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Objectives: Bronchiolitis is a common indication for mechanical ventilation in the PICU. Both bronchiolitis and invasive mechanical ventilation may cause adverse long-term pulmonary outcomes. This study investigates children with a history of invasive mechanical ventilation for bronchiolitis, addressing: 1) the extent, 2) potential explanatory factors, and 3) possible impact on daily life activities of adverse long-term pulmonary outcomes., Design: Single-center cohort study., Setting: Outpatient PICU follow-up clinic., Patients: Children 6-12 years old with a history of invasive mechanical ventilation for bronchiolitis (age < 2 yr)., Interventions: None., Measurements and Main Results: Long-term pulmonary outcomes were assessed by a standardized questionnaire and by spirometry. Nineteen out of 74 included children (26%) had adverse long-term pulmonary outcomes, of whom the majority had asthma (14/74, 19%). By logistic regression analysis, we assessed whether background characteristics and PICU-related variables were associated with long-term pulmonary outcomes. In general, we failed to identify any explanatory factors associated with adverse long-term pulmonary outcomes. Nonetheless, atopic disease in family and longer duration of invasive mechanical ventilation (days) were associated with greater odds of having asthma at follow-up (odds ratio, 6.4 [95% CI, 1.2-36.0] and 1.3 [95% CI, 1.0-1.7], respectively). Adverse pulmonary outcome at follow-up was associated with more frequent use of pulmonary medication after PICU discharge. In comparison with those without adverse pulmonary outcomes, we did not identify any difference in frequency of sports performance or school absenteeism., Conclusions: In this single-center cohort, one-quarter of the children attending follow-up with a history of invasive mechanical ventilation for bronchiolitis had adverse, mostly previously undetected, long-term pulmonary outcomes at 6-12 years. Atopic disease in family and longer duration of invasive mechanical ventilation were associated with presence of asthma. The presence of adverse pulmonary outcomes was associated with more frequent use of pulmonary medication after PICU discharge., Competing Interests: Dr. de Sonnaville’s institution received funding from Janivo, C.J. Vaillant, Louise and Vehmeijer charity foundations. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood., Methods: From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants <1 year using linked birth/death datasets from the National Vital Statistics System. Mortality was described overall and by infant birth and death characteristics. Bronchiolitis was included as the plausible upper limit of RSV, while influenza served as a comparator., Results: Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4-7.5), 19.8 (95% CI, 18.9-20.8), and 6.2 (95% CI, 5.7-6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among <29 weeks' gestational age infants (103.5; 95% CI, 81.8-129.1), American Indian/Alaskan Native (20.3; 95% CI, 11.6-33.0), and Medicaid-insured (7.3; 95% CI, 5.9-8.9). However, RSV mortality burden was greatest in full-term (53.7%), white (44.9%), and Medicaid-insured (61.7%) infants. Deaths outside the inpatient setting were 21% and 54% for RSV and bronchiolitis; more Medicaid- (58%) and other/unknown-insured (69%) infants with bronchiolitis died outside of the inpatient setting, compared to privately insured infants (48%) (P = .0327)., Conclusions: These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality., Competing Interests: Potential conflicts of interest. EpidStrategies received a grant from Sanofi for this research. H. R., M. S., X. J., N. M., L. C. B., and J. P. F. are employees of EpidStrategies. C. B. N. is an employee of Sanofi and may hold shares and/or stock options in the company. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Admission to a pediatric intensive care unit (PICU) has been associated with respiratory consequences in children with asthma and carries major implications for management control. Whereas respiratory syncytial virus (RSV) bronchiolitis has been associated with increasing intensity of wheezing, the relationship between RSV-bronchiolitis PICU admission and future asthma is unclear. This retrospective case-control study evaluated whether hospitalization in the PICU due to RSV bronchiolitis is more likely to be associated with future asthma in early life compared with hospitalization in a general pediatric ward., Methods: Children hospitalized due to RSV bronchiolitis between 2007 and 2019 in the PICU (study group) were compared to those hospitalized in a general pediatric ward (controls). Asthma prevalence was assessed by a follow-up questionnaire based on The International Study of Asthma and Allergies in Childhood questionnaire., Results: Sixty-three PICU patients and 66 controls were included. The PICU patients presented with more severe disease during RSV hospitalization. At follow-up, significantly more PICU patients aged 3-6 years had physician-diagnosed asthma, respiratory symptoms during the previous 12 months, and underwent respiratory treatment since hospital discharge compared to controls (14 [60.9%] vs. 4 [18.2%] patients; 15 [65.2%] vs. 6 [27.3%]; and 16 [69.6%] vs. 8 [36.4%]; respectively). These differences were no longer observed after 6 years of age., Conclusions: Children admitted to the PICU for RSV bronchiolitis are at higher risk for asthma in subsequent pre-school years and will require close respiratory follow-up than those admitted to general pediatric wards. Admission venue should be queried when asthma is suspected., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Bronchiolitis is the most frequent cause of hospitalization in infants younger than 1 year of age. We sought to evaluate the correlation between lymphocyte count and clinical manifestation in infants hospitalized with bronchiolitis., Materials and Methods: We performed a retrospective cohort study evaluating 1297 children hospitalized for bronchiolitis from 2004 to 2019. A nasal washing was tested for 14 respiratory viruses by PCR. A clinical severity score, ranging 0-8, was assigned at hospital admission. History and clinical course were recorded for each infant. Patients were divided in 3 groups according to lymphocyte count tertiles. Parents of enrolled patients have been phoned annually over 5 years to evaluate respiratory sequelae., Results: A total of 433 children had 2914.2 ± 745.5/mm 3 lymphocytes (Group 1), 432 had 4897.6 ± 561.5/mm 3 lymphocytes (Group 2) and 432 had 7884 ± 1903.3/mm 3 lymphocytes (Group 3). Group 1 patients were more frequently infected by RSV and presented with fever, a worse clinical severity score. They more frequently needed oxygen supplementation, underwent a prolonged hospitalization needed to be admitted to pediatric intensive care unit. Finally, they had more frequently a family history of eczema, wheezing and asthma. We found no differences between lymphocytes count and respiratory sequelae (at least two episodes of wheezing per year)., Conclusions: Infants with low lymphocyte count are more likely to have a worse clinical course of bronchiolitis., (© 2022 Wiley Periodicals LLC.)

