Viral Wheeze Research Articles

Anti-inflammatory drug therapy in asthma

Asthma is a disease with chronic inflammation of the airways and and-inflammatory treatment is a logical treatment. Inhaled corticosteroids [ICS] remain the cornerstone of anti-inflammatory therapy in recent international guidelines. Asthma cannot be cured by any medication: if the drug is discontinued, the disease manifestations return. This has been proven at all ages. In preschool children the diagnosis of asthma is difficult to establish. In this heterogeneous group ICS or leukotriene receptor antagonists [LTRA] are just as effective as placebo; in the future it will hopefully be possible to describe characteristics of responders. LTRA are an alternative in mild asthma, especially when mono-triggered viral related wheeze is present. Theophylline is effective and also has bronchodilatory properties, which need to be balanced against the relatively frequent side effects. The working mechanisms of anti-inflammatory asthma medications including ICS, LTRA, cromones, macrolides and theophylline are described.

Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study

BackgroundRhinovirus (RV) associated early wheezing has been recognized as an independent risk factor for asthma. The risk is more important than that associated with respiratory syncytial virus (RSV) disease. No comparative data are available on the immune responses of these diseases.ObjectiveTo compare T-helper1 (Th1), Th2 and T-regulatory (Treg) cell type cytokine responses between RV and RSV induced early wheezing.MethodsSystemic Th1-type (interferon [IFN] -gamma, interleukin [IL] -2, IL-12), Th2-type (IL-4, IL-5, IL-13) and Treg-type (IL-10) cytokine responses were studied from acute and convalescence phase serum samples of sole RV (n = 23) and RSV affected hospitalized wheezing children (n = 27). The pre-defined inclusion criteria were age of 3-35 months and first or second wheezing episode. Analysis was adjusted for baseline differences. Asymptomatic children with comparable demographics (n = 11) served as controls for RV-group.ResultsRV-group was older and had more atopic characteristics than RSV-group. At acute phase, RV-group had higher (fold change) IL-13 (39-fold), IL-12 (7.5-fold), IFN-gamma (6.0-fold) and IL-5 (2.8-fold) concentrations than RSV-group and higher IFN-gamma (27-fold), IL-2 (8.9-fold), IL-5 (5.6-fold) and IL-10 (2.6-fold) than the controls. 2-3 weeks later, RV-group had higher IFN-gamma (>100-fold), IL-13 (33-fold) and IL-10 (6.5-fold) concentrations than RSV-group and higher IFN-gamma (15-fold) and IL-2 (9.4-fold) than the controls. IL-10 levels were higher in acute phase compared to convalescence phase in both infections (p < 0.05 for all).ConclusionOur results support a hypothesis that RV is likely to trigger wheezing mainly in children with a predisposition. IL-10 may have important regulatory function in acute viral wheeze.

Anti‐inflammatory treatment of asthma: differentiation and trial‐and‐error

The relative lack of evidence for anti-inflammatory treatment of some phenotypes of asthma in children has been highlighted in recent guidelines and consensus reports specifically aiming at the paediatric population. Consequently, we are left with a need for defining treatment strategies in the clinical setting. The decision to initiate antiinflammatory treatment should be based on assessments of the individual child's age, the type of asthma, severity, heredity and atopic condition, adherence factors and sensitivity to systemic adverse effects of treatment options. Inhaled corticosteroids are potent anti-inflammatory agents that are effective in the whole spectrum of asthma in school age children. In toddlers with viral wheeze and in children with mild asthma oral leukotriene receptor antagonists or inhaled corticosteroids may be given on a trial-and-error basis. To treat all children with asthma equally effectively from infancy through adolescence does not mean that they should be treated identically and in some types of asthma a trial-and-error approach may be warranted.

High-dose fl uticasone in preschool viral wheezing: what is the real advantage?

High-dose fl uticasone in preschool viral wheezing: what is the real advantage?

