Version May 2024
INTRODUCTION — Viruses are the most common triggers of wheezing in childhood. In some children, respiratory viral infection will induce transient and episodic wheezing episodes, while, in others, wheezing with respiratory viruses will also influence future development of asthma. The heterogeneity in early childhood wheezing phenotypes introduces clinical challenges for treatment. The optimal management of acute episodes of virus-induced wheezing in infants and preschool children has yet to be determined [1]. Instituting or escalating asthma therapies, such as inhaled glucocorticoids, leukotriene modifiers, and bronchodilators, can be effective in controlling viral-induced wheezing symptoms in some patients. However, treatment decisions in children with wheezing episodes require an understanding of the risk factors for severe exacerbations and recurrent wheezing in young children. Therapeutic trials comparing variable recurrent wheezing phenotypes are ongoing and will be an important application of precision medicine to determine optimal medication treatments for children with recurrent virus-induced wheezing. (See "Wheezing phenotypes and prediction of asthma in young children" and "Risk factors for asthma".)
This topic reviews the treatment of young children with recurrent virus-induced wheezing, defined as a minimum of three to four wheezing exacerbations a year [2]. Guidelines from the Global Initiative for Asthma (GINA) [3] and National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) [4,5] provide recommendations for children based upon age and the frequency of viral episodes. Our approach is generally consistent with these guidelines. Treatment of bronchiolitis in infants and virus-induced asthma exacerbations in children and adults are discussed separately. The mechanisms by which viral respiratory infections cause wheezing and asthma exacerbations and the influence of viral infection on both the development and perpetuation of asthma are also discussed separately. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention" and "An overview of asthma management" and "Role of viruses in wheezing and asthma: An overview".)
Treatment of asthma in children, both for acute exacerbations and prevention of symptoms, is discussed in detail separately:
●(See "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms".)
●(See "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)
●(See "Acute asthma exacerbations in children younger than 12 years: Inpatient management".)
EPISODIC THERAPY — Episodic therapies are used to treat lower respiratory tract (LRT) symptoms in some young children with recurrent virus-induced wheezing. Antiinflammatory drugs are rarely used for acute LRT symptoms in these children.
Symptomatic relief — For symptomatic relief of acute LRT symptoms in children ≤4 years of age with recurrent virus-induced wheezing, we suggest an as-needed inhaled short-acting beta agonist (SABA) rather than no symptomatic treatment (table 1) [3-5]. Nebulized hypertonic saline in combination with a SABA is typically not used, because it has not consistently shown a significant advantage over SABA treatment alone.
●Inhaled short-acting beta agonists – Inhaled SABAs (albuterol/salbutamol, levalbuterol/levosalbutamol) are often first-line therapy for treatment of virus-induced wheezing. However, response to treatment can differ given the heterogeneity of diseases presenting as early childhood wheezing. In children with recurrent wheezing, SABAs are effective rescue treatments for the quick relief of symptoms (table 2). SABAs have not been shown to improve clinical outcomes, decrease the rate of hospital admission, or decrease the duration of hospitalization in children with bronchiolitis or acute cough [6,7]. The use of SABAs for acute symptoms and treatment of acute exacerbations in children with asthma is discussed in greater detail separately. (See "Beta agonists in asthma: Acute administration and prophylactic use" and "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Inhaled short-acting beta-2 agonists' and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)
●Hypertonic saline – Nebulized hypertonic saline combined with a SABA has been studied but is not used routinely, because it does not have a clear benefit over SABA alone in patients with acute virus-induced wheezing. Limited data suggest that inhaled hypertonic saline in combination with a SABA may be effective in treating young children with acute episodes of virus-induced wheezing. The use of inhaled hypertonic saline for the treatment of LRT disease is based upon the hypothesis that viral infection, particularly with rhinovirus, leads to dehydration of the airway surface liquid and impaired mucus clearance [8-10]. Several randomized trials have reported decreased rates of hospital admission and decreased length of hospital stay in infants and children with acute bronchiolitis or acute virus-induced wheezing treated with inhaled hypertonic saline in addition to SABAs compared with SABAs alone, but other trials have not detected a significant difference between these treatments [11-15]. In addition, the studies with positive findings often excluded children with a history of prior wheezing and/or bronchiolitis, limiting the ability to draw conclusions about this therapy in children with recurrent wheezing episodes. Further study with randomized, controlled trials is needed before this treatment can be recommended for clinical use in young children with recurrent wheeze. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)
Antiinflammatory therapy — In children ≤4 years of age with recurrent virus-induced wheezing who have developed LRT symptoms in the setting of a viral infection, we suggest limiting treatment with systemic glucocorticoids to those who have a history of severe or refractory disease. This includes children who have a history of severe virus-induced wheezing exacerbations requiring hospitalization or emergency department (ED) visits, have not responded to intermittent high-dose inhaled glucocorticoid therapy previously, or have significant asthma risk factors and are on daily controller therapy. We typically do not use inhaled glucocorticoids, leukotriene receptor antagonists (LTRAs; montelukast), or macrolide antibiotics in young children with recurrent virus-induced wheezing who are symptomatic due to an acute viral infection, because they have not been shown to be effective in most patients.