Aim: The aim of this study was to assess the prevalence of discomfort in infants with severe bronchiolitis supported by noninvasive ventilation and to identify its potential risk factors., Methods: A single-centre retrospective observational study. Discomfort was assessed using the EDIN (Echelle de Douleur et d'Inconfort du Nouveau-né) scale., Results: Ninety-one infants (median age 34 days [Interquartile IQR 19-55], 52 (57%) boys) were included in our study. Overall, no patient had a mean EDIN score higher than 8 on Days 1, 2 and 3. On Days 1 and 2, patients supported by bilevel positive airway pressure (BiPAP) had a higher EDIN score compared with other patients (3.3 [SD 2.5] versus 2.6 [SD 2.2] on Day 1 and 2.9 (SD 2.1) versus 2.3 (SD 2.2) on Day 2, both p < 0.001)., Conclusion: Patients with severe bronchiolitis and supported by any type of noninvasive ventilation had a low degree of discomfort during the first 3 days of ICU stay. Patients requiring bilevel noninvasive ventilation appeared to have a higher degree of discomfort, while we found no correlation between the level of discomfort and the degree of respiratory distress., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: To assess association of Vitamin D deficiency with cardiac and pulmonary status in infants with acute bronchiolitis., Methods: Infants hospitalized with acute bronchiolitis were enrolled and classified as those with serum 25 hydroxyvitamin D (25-OHD) below or equal and above 20 ng/mL. The primary outcomes were cardiopulmonary involvement defined by elevation of NT-ProBNP, alteration of echocardiographic parameters and respiratory support requirements. The secondary outcomes were the need for PICU admission and duration of hospitalization., Results: Ninety two (50 males) infants with median (IQR) age 1 (0.5 - 3) months were included with median (IQR) serum 25 - OHD level 27.4 (11.4 - 40.3) ng/mL. Forty-three (47%) patients had serum below 20 ng/mL with left ventricle dysfunction (P=0.008), right ventricle dysfunction (P=0.008) and pulmonary hypertension (P=0.007) on echocardiography than those with serum 25 - OHD > 20 ng/mL. The median (IQR) serum NT - ProBNP levels were higher in those with low 25 - OHD levels than normal 25 - OHD levels [2232.2 (461.4 - 4313.3) and 830.4 (312.7 - 2579.5)], respectively; P=0.003. Low 25-OHD levels were associated with increased risk for PICU admission (OR 3.9 (95% CI 1.5-10.1); P=0.004), higher rates of non-invasive ventilation, (P= 0.048), mechanical ventilation (P=0.005), and longer duration of hospitalization (P=0.015)., Conclusion: Low serum vitamin D level was associated with clinical severity and impaired cardiac and pulmonary status in infants with acute bronchiolitis.

Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7-9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7-9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5-9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections (p = 0.04) and lower z-score FEV 1 than single-RSV-infections (p = 0.04) or coinfections (p = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV 1 values than coinfections (p = 0.03 and p = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV 1  < 80% (p = 0.007). FeNO value > 25 ppb was detected in 21(12.5%) cases, without differences between viral groups (p = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), (p = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients (p = 0.004). The respiratory morbidity at 7-9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones (p = 0.012). The respiratory morbidity at 7-9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age., (© 2022. The Author(s).)

Background: Cigarette smoking is a risk factor for interstitial lung abnormalities (ILAs) and interstitial lung diseases (ILDs). Investigation defining the relationships between ILAs/ILDs and clinical, radiographic, and pathologic findings in smokers have been incomplete. Employing a cohort undergoing surgical resection for lung nodules/masses, we (1) define the prevalence of ILAs/ILDs, (2) delineate their clinical, radiographic and pathologic predictors, and (3) determine their associations with mortality., Methods: Patients undergoing resection of lung nodules/masses between 2017 and 2020 at a rural Appalachian, tertiary medical center were retrospectively investigated. Predictors for ILAs/ILDs and mortality were assessed using multivariate logistic regression analysis., Results: In the total study cohort of 352 patients, radiographic ILAs and ILDs were observed in 35.2% and 17.6%, respectively. Among ILA patterns, subpleural reticular changes (14.8%), non-emphysematous cysts, centrilobular (CL) ground glass opacities (GGOs) (8% each), and mixed CL-GGO and subpleural reticular changes (7.4%) were common. ILD patterns included combined pulmonary fibrosis emphysema (CPFE) (3.1%), respiratory bronchiolitis (RB)-ILD (3.1%), organizing pneumonitis (2.8%) and unclassifiable (4.8%). The group with radiographic ILAs/ILDs had a significantly higher proportion of ever smokers (49% vs. 39.9%), pack years of smoking (44.57 ± 36.21 vs. 34.96 ± 26.22), clinical comorbidities of COPD (35% vs. 26.5%) and mildly reduced diffusion capacity (% predicated 66.29 ± 20.55 vs. 71.84 ± 23). Radiographic centrilobular and paraseptal emphysema (40% vs. 22.2% and 17.6% vs. 9.6%, respectively) and isolated traction bronchiectasis (10.2% vs. 4.2%) were associated with ILAs/ILDs. Pathological variables of emphysema (34.9% vs. 18.5%), any fibrosis (15.9% vs. 4.6%), peribronchiolar metaplasia (PBM, 8% vs. 1.1%), RB (10.3% vs. 2.5%), and anthracosis (21.6% vs. 14.5%) were associated with ILAs/ILDs. Histologic emphysema showed positive correlations with any fibrosis, RB, anthracosis and ≥ 30 pack year of smoking. The group with ILAs/ILDs had significantly higher mortality (9.1% vs. 2.2%, OR 4.13, [95% CI of 1.84-9.25])., Conclusions: In a rural cohort undergoing surgical resection, radiographic subclinical ILAs/ILDs patterns were highly prevalent and associated with ever smoking and intensity of smoking. The presence of radiographic ILA/ILD patterns and isolated honeycomb changes were associated with increased mortality. Subclinical ILAs/ILDs and histologic fibrosis correlated with clinical COPD as well as radiographic and pathologic emphysema emphasizing the co-existence of these pulmonary injuries in a heavily smoking population., (© 2022. The Author(s).)

Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide. Approximately a third of infants hospitalized with bronchiolitis develop asthma later in life. However, it is unclear what factors increase susceptibility to severe RSV-bronchiolitis and the subsequent asthma development. In recent years, the role of the gut and lung microbiota in airway diseases has received increased interest, and more studies have focused on this field. Different epidemiological studies and experimental animal models have associated early-life gut microbiota dysbiosis with an increased risk of lung disease later in life. This work will review published evidence that correlated environmental factors that affect the early-life microbiota composition and their role in developing severe RSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yagi, Asai, Huffnagle, Lukacs and Fonseca.)