Corticosteroids Not Recommended for Viral Wheeze in Ages 10 to 60 Months

Corticosteroids Not Recommended for Viral Wheeze in Ages 10 to 60 Months

Asthma in preschool children: the next challenge

To describe a prospective classification for preschool wheezers according to temporal symptom pattern, and summarize findings relating to the management of viral wheeze and the use of short-term therapy for intermittent severe wheeze. Phenotypes defined from cohort studies should only be applied retrospectively at school age. A new classification that can be applied prospectively is discussed. The importance of early rhinovirus-induced wheezing as a risk factor for asthma has become apparent. However, there is no benefit from short-course oral steroids for acute viral wheeze in the majority of cases. There is conflicting evidence for the role of intermittent montelukast or inhaled steroids in the treatment of acute, intermittent wheeze. A link between reduced vitamin D intake during pregnancy and increased preschool wheeze in offspring has emerged, suggesting a potential role for vitamin D supplementation in primary prevention. On the basis of current evidence, a trial of bronchodilators is first-line therapy for viral wheeze, and maintenance montelukast or inhaled steroids may be considered in preschool wheezers with persistent symptoms and risk factors for future asthma. No disease-modifying therapies are available. New therapeutic options for preschool wheezing disorders are desperately needed.

Danger of using an unreliable classification system for preschool wheeze

To the Editors: The management of preschool children with wheezing disorders remains challenging. Clinicians should, therefore, welcome the decision by the European Respiratory Society to establish a Task Force to address this problem. The Task Force recommends that the terms episodic (viral) wheeze and multi-trigger wheeze should be used to describe different clinical phenotypes of preschool wheeze 1. However, the report acknowledges that there is large …

Episodic Viral Wheezing in Preschool Children: What Works?

Pediatric Asthma, Allergy & ImmunologyVol. 22, No. 1 Pharmacotherapy UpdateEpisodic Viral Wheezing in Preschool Children: What Works?H. William KellyPharm.D.H. William KellyPharm.D.Search for more papers by this authorPublished Online:1 May 2009https://doi.org/10.1089/pai.2009.2201.phAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetails Volume 22Issue 1Mar 2009 Information© Mary Ann Liebert, Inc.To cite this article:H. William KellyPharm.D..Episodic Viral Wheezing in Preschool Children: What Works?.Pediatric Asthma, Allergy & Immunology.Mar 2009.39-42.http://doi.org/10.1089/pai.2009.2201.phPublished in Volume: 22 Issue 1: May 1, 2009Online Ahead of Print:April 8, 2009PDF download

Role of corticosteroids in preschool wheeze: going, going, but not gone

Inhaled and oral steroids are widely and benefi cially used in older children and adults, but their place in preschool and episodic (viral) wheeze is less clear. This paper reviews recommendations in the light of new clinical trials evidence. Inhaled corticosteroids do not prevent the progression from episodic wheeze to multitrigger wheeze and asthma later in childhood. They may be benefi cial to treat current symptoms in a small minority of atopic preschool children with multitrigger wheeze, especially those over 3 years old. Some in this group may benefi t from regular treatment; for the majority, there will be no benefi t. If a therapeutic trial is contemplated, then a three-stage protocol is advised, with a trial of discontinuing the medication. Oral steroids have been shown not to be useful for home or hospital treatment of episodic wheeze, but may be useful in very severe episodes needing high dependency care. There are safety issues with the use of steroids, including a possible effect on the developing alveoli. In summary, any form of steroid therapy should be used sparingly and on an individualized basis in preschool and episodic viral wheeze.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Wheezing Rhinovirus Illnesses During Early Childhood and the Subsequent Development of Asthma