●Oral glucocorticoids – The data are mixed regarding the use of oral glucocorticoids to treat virus-induced wheezing in preschoolers, in part due to the heterogeneity of studies and outcomes measured, as well as the heterogeneity of diseases leasing to wheezing in preschool children [16-22]. Overall, this approach does not appear to be effective in most patients with preschool wheezing. Systemic glucocorticoids may be beneficial in subgroups of patients (eg, those with recurrent episodes of virus-induced wheezing, atopic features, and/or family history of asthma) with severe symptoms that have required hospitalization or frequent emergency department (ED) visits or those who have failed other approaches such as intermittent high-dose inhaled glucocorticoids.
Several randomized trials have been conducted that vary in terms of clinical setting, dose of glucocorticoid administered, and patient population studied. Overall, oral glucocorticoids do not appear to reduce the need for hospital admission, but they may modestly shorten hospital length of stay and may reduce the need for SABA rescue therapy [17-21]. One study that compared the length of hospital stay in wheezing children 24 to 72 months of age (mean age 41 months) who were started on a three-day course of oral prednisolone in the ED reported a decreased hospital stay in children requiring admission for greater than seven hours [21]. A prior study in younger children (mean age 26 months) with fewer asthma risk factors that did not detect a significant difference in duration of hospitalization in those treated with a five-day course of prednisolone compared with those who were not [18,21].
Results from one subgroup analysis suggest that the response to systemic glucocorticoids during wheezing episodes requiring hospitalization may differ based upon the type of virus detected [17]. Another subgroup analysis in a multicenter trial noted lack of benefit of prednisolone treatment in children at high risk for atopic asthma (history of ≥4 wheezing episodes and a parent with asthma or clinician-diagnosed eczema) [18]. Additional studies are necessary to better define the characteristics of children who wheeze severely but intermittently and do or do not respond to oral glucocorticoid therapy. How glucocorticoid responsiveness relates to preschool children who will outgrow their asthma-like symptoms and those who will have asthma diagnosed later also needs to be studied. (See "Natural history of asthma", section on 'Wheezing during the first six years'.)
The use of systemic glucocorticoids in the treatment of bronchiolitis is reviewed in detail separately. (See "Overview of bronchiolar disorders in adults" and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)
●Inhaled glucocorticoids – Inhaled glucocorticoids do not appear to be effective when started after the onset of LRT symptoms in the setting of a viral infection. In one randomized trial of 276 preschool children with recurrent wheezing, there was no difference in the proportion of symptom-free days in those treated with a combination SABA and high-dose beclomethasone as needed for symptoms compared with a SABA alone (64.9 versus 61 percent, respectively) [23]. Similarly, there was no difference in symptom-free days (83 versus 82 percent, respectively) in another trial of 411 infants who were treated with a two-week course of low-dose budesonide or placebo started after a three-day episode of wheezing. The use of inhaled glucocorticoid therapy, started the first day of viral symptoms, for the prevention of LRT symptoms is discussed below. (See 'Intermittent preventive therapy' below.)
●Leukotriene receptor antagonists – A couple of randomized trials have examined the intermittent use of an LTRA, montelukast, to treat acute LRT symptoms in preschool children with recurrent wheezing [24,25]. Overall, these studies do not favor the use of intermittent LTRAs for acute wheezing episodes in young children. The first trial, which included both those treated at the onset of an upper respiratory tract infection (URI) and those treated for asthma symptoms, found a lower rate of unscheduled health care utilization for asthma in those treated with montelukast compared with placebo (odds ratio [OR] 0.65, 95% CI 0.47-0.89) but no significant differences in hospitalizations or rescue medication use [24]. The other trial, which randomly assigned 1358 children to intermittent montelukast or placebo at the onset of any subsequent wheezing episode over a 12-month period, did not find a difference between the groups in the frequency of unscheduled medical visits for wheezing episodes [25].