Wheezing is a common finding across patients of all age groups presenting to the emergency department and being hospitalized for respiratory distress, with most patients responding to standard therapeutics and having readily apparent diagnoses of asthma or bronchiolitis. We describe several clinical entities that may present with wheezing and respiratory distress, calling attention to the broad differential that may masquerade as asthma or bronchiolitis, and potentially lead to misdiagnosis, delayed diagnosis, or inappropriate treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Recent studies support the existence of several entities under the clinical diagnosis of bronchiolitis. Among infants with severe bronchiolitis, distinct profiles have been differentially associated with development of recurrent wheezing by age 3 years. However, their associations with actual asthma remain unclear., Objective: Our aim was to study the association between severe bronchiolitis profiles identified by using a clustering approach and childhood asthma., Methods: Among 408 children (aged <2 years) hospitalized with bronchiolitis in Finland (in 2008-2010), latent class analysis identified 3 bronchiolitis profiles: profile A (47%), characterized by history of wheezing and/or eczema, wheezing during acute illness, and rhinovirus infection; profile BC (38%), characterized by severe illness and respiratory syncytial virus infection; and profile D (15%), characterized by the least severely ill children, including mostly children without wheezing and with rhinovirus infection. The children were followed by questionnaire 4 years later (86% [n = 348]) and through a nationwide social insurance database 7 years later (99% [n = 403]). Current asthma at the 4- and 7-year follow-ups was defined by regular use (according to parental report and medical records) or purchase (according to the social insurance database) of asthma control medication., Results: Compared with risk of current asthma associated with profile BC, we observed increased risk of current asthma associated with profile A both at the 4-year follow-up (age- and sex-adjusted odds ratio = 2.42 [95% CI = 1.23-4.75]) and at the 7-year follow-up (age- and sex-adjusted odds ratio = 3.14 [95% CI = 1.33-7.42]). No significant difference in asthma risk was observed between profile D and profile BC., Conclusion: These longitudinal results provide further support for an association between a distinct severe bronchiolitis profile (characterized by a history of wheezing and/or eczema and rhinovirus infection) and risk of development childhood asthma., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Improved survival has shifted research focus toward understanding alternate PICU outcomes, including neurocognitive and functional changes. Bronchiolitis is a common PICU diagnosis, but its neuro-functional outcomes have not been adequately described in contemporary literature. The objective of the study is to describe the epidemiology and associated clinical characteristics of acute neuro-functional morbidity (ANFM) in critical bronchiolitis., Methods: Patients <2 years old admitted with bronchiolitis between 2014 and 2016 were identified. Demographics, medical history, length of stay (LOS), and need for intubation were collected. Children with a history of neurologic illness or illness associated with neurologic sequelae were termed "high risk"; others were termed "low risk." ANFM was defined both at PICU and hospital discharge as the presence of swallowing difficulty, nasogastric tube feeds, hypotonia, or lethargy. Variables were compared by using χ2 and Wilcoxon rank tests., Results: Among 417 children, 16.7% had ANFM, predominantly swallow difficulties (95.7%). Children with ANFM had lower weight (5.9 [4.4-8.2] vs 7.7 [5.5-9.7] kg, P = .001), longer LOS (6.6 [2.5-13.3] vs 1.9 [0.9-3.5] days, P < .001), intubation (51.4% vs 6.1%, P < .001) and high-risk status (37.1% vs 8.4%, P < .001). Among 362 low risk subjects, ANFM was identified in 44 (12%). In a multivariate logistic regression model, high-risk status, intubation, and ICU LOS were associated with ANFM. ANFM persisted to hospital discharge in 46% of cases., Conclusions: One out of 6 patients with critical bronchiolitis had documentation consistent with ANFM at PICU discharge. Risk factors included previous neurologic conditions, longer LOS, and intubation. Many were low-risk and/or did not require intubation, indicating a risk for neuro-functional morbidities despite moderate acuity., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: The effects of infection and developmental adaptations in infancy on the prevalence of subsequent atopy-related diseases at different ages during childhood are not fully determined. This study aims to examine the similarities and differences in the age-specific association of asthma, allergic rhinitis/conjunctivitis, and atopic dermatitis with early-life infection-related factors (i.e., daycare, older siblings, and severe airway infection) and developmental adaptations (i.e., preterm birth and rapid weight gain) in children., Methods: In this longitudinal cohort study (n = 47,015), children were followed from 0.5 to 11 years. The potential risks and protective factors, including daycare attendance at 0.5 years, existence of older siblings, history of hospitalization due to cold/bronchitis/bronchiolitis/pneumonia during 0.5-1.5 years, preterm birth, and rapid weight gain in the first 2.5 years, were assessed using multivariable logistic regression with adjustments for potential confounders., Results: A protective association was observed between early-life daycare attendance and asthma at 5.5-9 years, which disappeared after 10 years. A protective association was also noted throughout childhood between early daycare attendance and older siblings with allergic rhinitis/conjunctivitis. However, the association between early daycare and atopic dermatitis was found to be risky during childhood. In contrast, the early-life history of hospitalization owing to cold/bronchitis/bronchiolitis/pneumonia was identified to be a risk factor for developing both asthma and allergic rhinitis/conjunctivitis. Preterm birth was a significant risk factor for childhood asthma., Conclusion: Different age-specific patterns were demonstrated in the relationship between early daycare, severe airway infection, preterm birth, and atopy-related diseases in childhood., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Bacterial infection (BI), both community-acquired (CA-BI) and hospital-acquired (HAI), might present as a severe complication in patients with bronchiolitis. This study aimed to describe BI in children with severe bronchiolitis, and to define risk factors for BI., Methods: This was a prospective, descriptive study that included infants admitted to the pediatric intensive care unit (PICU) due to bronchiolitis between 2011 and 2017. The BROSJOD score was calculated to rate the severity of bronchiolitis., Results: Inclusion of 675 patients, with a median age of 47 days (IQR 25-99). 175 (25.9%) patients developed BI, considered HAI in 36 (20.6%). Patients with BI had higher BROSJOD score, PRISM III, and required invasive mechanical ventilation and inotropic support more frequently (p < 0.001). BI was independently associated with BROSJOD higher than 12 (OR 2.092, 95%CI 1.168-3.748) CA-BI was associated to BROSJOD > 12 (OR 2.435, 95%CI 1.379-4.297) and bacterial co-infection (OR 2.294 95%CI 1.051-5.008). Concerning HAI, an independent association was shown with mechanical ventilation longer than 7 days (OR 5.139 95%CI 1.802-14.652). Infants with BI had longer PICU and hospital stay (p < 0.001), Mortality was higher in patients with HAI., Conclusions: A quarter of infants with severe bronchiolitis developed BI. A BROSJOD > 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality., (© 2022. The Author(s).)

