mitigate the effects of O2 on developing airway structure and function, with moderate O2 and H2S effects on developing mouse airways showing a sex difference. Our study demonstrates the potential applicability of low-dose H2S toward alleviating the detrimental effects of hyperoxia on the premature lung.NEW & NOTEWORTHY Chronic airway disease is a short- and long-term consequence of premature birth. Understanding effects of O2 exposure during the perinatal period is key to identify targetable mechanisms that initiate and sustain adverse airway changes. Our findings show a beneficial effect of exogenous H2S on developing mouse airway structure and function with notable sex differences. H2S donors alleviate effects of O2 on airway hyperreactivity, contractility, airway smooth muscle thickness, and extracellular matrix deposition.

Premature infants have an increased risk of respiratory morbidity, including the development of recurrent wheezing. We sought to determine perinatal factors in late preterm infants associated with an increased risk of recurrent wheezing in the first 3 years of life.

A retrospective chart review of infants born between 32 and 36 weeks gestational age at a tertiary hospital from 2013 to 2016 was performed. Infants with any co-morbid medical conditions were excluded. Recurrent wheezing was identified by two or more visit diagnoses for reactive airway disease, wheezing-associated respiratory infection, wheezing, or asthma during the first 3 years of life. Those with recurrent wheezing were compared to matched preterm infants who did not develop wheezing.

Three hundred and fourteen late preterm infants were included in this study; 210 infants developed recurrent wheezing while 104 did not. Gender, sex, and race were comparable between both groups. Development of wheezing was associated with positive family history of asthma (p = .014), receiving antibiotics during the neonatal period (p < .001), requiring continuous positive airway pressure for <24 h (p = .019), and receiving supplemental oxygen during the newborn period (p = .023).

This study retrospectively identified risk factors associated with development of wheezing in late preterm infants. Prospective studies are needed to determine whether these factors will predict recurrent wheeze in this patient population.

Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) from a mine fire, background PM2.5, and allergic sensitisation later in childhood.

We measured specific immunoglobulin E (IgE) levels for seven common aeroallergens as well as total IgE levels in a cohort of children who had been exposed to the Hazelwood coal mine fire, either in utero or during their first two years of life, in a regional area of Australia where ambient levels of PM2.5 are generally low. We estimated personal exposure to fire-specific emissions of PM2.5 based on a high-resolution meteorological and pollutant dispersion model and detailed reported movements of pregnant mothers and young children during the fire. We also estimated the usual background exposure to PM2.5 at the residential address at birth using a national satellite-based land-use regression model. Associations between both sources of PM2.5 and sensitisation to dust, cat, fungi, and grass seven years after the fire were estimated with logistic regression, while associations with total IgE levels were estimated with linear regression.

No association was found between the levels of exposure at either developmental stage to fire-related PM2.5 and allergic sensitisation seven years after the event. However, levels of background exposure were positively associated with sensitisation to dust (OR = 1.90, 95%CI = 1.12,3.21 per 1 μg/m3).

Chronic but low exposure to PM2.5 in early life could be more strongly associated with allergic sensitisation in childhood than time-limited high exposure levels, such as the ones experienced during landscape fires.

Size at birth, an indicator of intrauterine growth, has been studied extensively in relation to subsequent health, growth and developmental outcomes. Our umbrella review synthesises evidence from systematic reviews and meta-analyses on the effects of size at birth on subsequent health, growth and development in children and adolescents up to age 18, and identifies gaps.

We searched five databases from inception to mid-July 2021 to identify eligible systematic reviews and meta-analyses. For each meta-analysis, we extracted data on the exposures and outcomes measured and the strength of the association.

We screened 16 641 articles and identified 302 systematic reviews. The literature operationalised size at birth (birth weight and/or gestation) in 12 ways. There were 1041 meta-analyses of associations between size at birth and 67 outcomes. Thirteen outcomes had no meta-analysis.Small size at birth was examined for 50 outcomes and was associated with over half of these (32 of 50); continuous/post-term/large size at birth was examined for 35 outcomes and was consistently associated with 11 of the 35 outcomes. Seventy-three meta-analyses (in 11 reviews) compared risks by size for gestational age (GA), stratified by preterm and term. Prematurity mechanisms were the key aetiologies linked to mortality and cognitive development, while intrauterine growth restriction (IUGR), manifesting as small for GA, was primarily linked to underweight and stunting.

Future reviews should use methodologically sound comparators to further understand aetiological mechanisms linking IUGR and prematurity to subsequent outcomes. Future research should focus on understudied exposures (large size at birth and size at birth stratified by gestation), gaps in outcomes (specifically those without reviews or meta-analysis and stratified by age group of children) and neglected populations.

CRD42021268843.

