Bronchiolitis In Infants Research Articles

Perfil clí­nico epidemiológico de bronquitis en lactantes atendidos en el Hospital II de Chocope

Este estudio tiene como finalidad determinar el perfil clínico epidemiológico de bronquiolitis en lactantes atenidos en el Hospital II Chocope, durante los años 2007 al 2016. Para ello se utilizó un método descriptivo, transversal; con una población de 984 lactantes. Durante los 10 años estudiados se encontró una incidencia del 5% al 10% de bronquiolitis, el grupo etario más frecuente estuvo entre los 6 a 12 meses; el género masculino se presentó entre un 61% a 82% y el femenino entre 18% a 39%. Entre los factores de riesgo estudiados se encontró que 91% tenía como factor de riesgo, atopia familiar; la prematuridad se encontró entre un 1% a 7%; cardiopatía congénita en un 1%; el tipo de lactancia materna exclusiva 30% a 69%, formula 7% a 37%, lactancia mixta 26% a 52%; las características clínicas más frecuentes fueron la tos, rinorrea, dificultad para alimentarse y taquipnea; el grado de severidad leve entre un 44% a 81%, moderada 14% a 36% y severa 7% a 19%; los signos de alarmas más saltantes fueron la fiebre y la pobre succión; los pacientes evolucionaron a la remisión entre un 58% a 88%, recaídas entre un 12% a 40%, no se reportaron muerte.

Prevention of Pediatric Respiratory Syncytial Virus Lower Respiratory Tract Illness: Perspectives for the Next Decade.

The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.

Acute Bronchiolitis in Infants and Allergic Asthma

Acute Bronchiolitis in Infants and Allergic Asthma

Toll-like receptor 1 and 10 variations increase asthma risk and review highlights further research directions.

This paper summarises variations in the genes encoding toll-like receptors (TLRs) in relation to the aetiology and outcome of infant bronchiolitis. It compares the literature with research carried out by our group. A mini review was conducted to provide context for a study carried out at the Department of Paediatrics, Tampere University Hospital, Finland. In 2000-2004, 187 infants were hospitalised for bronchiolitis and then followed up: 129 at 1.5years of age, 166 at 5-7years of age and 138 at 11-13years of age. The review showed that the Finnish bronchiolitis study was the only prospective study on the association between TLRs and the emergence of childhood asthma or lung function reduction after bronchiolitis in infancy. It found that TLR1 and TLR10 variant genotypes were associated with more asthma at 5-7 and 11-13years, with inconsistent results for the other eight TLR genes. Large population-based studies were also identified that stressed the importance of the TLR2 subfamily members in childhood asthma. Our study found that variations in the TLR1 and TLR10 genes increased the asthma risk after bronchiolitis. The mini review calls for further research on the TLR2 subfamily in bronchiolitis and childhood asthma.

Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus.

The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.

Preschool respiratory hospital admissions following infant bronchiolitis: a birth cohort study

BackgroundBronchiolitis causes significant infant morbidity worldwide from hospital admissions. However, studies quantifying the subsequent respiratory burden in children under 5 years are lacking.ObjectiveTo estimate the risk of subsequent respiratory hospital...

Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial.

Monoclonal antibody to respiratory syncytial virus (RSV; palivizumab) is recommend for prophylaxis of high-risk infants during bronchiolitis seasons but not for RSV bronchiolitis treatment. Our aim was to determine if palivizumab would be helpful in young infants with acute RSV bronchiolitis. Eligible infants ≤3 months old presenting to the pediatric emergency service with RSV-positive bronchiolitis requiring inpatient admission underwent double-blind random assignment to single-dose intravenous palivizumab (15 mg/kg) or placebo. The primary efficacy outcome was the need for inpatient readmission in the 3 weeks after discharge. Secondary outcomes were time to readiness for hospital discharge, need for PICU on the initial admission, and need for revisit not requiring readmission for the same illness during 3-week follow-up. A total of 420 infants (median age 49 days) diagnosed with RSV bronchiolitis were randomly assigned; 417 received treatment, and 413 completed follow-up. Readmission during follow-up was needed for 23 (11%) patients on palivizumab and 19 (9.3%) patients in the placebo group (difference 1.8%; 95% confidence interval -4.4% to 7.7%; P = .51). Geometric mean time to readiness for discharge was 29.5 hours for the palivizumab group and 30.2 hours for the placebo group (ratio 0.98; 95% confidence interval 0.81 to 1.20). No safety issues were reported. Intravenous palivizumab did not appear to help or harm young infants with acute RSV-positive bronchiolitis.