Bronchiolitis due to respiratory syncytial virus (RSV) or non-RSV agents is a health-menacing lower respiratory tract (LRT) disease of infants. Whereas RSV causes more severe disease than other viral agents may, genus-dominant fecal microbiota profiles have been identified in US hospitalized infants with bronchiolitis. We investigated the fecal microbiota composition of infants admitted to an Italian hospital with acute RSV (25/37 [67.6%]; group I) or non-RSV (12/37 [32.4%]; group II) bronchiolitis, and the relationship of fecal microbiota characteristics with the clinical characteristics of infants. Group I and group II infants differed significantly (24/25 [96.0%] versus 5/12 [41.7%]; P = 0.001) regarding 90% oxygen saturation (SpO 2 ), which is an increased respiratory effort hallmark. Accordingly, impaired feeding in infants from group I was significantly more frequent than in infants from group II (19/25 [76.0%] versus 4/12 [33.3%]; P = 0.04). Conversely, the median (IQR) length of stay was not significantly different between the two groups (seven [3-14] for group I versus five [5-10] for group II; P = 0.11). The 16S ribosomal RNA V3-V4 region amplification of infants' fecal samples resulted in 299 annotated amplicon sequence variants. Based on alpha- and beta-diversity microbiota downstream analyses, group I and group II infants had similar bacterial communities in their samples. Additionally, comparing infants having <90% SpO 2 ( n = 29) with infants having ≥90% SpO 2 ( n = 8) showed that well-known dominant genera ( Bacteroides , Bifidobacterium , Escherichia / Shigella , and Enterobacter / Veillonella ) were differently, but not significantly ( P = 0.44, P = 0.71, P = 0.98, and P = 0.41, respectively) abundant between the two subgroups. Overall, we showed that, regardless of RSV or non-RSV bronchiolitis etiology, no fecal microbiota-composing bacteria could be associated with the severity of acute bronchiolitis in infants. Larger and longitudinally conducted studies will be necessary to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 De Maio, Buonsenso, Bianco, Giaimo, Fosso, Monzo, Sali, Posteraro, Valentini and Sanguinetti.)

Introduction: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections., Aim: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis., Methods: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma., Results: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test., Conclusion: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma., (© 2021 Wiley Periodicals LLC.)

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)-induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma., Aim: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma., Methods: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots., Results: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24-7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48-4.99)., Conclusion: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: To evaluate the contribution of PICU care to increasing hospital charges for patients with bronchiolitis over a 10-year study period., Design: In this retrospective multicenter study, changes in annual hospital charges (adjusted for inflation) were analyzed using linear regression for subjects admitted to the PICU with invasive mechanical ventilation (PICU + IMV) and without IMV (PICU - IMV), and for children not requiring PICU care., Setting: Free-standing children's hospitals contributing to the Pediatric Health Information System (PHIS) database., Subjects: Children less than 2 years with bronchiolitis discharged from a PHIS hospital between July 2009 and June 2019. Subjects were categorized as high risk if they were born prematurely or had a chronic complex condition., Interventions: None., Measurements and Main Results: PICU patients were 26.5% of the 283,006 included subjects but accrued 66% of the total $14.83 billion in charges. Annual charges increased from $1.01 billion in 2009-2010 to $2.07 billion in 2018-2019, and PICU patients accounted for 83% of this increase. PICU + IMV patients were 22% of all PICU patients and accrued 64% of all PICU charges, but PICU - IMV patients without a high-risk condition had the highest relative increase in annual charges, increasing from $76.7 million in 2009-2010 to $377.9 million in 2018-2019 (374% increase, ptrend < 0.001)., Conclusions: In a multicenter cohort study of children hospitalized with bronchiolitis, PICU patients, especially low-risk children without the need for IMV, were the highest driver of increased hospital charges over a 10-year study period., Competing Interests: Dr. Shein received funding from Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Aim: Interleukin (IL) 1 receptor-like 1, encoded by the IL1RL1 gene, is a receptor for IL-33. In European birth cohorts, IL1RL1 rs102082293, rs10204137 (rs4988955), rs13424006 and rs13431828 (rs13048661) variations were associated with asthma at school age. In a Dutch multi-centre study, IL1RL1 rs1921622 variation was associated with severe bronchiolitis. We evaluated the associations of these five IL1RL1 variations with asthma and lung function at school age after hospitalisation for bronchiolitis in infancy., Methods: Follow-up data, including impulse oscillometry at age 5-7 and flow-volume spirometry at age 11-13 years, and the IL1RL1 genotype data were available for 141 children followed until 5-7 and for 125 children followed until 11-13 age years after bronchiolitis in infancy. The IL1RL1 rs10204137 and rs4988955, and the IL1RL1 rs13048661 and rs13431828, are 100% co-segregating in the Finnish population., Results: The variant IL1RL1 rs13048661/13431828 genotype was constantly associated with increased asthma risk by various definitions at 5-7 and 11-13 years of ages. The result was confirmed with analyses adjusted for current confounders and early-life environment-related factors. Statistical significances were lost, when maternal asthma and atopic dermatitis in infancy were included in the model., Conclusion: IL1RL1 rs13048661/13431828 variation was associated with post-bronchiolitis asthma outcomes at school age., (© 2021 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: To investigate the related risk factors for bronchiolitis obliterans (BO) in children with mycoplasma pneumonia (MP) bronchiolitis., Method: The clinical data of 227 children with MP bronchiolitis who were admitted to the II Department of Respiratory of Children's Hospital of Hebei Province from January 2018 to June 2020 were retrospectively analyzed. According to the sequelae of BO, they were divided into 32 cases in the BO group and 195 cases in the non-BO group. The univariate analysis was performed on the clinical and laboratory parameters of the two groups, and the multifactor logistic regression was performed further to determine the independent risk factors for the occurrence of BO in MP bronchiolitis, and then, the cut-off value with the maximum diagnostic value of indicators was found through the ROC curve analysis., Results: The results of univariate and multivariate logistic regression analysis showed that the independent risk factors for the occurrence of BO in MP bronchioles were longer duration of moist rales (OR = 1.203, P = 0.003), higher levels of serum lactate dehydrogenase (LDH) (OR = 1.005, P = 0.036), hypoxemia (OR = 7.442, P = 0.035), and pleural effusion (OR = 4.437, P = 0.004). The area under the ROC curve was 78.2%, 72.0%, 68.2%, and 71.0%, respectively ( P < 0.001). The cut-off value of duration of moist rales and levels of serum LDH are 7.5 d and 330 U/L, respectively., Conclusion: Children with MP bronchiolitis with high serum LDH level (≥330 U/L), combined with hypoxemia, pleural effusion, and lung wet rale duration (≥7.5 d), may be more prone to BO, in which lung wet rale duration prediction value is the largest. Among them, duration of pulmonary moist rales has the highest predictive value., Competing Interests: All authors declare that there is no conflict of interest., (Copyright © 2022 KunLing Huang et al.)

