Virus-induced Wheezing Research Articles

A Community-Guided Approach to Bronchiolitis: A Needs Assessment and Illness Perception Study.

The factors influencing caregivers' understanding of pediatric respiratory diseases, such as bronchiolitis, can guide patient care and the acceptability of treatment methods within the healthcare system. This study aims to identify illness perceptions and perform a needs assessment among caregivers of children diagnosed with respiratory diseases. This is a prospective, cross-sectional, questionnaire-driven study of a representative sample of caregivers whose children had an acute respiratory illness. The telephone-administered questionnaire was comprised of (1) demographic items; (2) illness perception questionnaire-revised (IPQ-R); and (3) items about personal barriers, the latter 2 of which employed a 5-point Likert response. Cronbach's alpha (α) was used to measure the internal consistency reliability for each item within the IPQ-R. The Pearson 2-tailed correlation coefficient was used to correlate questionnaire items. We included 75 caregivers whose children have been diagnosed with bronchiolitis (51%), reactive airway disease (RAD) (35%), asthma (33%), and wheezing (44%). We found no significance between the child's diagnosis and the site of recruitment. The most important components of the illness perception were illness coherence (α=0.849), psychological attributions (α=0.903), and barriers to diagnosis (α=0.633). Understanding caregivers' perceptions of respiratory diseases will lead to better treatment acceptance. We must clarify the terms used to define bronchiolitis from viral-induced wheezing, RAD, and the first asthma episode in older infants. Identifying caregivers' gaps in knowledge will help establish a cohesive approach to personalized treatment of respiratory diseases in children and their diagnosis.

Developing a nurse-led salbutamol weaning pathway for children and young people with asthma or viral-induced wheeze.

Acute asthma exacerbations and viral-induced wheeze are common presenting complaints on one general paediatric ward in a tertiary children's hospital in England. An inhaled beta 2 agonist, such as salbutamol, is the first-line treatment for these children and young people and they have frequent clinician reviews for salbutamol weaning before discharge. However, the informal salbutamol weaning practices used by nurses, as well as challenges in the recruitment and retention of paediatric trainee doctors, led to the development of a nurse-led salbutamol weaning pathway as a quality improvement project. Twelve nurses completed the associated nurse-led salbutamol weaning training, education and competency package and subsequently completed a questionnaire exploring their perceptions of the effect of the training package and pathway. After the training, all respondents reported feeling more confident in assessing the salbutamol requirements of children with wheeze. All of the respondents also felt that the introduction of the pathway and training would improve patient care and the confidence of children and young people, parents and carers in nurses' ability to assess children's salbutamol requirements. Time constraints were identified as a potential barrier to implementation of the pathway.

From preschool wheezing to asthma: Environmental determinants.

Wheezing is common among preschool children, representing a group of highly heterogeneous conditions with varying natural history. Several phenotypes of wheezing have been proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. Epidemiological and immunological studies across different populations have revealed the key role of environmental factors in influencing the progression from preschool wheezing to childhood asthma. Significant risk factors include severe respiratory infections, allergic sensitization, and exposure to tobacco smoke. In contrast, a farming/rural environment has been linked to asthma protection in both human and animal studies. Early and intense exposures to microorganisms and microbial metabolites have been demonstrated to alter host immune responses to allergens and viruses, thereby driving the trajectory away from wheezing illness and asthma. Ongoing clinical trials of candidate microbes and microbial products have shown promise in shaping the immune function to reduce episodes of viral-induced wheezing. Moreover, restoring immune training may be especially important for young children who had reduced microbial exposure due to pandemic restrictions. A comprehensive understanding of the role of modifiable environmental factors will pave the way for developing targeted prevention strategies for preschool wheezing and asthma.

Cost Utility of Intermittent Inhaled Corticosteroids in Preschoolers with Viral-Triggered Wheeze.

Background: Evidence has demonstrated that adding intermittent inhaled corticosteroids (ICS) to treatment with short-acting b2-agonists (SABAs) in children 5 years of age and younger who experience intermittent viral-induced wheezing (VIW) reduces the risk of severe exacerbations. However, there is concern about whether the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of intermittent ICS in children 5 years of age and younger who experience intermittent VIW. Methods: We constructed a probabilistic Markov model to estimate the cost and quality-adjusted life-years (QALYs) of intermittent ICS compared with SABA reliever therapy in preschoolers with viral-triggered wheezing in Colombia. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $5,180. Results: In an analysis of the Markov cohort model, we estimated a gain of 0.2 QALYs per patient per year on intermittent ICS compared with SABA and a reduction of cost per patient of USD $37 per year. This position of dominance negated the need to calculate an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses, our base case results were robust to variations of all assumptions and parameters. Conclusion: Adding intermittent ICS to treatment with SABAs in children 5 years of age and younger who experience intermittent VIW was found to be cost effective. These results could improve the use of health care resources, especially in settings with limited economic resources.

