More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers.

BACKGROUND: The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking). METHODS: A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants. RESULTS: After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking. CONCLUSIONS: Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers' QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.

A one-step method for generating antimicrobial nanofibre meshes via coaxial electrospinning.

Respiratory diseases, including influenza, infectious pneumonia, and severe acute respiratory syndrome (SARS), are a leading cause of morbidity and mortality worldwide. The recent COVID-19 pandemic claimed over 6.9 million lives globally. With the possibility of future pandemics, the creation of affordable antimicrobial meshes for protective gear, such as facemasks, is essential. Electrospinning has been a focus for much of this research, but most approaches are complex and expensive, often wasting raw materials by distributing antiviral agents throughout the mesh despite the fact they can only be active if at the fibre surface. Here, we report a low cost and efficient one-step method to produce nanofibre meshes with antimicrobial activity, including against SARS-CoV-2. Cetrimonium bromide (CTAB) was deposited directly onto the surface of polycaprolactone (PCL) fibres by coaxial electrospinning. The CTAB-coated samples have denser meshes with finer nanofibres than non-coated PCL fibres (mean diameter: ∼300 nm versus ∼900 nm, with mean pore size: ∼300 nm versus > 600 nm). The formulations have > 90% coating efficiency and exhibit a burst release of CTAB upon coming into contact with aqueous media. The CTAB-coated materials have strong antibacterial activity against Staphylococcus aureus (ca. 100%) and Pseudomonas aeruginosa (96.5 ± 4.1%) bacteria, as well as potent antiviral activity with over 99.9% efficacy against both respiratory syncytial virus and SARS-CoV-2. The CTAB-coated nanofibre mesh thus has great potential to form a mask material for preventing both bacterial and viral respiratory infections.

A manifesto for improving cancer detection: four key considerations when implementing innovations across the interface of primary and secondary care.

Improving cancer outcomes through innovative cancer detection initiatives in primary care is an international policy priority. There are unique implementation challenges to the roll-out and scale-up of different innovations, requiring synchronisation between national policy levers and local implementation strategies. We draw on implementation science to highlight key considerations when seeking to sustainably embed cancer detection initiatives within health systems and clinical practice. Points of action include considering the implications of change on the current configuration of responsibility for detecting cancer; investing in understanding how to adapt systems to support innovations; developing strategies to address inequity when planning innovation implementation; and anticipating and making efforts to mitigate the unintended consequences of innovation. We draw on examples of contemporary cancer detection issues to illustrate how to apply these recommendations to practice.

Human SARS-CoV-2 challenge uncovers local and systemic response dynamics.

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.

The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

Be present now, sleep well later: Mindfulness promotes sleep health via emotion regulation.

OBJECTIVE: Despite the popularity of mindfulness in research and interventions, information is missing about how and why mindfulness may benefit employee sleep health. Drawing from emotion regulation theory, we evaluate affective rumination, negative affect, and positive affect as potential mechanisms. We also explore differential effects of trait and state attentional mindfulness on both subjective (e.g., quality and sufficiency) and actigraphy-measured aspects (e.g., duration and wake after sleep onset) of sleep health. METHOD: Ecological momentary assessment and sleep actigraphy data were collected across two independent samples of health care workers (N1 = 60, N2 = 84). Ecological momentary assessment was also used to collect daily information on state mindfulness, affect, and rumination. RESULTS: Our results support rumination and, to a less consistent extent, negative affect as mediators of the association between mindfulness and sleep health but not positive affect. Trait and state mindfulness demonstrate comparable benefits for employee sleep health, but these benefits largely emerge for subjective sleep dimensions than actigraphy-measured. CONCLUSIONS: These findings support emotion regulation as a sound theoretical framework for sleep and mindfulness research and may support more informed workplace mindfulness interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Age-specific nasal epithelial responses to SARS-CoV-2 infection.

Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

"My Dead Body": Development, production, and reception of a documentary that publicly displays the dissection of a human donor.

