Infant Bronchiolitis Endotypes and the Risk of Developing Childhood Asthma: Lessons From Cohort Studies.

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention.

Respiratory Syncytial Virus Hospital-Based Burden of Disease in Children Younger Than 5 Years, 2015-2022.

Importance: Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV seasons were more severe than in past seasons, and age distribution may have shifted toward older children in the younger than 5 years age group. Objectives: To estimate age-specific changes in RSV hospital-based burden of disease before and after the COVID-19 pandemic and to compare incidence by Medicaid use. Design, Setting, and Participants: This retrospective cohort study included children younger than 5 years diagnosed with RSV and bronchiolitis at 50 US children's hospitals in 10 US geographic regions. The included participants had an encounter in intensive care, inpatient, emergency, or observational units, between June 1, 2015, and March 31, 2023. Exposures: Diagnosis of RSV, bronchiolitis, or both at encounter. Main Outcome and Measures: Incidence rate ratio of hospital use within each care unit before vs after the COVID-19 pandemic. It was hypothesized a priori that incidence of hospital use would increase overall in 2021 and 2022 compared with 2015 to 2019 and that the increase would be greater among children 12 months and older. Results: Of 924 061 study participants (median [IQR] age, 8 (5-16) months; 535 619 [58.0%] male), 348 077 (37.7%) were diagnosed with RSV. Of these, 187 850 (54.0%) were hospitalized. Incidence rate ratios of hospitalization increased for all ages in 2021 and 2022 compared with 2015 to 2019. Children aged 24 to 59 months were 4.86 (95% CI, 4.75-4.98) times as likely to be hospitalized in 2022 compared with 2015 to 2019, whereas infants aged 0 to 5 months were 1.77 (95% CI, 1.74-1.80) times as likely. Medicaid patients were more likely to be hospitalized than non-Medicaid patients regardless of year. Conclusions and Relevance: Hospitalizations for RSV and bronchiolitis demonstrated atypical seasonality in 2021 and 2022, with an overall increase in RSV encounters. Postpandemic RSV hospitalization increased for all ages, but especially among older children, whereas bronchiolitis hospitalization was decreased or unchanged compared with earlier seasons. These findings suggest some of the observed increase in RSV hospital use may be due to increased testing.

Infant Bronchiolitis Endotypes and the Risk of Developing Childhood Asthma: Lessons From Cohort Studies

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention. (AU)

Transition to Weight-Based High-Flow Nasal Cannula Use Outside of the ICU for Bronchiolitis.

Importance: Most children's hospitals have adopted weight-based high-flow nasal cannula (HFNC) bronchiolitis protocols for use outside of the intensive care unit (ICU) setting. Whether these protocols are achieving their goal of reducing bronchiolitis-related ICU admissions remains unknown. Objective: To measure the association between hospital transition to weight-based non-ICU HFNC use and subsequent ICU admission. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted with a controlled interrupted time series approach and involved 18 children's hospitals that contribute data to the Pediatric Health Information Systems database. The cohort included patients aged 0 to 24 months who were hospitalized with a diagnosis of bronchiolitis between January 1, 2010, and December 31, 2021. Data were analyzed from July 2023 to January 2024. Exposure: Hospital-level transition from ICU-only to weight-based non-ICU protocol for HFNC use. Data for the ICU-only group were obtained from a previously published survey. Main Outcomes and Measures: Proportion of patients with bronchiolitis admitted to the ICU. Results: A total of 86 046 patients with bronchiolitis received care from 10 hospitals in the ICU-only group (n = 47 336; 27 850 males [58.8%]; mean [SD] age, 7.6 [6.2] years) and 8 hospitals in the weight-based protocol group (n = 38 710; 22 845 males [59.0%]; mean [SD] age, 7.7 [6.3] years). Mean age and sex were similar for patients between the 2 groups. Hospitals in the ICU-only group vs the weight-based protocol group had higher proportions of Black (26.2% vs 19.8%) and non-Hispanic (81.6% vs 63.8%) patients and patients with governmental insurance (68.1% vs 65.9%). Hospital transition to a weight-based HFNC protocol was associated with a 6.1% (95% CI, 8.7%-3.4%) decrease per year in ICU admission and a 1.5% (95% CI, 2.8%-0.1%) reduction per year in noninvasive positive pressure ventilation use compared with the ICU-only group. No differences in mean length of stay or the proportion of patients who received invasive mechanical ventilation were found between groups. Conclusions and Relevance: Results of this cohort study of hospitalized patients with bronchiolitis suggest that transition from ICU-only to weight-based non-ICU HFNC protocols is associated with reduced ICU admission rates.

Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial.

BACKGROUND: Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects. METHODS: BREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child's sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home. DISCUSSION: We propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization. TRIAL REGISTRATION: NCT05615870. Registered on November 14, 2022.

High-flow nasal cannula therapy for infants with bronchiolitis.

BACKGROUND: Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is the most common cause of hospitalisation of infants. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality. Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen, and respiratory support. Traditionally, oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, at 2 to 3 L/kg per minute up to 60 L/min in children. It can provide some level of continuous positive airway pressure (CPAP) to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support, thus potentially lowering costs, with clinical advantages and fewer adverse effects. OBJECTIVES: To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, and Web of Science (from June 2013 to December 2022). In addition, we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles, and searched for conference abstracts. Date restrictions were imposed such that we only searched for studies published after the original version of this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/minute) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, risk of bias elements, and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy, and adverse events. MAIN RESULTS: In this update we included 15 new RCTs (2794 participants), bringing the total number of RCTs to 16 (2813 participants). Of the 16 studies, 11 compared high-flow to low-flow, and five compared high-flow to CPAP. These studies included infants less than 24 months of age as stated in our selection criteria. There were no significant differences in sex. We found that when comparing high-flow to low-flow oxygen therapy for infants with bronchiolitis there may be a reduction in the total length of hospital stay (mean difference (MD) -0.65 days, 95% confidence interval (CI) -1.23 to -0.06; P < 0.00001, I2 = 89%; 7 studies, 1951 participants; low-certainty evidence). There may also be a reduction in the duration of oxygen therapy (MD -0.59 days, 95% CI -1 to -0.18; P < 0.00001, I2 = 86%; 7 studies, 2132 participants; low-certainty evidence). We also found that there was probably an improvement in respiratory rate at one and 24 hours, and heart rate at one, four to six, and 24 hours in those receiving high-flow oxygen therapy when compared to pre-intervention baselines. There was also probably a reduced risk of treatment escalation in those receiving high-flow when compared to low-flow oxygen therapy (risk ratio (RR) 0.55, 95% CI 0.39 to 0.79; P = 0.001, I2 = 43%; 8 studies, 2215 participants; moderate-certainty evidence). We found no difference in the incidence of adverse events (RR 1.2, 95% CI 0.38 to 3.74; P = 0.76, I2 = 26%; 4 studies, 1789 participants; low-certainty evidence) between the two groups. The lack of comparable outcomes in studies comparing high-flow and CPAP, as well as the small numbers of participants, limited our ability to perform meta-analysis on this group. AUTHORS' CONCLUSIONS: High-flow nasal cannula therapy may have some benefits over low-flow oxygen for infants with bronchiolitis in terms of a greater improvement in respiratory and heart rates, as well as a modest reduction in the length of hospital stay and duration of oxygen therapy, with a reduced incidence of treatment escalation. There does not appear to be a difference in the number of adverse events. Further studies comparing high-flow nasal cannula therapy and CPAP are required to demonstrate the efficacy of one modality over the other. A standardised clinical definition of bronchiolitis, as well as the use of a validated clinical severity score, would allow for greater and more accurate comparison between studies.

Air pollution and bronchiolitis: a case-control study in Antwerp, Belgium.

This case-control study aimed to investigate the association between short-term (1 to 5 days) and medium-term (31 days) exposure to air pollutants (PM2.5, PM10, BC, NO2) at home/daycare and the risk of 'severe bronchiolitis' (defined as 'requiring hospitalization for bronchiolitis') in children under 2 years in Antwerp, Belgium. We included 118 cases and 79 controls admitted to three general hospitals from October 2020 to June 2021. Exposure levels were predicted using an interpolation model based on fixed measuring stations. We used unconditional logistic regression analysis to assess associations, with adjustment for potential confounders. There were hardly any significant differences in the day-to-day air pollution values between cases and controls. Medium-term (31 days) exposure to PM2.5, PM10, and NO2 was however significantly higher in cases than controls in univariate analysis. Logistic regression revealed an association between severe bronchiolitis and interquartile range (IQR) increases of PM2.5 and PM10 at home and in daycare, as well as IQR increases of NO2 in daycare. Controls were however overrepresented in low pollution periods. Time-adjustment reduced the odds ratios significantly at home for PM2.5 and PM10 (aOR 1.54, 95%CI 0.51-4.65; and 2.69, 95%CI 0.94-7.69 respectively), and in daycare for. PM2.5 (aOR 2.43, 95%CI 0.58-10.1). However, the association between severe bronchiolitis and medium-term air pollution was retained in daycare for IQR increases of PM10 (aOR 5.13, 95%CI 1.24-21.28) and NO2 (aOR 3.88, 95%CI 1.56-9.61) in the time-adjusted model.  Conclusion: This study suggests a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM10 and NO2), particularly in daycare. Larger studies are warranted to confirm these findings. What is Known: • Bronchiolitis is a leading cause of hospitalization in infants globally and causes a yearly seasonal wave of admissions in paediatric departments worldwide. • Existing studies, mainly from the USA, show heterogeneous outcomes regarding the association between air pollution and bronchiolitis. What is New: • There is a possible link between severe bronchiolitis and medium-term (31 days) air pollution exposure (PM10 and NO2), particularly in daycare. • Larger studies are needed to validate these trends.