Periostin and IFN-γ levels in serum and nasopharyngeal aspirate in infants with viral-induced wheezing - 2 year follow-up.

The present study assesses the immune response in children with viral-induced wheezing by examining the two factors-interferon-gamma (IFN-γ) and periostin in serum and nasopharyngeal aspirate (NPA). The aim was to find a pattern with the severity and frequency of wheezing episodes. Sixty-nine infants (40 boys and 29 girls), with a mean age of 11.4±6 (2 - 23) months, hospitalized with a first or recurrent episode of bronchial obstruction were enrolled in this study. The serum and NPA concentrations of IFN-γ and periostin were assessed by ELISA methodology. Fifty of the children (72%) were followed for 2 years. We detected lower NPA IFN-γ production in boys, infants with atopic status, family history of asthma, and respiratory syncytial virus infection. Recurrent wheezing in children was associated with a twice lower concentration of IFN-γ in NPA compared to those with the first episode (7.1 vs. 14.8 pg/ml, p=0.05). Higher serum periostin level was established in children over 12 mo in the group of recurrent wheezers with persistent manifestations compared to those without symptoms during the follow-up (410.5 vs. 269.7 ng/ml, p = 0.03). Multivariate logistical regression model assessed high level of serum periostin, male gender, atopy, family history of asthma, and severity of the attack as significant risk factors for persistent compared to intermittent wheezing (r < sup > 2 < /sup > = 0.87, p = 0.04). Our results demonstrated that recurrent viral-induced wheezing is associated with decreased IFN-γ production and increased periostin response and their correlation with severity and persistence of symptoms were the main outcome measures.

Impact of Oral Corticosteroids on Respiratory Outcomes in Acute Preschool Wheeze: A Randomised Clinical Trial

To determine if oral prednisolones given to acutely wheezing preschool-aged children alter respiratory outcomes.A total of 3247 children (aged 24–59 months) with acute wheezing episodes between August 2014 and September 2016 in 3 New Zealand emergency departments (EDs) were potentially eligible. A total of 493 were randomly assigned, and 477 patients were included in the intention-to-treat analysis (238 in the prednisolone group and 239 in the placebo group). Primary outcome data were available on 393 patients (82% overall; 195 (79%) in the prednisolone group and 198 (83%) in the placebo group). Children <24 months of age were purposely excluded, ensuring that those with bronchiolitis were not included.In this double-blind placebo-controlled trial, preschool-aged children with viral-induced wheeze who presented to the ED were randomly assigned to receive 3 days of prednisolone (2 mg/kg) or a placebo. The primary outcome measure was a change in the validated Preschool Respiratory Assessment Measure (PRAM) score 24 hours after the intervention. Secondary outcomes included PRAM score at 4 hours, admission rate, length of ED and inpatient stay, amount of albuterol given in 48 hours, additional treatment with open-label prednisolone, time to return to normal activity, and adverse events, including the need for intravenous (IV) medication, ICU admission, and representation to the ED or primary care provider within 7 days. Pediatric Respiratory Assessment Measure (PRAM) scores (ranging from 0–12) were calculated on the basis of suprasternal retractions, scalene retractions, wheezing, and oxygen saturation in room air. The study was designed as an equivalence trial and powered (power: 95%) to detect the minimal difference in PRAM scores that would disprove the null hypothesis that corticosteroids and placebo are equivalent treatments. In a pilot study (n = 137), researchers determined a SD of 2.3 for change in PRAM score at 24 hours was significant. Therefore, analysis was by intention to treat.Between groups, there was no difference in the primary outcome, the change in PRAM score at 24 hours (difference between means: −0.39; 95% confidence interval [CI]: −0.84 to 0.06, P = .09). The median PRAM score at 24 hours for both groups was 0, with only approximately one-third in either group showing mild disease (PRAM score 1–4) and few with PRAM scores >4 (2.0% and 3.6% in treatment and control groups, respectively). Change in PRAM score at 4 hours was significantly different in the treatment group (−0.67; 95% CI: −1.18 to −0.16; P = .01). No difference in length of ED stay was observed (−0.57; 95% CI: −1.15 to 0.02; P = .06), although admission to the hospital occurred more often in the placebo group (0.67; 95% CI: 0.45 to 1.01; P = .05) as well as additional corticosteroid (0.22; 95% CI: 0.06 to 0.79; P = .01) and IV medication use (0.27; 95% CI: 0.07 to 0.96; P = .03). No difference was observed in representation to the hospital or the primary care provider within 7 days (P = .33 and P = .22, respectively) or ICU admission (undefined P value because only 2 total children went to the ICU) as well as the amount of albuterol given in 48 hours (P = .27).Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool-aged children presenting with acute wheezing to the ED because most children improved after 24 hours regardless of initial treatment. Subgroup analyses revealed no evidence that the 24-hour treatment effect differed for albuterol responsive children, those with a positive Asthma Predictive Index, or more severe disease at presentation (higher PRAM score). However, those who received prednisolone had less respiratory distress 4 hours after medication administration and a reduced requirement for hospital admission, additional corticosteroid, or IV treatment. These findings suggest that early in-hospital administration of oral prednisolone to preschoolers with wheeze may prevent further deterioration and requirement for escalation of therapy. Additionally, considering the lack of significant difference at 24 hours, oral prednisolone may improve short-term respiratory outcomes for preschoolers presenting with wheeze. However, subsequent doses of oral prednisolone may provide no additional therapeutic benefit.With this robustly designed randomized controlled trial, we are reminded that wheezing preschoolers are a heterogeneous group with numerous factors contributing to a wheezy phenotype. We should consider that they should not be treated the same as older asthmatics, with regards to corticosteroids. With this study, the authors question oral steroid dosing dogma and demonstrate that oral prednisolone may improve short-term respiratory outcomes for wheezing preschoolers but subsequent doses of oral prednisolone may provide no additional therapeutic benefit. Further studies are needed in this population to understand the timing and dosing of corticosteroids.