Recently, there has been an emphasis on keeping the study of anatomy using donor material confined to the domain of medical and allied healthcare professionals. Given the abundance of both accurate and inaccurate information online, coupled with a heightened focus on health following the COVID-19 pandemic, one may question whether it is time to review who can access learning anatomy using donors. In 2019, Brighton and Sussex Medical School (BSMS) obtained a Human Tissue Authority Public Display license with the aim of broadening the reach of who could be taught using donor material. In 2020, BSMS received its first full-body donor with consent for public display. Twelve workshops were delivered to student groups who do not normally have the opportunity to learn in the anatomy laboratory. Survey responses (10.9% response rate) highlighted that despite being anxious about seeing inside a deceased body, 95% felt more informed about the body. A documentary "My Dead Body" was filmed, focusing on the rare cancer of the donor Toni Crews. Viewing figures of 1.5 million, and a considerable number of social media comments highlighted the public's interest in the documentary. Thematic analysis of digital and social media content highlighted admiration and gratitude for Toni, the value of education, and that while the documentary was uncomfortable to watch, it had value in reminding viewers of life, their bodies, and their purpose. Fully consented public display can create opportunities to promote health-conscious life choices and improve understanding of the human body.

flepiMoP: The evolution of a flexible infectious disease modeling pipeline during the COVID-19 pandemic.

The COVID-19 pandemic led to an unprecedented demand for projections of disease burden and healthcare utilization under scenarios ranging from unmitigated spread to strict social distancing policies. In response, members of the Johns Hopkins Infectious Disease Dynamics Group developed flepiMoP (formerly called the COVID Scenario Modeling Pipeline), a comprehensive open-source software pipeline designed for creating and simulating compartmental models of infectious disease transmission and inferring parameters through these models. The framework has been used extensively to produce short-term forecasts and longer-term scenario projections of COVID-19 at the state and county level in the US, for COVID-19 in other countries at various geographic scales, and more recently for seasonal influenza. In this paper, we highlight how the flepiMoP has evolved throughout the COVID-19 pandemic to address changing epidemiological dynamics, new interventions, and shifts in policy-relevant model outputs. As the framework has reached a mature state, we provide a detailed overview of flepiMoP's key features and remaining limitations, thereby distributing flepiMoP and its documentation as a flexible and powerful tool for researchers and public health professionals to rapidly build and deploy large-scale complex infectious disease models for any pathogen and demographic setup.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

fNIRS is capable of distinguishing laterality of lower body contractions.

The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. However, the spatial resolution of fNIRS is lower than that of other imaging modalities. It is unclear whether fNIRS has sufficient spatial resolution to differentiate nearby areas of the cortex, such as the leg areas of the motor cortex. Therefore, the purpose of this study was to determine fNIRS' ability to discern laterality of lower body contractions. Activity in the primary motor cortex was recorded in forty participants (mean = 23.4 years, SD = 4.5, female = 23, male = 17) while performing unilateral lower body contractions. Contractions were performed at 30% of maximal force against a handheld dynamometer. These contractions included knee extension, knee flexion, dorsiflexion, and plantar flexion of the left and right legs. fNIRS signals were recorded and stored for offline processing and analysis. Channels of fNIRS data were grouped into regions of interest, with five tolerance conditions ranging from strict to lenient. Four of five tolerance conditions resulted in significant differences in cortical activation between hemispheres. During right leg contractions, the left hemisphere was more active than the right hemisphere. Similarly, during left leg contractions, the right hemisphere was more active than the left hemisphere. These results suggest that fNIRS has sufficient spatial resolution to distinguish laterality of lower body contractions. This makes fNIRS an attractive technology in research and clinical applications in which laterality of brain activity is required during lower body activity.

Ten-Year Stability of an Insomnia Sleeper Phenotype and Its Association With Chronic Conditions.