●Antibiotics – The potential utility of macrolides as immunomodulatory therapy in the treatment of recurrent wheezing/asthma has been widely debated given their antiinflammatory properties and antimicrobial effects against Mycoplasma pneumonia and Chlamydia pneumonia. One randomized trial provided some evidence for the early use of azithromycin to shorten the duration of episodes of recurrent wheeze in young children. In a this trial, 72 children one to three years of age with recurrent asthma-like symptoms were randomly assigned to oral azithromycin (10 mg/kg once daily for three days) or placebo for each episode of asthma-like symptoms lasting at least three days [26]. Treatment with azithromycin significantly decreased the duration of the episode by 63 percent, with a mean episode duration of 3.4 days in those treated with azithromycin compared with 7.7 days in those who received placebo. A greater response was seen with earlier initiation of treatment (83 percent if azithromycin was initiated before day 6 of symptoms versus 36 percent if initiated after day 6). Adverse event rates were similar in the two groups. Patterns of bacterial resistance after treatment were not investigated. However, further study is needed prior to recommending widespread use of azithromycin for this indication. (See "Investigational agents for asthma", section on 'Macrolide antibiotics'.)
PREVENTIVE THERAPY — Preventive therapy includes intermittent antiinflammatory therapy given at the onset of a viral upper respiratory tract infection (URI) and daily controller therapy.
Intermittent preventive therapy — In children ≤4 years of age with recurrent virus-induced wheezing who do not meet the criteria for daily controller therapy (see 'Who to treat' below), we suggest starting a short course of a high-dose inhaled glucocorticoid (table 3) at the onset of a viral URI. Low-dose inhaled glucocorticoids have not shown similar efficacy. We typically do not use a short course of montelukast, oral glucocorticoid, or a macrolide antibiotic at the onset of a URI in young children with intermittent wheezing, because they have not been shown to be effective in most patients.
●Inhaled glucocorticoids – Intermittent inhaled glucocorticoids for the prevention of virus-induced wheezing in young children have been examined in several randomized trials and two systematic reviews [2,27-33]. These studies are difficult to compare because of differences in dose of inhaled glucocorticoid used, timing of when the medication is started in relation to the URI, and primary outcome measured [34]. However, overall, these studies suggest that intermittent high-dose inhaled glucocorticoids (table 3), started at the onset of a URI and continued for up to 10 days, may decrease asthma-type symptoms and rescue oral glucocorticoid use in preschool children with virus-associated wheezing who are not on daily inhaled glucocorticoid therapy. This approach may be particularly effective in patients with asthma risk factors. There may be slight deficits in growth in some children, although the data are limited. Growth in children who are prescribed this approach should be carefully monitored. It is unclear if intermittent high-dose inhaled glucocorticoids are effective if started after the onset of wheezing in the setting of a URI. Intermittent use of standard (low to medium) doses of inhaled glucocorticoids (table 3) does not appear to be effective in this population, particularly when started after the onset of lower respiratory tract (LRT) symptoms. (See 'Symptomatic relief' above.)
A systematic review from 2000 identified three trials of preschool children with recurrent wheeze given episodic high-dose inhaled glucocorticoids for 5 to 10 days starting at the onset of a URI [28]. Two of these studies showed a reduced requirement for oral glucocorticoids (risk ratio [RR] 0.53, 95% CI 0.27-1.04), and all showed modest decreases in symptom scores. Most subsequent larger trials have confirmed these findings. In one trial of 129 children, a short course of high-dose fluticasone propionate started at the onset of a URI decreased the use of rescue oral glucocorticoids compared with placebo (8 versus 18 percent of URIs required such rescue treatment, respectively) [29]. However, smaller gains in height and weight were seen in the treatment group (-0.33 cm and -0.64 kg) compared with placebo over the 6- to 12-month study period. In another trial of 278 children aged 12 to 53 months with recurrent wheezing and a positive asthma predictive index, episodic use of high-dose inhaled budesonide started early in the course of a URI was as effective as chronic daily low-dose budesonide with respect to frequency of exacerbations requiring oral glucocorticoid therapy [2]. There were also no significant differences between the two groups in bronchodilator use, episode-free days, or severity of symptoms during respiratory tract illnesses. Furthermore, treatment with intermittent high-dose budesonide resulted in a lower cumulative exposure to budesonide as compared with daily budesonide therapy. In contrast, another trial using high-dose budesonide at the start of a URI did not find any difference in rescue oral glucocorticoid use or proportion of episode-free days compared with intermittent montelukast or placebo in 238 children one to six years of age with moderate-to-severe intermittent wheezing [30]. Symptom scores for trouble breathing and interference with activity were moderately decreased in the treatment groups compared with placebo, particularly during the first few days of treatment.