Background: Hospitalisation for bronchiolitis is a risk factor for asthma and impaired lung function during childhood, but outcomes in young adults are poorly described. Our primary aim was to study the prevalence of asthma and atopy, and lung function at 17-20 years of age after bronchiolitis in infancy and, secondarily, the impact of viral aetiology (respiratory syncytial virus (RSV) vs non-RSV) and sex on these outcomes., Methods: This Norwegian cohort study enrolled 225 young adults hospitalised for bronchiolitis in infancy during 1996-2001 and 167 matched control subjects. The follow-up included questionnaires for asthma and examinations of lung function and atopy. Outcomes were analysed by mixed effects regressions., Results: Current asthma was more frequent in the postbronchiolitis group versus the control group: 25.1% (95% CI 19.0% to 31.2%) vs 13.1% (95% CI 7.9% to 18.2%), but not atopy: 44.3% (95% CI 37.1% to 51.5%) vs 48.2% (95% CI 40.5% to 55.8%), adjusted predicted proportions (95% CIs). Asthma prevalence did not differ between the RSV group and the non-RSV group: 24.0% (95% CI 16.1% to 32.0%) vs 23.8% (95% CI 12.8% to 34.7%) nor between sexes. Forced expiratory volume in 1 s (FEV 1 ), the ratio FEV 1 /forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC, were lower in the postbronchiolitis group., Conclusion: Young adults hospitalised for bronchiolitis had higher prevalence of asthma, but not atopy, and a more obstructive lung function pattern than control subjects. The asthma prevalence was high after both RSV bronchiolitis and non-RSV bronchiolitis, and there was no difference between sexes. Bronchiolitis in infancy is associated with respiratory morbidity persisting into young adulthood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Endemic coronaviruses have been found in acute bronchiolitis, mainly as a coinfecting virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for respiratory illness in hospitalized children. The characteristics of patients with bronchiolitis have not been extensively described., Methods: Cross-sectional study of patients with bronchiolitis and SARS-CoV-2 infection enrolled in a prospective multicenter cohort of children hospitalized with COVID-19 in Spain from March 1, 2020 to February 28, 2021., Results: Twelve of 666 children infected with SARS-CoV-2 who required hospital admission met the diagnostic criteria for bronchiolitis (1.8%). Median age was 1.9 months (range: 0.4-10.1). Six cases had household contact with a confirmed or probable COVID-19 case. Main complaints were cough (11 patients), rhinorrhea (10), difficulty breathing (8), and fever (8). Eleven cases were classified as mild or moderate and one as severe. Laboratory tests performed in seven patients did not evidence anemia, lymphopenia, or high C-reactive protein levels. Chest X-rays were performed in six children, and one case showed remarkable findings. Coinfection with metapneumovirus was detected in the patient with the most severe course; Bordetella pertussis was detected in another patient. Seven patients required oxygen therapy. Albuterol was administered in four patients. One patient was admitted to the pediatric intensive care unit. Median length of admission was 4 days (range: 3-14). No patient died or showed any sequelae at discharge. Two patients developed recurrent bronchospasms., Conclusion: SARS-CoV-2 infection does not seem to be a main trigger of severe bronchiolitis, and children with this condition should be managed according to clinical practice guidelines., (© 2021 Wiley Periodicals LLC.)

Objectives: Evaluation of potential benefits of noninvasive ventilation for bronchiolitis has been precluded in part by the absence of large, adequately powered studies. The objectives of this study were to characterize temporal trends in and associations between the use of noninvasive ventilation in bronchiolitis and two clinical outcomes, invasive ventilation, and cardiac arrest., Design: Multicenter retrospective cross-sectional study., Setting: Forty-nine U.S. children's hospitals participating in the Pediatric Health Information System database., Patients: Infants under 12 months old who were admitted from the emergency department with bronchiolitis between January 1, 2010, and December 31, 2018., Measurements and Main Results: Primary outcomes were rates of noninvasive ventilation, invasive ventilation, and cardiac arrest. Trends over time were assessed with univariate logistic regression. In the main analysis, hospital-level multivariable logistic regression evaluated rates of outcomes including invasive ventilation and cardiac arrest among hospitals with high and low utilization of noninvasive ventilation. The study included 147,288 hospitalizations of infants with bronchiolitis. Across the entire study population, noninvasive and invasive ventilation increased between 2010 and 2018 (2.9-8.7%, 2.1-4.0%, respectively; p < 0·001). After adjustment for markers of severity of illness, hospital-level noninvasive ventilation (high vs low utilization) was not associated with differences in invasive ventilation (5.0%, 1.8%, respectively, adjusted odds ratio, 1.8; 95% CI, 0·7-4·6) but was associated with increased cardiac arrest (0.36%, 0.02%, respectively, adjusted odds ratio, 25.4; 95% CI, 4.9-131.0)., Conclusions: In a large cohort of infants at children's hospitals, noninvasive and invasive ventilation increased significantly from 2010 to 2018. Hospital-level noninvasive ventilation utilization was not associated with a reduction in invasive ventilation but was associated with higher rates of cardiac arrest even after controlling for severity. Noninvasive ventilation in bronchiolitis may incur an unintended higher risk of cardiac arrest, and this requires further investigation., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Increasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy., Methods: This study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5-7 and 10-13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5-7 years of age and from 89 participants with flow-volume spirometry at 10-13 years of age., Results: Asthma diagnosis at <12 months of age showed a significant association with irreversible airway obstruction at 10-13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5-7 years of age were associated with irreversible airway obstruction at 10-13 years of age., Conclusion: Asthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10-13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neurological morbidity is a growing concern in children with severe bronchiolitis. The aim of the study was to evaluate the frequency of occurrence and the factors associated with seizures in very young infants < 3 months of age, admitted to a pediatric intensive care unit (PICU) for severe bronchiolitis. We performed a single center retrospective cohort study evaluating occurrence of seizures in infants admitted to the PICU between 2010 and 2018 for severe bronchiolitis. We described characteristics of the patients, laboratory test, brain imaging, and electroencephalogram results, as well as the treatment used. We conducted a multivariable logistic regression to identify factors associated with the occurrence of seizures. A p value < 0.05 was considered significant. A total of 805 patients were included in the study; 722 (89.6%) were mechanically ventilated. Twenty-six infants (3.2%, 95% confidence interval, 95% CI [2.1%; 4.7%]) had seizures shortly prior to admission or during PICU stay. In the multivariable analysis, hyponatremia (odds ratio, OR: 4.6, 95%CI [1.86; 11.43], p = 0.001) and invasive ventilation (OR: 2.6, 95% CI [1.14; 5.9], p < 0.001) were associated with an increased likelihood of seizures occurrence.Conclusion: Seizures occur in at least 3% of very young infants with severe bronchiolitis, and the characteristics of these are different to those experienced by older infants, but they shared the same risk factors (hyponatremia and mechanical ventilation). This highlights the extrapulmonary morbidity associated with bronchiolitis in this population. What is Known: • Bronchiolitis is the leading cause of pediatric intensive care admission and use of mechanical ventilation in infants. • Neurological morbidities have to be investigated in this population at risk of neurological complications. What is New: • Seizure is a complication in at least 3% of very young infants with severe bronchiolitis. • Seizure characteristics are different, but the main risk factors are the same than in older infants (hyponatremia and mechanical ventilation)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