High-flow Oxygen Therapy for Treating Bronchiolitis in Infants.

High-flow Oxygen Therapy for Treating Bronchiolitis in Infants.

Estimating seasonal onsets and peaks of bronchiolitis with spatially and temporally uncertain data.

RSV bronchiolitis (an acute lower respiratory tract viral infection in infants) is the most common cause of infant hospitalizations in the United States (US). The only preventive intervention currently available is monthly injections of immunoprophylaxis. However, this treatment is expensive and needs to be administered simultaneously with seasonal bronchiolitis cycles in order to be effective. To increase our understanding of bronchiolitis timing, this research focuses on identifying seasonal bronchiolitis cycles (start times, peaks, and declinations) throughout the continental US using data on infant bronchiolitis cases from the US Military Health System Data Repository. Because this data involved highly personal information, the bronchiolitis dates in the dataset were "jittered" in the sense that the recorded dates were randomized within a time window of the true date. Hence, we develop a statistical change point model that estimates spatially varying seasonal bronchiolitis cycles while accounting for the purposefully introduced jittering in the data. Additionally, by including temperature and humidity data as regressors, we identify a relationship between bronchiolitis seasonality and climate. We found that, in general, bronchiolitis seasons begin earlier and are longer in the southeastern states compared to the western states with peak times lasting approximately 1 month nationwide.

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus.

PurposeRespiratory syncytial virus (RSV) can cause serious respiratory illnesses such as pneumonia, asthma, and bronchiolitis in infants and elderly or immunocompromised individuals. An RSV vaccine has yet to be developed; only prophylactic anti-RSV antibody is commercially available. So, we investigated whether our vaccine candidate is able to induce type 1 CD4+ T helper (Th1), CD8+ T-cell responses, and protective immunity without vaccine-enhanced disease (VED) against RSV.Materials and MethodsWe used RSV G protein fragment (Gcf A) with recombinant baculovirus capable of expressing the RSV M2 protein (Bac M2) as a vaccine candidate, and injected this vaccine (Gcf A/Bac M2) intramuscularly, and challenged with RSV intranasally into mice. Enzyme-linked immunosorbent assay, flow cytometry, plaque assay, and weight measurement were performed to confirm humoral immunity, cellular immunity, and protective immunity.ResultsThe Gcf A/Bac M2 formulation induced a stronger IgG response to Gcf A than Gcf A inoculation alone, and the ratio of IgG1/IgG2a indicated that the responses shifted predominantly to Th1. In addition, both RSV G-specific Th1 responses and RSV M2-specific CD8+ T-cell responses were induced, and G protein-associated eosinophilic infiltration was suppressed compared to the control group. Moreover, the Gcf A/Bac M2 group showed effective protection after an RSV challenge.ConclusionBac M2 could serve as a vaccine with intrinsic adjuvant activity, and the Gcf A/Bac M2 shows promise as a vaccine candidate for inducing protective immunity without inciting VED.

RSV versus non-RSV bronchiolitis in infants and young children – the bedside characteristics of one epidemic season

RSV versus non-RSV bronchiolitis in infants and young children – the bedside characteristics of one epidemic season

Respiratory syncytial virus: diagnosis, prevention and management.

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection.

1335. Safety and Pharmacokinetic Profile of PC786, a Novel Inhibitor of Respiratory Syncytial Virus L-protein Polymerase, in a Single and Multiple-Ascending Dose Study in Healthy Volunteer and Mild Asthmatics