2020 NAEPP Guidelines Update and GINA 2021—Asthma Care Differences, Overlap, and Challenges

The 2020 National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group (NAEPP [2020 Focused Asthma Update]) guidelines and the Global Initiative for Asthma (GINA) 2021 strategy report are compared in this Rostrum article. The methodologies of each publication are described. Subsequently, 4 different selected pharmacological recommendations are compared in the 2 documents: step 1 for children 0 to 4 years of age with viral-induced wheezing, step 2 in ages 12 years and older with the intermittent use of inhaled corticosteroid, steps 3 and 4 with single-inhaler maintenance and reliever therapy with inhaled corticosteroids-formoterol (SMART), and steps 3, 4, and 5 with add-on long-acting muscarinic antagonist therapy. Nonpharmacological recommendations are also considered and contrasted, including for exhaled nitric oxide, environmental control, immunotherapy, and bronchial thermoplasty. Similarities and differences in these 2 documents are highlighted, and recommendations are made about harmonizing the approaches where possible.

Treatment of Bronchiolitis Using Nebulized Hypertonic Saline in Asthma-Prone and Non-Asthma-Prone Patients

Background: In bronchiolitis, children under the age of two experience cough, dyspnea and wheezing, following a viral upper respiratory infection. Frequently recurrent bronchiolitis in infants with atopic background is the best example of asthma-prone viral-induced wheeze. In bronchiolitis management, inhaled hypertonic saline is the subject of debate among pediatricians and researchers. Nebulized hypertonic saline acts by increasing fluidity of airway surface liquid. Bronchospasm is a theoretical risk for inhaled hypertonic saline when used without adjunctive bronchodilators. Objective: To compare the response to nebulized hypertonic saline plus B 2 agonists, with nebulized isotonic saline plus B 2 agonists, in asthma-prone and non-asthma-prone bronchiolitis patients. Patients and methods: This study was a randomized double blind controlled trial, which was carried out at Pulmonology Unit, Pediatric Department, Zagazig University Children Hospital. The study was conducted on 104 infants with acute viral bronchiolitis of mild to moderate severity. They were divided into two groups 52 in each group. Group 1: Asthma-prone patients and group 2, which included non-asthma-prone patients. Patients were randomly assigned to receive inhalation of 0.3 mg/kg salbutamol added to 5 ml of either normal saline 0.9% or hypertonic saline 3%. Within each group the number of patients receiving hypertonic or isotonic saline inhalation was equal to 26. Results: Nebulized hypertonic saline salbutamol mixture resulted in better improvement of the studied asthma-prone and non-asthma prone bronchiolitis patients. Hypertonic saline decreased case severity and days of hospital stay. Conclusion: Nebulized hypertonic saline shortened the days of hospital admission and improved the respiratory distress in mild to moderate bronchiolitis. Nebulized hypertonic saline is equally effective in asthma-prone and non-asthma-prone patients and its beneficial effect outweighs its theoretical broncho-constrictive effect.