RationaleThe contribution of specific viral respiratory wheezing illnesses in infancy and early childhood to the subsequent development of asthma by age 6 years has not clearly been established.Methods259 children were followed prospectively from birth to 6 years in the COAST (Childhood Origins of ASThma) study. The etiology and timing of specific wheezing viral respiratory illnesses during early childhood was assessed comprehensively using nasal lavage, culture and RT-PCR. The developmental relationships of both wheezing illnesses and allergic sensitization in early childhood and asthma at age 6 years were analyzed.ResultsRhinovirus (RV) wheezing (OR = 2.8 95% CI 1.4 5.6) and allergic sensitization (OR = 3.6 95% CI 1.7 7.7) in the first year of life were independently and similarly associated with increased risk of asthma at 6 years of age. By the third year of life, RV wheezing (OR = 25.6 95% CI 8.2 79.6) had a stronger association with asthma at age 6 years than allergic sensitization (OR = 3.4 95% CI 1.7 6.9). Nearly 90% (26 of 30) of children who wheezed with RV in year 3 had asthma at 6 years of age, regardless of the presence or absence of allergic sensitization.ConclusionRV wheezing illnesses and allergic sensitization in early childhood are both independent and additive risk factors for the development of asthma at 6 years of age. RationaleThe contribution of specific viral respiratory wheezing illnesses in infancy and early childhood to the subsequent development of asthma by age 6 years has not clearly been established. The contribution of specific viral respiratory wheezing illnesses in infancy and early childhood to the subsequent development of asthma by age 6 years has not clearly been established. Methods259 children were followed prospectively from birth to 6 years in the COAST (Childhood Origins of ASThma) study. The etiology and timing of specific wheezing viral respiratory illnesses during early childhood was assessed comprehensively using nasal lavage, culture and RT-PCR. The developmental relationships of both wheezing illnesses and allergic sensitization in early childhood and asthma at age 6 years were analyzed. 259 children were followed prospectively from birth to 6 years in the COAST (Childhood Origins of ASThma) study. The etiology and timing of specific wheezing viral respiratory illnesses during early childhood was assessed comprehensively using nasal lavage, culture and RT-PCR. The developmental relationships of both wheezing illnesses and allergic sensitization in early childhood and asthma at age 6 years were analyzed. ResultsRhinovirus (RV) wheezing (OR = 2.8 95% CI 1.4 5.6) and allergic sensitization (OR = 3.6 95% CI 1.7 7.7) in the first year of life were independently and similarly associated with increased risk of asthma at 6 years of age. By the third year of life, RV wheezing (OR = 25.6 95% CI 8.2 79.6) had a stronger association with asthma at age 6 years than allergic sensitization (OR = 3.4 95% CI 1.7 6.9). Nearly 90% (26 of 30) of children who wheezed with RV in year 3 had asthma at 6 years of age, regardless of the presence or absence of allergic sensitization. Rhinovirus (RV) wheezing (OR = 2.8 95% CI 1.4 5.6) and allergic sensitization (OR = 3.6 95% CI 1.7 7.7) in the first year of life were independently and similarly associated with increased risk of asthma at 6 years of age. By the third year of life, RV wheezing (OR = 25.6 95% CI 8.2 79.6) had a stronger association with asthma at age 6 years than allergic sensitization (OR = 3.4 95% CI 1.7 6.9). Nearly 90% (26 of 30) of children who wheezed with RV in year 3 had asthma at 6 years of age, regardless of the presence or absence of allergic sensitization. ConclusionRV wheezing illnesses and allergic sensitization in early childhood are both independent and additive risk factors for the development of asthma at 6 years of age. RV wheezing illnesses and allergic sensitization in early childhood are both independent and additive risk factors for the development of asthma at 6 years of age.