OBJECTIVE: To identify distinct sleep health phenotypes in adults, examine transitions in sleep health phenotypes over time, and subsequently relate these to the risk of chronic conditions. METHODS: A national sample of adults from the Midlife in the United States study ( N = 3683) provided longitudinal data with two time points (T1: 2004-2006, T2: 2013-2017). Participants self-reported on sleep health (regularity, satisfaction, alertness, efficiency, duration) and the number and type of chronic conditions. Covariates included age, sex, race, education, education, partnered status, number of children, work status, smoking, alcohol, and physical activity. RESULTS: Latent transition analysis identified four sleep health phenotypes across both time points: good sleepers, insomnia sleepers, weekend catch-up sleepers, and nappers. Between T1 and T2, the majority (77%) maintained their phenotype, with the nappers and insomnia sleepers being the most stable. In fully adjusted models with good sleepers at both time points as the reference, being an insomnia sleeper at either time point was related to having an increased number of total chronic conditions by 28%-81% at T2, adjusting for T1 conditions. Insomnia sleepers at both time points were at 72%-188% higher risk for cardiovascular disease, diabetes, depression, and frailty. Being a napper at any time point related to increased risks for diabetes, cancer, and frailty. Being a weekend catch-up sleeper was not associated with chronic conditions. Those with lower education and unemployed were more likely to be insomnia sleepers; older adults and retirees were more likely to be nappers. CONCLUSION: Findings indicate a heightened risk of chronic conditions involved in suboptimal sleep health phenotypes, mainly insomnia sleepers.

Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability.

BACKGROUND: Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic PLXND1 and PLXNA1 variants have so far been associated with Mendelian genetic disease. METHODS: Eight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice. RESULTS: Rare biallelic pathogenic variants in plexin B2 (PLXNB2), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. Plxnb2 expression was detected in differentiating ameloblasts. CONCLUSION: We identify rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in Plxnb2 knockout mice, and, together with the rarity of human PLXNB2 variants, may explain why pathogenic variants in PLXNB2 have not been reported previously.

Adequacy of clinical guideline recommendations for patients with low-risk cancer managed with monitoring: systematic review.

OBJECTIVES: The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk cancer. It appraised the quality of guidelines and determined whether the guidelines adequately identified patients for monitoring, specified which tests to use, defined monitoring intervals, and stated triggers for further intervention. It then assessed the evidence to support each recommendation. STUDY DESIGN AND SETTING: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched PubMed and Turning Research into Practice databases for national and international guidelines' that were written in English and developed or updated between 2012 and 2023. Quality of individual guidelines was assessed using the AGREE II tool. RESULTS: Across the 41 published guidelines, 48 different recommendations were identified: 15 (31%) for prostate cancer, 11 (23%) for renal cancer, 6 (12.5%) for thyroid cancer, and 10 (21%) for blood cancer. The remaining 6 (12.5%) were for brain, gastrointestinal, oral cavity, bone and pheochromocytoma and paraganglioma cancer. When combining all guidelines, 48 (100%) stated which patients qualify for monitoring, 31 (65%) specified which tests to use, 25 (52%) provided recommendations for surveillance intervals, and 23 (48%) outlined triggers to initiate intervention. Across all cancer sites, there was a strong positive trend with higher levels of evidence being associated with an increased likelihood of a recommendation being specific (P = 0.001) and the evidence for intervals was based on expert opinion or other guidance. CONCLUSION: With the exception of prostate cancer, the evidence base for monitoring low-risk cancer is weak and consequently recommendations in clinical guidelines are inconsistent. There is a lack of direct evidence to support monitoring recommendations in the literature making guideline developers reliant on expert opinion, alternative guidelines, or indirect or nonspecific evidence.

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031.

From Pre-test and Post-test Probabilities to Medical Decision Making.