Recent trends in management of bronchial asthma

Bronchial Asthma is the most common chronic inflammatory disease of lungs. The prevalence of asthma is increasing worldwide, and the disease possesses a substantial global health and economic burden. Asthma involves both the large and the small-conducting airways, and is characterized by a combination of inflammation and structural remodeling. Disease progression occurs in the context of a developmental background in which the postnatal acquisition of asthma is strongly linked with allergic sensitization. Most asthma cases follow a variable course, involving viral-induced wheezing and allergen sensitization, that is associated with various underlying mechanisms (or endotypes) that can differ between individuals. Each set of endotypes, in turn, produces specific asthma characteristics that evolve across the life course of the patient. Strong genetic and environmental drivers of asthma interconnect through novel epigenetic mechanisms that operate prenatally and throughout childhood. Asthma can spontaneously remit or begin de novo in adulthood, and the factors that lead to the emergence and regression of asthma, irrespective of age, are poorly understood. Nonetheless, there is mounting evidence that supports a primary role for structural changes in the airways with asthma acquisition, on which altered innate immune mechanisms and microbiota interactions are superimposed. On the basis of the identification of new causative pathways, the sub-phenotyping of asthma across the life course of patients is paving the way for more-personalized and precise pathway-specific approaches for the prevention and treatment of asthma, creating the real possibility of total prevention and cure for this chronic inflammatory disease.

Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze.

Abnormal wound repair has been observed in the airway epithelium of patients with chronic respiratory diseases, including asthma. Therapies focusing on repairing vulnerable airways, particularly in early life, present a potentially novel treatment strategy. We report defective lower airway epithelial cell repair to strongly associate with common pre-school-aged and school-aged wheezing phenotypes, characterized by aberrant migration patterns and reduced integrin α5β1 expression. Next generation sequencing identified the PI3K/Akt pathway as the top upstream transcriptional regulator of integrin α5β1, where Akt activation enhanced repair and integrin α5β1 expression in primary cultures from children with wheeze. Conversely, inhibition of PI3K/Akt signaling in primary cultures from children without wheeze reduced α5β1 expression and attenuated repair. Importantly, the FDA-approved drug celecoxib - and its non-COX2-inhibiting analogue, dimethyl-celecoxib - stimulated the PI3K/Akt-integrin α5β1 axis and restored airway epithelial repair in cells from children with wheeze. When compared with published clinical data sets, the identified transcriptomic signature was also associated with viral-induced wheeze exacerbations highlighting the clinical potential of such therapy. Collectively, these results identify airway epithelial restitution via targeting the PI3K-integrin α5β1 axis as a potentially novel therapeutic avenue for childhood wheeze and asthma. We propose that the next step in the therapeutic development process should be a proof-of-concept clinical trial, since relevant animal models to test the crucial underlying premise are unavailable.

Evolving concepts in how viruses impact asthma: A Work Group Report of the Microbes in Allergy Committee of the American Academy of Allergy, Asthma & Immunology

Over the past decade, there have been substantial advances in our understanding about how viral infections regulate asthma. Important lessons have been learned from birth cohort studies examining viral infections and subsequent asthma and from understanding the relationships between host genetics and viral infections, the contributions of respiratory viral infections to patterns of immune development, the impact of environmental exposure on the severity of viral infections, and how the viral genome influences host immune responses to viral infections. Further, there has been major progress in our knowledge about how bacteria regulate host immune responses in asthma pathogenesis. In this article, we also examine the dynamics of bacterial colonization of the respiratory tract during viral upper respiratory tract infection, in addition to the relationship of the gut and respiratory microbiomes with respiratory viral infections. Finally, we focus on potential interventions that could decrease virus-induced wheezing and asthma. There are emerging therapeutic options to decrease the severity of wheezing exacerbations caused by respiratory viral infections. Primary prevention is a major goal, and a strategy toward this end is considered.