To assess the association between birth weight and childhood asthma risk using data from the 2019-2020 National Survey of Children's Health database.

Cross-sectional study.

The USA.

A representative cohort of American children.

The exposure of this study was birth weight regardless of gestational age. Birth weight was divided into three groups: <1500 g, 1500-2500 g and >2500 g.

Primary outcomes were parent-reported diagnosis of asthma.

The Rao-Scott χ2 test was used to compare the groups. The main analyses examined the association between birth weight and parent-report asthma in children using univariable and multivariable logistic models adjusting for preterm birth, age, sex, race, family poverty, health insurance, smoking, maternal age. Subgroup analysis was performed based on interaction test.

A total of 60 172 children aged 3-17 years were enrolled in this study; of these, 5202 (~8.6%) had asthma. Children with asthma were more likely to be born preterm, with low birth weight (LBW) or very LBW (VLBW). The incidence of asthma was the highest in VLBW children at 20.9% and showed a downward trend with an increase in birth weight class, with rates of 10.7% and 8.1% in the LBW and normal birthweight groups, respectively. Children with VLBW (OR 1.97; 95% CI 1.29 to 3.01) had higher odds of developing asthma in the adjusted analysis model. However, VLBW was only shown to be a risk factor for asthma among Hispanics, black/African-Americans and children between the ages of 6 and 12 years, demonstrating racial and age disparities.

VLBW increases the risk of childhood asthma; however, racial and age disparities are evident.

The past decades have seen markedly improved survival of increasingly immature preterm infants, yet major health complications persist. This is particularly true for bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, which has become the most common sequelae of prematurity and a significant predictor of respiratory morbidity throughout childhood as well as adult life, neurodevelopmental disability, cardiovascular disease, and even death. The need for novel approaches to reduce BPD and related complications of prematurity has never been more critical. Thus, despite major advances in the use of antenatal steroids, surfactant therapy, and improvements in respiratory support, there is a persistent need for developing therapeutic strategies that more specifically reflect our growing understanding of BPD in the post-surfactant age, or the "new BPD." In contrast with the severe lung injury leading to marked fibroproliferative disease from the past, the "new BPD" is primarily characterized by an arrest of lung development as related to more extreme prematurity. This distinction and the continued high incidence of BPD and related sequelae suggest the need to identify therapies that target critical mechanisms that support lung growth and maturation in conjunction with treatments to improve respiratory outcomes across the lifespan. As the prevention of BPD and its severity remains a primary goal, we highlight the concept from preclinical and early clinical observations that insulin-like growth factor 1 (IGF-1) can potentially support the natural sequence of lung growth as a replacement therapy after preterm birth. Data supporting this hypothesis are robust and include observations that low IGF-1 levels persist after extremely preterm birth in human infants and strong preclinical data from experimental models of BPD highlight the therapeutic benefit of IGF-1 in reducing disease. Importantly, phase 2a clinical data in extremely premature infants where replacement of IGF-1 with a human recombinant human IGF-1 complexed with its main IGF-1 binding protein 3, significantly reduced the most severe form of BPD, which is strongly associated with multiple morbidities that have lifelong consequences. As physiologic replacement therapy of surfactant heralded the success of reducing acute respiratory distress syndrome in preterm infants, the paradigm has the potential to become the platform for discovering the next generation of therapies like IGF-1, which becomes deficient after extremely premature birth where endogenous production by the infant is not sufficient to maintain the physiologic levels adequate to support normal organ development and maturation.

The use of respiratory support strategies such as continuous positive airway pressure in premature infants can substantially stretch highly compliant perinatal airways, leading to airway hyperreactivity and remodeling in the long term. The mechanisms by which stretch detrimentally affects the airway are unknown. Airway smooth muscle cells play a critical role in contractility and remodeling. Using 18-22-wk gestation human fetal airway smooth muscle (fASM) as an in vitro model, we tested the hypothesis that mechanosensitive Piezo (PZ) channels contribute to stretch effects. We found that PZ1 and PZ2 channels are expressed in the smooth muscle of developing airways and that their expression is influenced by stretch. PZ activation via agonist Yoda1 or stretch results in significant [Ca2+]i responses as well as increased extracellular matrix production. These data suggest that functional PZ channels may play a role in detrimental stretch-induced airway changes in the context of prematurity.NEW & NOTEWORTHY Piezo channels were first described just over a decade ago and their function in the lung is largely unknown. We found that piezo channels are present and functional in the developing airway and contribute to intracellular calcium responses and extracellular matrix remodeling in the setting of stretch. This may improve our understanding of the mechanisms behind development of chronic airway diseases, such as asthma, in former preterm infants exposed to respiratory support, such as continuous positive airway pressure (CPAP).

The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes.

