Development Of Recurrent Wheezing Research Articles

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze

BackgroundEarly life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. ObjectiveTo investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). MethodsA total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. ResultsUpper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). ConclusionAzithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. Trial RegistrationThis study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

Association between household cleaning product exposure in infancy and development of recurrent wheeze and asthma.

Household chemicals may act as irritants in the lungs; however, their association with recurrent wheeze and asthma in children remains controversial. We aimed to investigate if household cleaning product exposure in infancy is associated with recurrent wheezing and asthma development in children. We analyzed data from two cohorts: MARC-35 consisting of 815 children with history of severe bronchiolitis in infancy, and MARC-43 consisting of 525 healthy children in infancy. Frequency of use of cleaning product at the child's home during infancy was collected via telephone interview with parents. Outcomes were recurrent wheezing by age 3years and asthma diagnosis at age 6years. In MARC-35, there was no association between cleaning product exposure in infancy and recurrent wheeze (adjusted HR = 1.01 [95% CI 0.66-1.54] for 4-7days/week exposure frequency), nor asthma (adjusted OR = 0.91 [95% CI 0.51-1.63]). In MARC-43, there was also no association between cleaning product exposure in infancy and recurrent wheeze (adjusted HR = 0.69 [95% CI 0.29-1.67] for 4-7days/week exposure frequency). We found no association between household cleaning product exposure in infancy and later development of recurrent wheeze or asthma, even among children who are at high risk for asthma due to history of severe bronchiolitis.

Severe bronchiolitis profiles and risk of asthma development in Finnish children

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. Our aim was to study the association between severe bronchiolitis profiles identified by using a clustering approach and childhood asthma. 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. Compared with risk of current asthma associated with profile BC, we observed increased risk of current asthma associated with profile Aboth 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. 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.

Respiratory morbidity associated with viral respiratory infections during neonatal stage in premature infants.

Very low birth weight (VLBW) infants are highly susceptible to viral respiratory infections (VRIs), even during admission to the neonatal intensive care unit (NICU). Although the role of VRI in childhood in the development of recurrent wheezing and long-term asthma is well known, information on the impact in later morbidity of VRI in the neonatal period is lacking. We aimed to explore the occurrence of recurrent wheezing over the first 2 years of life according to VRI status during NICU admission. During April 2016 and December 2017, infants below 32 weeks of gestation were prospectively studied in VRI surveillance during NICU admission. Families were contacted between September 2018 and May 2019 by a telephone questionnaire. A total of 99 patients were enrolled. The mean gestational age and birth weight were 28.8 (1.9) weeks and 1118 (329) g, respectively. During the first 2 years of life, neither episodes of wheezing nor the respiratory impairment-related hospital admissions differed between positive and negative VRI infants. Episodes of wheezing and respiratory impairment-related hospital admissions, as well as specific respiratory treatment prescription, were more frequent within the first 2 years in infants who had suffered symptomatic VRI during NICU admission. Symptomatic VRI in VLBW infants is associated with long-term respiratory morbidity. The early surveillance of VRI in the preterm infant during NICU admission is justified for prognostic counseling and closely monitoring after discharge. Routine instruction on asthma-related risk factorsand early prescription of antiasthmatic treatments, when indicated, should be established.

Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze

K Hasegawa, JM Mansbach, YA Bochkov. JAMA Pediatrics. 2019;61(3):544–552 To evaluate whether bronchiolitis in infancy caused by rhinovirus C is a stronger risk factor for recurrent wheeze than bronchiolitis caused by respiratory syncytial virus (RSV) or rhinovirus A or B. 716 infants in a multi-center prospective cohort study who were hospitalized for bronchiolitis due to rhinovirus and/or RSV from November 2011 – April 2014. The primary exposure of interest was viral infection (RSV, rhinovirus A, B or C) based on PCR of nasopharyngeal samples. The primary outcome was recurrent wheeze by age 3 years (according to 2007 …

Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze.

Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze. A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze. In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30). Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.

Airway microbiome, host immune response and recurrent wheezing in infants with severe respiratory syncytial virus bronchiolitis

Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6months of age or less were included and followed up until the age of 3years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively. Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P=.003), CXCL8 (P=.004), CCL5 (P=.029), IL-6 (P=.004), and IL-13 (P<.001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r=0.246, P=.037) level, and that of Moraxella was associated with IL-6 level (r=0.236, P=.046) and IL-10 level (r=0.266, P=.024). Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.