Wheeze and asthma prevalence and related health‐service use in white and south Asian pre‐schoolchildren in the United Kingdom

Epidemiological data for south Asian children in the United Kingdom are contradictory, showing a lower prevalence of wheeze, but a higher rate of medical consultations and admissions for asthma compared with white children. These studies have not distinguished different asthma phenotypes or controlled for varying environmental exposures. To compare the prevalence of wheeze and related health-service use in south Asian and white pre-schoolchildren in the United Kingdom, taking into account wheeze phenotype (viral and multiple wheeze) and environmental exposures. A postal questionnaire was completed by parents of a population-based sample of 4366 white and 1714 south Asian children aged 1-4 years in Leicestershire, UK. Children were classified as having viral wheeze or multiple trigger wheeze. The prevalence of current wheeze was 35.6% in white and 25.5% in south Asian 1-year-olds (P<0.001), and 21.9% and 20.9%, respectively, in children aged 2-4 years. Odds ratios (ORs) (95% confidence interval) for multiple wheeze and for viral wheeze, comparing south Asian with white children, were 2.21 (1.19-4.09) and 1.43 (0.77-2.65) in 2-4-year-olds after controlling for socio-economic conditions, environmental exposures and family history. In 1-year-olds, the respective ORs for multiple and viral wheeze were 0.66 (0.47-0.92) and 0.81 (0.64-1.03). Reported GP consultation rates for wheeze and hospital admissions were greater in south Asian children aged 2-4 years, even after adjustment for severity, but the use of inhaled corticosteroids was lower. South Asian 2-4-year-olds are more likely than white children to have multiple wheeze (a condition with many features of chronic atopic asthma), after taking into account ethnic differences in exposure to some environmental agents. Undertreatment with inhaled corticosteroids might partly explain their greater use of health services.

Prednisolone is effective in infants and children hospitalised for certain viral infection-associated recurrent wheezing,

Prednisolone is effective in infants and children hospitalised for certain viral infection-associated recurrent wheezing,

The Relationship Between Early Respiratory Viral Infections and Subsequent Wheezing and Asthma

The Relationship Between Early Respiratory Viral Infections and Subsequent Wheezing and Asthma

Controversies in the management of preschool viral wheeze

The clinical diagnosis of asthma represents several putative wheeze phenotypes, each associated with a unique cluster of risk factors, underlying inflammation, and response to therapy. In school-age children, the 'classical' atopic asthma phenotype predominates. By contrast, asthma in children aged between 1 and 5 years is frequently characterised by transient episodes of wheeze trigged by viral colds, with few or no interval symptoms (preschool viral wheeze). This phenotype has a different cluster of risk factors from atopic asthma and thus might not respond to asthma therapies of proven efficacy in older children. The objective of this review is to look at the current evidence in the management of 'preschool viral wheeze'.

Parent-initiated oral corticosteroid therapy for intermittent wheezing illnesses in children

Intermittent wheezing illnesses, which include viral associated wheeze and asthma, are amongst the most common reasons for children to present urgently to a doctor. Whether parents should commence oral corticosteroids (OCS) for an episode of acute wheeze in their child without waiting for a medical review is an important question, as the potential benefits of early oral corticosteroid intervention have to be weighed against the potential adverse effects of treatment. The objectives were to assess the benefits and harmful effects of parent-initiated OCS, in the management of intermittent wheezing illnesses in children, based on the results of randomised clinical trials. The Cochrane Airways Group Specialised Register, The Cochrane Controlled Trials Register (CENTRAL), MEDLINE, EMBASE, LILACS, Web of Science and Dissertation Abstracts were combined (all searched November 2005). Manufacturers and researchers in the field were also contacted. Only randomised clinical trials studying patients aged between one and eighteen years old, with an intermittent wheezing illness (asthma, viral wheeze, preschool viral wheeze) were included. Interventions encompassed OCS at any dose or duration versus placebo or other drug combination. The trials could be unpublished or published and no language limitations were applied. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. The statistical package (RevMan 4.2) provided by the Cochrane Collaboration was used. From 572 original citations, a total of 2 randomised clinical trials (303 randomised participants) were included. The quality of the included trials was high; however, marked clinical heterogeneity precluded a meta-analysis. The two trials did not find evidence that parent-initiated OCS are associated with a benefit in terms of hospital admissions, unscheduled medical reviews, symptoms scores, bronchodilator use, parent and patient impressions, physician assessment, or days lost from work or school. Adverse outcomes were inadequately documented. Limited current evidence is available and it is inconclusive regarding the benefit from parent-initiated OCS in the treatment of intermittent wheezing illnesses in children. Widespread use of this strategy cannot be recommended until the benefits and harms can be clarified further.