Participants aged 6-23 born ≤32 (N = 288; 132 with bronchopulmonary dysplasia) and ≥37 weeks' gestation (N = 76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400 μg salbutamol was classified according to published criteria.

A BDR was identified in 30.9% (n = 85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k = 0.26; 95% confidence interval [CI] 0.18-0.40, p < .001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs. 11%, p = .010) and baseline resistance (Rrs5 z-score mean difference (MD) = 0.86, 95% CI 0.07-1.65, p = .025), but similar baseline spirometry to the group without a BDR (forced expiratory volume in 1 s [FEV1 ] z-score MD = -0.01, 95% CI -0.66 to 0.68, p > .999). Oscillometry was more feasible than spirometry (95% success rate vs. 85% (FEV1 ), 69% (forced vital capacity) success rate, p < .001), however being born preterm did not affect test feasibility.

In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to those measured by spirometry, and thus these tests should not be used interchangeably.

Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD).

We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas.

This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma.

Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, -0.021; 95% CI, -0.031 to -0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005).

Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

The Spanish Guideline on the Management of Asthma, better known by its acronym in Spanish GEMA, has been available for more than 20 years. Twenty-one scientific societies or related groups both from Spain and internationally have participated in the preparation and development of the updated edition of GEMA, which in fact has been currently positioned as the reference guide on asthma in the Spanish language worldwide. Its objective is to prevent and improve the clinical situation of people with asthma by increasing the knowledge of healthcare professionals involved in their care. Its purpose is to convert scientific evidence into simple and easy-to-follow practical recommendations. Therefore, it is not a monograph that brings together all the scientific knowledge about the disease, but rather a brief document with the essentials, designed to be applied quickly in routine clinical practice. The guidelines are necessarily multidisciplinary, developed to be useful and an indispensable tool for physicians of different specialties, as well as nurses and pharmacists. Probably the most outstanding aspects of the guide are the recommendations to: establish the diagnosis of asthma using a sequential algorithm based on objective diagnostic tests; the follow-up of patients, preferably based on the strategy of achieving and maintaining control of the disease; treatment according to the level of severity of asthma, using six steps from least to greatest need of pharmaceutical drugs, and the treatment algorithm for the indication of biologics in patients with severe uncontrolled asthma based on phenotypes. And now, in addition to that, there is a novelty for easy use and follow-up through a computer application based on the chatbot-type conversational artificial intelligence (ia-GEMA).

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm birth survivors characterized by inflammation, impaired alveolarization and dysmorphic vasculature. Activated IL-17A+ lymphocytes are key drivers of inflammation in preterm infants. We have shown that in immature mice chronic airway exposure to lipopolysaccharide (LPS) induces pulmonary inflammation, increased IL-17a expression, and hypoalveolarization, a BPD-like phenotype. The source of IL-17a and contribution to lung pathology is unknown. The natural-killer group 2, member D (NKG2D) receptor mediates activation and IL-17a production in γδ T cells by binding to stress molecules. LPS induces NKG2D ligand expression, including Rae-1 and MULT1. We hypothesized that IL-17a+ γδ T cells and NKG2D signaling mediate neonatal LPS-induced lung injury. Immature C57BL/6J (wild type), Nkg2d-/- or Tcrd-/- (lacking γδ T cells) mice were inoculated with 3ug/10ul of LPS from E. coli O26:B6 or 10ul of PBS intranasally on day of life 3, 5, 7, and 10. Selected mice were treated with neutralizing antibodies against IL-17a, or NKG2D intraperitoneally. Lung immune cells were assessed by flow cytometry and gene expression was analyzed by qPCR. Alveolar growth was assessed by lung morphometry. We established that anti-IL-17a antibody treatment attenuated LPS-induced hypoalveolarization. We found that LPS induced the fraction of IL-17a+NKG2D+ γδ T cells, a major source of IL-17a in the neonatal lung. LPS also induced lung mRNA expression of NKG2D, Rae-1, MULT1, and the DNA damage regulator p53. Anti-NKG2D treatment attenuated the effect of LPS on γδ T cell IL-17a expression, immune cell infiltration and hypoalveolarization. LPS-induced hypoalveolarization was also attenuated in Nkg2d-/- and Tcrd-/- mice. In tracheal aspirates of preterm infants IL-17A and its upstream regulator IL-23 were higher in infants who later developed BPD. Also, human ligands of NKG2D, MICA and MICB were present in the aspirates and MICA correlated with median FiO2. Our novel findings demonstrate a central role for activated IL-17a+ γδ T cells and NKG2D signaling in neonatal LPS-induced lung injury. Future studies will determine the role of NKG2D ligands and effectors, other NKG2D+ cells in early-life endotoxin-induced lung injury and inflammation with a long-term goal to understand how inflammation contributes to BPD pathogenesis.

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.