Molecular Diagnosis of Atypical Pneumonia Infection in Children Presenting with Acute Respiratory Tract Infection Attending Yangon Children’s Hospital

Acute respiratory tract infection (ARI) is a clinical condition which causes high morbidity and mortality, especially in infants and young children. Pneumonia is a common complication of respiratory tract infection. Atypical pneumonia, which is commonly caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legi-onella pneumophila, is difficult to be detected because the causal bacteria cannot be diagnosed by routine culture method and presenting with non-specific clinical symptoms. This study aimed to diagnose the atypical pneumonia infection in children presenting with ARI attending Yangon Children’s Hospital during 2014-15 by using multiplex polymerase chain reaction (M-PCR). The bacterial DNA was extracted from nasopharyngeal swab samples by using Qiagen DNA minikit and detected by M-PCR. Of 245 patients with ARI, 140(57%) were males and 105(43%) were females. Eleven samples (4.4%) were positive for atypical pneumonia infection, among which 4(1.6%) were Mycoplasma pneumoniae,5(2%) were Chlamydophila pneumoniae and 2(0.8%) were Legionella pneumophila. The atypical pneumonia cases were mostly seen among the age of 1 to 5 years and sex distribution was nearly equal. The infected cases were detected from pneumonia (36.4%), severe pneumonia (27.3%), viral-induced wheeze (18.2%), severe bronchiolitis (9.1%) and bronchiolitis (9.1%). This study highlights the role of atypical pneumonia infection in ARI cases among children.

Wheezing in children: Approaches to diagnosis and management.

Wheezing in children: Approaches to diagnosis and management.

Viral infections in wheezing disorders.

Over the past year, studies into virus-induced wheeze in children have shifted towards investigations that examine the mechanisms by which respiratory viruses cause wheeze and an increase in studies examining the effects of novel interventions to reduce wheezing exacerbations. Studies on rhinovirus species (RV)-C infection have found that this is associated with a decrease in expression of CDHR3, the cellular receptor specific for this virus, and a decrease in interferon-β expression, both of which are likely to favour RV-C infection. Recent clinical trials in children have found a decrease in wheezing exacerbations with both anti-respiratory syncytial virus antibody and anti-immunoglobulin E antibody therapy, and a clinical trial of prednisolone in children with their first RV-induced wheeze showed that only those with an RV viral count >7000 copies·mL-1 responded. Further studies on the effects of bacterial lysates on immune system function continue to support the potential of this approach to reduce virus-induced wheezing exacerbations in children. These studies and many previous investigations into immunomodulation using bacterial lysates have led to the funding and commencement of a large study in which long-term administration of a bacterial lysate in young children will be assessed for its ability to prevent asthma.

The IL-4 rs2070874 polymorphism may be associated with the severity of recurrent viral-induced wheeze.

Childhood recurrent wheezing and consequently asthma corresponds to various phenotypes. Our aim was to link genetic variants of asthma candidate genes to the phenotypes of early onset wheezing. We included very young consecutive children presenting with recurrent wheezing who had been evaluated for the severity of wheezing, associated atopic comorbidities, and tested for biomarkers of atopy and inflammation. All were genotyped for 16 single nucleotide polymorphisms (SNPs) linked with asthma or atopy. An unsupervised hierarchical bottom-up method was used for clustering the phenotypes and a multinomial logistic regression was performed for each individual SNP. We replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.5 ± 7.9 months: cluster 1 (nonatopic uncontrolled severe wheeze), n = 207, a severe viral-induced wheeze, cluster 2 (atopic multiple trigger wheeze), n = 61, with multiple allergic comorbidities, and cluster 3 (episodic viral wheeze), n = 49, a mild viral-induced wheeze. The TT-genotype of the IL-4 rs2070874 polymorphism was significantly associated with the nonatopic uncontrolled severe wheeze compared to the episodic viral wheeze (OR 7.9; CI95% [2.5-25.3]; P = 0.001). Association between the TT-genotype of IL-4 rs2070874 polymorphism and a severe phenotype of viral-induced wheeze further underlines the role IL-4 plays in the inflammation pathway leading to viral respiratory infections.