In one trial of 525 children with history of virus-induced wheezing who presented to their pediatrician with a URI and were randomly assigned treatment with low-dose beclomethasone or placebo, no difference was seen in the incidence of wheezing during the 10-day treatment period [32].
●Oral glucocorticoids – Results from one small observational study suggested that early treatment with systemic glucocorticoids at the first sign of a URI could reduce the symptoms of virus-induced exacerbations, emergency department (ED) visits, and hospitalizations in preschool children with recurrent virus-induced wheezing [35], although these findings have never been confirmed in a randomized trial.
●Leukotriene receptor antagonists – Several randomized trials have examined the intermittent use of a leukotriene receptor antagonist (LTRA), montelukast, for prevention of symptoms in preschool children with recurrent virus-induced wheezing [24,30,36]. Overall, the studies do not favor the use of intermittent LTRAs for prevention of acute wheezing episodes in young children. This finding was confirmed in a meta-analysis, which did not detect a significant difference in the number of episodes requiring treatment with oral glucocorticoids in those treated with intermittent LTRA compared with placebo (odds ratio [OR] 0.77, 95% CI 0.48-1.25) [37].
In one of the studies previously discussed, measures of severity of acute illness were decreased in children treated at the first sign of a URI with high-dose budesonide or montelukast compared with placebo, but no difference was seen in the proportion of episode-free days or rescue oral glucocorticoid use over the 12-month study period [30]. A similar randomized trial that included older children as well found a modest reduction in unscheduled visits, symptoms, days off from school/childcare, and caregiver time off from work in the montelukast group compared with placebo but did not show a significant difference in rescue medication use or hospitalizations [24]. Another randomized trial found no change in the number of asthma episodes in children ages six months to five years who were treated with intermittent montelukast begun at the onset of viral symptoms [36].
●Antibiotics – The potential utility of macrolides as immunomodulatory therapy in the treatment of recurrent wheezing/asthma has been widely debated given their antiinflammatory properties and antimicrobial effects against Mycoplasma pneumonia and Chlamydia pneumonia. One multicenter randomized trial provided some evidence for the early use of azithromycin in preventing LRT illness (LRTI) in preschool children with a history of severe recurrent wheezing [38]. Treatment was initiated at the onset of respiratory illness in conjunction with signs/symptoms that usually preceded the development of a severe LRTI specific to each child. In this trial, 607 children were randomly assigned to oral azithromycin (12 mg/kg once daily) or placebo for five days in addition to albuterol. The risk of progressing to severe LRTI was significantly lower in the treatment group compared with the control (hazard ratio [HR] 0.64, 95% CI 0.41-0.98). However, there was no difference in urgent care utilization, ED visits, or hospitalizations. In addition, the results of the study were not affected by the type of virus detected during respiratory illness, the presence of a positive asthma predictive index, age, or sex. Further study is needed prior to recommending widespread use of azithromycin for this indication. (See "Investigational agents for asthma", section on 'Macrolide antibiotics'.)
Daily controller therapy — An alternative approach to prevention of virus-induced wheezing is continuous, rather than episodic, therapy.
Who to treat — Initiation of controller medication for children ages zero to four years is based upon the severity of symptoms and exacerbations, the frequency of exacerbations, and the risk of development of subsequent asthma (table 1) [3-5].