Addressing global health disparities in the management of RSV infection in infants and children: Strategies for preventing bronchiolitis and post-bronchiolitis recurrent wheezing.

Background: The topic of equitable access to health care and its impact on exacerbating worldwide inequities in child health not only strikes at the heart of our health-care delivery systems but also deeply resonates with our collective social consciences. Nowhere is this better seen on a global scale than in the burden of illness caused by respiratory syncytial virus (RSV) infection, which extracts the most severe morbidity and mortality in infants and children in low- and middle-income countries (LMIC). This report addresses global health disparities that exist in the management of RSV infection in infants and children, and offers strategies for preventing bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Methods: A systematic literature review was conducted across the PubMed data bases of RSV infection and the socioeconomic impact of bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Results: The results of the present study address the many issues that deal with the question if prevention of RSV bronchiolitis can mitigate recurrent wheezing episodes and links RSV risks, downstream effects, prevention, malnutrition, and socioeconomic restraints of developing countries with a call for possible global action. Conclusion: The present study stresses the importance of considering the linkage between malnutrition and disease susceptibility because of the known relationships between undernutrition and greater vulnerability to infectious diseases, including RSV infection. These complex interactions between infectious disease and undernutrition also raise issues on the longer-term sequelae of postbronchiolitis recurrent wheezing. This prompts a discussion on whether industrialized countries should prioritize the provision of newly developed monoclonal antibodies and RSV vaccines to LMICs or whether vital nutritional needs should be a first focus. The resolution of these issues will require research and greater international discourse.

Vacunar a la embarazada puede prevenir la bronquiolitis por virus respiratorio sincitial en el lactante / Vaccinating pregnant women can prevent respiratory syncytial virus bronchiolitis in infants

Conclusiones de los autores del estudio: la vacuna de proteína F prefusión contra el virus respiratorio sincitial, administrada a embarazadas en el último trimestre de embarazo, previene de infecciones respiratorias graves por dicho virus en sus lactantes, sin efectos adversos de importancia. Comentario de los revisores: la vacuna parece eficaz y segura, aunque las estimaciones de eficacia son imprecisas. Constituye una opción preventiva alternativa a la administración de nirsevimab en el recién nacido, con expectativas de impacto equiparables. (AU)

Authors´ conclusions: prefusion F protein vaccine against respiratory syncytial virus administered to pregnant women in the last trimester of pregnancy prevents this virus severe respiratory infections in their infants, without important adverse effects. Reviewers´ commentary: the vaccine appears effective and safe, although its efficacy estimates are imprecise. It constitutes an alternative preventive option to the administration of nirsevimab in the newborn, with comparable impact expectations. (AU)

Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort.

BACKGROUND: Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children. METHODS: History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 - 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders. RESULTS: Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation. CONCLUSIONS: Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Nasopharyngeal and Peripheral Blood Type II Interferon Signature Evaluation in Infants during Respiratory Syncytial Virus Infection.

Background and Objectives: In this study, we applied one-step real time rt-PCR technology type II INF signature to blood and nasopharyngeal (NPS) swabs of acute early recovery children < 1 years hospitalized for bronchiolitis with laboratory-confirmed RSV infection. Materials and Methods: A prospective observational case-control study was conducted in 2021-2022. The study took place in Children Hospital "Regina Margherita", Torino Italy. The study included 66 infants, of which 30 patients were hospitalized for bronchiolitis due to RSV infection and 36 age-matched controls. Inclusion criteria included a positive RSV test for infants with bronchiolitis. We collected peripheral blood and nasopharyngeal swabs for relative quantification of type II Interferon signature by One-Step Multiplex PCR real time. Results: IFN levels were downregulated in the peripheral blood of bronchiolitis patients; these data were not confirmed in the nasopharyngeal swab. There was no correlation between NPS and the type II IFN score in peripheral blood. Conclusions: our study shows for the first time that type II IFN score was significant reduced in peripheral blood of infants with bronchiolitis by RSV compared to age-matched healthy controls; in the NPS swab this resulted downregulation was not statistically significant and the type II IFN score in the NPS swab can be used as marker of resolution of infection or improvement of clinical conditions.