Increased Moraxella and Streptococcus species abundance after severe bronchiolitis is associated with recurrent wheezing

BackgroundThe role of the airway microbiome in the development of recurrent wheezing and asthma remains uncertain, particularly in the high-risk group of infants hospitalized for bronchiolitis.ObjectiveWe sought to examine the relation of the nasal microbiota at bronchiolitis-related hospitalization and 3 later points to the risk of recurrent wheezing by age 3 years.MethodsIn 17 US centers researchers collected clinical data and nasal swabs from infants hospitalized for bronchiolitis. Trained parents collected nasal swabs 3 weeks after hospitalization and, when healthy, during the summer and 1 year after hospitalization. We applied 16S rRNA gene sequencing to all nasal swabs. We used joint modeling to examine the relation of longitudinal nasal microbiota abundances to the risk of recurrent wheezing.ResultsAmong 842 infants hospitalized for bronchiolitis, there was 88% follow-up at 3 years, and 31% had recurrent wheezing. The median age at enrollment was 3.2 months (interquartile range, 1.7-5.8 months). In joint modeling analyses adjusting for 16 covariates, including viral cause, a 10% increase in relative abundance of Moraxella or Streptococcus species 3 weeks after day 1 of hospitalization was associated with an increased risk of recurrent wheezing (hazard ratio [HR] of 1.38 and 95% high-density interval [HDI] of 1.11-1.85 and HR of 1.76 and 95% HDI of 1.13-3.19, respectively). Increased Streptococcus species abundance the summer after hospitalization was also associated with a greater risk of recurrent wheezing (HR, 1.76; 95% HDI, 1.15-3.27).ConclusionsEnrichment of Moraxella or Streptococcus species after bronchiolitis hospitalization was associated with recurrent wheezing by age 3 years, possibly providing new avenues to ameliorate the long-term respiratory outcomes of infants with severe bronchiolitis.

Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3years of life. Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0 weeks' gestation and followed for 3years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

2352. Increased on Childhood Recurrent Wheezing and Asthma After Respiratory Syncytial Viral (RSV) Infection in Full-Term Infants

BackgroundStudies suggest that RSV infection early in life is associated with the development of recurrent wheezing, yet, information on large population-based studies among US full-term healthy infants is incomplete. The objective of this study was to evaluate the risk of developing post-RSV recurrent wheezing/asthma during childhood among full-term infants in a US commercially insured population.MethodsRetrospective, observational study used data from Truven MarketScan Commercial Claims and Encounters Database (January 1, 2000–December 31, 2016) to identify full-term infants with and without a RSV diagnosis in the first year of life (RSV and non-RSV cohorts respectively). Infants were excluded if they had any of the following: prematurity (<37 weeks’ gestation), low birth weight, small for gestational age, congenital heart or chronic lung disease, asthma or wheezing; or had received palivizumab. At least 2 years’ continuous follow-up post birth was required throughout the ≤5-year follow-up period. RSV/non-RSV infants were 1:1 matched for gender, region and health plan type. Cumulative incidence of recurrent wheezing or asthma was identified by ICD-9/10 codes, through 1, 2, 3 and 4 years (Y)’ post-index (1 year after birth) follow-up, and analyzed using conditional logistic regression.ResultsMatched RSV/non-RSV pairs totaled 38,494 (Y1), 25,603 (Y2), 17,429 (Y3), and 11,921 (Y4) for the years’ follow-up. Demographic characteristics, birth year and month were evenly represented between cohorts. Other infections during the perinatal period were more common in the RSV vs. the non-RSV cohort (5.4% vs. 3.2%; P < 0.0001), as were other respiratory conditions (5.8% vs. 2.6%; P < 0.0001), and antibiotic use (76.7% vs. 44.7%; P < 0.0001). Rates of influenza and pneumococcal vaccinations were comparable between cohorts. Cumulative incidence of recurrent wheezing or asthma in the RSV cohort was more than two-fold higher compared with the non-RSV cohort for each follow-up period (P < 0.001) (Figure 1).ConclusionHealthy, full-term, commercially insured children infected with RSV during the first year of life had from 2.2- to 3.6-fold increased risk of developing recurrent wheezing or asthma in the next 1–4 years. This reveals an important medical need for interventions targeting RSV infection in infants.Figure 1.Disclosures A. Mejias, Janssen: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Abbvie: CME talks, Speaker honorarium. B. Wu, Janssen Scientific Affairs, LLC: Employee and Shareholder, Salary. N. Tandon, Janssen Scientific Affairs: Employee and Shareholder, Salary and stocks. W. Chow, Janssen Scientific Affairs, LLC: Employee and Shareholder, Salary and stocks. N. Connolly, Janssen Scientific Affairs, LLC: Employee and Shareholder, Salary and Stocks. S. Lakhotia, Janssen Scientific Affairs, LLC: Research Contractor, Fee for service. E. Franco, Janssen Scientific Affairs, LLC: Employee and Shareholder, Salary and stocks. O. Ramilo, Janssen Scientific Affairs, LLC: Consultant, Consulting fee.

Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

A better understanding of bronchiolitis heterogeneity might help clarify its relationship with the development of recurrent wheezing and asthma. We sought to identify severe bronchiolitis profiles using a clustering approach and to investigate for the first time their association with allergy/inflammatory biomarkers, nasopharyngeal microbiota, and development of recurrent wheezing by age 3years. We analyzed data from a prospective, 17-center US cohort study of 921 infants (age <1year) hospitalized with bronchiolitis (2011-2014 winters) with posthospitalization follow-up. Severe bronchiolitis profiles at baseline (hospitalization) were determined by using latent class analysis based on clinical factors and viral etiology. Blood biomarkers and nasopharyngeal microbiota profiles were determined by using samples collected within 24hours of hospitalization. Recurrent wheezing by age 3years was defined based on parental report of breathing problem episodes after discharge. Three severe bronchiolitis profiles were identified: profile A(15%), which was characterized by a history of breathing problems/eczema during infancy and non-respiratory syncytial virus (mostly rhinovirus) infection; profile B (49%), which has the largest probability of respiratory syncytial virus infection and resembled classic respiratory syncytial virus-induced bronchiolitis; and profile C (36%), which was composed of the most severely ill group. Profile Ainfants had higher eosinophil counts, higher cathelicidin levels, and increased proportions of Haemophilus-dominant or Moraxella-dominant microbiota profiles. Compared with profile B, we observed significantly increased risk of recurrent wheezing in children with profile A(hazard ratio, 2.64; 95% CI, 1.90-3.68) and, to a lesser extent, with profile C (hazard ratio, 1.51; 95% CI, 1.14-2.01). Although longer follow-up is needed, our results might help identify, among children hospitalized for bronchiolitis, subgroups with particularly increased risk of asthma.

Respiratory Syncytial Virus Seasonality: A Global Overview.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.

Functional Impairment of Mononuclear Phagocyte System by the Human Respiratory Syncytial Virus.

The mononuclear phagocyte system (MPS) comprises of monocytes, macrophages (MΦ), and dendritic cells (DCs). MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV). The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma. Monocytes, MΦ, and DCs significantly contribute to acute inflammation during hRSV-induced bronchiolitis and asthma exacerbation. Furthermore, these cells seem to be an important component for the association between hRSV and reactive airway disease. After hRSV infection, the first cells encountered by the virus are respiratory epithelial cells, alveolar macrophages (AMs), DCs, and monocytes in the airways. Because AMs constitute the predominant cell population at the alveolar space in healthy subjects, these cells work as major innate sentinels for the recognition of pathogens. Although adaptive immunity is crucial for viral clearance, AMs are required for the early immune response against hRSV, promoting viral clearance and controlling immunopathology. Furthermore, exposure to hRSV may affect the phagocytic and microbicidal capacity of monocytes and MΦs against other infectious agents. Finally, different studies have addressed the roles of different DC subsets during infection by hRSV. In this review article, we discuss the role of the lung MPS during hRSV infection and their involvement in the development of bronchiolitis.

P.1.a.009 - Meta-analysis of CYP2C19 association with efficacy and side effects of citalopram and escitalopram

Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation.We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life.The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age.By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW.Neonatal BCG had no effect on the development of RW before 13 months of age.

Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias

IntroductionIt is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. Patients and methodsA total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. ResultsA total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P<.001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P<.001 (OR: 2.18; 95% CI: 1.05-4.5). ConclusionsIn our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections.