BackgroundRSV is the most common cause of bronchiolitis in infants and is responsible for severe respiratory infections in the elderly and immunocompromised populations. RSV replicates in the columnar epithelial cells of the proximal and distal airways which are accessible to inhaled therapies. PC786 is a potent non-nucleoside RSV L-protein polymerase inhibitor designed for inhaled delivery. In preclinical studies, PC786 exhibits prolonged lung tissue residence with minimal systemic exposure, thus limiting the potential for adverse systemic effects.MethodsA phase 1 study was conducted to evaluate the safety and pharmacokinetics of PC786 delivered in a suspension formulation by nebulizer (PARI LC SPRINT® device). Healthy volunteers (HVs) received placebo or PC786 as single ascending doses (0.5–20 mg, Cohort (C) 1), 5 mg BD for 7 days (C2), or 10 mg BD for 7 days (C3). Mild asthmatics received a single dose of PC786 5 mg or placebo (C4). PC786 PK was measured in plasma and in nasal mucosal lining fluid (MLF) collected using a synthetic absorptive matrix.ResultsPC786 was well tolerated, with no significant adverse clinical nor laboratory findings. Following single inhaled doses PC786 appeared rapidly in the plasma; mean plasma Cmax of 190, 571, 1,760, and 3,270 pg/mL, for the 0.5, 2, 8, and 20 mg doses, respectively, were measured on average at 0.68 to 0.93 hours (Tmax) post-inhalation. Following administration of 5 mg BD (C2) the extent of accumulation was approximately 2-fold. The geometric mean apparent terminal half-life measured following 10 mg BD (C3) was 97 hours. The ratio of MLF:plasma concentrations ranged from 6,347 (+2 hours) to 1,050 (+24h).ConclusionPC786 was well tolerated by HVs and asthmatics. The compound showed a rapid Tmax, suggesting rapid exposure of the respiratory epithelium. The PC786 concentrations in MLF exceed the IC90 for RSV, but circulating plasma concentrations were low. The MLF:plasma measured in this study was consistent with lung:plasma ratios measured in preclinical studies. The long plasma half-life is consistent with slow absorption from the lung being the dominant process controlling systemic kinetic behavior. The long t½ and 2-fold accumulation ratio observed on repeat dosing supports once daily dosing in subsequent studies.Disclosures L. Cass, Pulmocide Ltd.: Employee and Shareholder, Salary. A. Davis, Pulmocide Ltd.: Employee and Shareholder, Salary. A. Murray, Pulmocide Ltd.: Employee and Shareholder, Salary. K. Woodward, Pulmocide Ltd.: Consultant, Consulting fee. K. Ito, Pulmocide Ltd.: Employee and Shareholder, Salary. P. Strong, Pulmocide Ltd.: Board Member, Employee and Shareholder, Salary. G. Rapeport, Pulmocide Ltd.: Board Member, Employee and Shareholder, Salary.

Prolonged slow expiration technique improves recovery from acute bronchiolitis in infants: FIBARRIX randomized controlled trial

Objective: To examine the effect of prolonged slow expiration respiratory physiotherapy treatment on the acute bronchiolitis severity scale and O2 saturation at short-time and at medical discharge in infants and the hospital stay. Design: Randomized controlled trial. Setting: Infants’ unit of university hospital. Participants: Infants with acute bronchiolitis (N = 80). Intervention: Infants were randomized into respiratory treatment (RT) with prolonged slow expiration or treatment as usual (control) for one-week period. Main outcome measures: The primary outcomes were Acute Bronchiolitis Severity Scale score and O2 saturation, recorded shortly after each intervention during the stay and at medical discharge, and the hospital stay. Results: The RT had a significantly lower Acute Bronchiolitis Severity Scale 10-minute after the first intervention (mean difference −1.7 points, 95% confidence interval (CI) −3.0 to −0.38), 2 hours after (–2.0 points, 95% CI −3.2 to −0.86) and the last day before medical discharge (−1.3 points, 95% CI −2.1 to 0.51). No changes were detected in O2 saturation. The survival analysis of time at medical discharge showed decrease in the average number of days to achieve an Acute Bronchiolitis Severity Scale of less than 2 points (RT: 2.6 days, 95% CI 2.1–3.1; Control: 4.4 days, 95% CI 3.6–5.1). Conclusion: A prolonged slow expiration physiotherapy reduces Acute Bronchiolitis Severity Scale scores and does not change O2 saturation. Infants in RT group stay less days in hospital than infants in control group and no adverse events were detected.

Population-based trends and underlying risk factors for infant respiratory syncytial virus and bronchiolitis hospitalizations.