The therapy of pre‐school wheeze: Appropriate and fair?

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.

Bacterial coinfections in children with viral wheezing

Bacterial coinfections occur in respiratory viral infections, but the attack rates and the clinical profile are not clear. The aim of this study was to determine bacterial coinfections in children hospitalized for acute expiratory wheezing with defined viral etiology. A total of 220 children aged 3 months to 16 years were investigated. The viral etiology of wheezing was confirmed by viral culture, antigen detection, serologic investigation, and/or PCR. Specific antibodies to common respiratory bacteria were measured from acute and convalescent serum samples. All children were examined clinically for acute otitis media, and subgroups of children were examined radiologically for sinusitis and pneumonia. Rhinovirus (32%), respiratory syncytial virus (31%), and enteroviruses (31%) were the most common causative viruses. Serologic evidence of bacterial coinfection was found in 18% of the children. Streptococcus pneumoniae (8%) and Mycoplasma pneumoniae (5%) were the most common causative bacteria. Acute otitis media was diagnosed in 44% of the children. Chest radiographs showed alveolar infiltrates in 10%, and paranasal radiographs and clinical signs showed sinusitis in 17% of the older children studied. Leukocyte counts and serum C-reactive protein levels were low in a great majority of patients. Viral lower respiratory tract infection in children is often associated with bacterial-type upper respiratory tract infections. However, coexisting bacterial lower respiratory tract infections that induce systemic inflammatory response are seldom detected.

Phenotype specific treatment of obstructive airways disease in infancy and childhood: new recommendations of the Swiss Paediatric Pulmonology Group.

In 2003 and 2004 the Swiss Paediatric Pulmonology Group (SAPP) revised the recommendations for the management of obstructive airways disease in infancy and childhood (Paediatrica 2004;15:13-28) and published recommendations for the management of acute bronchiolitis in infancy (Paediatrica 2003;14:18-21). The concept underlying these new guidelines is the fact that childhood wheezing illness encompasses a range of disorders or phenotypes with a similar clinical manifestation (wheeze, cough and breathlessness) but varying pathology, aetiology, prognosis and response to treatment. Based on the available scientific evidence, phenotype-specific and age-dependent management of wheezing illness is advocated in the revised guidelines. Major changes compared to earlier recommendations include a stepwise approach to management depending on age, phenotype and severity of disease and use of beta 2-agonists purely on an on-demand basis. Comparison of these recommendations with epidemiological data on current treatment practice of obstructive airways disease in Swiss children suggests that many children with bronchiolitis and mild viral wheeze might be overtreated while management of children with severe persistent symptoms could be improved.

Phenotype specific treatment of obstructive airways disease in infancy and childhood: new recommendations of the Swiss Paediatric Pulmonology Group.

In 2003 and 2004 the Swiss Paediatric Pulmonology Group (SAPP) revised the recommendations for the management of obstructive airways disease in infancy and childhood (Paediatrica 2004;15:13-28) and published recommendations for the management of acute bronchiolitis in infancy (Paediatrica 2003;14:18-21). The concept underlying these new guidelines is the fact that childhood wheezing illness encompasses a range of disorders or phenotypes with a similar clinical manifestation (wheeze, cough and breathlessness) but varying pathology, aetiology, prognosis and response to treatment. Based on the available scientific evidence, phenotype-specific and age-dependent management of wheezing illness is advocated in the revised guidelines. Major changes compared to earlier recommendations include a stepwise approach to management depending on age, phenotype and severity of disease and use of beta 2-agonists purely on an on-demand basis. Comparison of these recommendations with epidemiological data on current treatment practice of obstructive airways disease in Swiss children suggests that many children with bronchiolitis and mild viral wheeze might be overtreated while management of children with severe persistent symptoms could be improved.