We recommend initiating controller therapy in children who have had ≥4 episodes of wheezing in the past year that lasted more than one day and affected sleep and who have the following risk factors for persistent asthma [39,40] (see "Risk factors for asthma" and "Role of viruses in wheezing and asthma: An overview" and "Wheezing phenotypes and prediction of asthma in young children"):
●One of the following – Parental history of asthma, clinician diagnosis of atopic dermatitis, evidence of sensitization to aeroallergens
or
●Two of the following – Evidence of sensitization to foods, ≥4 percent peripheral blood eosinophilia, wheezing apart from viral URIs
We also suggest the initiation of controller medications for the following children [4]:
●Those aged zero to four years who consistently require quick-relief medications more than two days per week for a period of more than four weeks.
●Infants and young children experiencing severe exacerbations less than six weeks apart or those who have two or more exacerbations requiring systemic glucocorticoids within six months.
●Children with intermittent disease who experience severe exacerbations, especially during periods when they are likely to be exposed to known triggers, such as seasonal pollens or respiratory viruses [41].
Chronic controller therapy in children with asthma is discussed in detail separately. (See "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control" and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies".)
Choice of treatment — For children ≤4 years of age with recurrent wheezing who meet the criteria for daily controller therapy, we recommend an inhaled glucocorticoid rather than montelukast, an oral LTRA. Standard doses of inhaled glucocorticoids given daily are effective in preventing episodic virus-induced wheezing in young children, particularly in patients with a clinical diagnosis of asthma, a history of recurrent wheezing with rhinovirus-induced illness, or other asthma risk factors [39,42-44]. Montelukast may mitigate virus-induced recurrent wheezing/asthma exacerbations in some children but overall is not as effective as inhaled glucocorticoids. In addition, montelukast is associated with potential neuropsychiatric adverse effects, limiting its use for mild asthma. (See "Antileukotriene agents in the management of asthma", section on 'Adverse effects'.)
●Daily inhaled glucocorticoids – The efficacy of daily inhaled glucocorticoids in young children with recurrent virus-induced wheezing has been demonstrated in randomized trials and meta-analyses. In a meta-analysis of 15 trials involving 3278 children with recurrent wheezing and asthma symptoms, daily inhaled glucocorticoid therapy reduced exacerbations compared with placebo (13 versus 24 percent, respectively; RR 0.70, 95% CI 0.61–0.79) [44]. An earlier meta-analysis had similar findings and also reported that while the efficacy of daily inhaled glucocorticoid therapy was higher in patients with a diagnosis of asthma, the effect size was independent of atopy and age (infants versus preschoolers) [42].
Data on the effect of daily inhaled glucocorticoid therapy on linear growth velocity in this age group are mixed, although the majority of studies show minimal to no effect [39,45-51]. Results from one study suggest that younger (less than three years old), smaller preschoolers are at greater risk for growth effects [45]. Further studies are needed. The potential adverse effects of inhaled glucocorticoids are discussed in greater detail separately. (See "Major side effects of inhaled glucocorticoids".)
●Daily leukotriene receptor antagonists – Montelukast was studied in a randomized trial of 549 children aged two to five years of age with intermittent asthma symptoms [52]. Over 12 months of treatment, montelukast decreased the average rate of exacerbations by 32 percent and the time to first exacerbations by two months compared with placebo. However, the need for systemic glucocorticoids was not significantly different between treatment groups, and the exacerbations studied were not exclusively limited to virus-induced asthma exacerbations.
Another study investigated the effects of montelukast 4 or 5 mg orally versus budesonide inhalation 0.5 mg once daily in children two to eight years old with mild asthma or recurrent wheezing [53]. Subjects were given additional asthma medications, either twice-daily inhaled budesonide or oral glucocorticoids, for increased asthma symptoms. No significant difference was found between groups for time to first supplemental asthma medication use over a 52-week period, the primary outcome of the study. However, exacerbations rates were lower in the budesonide group versus the montelukast group. This study was not limited to children who suffered from intermittent wheezing episodes or virus-induced asthma exacerbations [53].
PREVENTION OF SYMPTOMATIC VIRAL INFECTIONS — Controlling the frequency of symptomatic viral infections is an area of interest. Prevention strategies include antiviral therapies and therapies to modulate the inflammatory response to viruses. Efforts to develop antiviral agents for rhinoviruses, the most common cause of virus-induced wheezing illness, are technically challenging due to the many rhinovirus subtypes and are not available at this time. Given the role respiratory syncytial virus (RSV) plays in early childhood wheezing episodes, palivizumab, a monoclonal antibody that prevents RSV infection in infants and preschool children, has been widely studied. Its use is associated with a decrease in the subsequent rate of recurrent wheezing compared with untreated controls [54-56]. Although palivizumab is not indicated for treatment of bronchiolitis in the acute setting, it may be useful in the prevention of subsequent recurrent wheezing in young children, particularly preterm infants. (See "Respiratory syncytial virus infection: Prevention in infants and children".)