Respiratory syncytial virus subtypes in children with bronchiolitis: does it correlate with clinical severity?

BACKGROUND: In this retrospective study, we aimed to evaluate the factors associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children aged under 2 years who were admitted to the Children's Hospital of Hebei between June 2018 and January 2019. METHODS: Sputum samples positive for RSV via multiplex PCR were subtyped using real-time PCR. Data collected included risk factors for disease severity, demographics, microbiology, and outcomes. RESULTS: Of the 82 children with RSV bronchiolitis, 79 were treated and discharged with improvement, while 3 died. All three patients had underlying medical conditions, including complex congenital heart disease and severe combined immunodeficiency. Further, disease severity was associated with preexisting underlying disease, fever duration, and bacterial co-infection, but not with the RSV subtype. CONCLUSIONS: Our findings suggest that an appropriate therapeutic regimen should include the detection of bacterial co-infections and the identification of underlying diseases for the effective management of severe RSV bronchiolitis.

Probabilistic Linkage Creates a Novel Database to Study Bronchiolitis Care in the PICU.

OBJECTIVES: Lack of a comprehensive database containing diagnosis, patient and clinical characteristics, diagnostics, treatments, and outcomes limits needed comparative effectiveness research (CER) to improve care in the PICU. Combined, the Pediatric Hospital Information System (PHIS) and Virtual Pediatric Systems (VPS) databases contain the needed data for CER, but limits on the use of patient identifiers have thus far prevented linkage of these databases with traditional linkage methods. Focusing on the subgroup of patients with bronchiolitis, we aim to show that probabilistic linkage methods accurately link data from PHIS and VPS without the need for patient identifiers to create the database needed for CER. METHODS: We used probabilistic linkage to link PHIS and VPS records for patients admitted to a tertiary children's hospital between July 1, 2017 to June 30, 2019. We calculated the percentage of matched records, rate of false-positive matches, and compared demographics between matched and unmatched subjects with bronchiolitis. RESULTS: We linked 839 of 920 (91%) records with 4 (0.5%) false-positive matches. We found no differences in age (P = .76), presence of comorbidities (P = .16), admission illness severity (P = .44), intubation rate (P = .41), or PICU stay length (P = .36) between linked and unlinked subjects. CONCLUSIONS: Probabilistic linkage creates an accurate and representative combined VPS-PHIS database of patients with bronchiolitis. Our methods are scalable to join data from the 38 hospitals that jointly contribute to PHIS and VPS, creating a national database of diagnostics, treatment, outcome, and patient and clinical data to enable CER for bronchiolitis and other conditions cared for in the PICU.

Patient-Centered Outcomes in Bronchiolitis.

OBJECTIVES: We examined the impact of hospitalization for bronchiolitis on patient-centered outcomes across patients with varying levels of support. METHODS: The participants included primary caregivers of children aged 0 to 24 months hospitalized for bronchiolitis at an 150-bed tertiary care children's hospital. Data were collected using a 30-item questionnaire examining quality of life impact, adapted from the previously validated survey, the Impact of Bronchiolitis Hospitalization Questionnaire.1 The survey contained questions asking to what extent the hospitalization interfered with different aspects of care. After all surveys were collected, the patients were split into groups categorized by level of support and defined as no support, low support (low-flow nasal cannula only or nasogastric [NG] only), moderate support (high-flow nasal cannula without NG), high support (high-flow nasal cannula with NG support), and positive pressure (with or without NG support). Descriptive statistics were used to examine the distribution of mean impact scores across these groups. RESULTS: A total of 92 caregivers and their children were included. The mean impact score for variables of difficult to hold, difficult to bond, and breastfeeding disruption increased with greater levels of support with P values of P = .003, P = .04, and P < .001, respectively. CONCLUSIONS: We found that the impact on patient-reported outcomes varied by level of support, as defined here, among children hospitalized with bronchiolitis, with significant impacts being in areas of caregiver bonding, caregiver holding, and breastfeeding.

Bacterial small RNAs may mediate immune response differences seen in respiratory syncytial virus versus rhinovirus bronchiolitis.

Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35th Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., Haemophilus influenzae, Moraxella catarrhalis, Moraxella nonliquefaciens, and Streptococcus pneumoniae). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.