Thai pediatricians' current practice toward childhood asthma

ABSTRACTBackground: Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). Objectives: We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. Methods: A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians. Asthma diagnosis and management were evaluated for compliance with standard guidelines. The practices of PCP and RS were compared. Results: From 800 surveys distributed, there were 405 respondents (51%). Most respondents (81%) were PCP, who preferred to use clinical diagnosis rather than laboratory investigations to diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians prescribed at least one controller. For exercise-induced bronchospasm, 55% of the pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p < 0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of an acute asthmatic attack. Conclusions: Most of the Thai pediatricians' practices toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics, and antihistamines than RS.

An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram-negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant studies have reported that the TLR family is crucial in mediating the link between viral components and immunologic responses to infection. Of note, TLR4 activation has been associated with disease severity during RSV infection. In the present study, we identified that LPS aggravated RSV-induced AHR and airway inflammation in BALB/c mice using an RSV coinfection model. We found that the airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue play a role in inducing AHR and airway inflammation upon RSV and bacteria coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling pathway. These results may aid in the development of novel treatments and improve vaccine design.

Managing acute respiratory tract infections in children.

Respiratory tract infections (RTIs), including community-acquired pneumonia (CAP), bronchiolitis, viral-induced wheeze and croup, account for more primary care consultations than any other illness group and are the most likely reason for a parent or carer to contact a health professional. The majority of RTIs in fully immunised children are usually self-limiting. However, in a small percentage of children RTIs may become life threatening and it is crucial that all front-line health professionals are able to recognise and identify these children who are at risk of deterioration. To ensure this, fast recognition of symptoms is important, with care taken to exclude any 'red flag' features that may prompt a referral to secondary care. Nurses are well placed to reassure and support families, and to provide education regarding the facts about fever, the appropriate use of a single antipyretic medication, how to avoid dehydration in children with RTIs, and the beneficial role of immunisation in preventing infection. It is also important to explain in cases of CAP where antibiotics are necessary about how soon to expect a response, any side effects from antibiotics, and to provide 'safety net advice' on when to consider reassessment for the child. An illustrative case study is included to highlight some of the challenges that are likely to be encountered in clinical practice.

A meta-analysis of montelukast for recurrent wheeze in preschool children

There is conflicting evidence of the effectiveness of montelukast in preschool wheeze. A recent Cochrane review focused on its use in viral-induced wheeze; however, such subgroups are unlikely to exist in real life and change with time, recently highlighted in an international consensus report. We have therefore sought to investigate the effectiveness of montelukast in all children with preschool wheeze (viral-induced and multiple-trigger wheeze). The PubMed, Cochrane Library, Ovid Medline and Ovid EMBASE were screened for randomised controlled trials (RCTs), examining the efficacy of montelukast compared with placebo in children with the recurrent preschool wheeze. The primary endpoint examined was frequency of wheezing episodes. Five trials containing 3960 patients with a preschool wheezing disorder were analysed. Meta-analyses of studies of intermittent montelukast showed no benefit in preventing episodes of wheeze (mean difference (MD) 0.07, 95% confidence interval (CI) −0.14 to 0.29; mean for montelukast 2.68 vs placebo 2.54 (p = 0.5)), reducing unscheduled medical attendances (MD −0.13, 95% CI −0.33 to 0.07; mean for montelukast 1.62 vs placebo 1.78 (p = 0.21)) and reducing oral corticosteroids (MD −0.06, 95% CI −0.16 to 0.02; mean for montelukast 0.35 vs placebo 0.36 (p = 0.25)). The pooled results of the continuous regimen showed no significant difference in the number of wheezing episodes between the montelukast and placebo groups (MD −0.40, 95% CI −1.00 to 0.19; mean for montelukast 2.05 vs placebo 2.37 (p = 0.18)).Conclusions: This review highlights that the currently available evidence does not support the use of montelukast in preschool children with recurrent wheeze. We recommend further studies to investigate if a ‘montelukast responder’ phenotype exists, and how these can be easily identified in the clinical setting.What is Known:• Current guidelines recommend montelukast use in preschool children with recurrent wheeze.• A recent Cochrane review has found montelukast to be ineffective at reducing courses of oral corticosteroids for viral-induced wheeze.What is New:• This meta-analysis has examined all children with preschool wheeze and found that montelukast was not effective at preventing wheezing episodes or reducing unscheduled medical attendances.• A specific montelukast responder phenotype may exist, but such patients should be sought in larger multicentre RCTs.

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity.

Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.