Recurrent wheezing and asthma after bocavirus bronchiolitis

BackgroundHuman bocavirus (HBoV) was recently discovered and identified as an important cause of respiratory infection in young children. However, the relationship between HBoV-bronchiolitis and the development of recurrent wheezing has not yet been established. ObjectiveWe designed this study in order to describe the mid-term outcome, regarding the development of recurrent wheezing and asthma of HBoV-bronchiolitis patients and to compare it with RSV-bronchiolitis infants. MethodsWe studied 80 children (10 with HBoV and 70 with RSV infection), currently aged ≥4 years and previously hospitalised during the seasons 2004–2009 due to acute bronchiolitis. Epidemiological and clinical data were collected through structured clinical interviews at the follow-up visit. Spirometry and skin prick tests to common food and inhaled allergens were performed. ResultsAll HBoV-patients developed recurrent wheezing and half of them had asthma at age 5–7 years. Almost 30% required hospital admission for recurrent wheezing. Asthma (odds ratio (OR)=1.28) and current asthma (OR=2.18) were significantly more frequent in children with HBoV-bronchiolitis than in RSV-bronchiolitis. FEV1 values were 99.2±4.8 in HBoV-group vs. 103±11 in RSV-group, p: 0.09. No differences were found with respect to allergic rhinitis, atopic dermatitis, food allergy, proportion of positive prick tests, and family history of atopy or asthma. ConclusionsSevere HBoV-bronchiolitis in infancy was strongly associated with asthma at 5–7 years.

Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis

Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis

Rhinovirus infections in infancy and early childhood

Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma. Several studies in infants at high-risk for atopy and asthma and in hospitalised children have demonstrated that recurrent wheezing illnesses induced by RVs early in life are a risk factor for the development of asthma later in childhood. However, underlying mechanisms are poorly understood. The question whether RVs are directly involved in the development of childhood wheeze and asthma, or whether symptomatic RV infections only represent a proxy for infants prone to develop obstructive lung diseases, is still open. In this review we provide an overview on the role of RVs as important disease-causing agents from infancy to early childhood and discuss their contribution to the subsequent development of childhood wheeze and/or asthma.

Rhinoviruses: markers of, or causative for, recurrent wheeze and asthma?

Rhinovirus (RV) infections occur early and recurrently in life and impose a large burden of disease in infants and young children [1–3]. RVs are the most frequent pathogens detected during both upper and lower respiratory tract infections and are associated with a large spectrum of clinical outcomes in this age group [4, 5]. In the very young, they are one of the leading agents of bronchiolitis, second only to respiratory syncytial virus (RSV), and in children aged >12 months of age they are predominant pathogens associated with wheezing episodes [6–8]. In addition to their impact on short-term morbidity, RVs have been shown to represent an important pathogenic factor in the development of recurrent wheeze and asthma; a role which is yet not fully understood [9–12]. Several studies have been conducted over the past few years evaluating the influence of RV infections in early life on the development and incidence of wheezing and asthma [13–17]. They have clearly demonstrated that RV-associated wheezing is a risk factor for asthma development, and that approximately one third of infants with recurrent RV-induced wheezing illnesses go on to develop asthma. Unfortunately, most of these studies have been conducted in infants at high risk for atopy and asthma and not in unselected populations, or have included hospitalised children of a wide age range. These are significant limitations in the understanding of the respective influences of virus infections, atopy, age and maturity of the immune system …

Nasopharyngeal prostaglandin E2 in infant bronchiolitis

ABSTRACTThe mechanism by which severe bronchiolitis can result in the development of recurrent childhood wheeze is unclear. However, mucosal inflammation and immune activation may play a major role. Prostaglandin (PG) E2 has been highlighted as a possible therapeutic target for both the treatment of bronchiolitis and the prevention of subsequent airway hyperresponsiveness. The aim of this pilot study was to examine PGE2 in the airways of infants hospitalised with bronchiolitis. Nasopharyngeal aspirates (NPA) were collected from 18 infants within 12 hours of admission and assayed by enzyme immunoassays for PGE2, interleukin (IL)-10, and IL-12, as well as cyclooxygenase (COX) 1 and 2 activity. NPA PGE2 concentration correlated with length of illness preadmission, but was not related to disease severity, causal virus, or IL-10. NPA COX 1 and 2 activity and IL-12 were all below the level of detection. Neither NPA PGE2 nor disease severity was related to development of recurrent wheeze over 3 years following bronchiolitis. These data suggest that nasopharygeal PGE2 at hospital admission may be neither directly causal or diagnostic of severity of infant bronchiolitis, or prognostic of development of recurrent wheeze. However, large-cohort temporal examinations are required to adequately define this mediator as a therapeutic target for bronchiolitis.