ObjectiveRespiratory syncytial virus (RSV) is a common pathogen during infancy, with the potential to cause serious disease and mortality in high-risk groups. The objective of this study was to characterize trends of RSV and bronchiolitis hospitalizations in the first year in a population-based cohort and assess differences in trends according to risk status.MethodsUsing an observational retrospective cohort design, we examined a California population-based dataset of vital statistics linked to hospital discharge data for up to 1 year after birth from 1997–2011. Infants were categorized by medical condition and then by gestational age. Medical conditions of interest included chronic lung disease, certain congenital heart diseases, or others known to affect risk for developing severe bronchiolitis. The primary outcome was hospitalization due to RSV; secondary outcome was hospitalization for unspecified bronchiolitis (UB) not coded as RSV. Annual person-year rates were calculated for infants <12 months of age during January to December of each year.ResultsOf 7,298,401 infants born during the study period, 121,230 (1.7%) had a medical condition associated with risk; these infants experienced 6853 RSV and 6568 UB hospitalizations in the first year. In infants without medical conditions, 96,694 RSV and 69,886 UB hospitalizations occurred. All-cause infant hospitalizations declined over time from 12.2 to 9.3 per 100 person-years. RSV hospitalization rates for infants with medical conditions decreased from 7.6 to 3.4 per 100 person-years, with the largest relative decline in infants with chronic lung disease (12.0 to 5.0 per 100 person-years). For infants without medical conditions, RSV hospitalizations declined from 1.4 to 0.8 per 100 person-years, with greater decreases among preterm infants with earlier gestational age. UB hospitalization rates remained relatively stable across the study years, from 6.2 to 5.4 and 1.0 to 0.8 per 100 person-years for infants with and without medical conditions.ConclusionsVarious interventions may have contributed to observed decreases in RSV hospitalizations from 1998–2011, which were greater in high-risk populations recommended for RSV immunoprophylaxis and not observed with UB. Further efforts to promote evidence-based practice and optimal targeting of appropriate interventions will ensure continued improvement in care for vulnerable infants.

Prevalence of infant bronchiolitis-coded healthcare encounters attributable to RSV.

AimWe sought to determine the proportion of bronchiolitis episodes attributable to respiratory syncytial virus (RSV) among ICD‐9 coded infant bronchiolitis episodes which were tested for RSV.MethodsBronchiolitis healthcare encounters were extracted from Kaiser Permanente Northern California databases for years 2006 to 2009. We used ICD‐9 codes for bronchiolitis to capture bronchiolitis‐related healthcare encounters including hospital admissions (Hospitalization), emergency department visits (EDV), and outpatient visits (OPV). We reported the monthly proportion of RSV‐positive bronchiolitis episodes among tested bronchiolitis episodes. We used logistic regression to assess association between bronchiolitis episodes and patient demographic and health care characteristics. We also used logistic regression to assess association between decision to test and patient demographics and health care characteristics.ResultsAmong 10,411 ICD‐9 coded infant bronchiolitis episodes, 29% were RSV tested. Fifty one percent of those tested were RSV positive. Between December and February, and in infants ≤6 months, the proportion of bronchiolitis episodes that were attributable to RSV was 77.2% among hospitalized episodes, 78.3% among EDV episodes, and 60.9% among OPV episodes, respectively. The proportion of RSV‐positive bronchiolitis episodes varied based upon infant age at diagnosis, level of health care service used, and time of the year of the episode.ConclusionEstimation of the proportion of ICD‐9 coded bronchiolitis episodes attributable to RSV is more specific when restricting to bronchiolitis episodes during peak months, younger infant age, and those requiring higher level of healthcare.

Respiratory health inequality starts early: The impact of social determinants on the aetiology and severity of bronchiolitis in infancy.

To define the impact of demographics on the incidence, aetiology and clinical course of viral bronchiolitis in infants younger than 2 years of age. Retrospective case review of all viral bronchiolitis admissions for patients aged younger than 2 years old from January 1 2014 to 31 December 2015 at Wellington Regional Hospital, New Zealand. Demographic data, second-hand smoke exposure (SHSE) and presence of predisposing conditions were collected, along with outcome data including use of respiratory support and intensive care unit (ICU) admission. This was compared to background rates calculated from regional census data. There were 556 admissions included (11% of paediatric medical admissions); 49% tested positive for respiratory syncytial virus (RSV) (84% tested), and 40% of admissions received positive pressure respiratory support and 10% ICU admission. Admission rates ranged from 9.6 to 77 per 1000/year, with higher rates seen in those from areas of high deprivation. Admission rates by deprivation varied according to aetiology. RSV-positive admission rates increased from 9.7 per 1000/year to 24.6 per 1000/year in the least to most deprived areas, whereas non-RSV admissions showed even greater disparity, increasing from 10.1 per 1000/year to 37.5 per 1000/year (both P < 0.0001). This study further reinforces that material deprivation contributes significantly to poor health outcomes that are apparent in infancy. SHSE is a potent risk factor for adverse respiratory outcomes in this patient population. Ongoing efforts to eradicate smoking and reduce material inequality need to continue.