Objectives: Acute bronchiolitis commonly causes respiratory failure in children ≤2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities., Methods: Hospital discharge records of children with bronchiolitis aged ≤2 years were obtained for 1997-2012 from the Kid's Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities., Results: There were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n = 8697) was more likely to have OSA [241 (2.77%) vs 1293 (0.14%), p < 0.001] compared to the non-DS group (n = 920,264). Multivariable logistic regression showed that OSA was associated with IMV (adjusted odds ratio [OR], 3.32 [95% CI 2.54-4.35], p < 0.0001) in all children with bronchiolitis; and in those with DS, it was associated with IMV (adjusted OR, 2.34 [95% CI 1.38-3.97], p = 0.002), NIMV (adjusted OR, 8.21 [95% CI 4.48-15.04], p < 0.0001) and IACH (adjusted β, 0.18 [95% CI 0.02-0.34], p = 0.031)., Conclusions: OSA is independently associated with assisted ventilation in all children hospitalized with bronchiolitis, regardless of DS-associated comorbidities in those with DS. The severity of bronchiolitis in children with DS may be driven by the high prevalence of OSA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Young children with rhinovirus (RV) infection-particularly bronchiolitis-are at high risk for developing childhood asthma. Emerging evidence suggests clinical heterogeneity within RV bronchiolitis. However, little is known about these biologically distinct subgroups (endotypes) and their relations with asthma risk., Objective: We aimed to identify RV bronchiolitis endotypes and examine their longitudinal relations with asthma risk., Methods: As part of a multicenter prospective cohort study of infants (age <12 months) hospitalized for bronchiolitis, we integrated clinical, RV species (RV-A, RV-B, and RV-C), nasopharyngeal microbiome (16S rRNA gene sequencing), cytokine, and metabolome (liquid chromatography tandem mass spectrometry) data collected at hospitalization. We then applied network and clustering approaches to identify bronchiolitis endotypes. We also examined their longitudinal association with risks of developing recurrent wheeze by age 3 years and asthma by age 5 years., Results: Of 122 infants hospitalized for RV bronchiolitis (median age, 4 months), we identified 4 distinct endotypes-mainly characterized by RV species, microbiome, and type 2 cytokine (T2) response: endotype A, virus RV-C microbiome mixed T2 low ; endotype B, virus RV-A microbiome Haemophilus T2 low ; endotype C, virus RSV/RV microbiome Streptococcus T2 low ; and endotype D, virus RV-C microbiome Moraxella T2 high . Compared with endotype A infants, endotype D infants had a significantly higher rate of recurrent wheeze (33% vs 64%; hazard ratio, 2.23; 95% CI, 1.00-4.96; P = .049) and a higher risk for developing asthma (28% vs 59%; odds ratio, 3.74: 95% CI, 1.21-12.6; P = .03)., Conclusions: Integrated-omics analysis identified biologically meaningful RV bronchiolitis endotypes in infants, such as one characterized by RV-C infection, Moraxella-dominant microbiota, and high T2 cytokine response, at higher risk for developing recurrent wheeze and asthma. This study should facilitate further research toward validating our inferences., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: 25(OH) vitamin D levels are inversely associated with respiratory infections and childhood wheezing., Objective: To evaluate serum 25(OH) vitamin D levels in infants and toddlers with acute bronchiolitis, compared to subjects with non-respiratory febrile illness., Methods: A prospective cross-sectional case-control study which compared serum 25(OH) vitamin D levels between infants and toddlers diagnosed with acute bronchiolitis to subjects with non-respiratory febrile illness. Multivariate logistic regression, adjusted for age, sex, ethnicity and nutrition was performed. Correlation between serum vitamin D levels and bronchiolitis severity was assessed via Modified Tal Score and length of hospital stay (LOS)., Results: One hundred twenty-seven patients aged < 24 months were recruited; 80 diagnosed with acute bronchiolitis and 47 patients with non- respiratory febrile illnesses. Both groups had similar demographics aside from age (median [IQR] 5 [3-9] vs. 9 [5-16] months in the bronchiolitis group compared to control group (p = 0.002)). Serum 25(OH) vitamin D levels were significantly lower in the bronchiolitis group; median [IQR] 28[18-52] vs. 50[25-79] nmol/L, respectively, (p = 0.005). Deficient vitamin D levels (< 50 nmol/L) was found more frequently in the bronchiolitis group than controls; 73% vs. 51% (p = 0.028). Multivariate logistic regression showed vitamin D deficiency was more probable in bronchiolitis patients; OR [95% CI] 3.139[1.369-7.195]. No correlation was found between serum vitamin D levels and bronchiolitis severity, which was assessed via Modified Tal Score and by length of hospital stay., Conclusion: Children with acute bronchiolitis displayed significantly lower vitamin D levels than children with non-respiratory acute febrile illnesses.

Background: Bronchiolitis is a common cause of hospitalisation of infants less than a year old, with most infants recovering without complications. Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis. Antimicrobial stewardship programmes do not recommend antibiotics for viral infections in neonates unless documented evidence of secondary bacterial infection is present., Case Report: We present the case of a 7-day-old infant admitted to hospital with chest retractions and fever. The baby was hospitalised, empirical antibiotic therapy was administered, and non-invasive ventilation was started. When the viral aetiology was identified and clinical conditions improved, antibiotics were discontinued. However, after 48 hours, the newborn's condition worsened because of pneumococcal septic shock. Intravenous fluids, catecholamine support, and wide-spectrum antibiotics were administered. Non-invasive ventilation was re-started and continued until the full recovery., Conclusions: There is increasing evidence that RSV and S. pneumoniae co-infect and interact with each other, thus increasing respiratory diseases' severity. We provide a brief overview of the main international guidelines for managing bronchiolitis. Guidelines suggest avoidance of antibiotics use when the diagnosis of viral bronchiolitis is confirmed. We discuss the uncertainties regarding antibiotic use, especially in younger infants, who are more exposed to risks of bacterial superinfection.

The Pediatric Acute Lung Injury Consensus Conference (PALICC) published pediatric-specific guidelines for the definition, management, and research in pediatric acute respiratory distress syndrome (PARDS). Acute viral bronchiolitis (AVB) remains one of the leading causes of admission to PICU. Respiratory syncytial virus (RSV) is the most common cause of AVB. We aimed to evaluate the incidence of PARDS in AVB and identify the risk of RSV as a trigger pathogen for PARDS. This study is a retrospective single-center observational cohort study including children < 2 years of age admitted to the pediatric intensive care unit at St Mary's Hospital, London, and presented with AVB in 3 years (2016-2018). Clinical and demographic data was collected; PALICC criteria were applied to define PARDS. Data was expressed as median (IQR range); non-parametric tests were used. In this study, 144 infants with acute viral bronchiolitis were admitted to PICU in the study period. Thirty-nine infants fulfilled criteria of PARDS with RSV as the most common virus identified. Bacterial infection was identified as a risk factor for development of PARDS in infants with AVB.Conclusion: AVB is an important cause of PARDS in infants. RSV is associated with a higher risk of PARDS in AVB. Bacterial co-infection is a significant risk factor for development of PARDS in AVB. What is Known: • Bronchiolitis is a common cause of respiratory failure in children under 2 years. • ARDS is a common cause of PICU admission. What is New: • Evaluation of bronchiolitis as a cause of PARDS according to the PALLIC criteria. • Evaluation of different viruses' outcome in PARDS especially RSV as a commonest cause of AVB.