Background: A central goal of modern evidence-based medicine is the development of simple and easy to use tools that help clinicians integrate quantitative information into medical decision-making. The Bayesian Pre-test/Post-test Probability (BPP) framework is arguably the most well known of such tools and provides a formal approach to quantify diagnostic uncertainty given the result of a medical test or the presence of a clinical sign. Yet, clinical decision-making goes beyond quantifying diagnostic uncertainty and requires that that uncertainty be balanced against the various costs and benefits associated with each possible decision. Despite increasing attention in recent years, simple and flexible approaches to quantitative clinical decision-making have remained elusive. Methods: We extend the BPP framework using concepts of Bayesian Decision Theory. By integrating cost, we can expand the BPP framework to allow for clinical decision-making. Results: We develop a simple quantitative framework for binary clinical decisions (e.g., action/inaction, treat/no-treat, test/no-test). Let p be the pre-test or post-test probability that a patient has disease. We show that r*=(1-p)/p represents a critical value called a decision boundary. In terms of the relative cost of under- to over-acting, r* represents the critical value at which action and inaction are equally optimal. We demonstrate how this decision boundary can be used at the bedside through case studies and as a research tool through a reanalysis of a recent study which found widespread misestimation of pre-test and post-test probabilities among clinicians. Conclusions: Our approach is so simple that it should be thought of as a core, yet previously overlooked, part of the BPP framework. Unlike prior approaches to quantitative clinical decision-making, our approach requires little more than a hand-held calculator, is applicable in almost any setting where the BPP framework can be used, and excels in situations where the costs and benefits associated with a particular decision are patient-specific and difficult to quantify.

The US COVID-19 and Influenza Scenario Modeling Hubs: Delivering long-term projections to guide policy.

Between December 2020 and April 2023, the COVID-19 Scenario Modeling Hub (SMH) generated operational multi-month projections of COVID-19 burden in the US to guide pandemic planning and decision-making in the context of high uncertainty. This effort was born out of an attempt to coordinate, synthesize and effectively use the unprecedented amount of predictive modeling that emerged throughout the COVID-19 pandemic. Here we describe the history of this massive collective research effort, the process of convening and maintaining an open modeling hub active over multiple years, and attempt to provide a blueprint for future efforts. We detail the process of generating 17 rounds of scenarios and projections at different stages of the COVID-19 pandemic, and disseminating results to the public health community and lay public. We also highlight how SMH was expanded to generate influenza projections during the 2022-23 season. We identify key impacts of SMH results on public health and draw lessons to improve future collaborative modeling efforts, research on scenario projections, and the interface between models and policy.

Neutrophil responses to RSV infection show differences between infant and adult neutrophils.

INTRODUCTION: Respiratory syncytial virus (RSV) causes a severe respiratory condition, bronchiolitis, in infants but not in adults. Bronchiolitis is characterised by neutrophilic infiltration in the airways, but whether neutrophils enhance recovery from infection or contribute to its pathology remains unknown. METHODS: We used a novel in-vitro model to compare term umbilical cord blood (infant) (n=17 donors) and adult neutrophils (n=15 donors) during migration across RSV-infected differentiated human nasal airway epithelial cells (AECs) in a basolateral to apical direction. RESULTS: Greater numbers of infant neutrophils (mean (95% CI)) (336 684 (242 352 to 431 015)) migrated across RSV-infected AECs to the apical compartment (equivalent to the airway lumen) compared with adult neutrophils (56 586 (24 954 to 88 218)) (p<0.0001). Having reached the apical compartment of infected AECs, much greater numbers of infant neutrophils (140 787 (103 117 to 178 456)) became apoptotic compared with adult (5853 (444 to 11 261)) (p=0.002). Infant neutrophils displayed much greater expression of CD11b, CD64, neutrophil elastase (NE) and myeloperoxidase (MPO) than adult neutrophils at baseline and at all points of migration. However, as adult neutrophils migrated, expression of CD11b, CD64, NE and MPO became greater than at baseline. DISCUSSION: The high proportion of infant neutrophils migrating across RSV-infected AECs correlates with the neutrophilic infiltrate seen in infants with severe RSV bronchiolitis, with large numbers undergoing apoptosis, which may represent a protective mechanism during infection. Compared with adult neutrophils, infant neutrophils already have high expression of surface markers before contact with AECs or migration, with less capacity to increase further in response to RSV infection or migration.