Recent advances in understanding rhinovirus immunity

Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma, bronchiolitis in infants, and significant lower respiratory tract infections in children, the immunosuppressed, and the elderly. The large number of rhinovirus strains (currently about 160) and their antigenic diversity are significant obstacles in vaccine development. The phenotype of immune responses induced during rhinovirus infection can affect disease severity. Recognition of rhinovirus and a balance of innate responses are important factors in rhinovirus-induced morbidity. Immune responses to rhinovirus infections in healthy individuals are typically of the T helper type 1 (Th1) phenotype. However, rhinovirus-driven asthma exacerbations are additionally characterised by an amplified Th2 immune response and airway neutrophilia. This commentary focuses on recent advances in understanding immunity toward rhinovirus infection and how innate and adaptive immune responses drive rhinovirus-induced asthma exacerbations.

The effect of outdoor air pollution on the risk of hospitalisation for bronchiolitis in infants: a systematic review.

ObjectiveTo systematically review the evidence around the effect of ambient levels of particulate and gaseous pollutants, and the risk of hospitalisation with bronchiolitis for infants under two years of age.DesignSystematic review of observational epidemiological studies including cohort, time series, case crossover and case control study designs.Data sourcesMedline, Scopus, and Web of Science searched to November 2017 with no language restrictions.Eligibility criteriaStudies investigating impact of air pollution levels on particulate pollutants (diameter <2.5 μm (PM2.5) or <10 μm (PM10) and gaseous pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), carbon monoxide (CO), ozone (O3)) on hospital admission for bronchiolitis.Main outcome measureRisk of hospitalisation from bronchiolitis.ResultsEight studies were eligible for review. Long term exposure to PM2.5 may be associated with increased risk of hospitalisation for bronchiolitis. SO2 may also be associated with hospitalisation, but results for other pollutants are inconsistent between studies. In three of the five studies that showed a positive association between air pollutants and hospitalisation, measured concentrations were below World Health Organization (WHO) recommended levels.ConclusionsCertain particulate and gaseous pollutants may have a clinically relevant effect on hospital admissions for bronchiolitis in children below age two years old. Large cohort or time series studies are needed to examine this possible association.ProtocolThe protocol can be found at PROSPERO (CRD42017080643).

Serum soluble receptor for advanced glycation end-products during acute bronchiolitis in infant: Prospective study in 93 cases.

ABSTRACTIntroductionAcute bronchiolitis is a major cause of acute respiratory distress in infants. The soluble receptor for advanced glycation end‐products (sRAGE) is a biomarker of pulmonary damage processes, with a diagnostic and a prognostic value in acute respiratory distress syndrome (ARDS). The RAGE pathway is also implicated in the pathogenesis of other respiratory diseases like asthma, but the value of sRAGE levels in acute bronchiolitis remains under‐investigated.Material and methodsA prospective, observational, and analytical study was conducted at Clermont‐Ferrand University Hospital. The main objective was to evaluate the correlation between serum sRAGE and clinical severity of bronchiolitis in hospitalized infants aged <1 year. We analyzed correlations between serum sRAGE and Wainwright score, short‐term morbidity attributable to bronchiolitis, causal viruses and risk for recurrent wheezing at 1 year.ResultsThe study included 93 infants. sRAGE levels were significantly lower in acute bronchiolitis patients (mean 1101 pg/mL) than in controls (2203 pg/mL, P < 0.001) but did not correlate with clinical severity. No correlation was found between serum sRAGE and severity score, respiratory viruses, and recurrent wheezing at 1 year. Serum sRAGE levels were negatively correlated with age (r = −0.45, P < 0.001).ConclusionSerum sRAGE levels are decreased in acute bronchiolitis but not correlated with disease severity. sRAGE levels should be age‐adjusted in infants. Serum sRAGE levels measured in the setting of acute bronchiolitis were not predictive of recurrent wheezing.