Case Presentation: A 54-year-old man sought treatment at the ED for a productive cough with green phlegm of approximately 6 months' duration that was accompanied by a 10-pound weight loss, night sweats, and occasional subjective fevers. He had made several prior visits to the ED for the cough and was hospitalized 4 months earlier for similar symptoms, at which time he underwent a bronchoscopy with BAL and was discharged with antibiotics for presumed pneumonia. He did not report any itching, rashes, sinus infections, joint swelling, joint pain, or GI symptoms. His long-term medications included omeprazole and amlodipine. The patient had a past medical history of grade III follicular lymphoma for which he completed six cycles of bendamustine 4 years before presentation and had been in remission since. He was a never smoker, had a recent travel history to the Dominican Republic 8 months before admission, and had no recent sick contacts., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty-one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed for up to the age of 3 years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L-lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism, and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L-lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood., (© 2020 APMIS. Published by John Wiley & Sons Ltd.)

Background: Acute respiratory illnesses cause substantial morbidity worldwide. Cough is a common symptom in these childhood respiratory illnesses, but no large cohort data are available on whether various cough characteristics can differentiate between these etiologies., Research Question: Can various clinically based cough characteristics (frequency [daytime/ nighttime], the sound itself, or type [wet/dry]) be used to differentiate common etiologies (asthma, bronchiolitis, pneumonia, other acute respiratory infections) of acute cough in children?, Study Design and Methods: Between 2017 and 2019, children aged 2 weeks to ≤16 years, hospitalized with asthma, bronchiolitis, pneumonia, other acute respiratory infections, or control subjects were enrolled. Spontaneous coughs were digitally recorded over 24 hours except for the control subjects, who provided three voluntary coughs. Coughs were extracted and frequency defined (coughs/hour). Cough sounds and type were assessed independently by two observers blinded to the clinical data. Cough scored by a respiratory specialist was compared with discharge diagnosis using agreement (Cohen's kappa coefficient [қ]), sensitivity, and specificity. Caregiver-reported cough scores were related with objective cough frequency using Spearman coefficient (r s )., Results: A cohort of 148 children (n = 118 with respiratory illnesses, n = 30 control subjects), median age = 2.0 years (interquartile range, 0.7-3.9), 58% males, and 50% First Nations children were enrolled. In those with respiratory illnesses, caregiver-reported cough scores and wet cough (range, 42%-63%) was similar. Overall agreement in diagnosis between the respiratory specialist and discharge diagnosis was slight (қ = 0.13; 95% CI, 0.03 to 0.22). Among diagnoses, specificity (8%-74%) and sensitivity (53%-100%) varied. Interrater agreement in cough type (wet/dry) between blinded observers was almost perfect (қ = 0.89; 95% CI, 0.81 to 0.97). Objective cough frequency was significantly correlated with reported cough scores using visual analog scale (r s  = 0.43; bias-corrected 95% CI, 0.25 to 0.56) and verbal categorical description daytime score (r s  = 0.39; bias-corrected 95% CI, 0.22 to 0.54)., Interpretation: Cough characteristics alone are not distinct enough to accurately differentiate between common acute respiratory illnesses in children., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

Background: The close association between bronchiectasis and nontuberculous mycobacterial pulmonary disease (NTM-PD) is well-known. However, the clinical impact of subsequent new-onset NTM-PD in bronchiectasis patients has not been elucidated. The aim of this study is to investigate the clinical courses and radiographic changes of patients with bronchiectasis in whom NTM-PD subsequently developed., Methods: A total of 221 patients with bronchiectasis who had participated in a non-NTM bronchiectasis cohort between July 1st 2011 and August 31st 2019 at Seoul National University Hospital were included in this study. The data of patients in whom NTM-PD developed during this observation period were analyzed; specifically, changes in the Bronchiectasis Severity Index (BSI) and lesions on computerized tomography (CT) scan of the chest arising during the observation period., Results: During the observation period, NTM was isolated from 35 patients. A total of 31 patients (14.0%) satisfied the diagnostic criteria of NTM-PD. The median time from enrollment in the cohort to the development of subsequent NTM-PD was 37 months (Interquartile range [IQR], 18-78 months). Mycobacterium avium complex was the most common pathogen (80.6%). Twelve patients underwent antibiotic treatment for NTM-PD with a median interval of 20 months (IQR, 13-30) from the time of NTM-PD diagnosis. When NTM-PD developed, the severity and extent of bronchiectasis, cellular bronchiolitis, and the extent of nodules worsened on CT scans, while BSI did not change., Conclusions: NTM-PD can develop in previously negative bronchiectasis patients. It is associated with worsening radiographic lesions. Active screening of non-NTM bronchiectasis patients for new-onset NTM infection should be considered, especially if radiographic findings worsen. The BSI is not a reliable predictor of new-onset NTM-PD., Trial Registration: This study was performed at Seoul National University Hospital ( NCT01616745 ).

Background: Bronchiolitis is often described to follow an expected clinical trajectory, with a peak in severity between days 3 and 5. This predicted trajectory may influence anticipatory guidance and clinical decision-making. We aimed to determine the association between day of illness at admission and outcomes, including hospital length of stay, receipt of positive-pressure ventilation, and total cough duration., Methods: We compiled data from 2 multicenter prospective studies involving bronchiolitis hospitalizations in patients <2 years. Patients were excluded for complex conditions. We assessed total cough duration via weekly postdischarge phone calls. We used mixed-effects multivariable regression models to test associations between day of illness and outcomes, with adjustment for age, sex, insurance (government versus nongovernment), race, and ethnicity., Results: The median (interquartile range) day of illness at admission for 746 patients was 4 (2-5) days. Day of illness at admission was not associated with length of stay (coefficient 0.01 days, 95% confidence interval [CI]: -0.05 to 0.08 days), positive-pressure ventilation (adjusted odds ratio: 1.0, 95% CI: 0.9 to 1.1), or total cough duration (coefficient 0.33 days, 95% CI: -0.01 to 0.67 days). Additionally, there was no significant difference in day of illness at discharge in readmitted versus nonreadmitted patients (5.9 vs 6.4 days, P = .54). The median cough duration postdischarge was 6 days, with 65 (14.3%) patients experiencing cough for 14+ days., Conclusions: We found no associations between day of illness at admission and outcomes in bronchiolitis hospitalizations. Practitioners should exercise caution when making clinical decisions or providing anticipatory guidance based on symptom duration., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Although nearly 3,000 e-cigarette-related hospitalizations have been reported in North America, the long-term outcomes in these patients have not been described. We followed an 18-year-old boy who survived acute critical illness and respiratory failure related to 5 months of e-cigarette use. Chronic irreversible airflow obstruction and markedly abnormal 129 Xe MRI ventilation heterogeneity was observed and persisted 8 months after hospital discharge, despite improvement in quality-of-life and chest CT findings. Lung clearance index and oscillometry measures were also highly abnormal at 8 months postdischarge. Although 129 Xe MRI ventilation abnormalities were dominant in the lung apices and central lung regions, the pattern of ventilation defects was dissimilar to ventilation heterogeneity observed in patients with obstructive lung disease, such as asthma and COPD. Our findings underscore the long-term functional impacts of e-cigarette-related lung injury in survivors of critical illness; longitudinal evaluations may shed light on the pathophysiologic mechanisms that drive e-cigarette-related lung disease., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Importance: Posthospitalization follow-up visits are prescribed frequently for children with bronchiolitis. The rationale for this practice is unclear, but prior work has indicated that families value these visits for the reassurance provided. The overall risks and benefits of scheduled visits have not been evaluated., Objective: To assess whether an as-needed posthospitalization follow-up visit is noninferior to a scheduled posthospitalization follow-up visit with respect to reducing anxiety among parents of children hospitalized for bronchiolitis., Design, Setting, and Participants: This open-label, noninferiority randomized clinical trial, performed between January 1, 2018, and April 31, 2019, assessed children younger than 24 months of age hospitalized for bronchiolitis at 2 children's hospitals (Primary Children's Hospital, Salt Lake City, Utah, and Lucile Packard Children's Hospital, Palo Alto, California) and 2 community hospitals (Intermountain Riverton Hospital, Riverton, Utah, and Packard El Camino Hospital, Mountain View, California). Data analysis was performed in an intention-to-treat manner., Interventions: Randomization (1:1) to a scheduled (n = 151) vs an as-needed (n = 153) posthospitalization follow-up visit., Main Outcome and Measures: The primary outcome was parental anxiety 7 days after hospital discharge, measured using the anxiety portion of the Hospital Anxiety and Depression Scale, which ranged from 0 to 28 points, with higher scores indicating greater anxiety. Fourteen prespecified secondary outcomes were assessed., Results: Among 304 children randomized (median age, 8 months; interquartile range, 3-14 months; 179 [59%] male), the primary outcome was available for 269 patients (88%). A total of 106 children (81%) in the scheduled follow-up group attended a scheduled posthospitalization visit compared with 26 children (19%) in the as-needed group (absolute difference, 62%; 95% CI, 53%-71%). The mean (SD) 7-day parental anxiety score was 3.9 (3.5) among the as-needed posthospitalization follow-up group and 4.2 (3.5) among the scheduled group (absolute difference, -0.3 points; 95% CI, -1.0 to 0.4 points), with the upper bound of the 95% CI within the prespecified noninferiority margin of 1.1 points. Aside from a decreased mean number of clinic visits (absolute difference, -0.6 visits per patient; 95% CI, -0.4 to -0.8 visits per patient) among the as-needed group, there were no significant between-group differences in secondary outcomes, including readmissions (any hospital readmission before symptom resolution: absolute difference, -1.6%; 95% CI, -5.7% to 2.5%) and symptom duration (time from discharge to cough resolution: absolute difference, -0.6 days; 95% CI, -2.4 to 1.2 days; time from discharge to child reported "back to normal": absolute difference, -0.8 days; 95% CI, -2.7 to 1.0 days; and time from discharge to symptom resolution: absolute difference, -0.6 days; 95% CI, -2.5 to 1.3 days)., Conclusions and Relevance: Among parents of children hospitalized for bronchiolitis, an as-needed posthospitalization follow-up visit is noninferior to a scheduled posthospitalization follow-up visit with respect to reducing parental anxiety. These findings support as-needed follow-up as an effective posthospitalization follow-up strategy., Trial Registration: ClinicalTrials.gov Identifier: NCT03354325.

Background and Objectives: International patterns of antibiotic use and laboratory testing in bronchiolitis in emergency departments are unknown. Our objective is to evaluate variation in the use of antibiotics and nonindicated tests in infants with bronchiolitis in 38 emergency departments in Pediatric Emergency Research Networks in Canada, the United States, Australia and New Zealand, the United Kingdom and Ireland, and Spain and Portugal. We hypothesized there would be significant variation, adjusted for patient characteristics., Methods: We analyzed a retrospective cohort study of previously healthy infants aged 2 to 12 months with bronchiolitis. Variables examined included network, poor feeding, dehydration, nasal flaring, chest retractions, apnea, saturation, respiratory rate, fever, and suspected bacterial infection. Outcomes included systemic antibiotic administration and urine, blood, or viral testing or chest radiography (CXR)., Results: In total, 180 of 2359 (7.6%) infants received antibiotics, ranging from 3.5% in the United Kingdom and Ireland to 11.1% in the United States. CXR (adjusted odds ratio [aOR] 2.3; 95% confidence interval 1.6-3.2), apnea (aOR 2.2; 1.1-3.5), and fever (aOR 2.4; 1.7-3.4) were associated with antibiotic use, which did not vary across networks ( P = .15). In total, 768 of 2359 infants (32.6%) had ≥1 nonindicated test, ranging from 12.7% in the United Kingdom and Ireland to 50% in Spain and Portugal. Compared to the United Kingdom and Ireland, the aOR (confidence interval) results for testing were Canada 5.75 (2.24-14.76), United States 4.14 (1.70-10.10), Australia and New Zealand 2.25 (0.86-5.74), and Spain and Portugal 3.96 (0.96-16.36). Testing varied across networks ( P < .0001) and was associated with suspected bacterial infections (aOR 2.12; 1.30-2.39) and most respiratory distress parameters. Viral testing (591 of 768 [77%]) and CXR (507 of 768 [66%]) were obtained most frequently., Conclusions: The rate of antibiotic use in bronchiolitis was low across networks and was associated with CXR, fever, and apnea. Nonindicated testing was common outside of the United Kingdom and Ireland and varied across networks irrespective of patient characteristics., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Infants with the respiratory syncytial virus (RSV) and human rhinovirus respiratory infection (HRV) produce inflammatory interleukins (ILs) in the respiratory epithelium. The aim of this study was to evaluate the levels of interleukin-8 in RSV negative and RSV positive patients. This study search was conducted without a time limit until 2020 through the databases of PubMed, Wiley, Springer, ScienceDirect and Google Scholar search engines, by two researchers independently. The random-effects model was used to compare of interleukin-8 in RSV negative vs. RSV positive patients, using Revman software version 5 meta-analysis software. Totally, 921 patients were evaluated (207 RSV-negative and 714 RSV-positive). The mean concentration of IL8 in RSV positive patients was 15.02 pg/ml (95% CI: 13.68- 16.35%).  According to the meta-analysis results, the standardized mean difference (SMD) of IL8 concentration between RSV-positive and negative patients was 6.31 pg/ml) (95% confidence interval: 2.50- 10.13%). subtotal analysis of the IL8 laboratory assessment method revealed that there was no significant SMD deference in the studies that have used chemiluminescence (P=0.21). while IL8 concentrations were significantly higher in RSV positives in ELISA and Magnetic bead-based assays (P&lt;0.05).  It appears that RSV positive patients may have greater levels of IL8 than RSV negative ones; whereas the synthesis of IL8 tends to be more secreted into the nasopharyngeal space; whereas the evaluation approach can also affect the results.