An alternative investigational approach to preventing viral upper respiratory tract infections (URIs) has centered around altering the early microbiome of children to prevent future respiratory tract illnesses. In one small randomized trial, a reduction in wheezing episodes was seen in young children treated with a bacterial extract of eight respiratory tract pathogens compared with placebo [57], but further therapeutic studies have not been published, and no US Food and Drug Administration (FDA) approved product for this use is available.
The use of vitamin D has also been studied since vitamin D may influence responses to airway pathogens, respiratory system development, and susceptibility to respiratory tract infections. However, vitamin D regimens used have been variable, and studies have not demonstrated long-term benefit. One randomized, controlled trial in preterm infants showed a lowering of recurrent wheezing in children who used sustained vitamin D supplementation in the first year of life but no difference in the rate of upper or lower respiratory tract infections or in the development of asthma, eczema, or atopy [58,59].
Observations during the coronavirus disease 2019 (COVID-19) pandemic have shown that public health and behavioral intervention such as handwashing, the use of masks, and physical distancing can affect the frequency of wheezing illnesses in children. These measures enacted to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission were also associated with significantly reduced pediatric respiratory and asthma exacerbations requiring emergency department (ED) visits and hospitalizations [60-62]. Future seasonal and targeted use of these infection control measures may be a beneficial population health intervention for the prevention of recurrent wheezing in children during peak virus seasons.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiolitis in infants and children" and "Society guideline links: Asthma in children".)
SUMMARY AND RECOMMENDATIONS
●Definition – Recurrent virus-induced wheezing is defined as a minimum of three to four wheezing exacerbations in the setting of a viral upper respiratory tract infection (URI) within a year. The optimal management of virus-induced wheezing in infants and preschool children is uncertain, in part because of the heterogeneity of wheezing phenotypes. The specific therapy for each patient is individualized based upon the severity of symptoms and prior responses to available treatments. Treatment of infants and young children with their first episode of wheezing (eg, bronchiolitis) and therapy for children with established asthma are discussed separately. (See 'Introduction' above and "Bronchiolitis in infants and children: Treatment, outcome, and prevention" and "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms" and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies" and "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)
●Episodic management – Our approach to managing episodes of recurrent virus-induced wheezing in children ≤4 years of age is as follows:
•Symptomatic relief – For acute symptomatic relief, we suggest an as-needed inhaled short-acting beta agonist (SABA) (table 2) rather than no symptomatic therapy (Grade 2C). Inhaled SABAs are effective for rescue treatment of acute asthma symptoms and are likely to provide relief to patients with recurrent episodes of virus-induced wheezing. However, the response can be variable. SABAs do not appear to be effective for young children with bronchiolitis. (See 'Symptomatic relief' above and "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms", section on 'Short-acting beta agonists (SABAs)' and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)
•Acute management of children with a history of severe or refractory symptoms – For patients with a history of severe or refractory disease who have developed lower respiratory tract (LRT) symptoms in the setting of a viral infection, we suggest systemic glucocorticoid therapy rather than no antiinflammatory therapy (Grade 2C). This includes children who have a history of severe virus-induced wheezing exacerbations requiring hospitalization or emergency department (ED) visits, have not responded to intermittent high-dose inhaled glucocorticoid therapy previously, or have significant asthma risk factors and are on daily controller therapy. (See 'Antiinflammatory therapy' above.)
●Preventive therapy – Our approach to preventive therapy in young children ≤4 years of age with recurrent virus-induced wheezing is as follows:
•Children with intermittent nonsevere episodes – For young children who have intermittent episodes of virus-induced wheezing that are not severe, we suggest a short course of high-dose inhaled glucocorticoid (table 3) initiated at the onset of URI symptoms (ie, before wheezing has occurred) rather than no preventative therapy (Grade 2B) and rather than lower doses of inhaled glucocorticoid or other preventative therapies (eg, montelukast, oral glucocorticoid, or macrolide antibiotic) (Grade 2C). Children with more frequent or severe episodes are treated with daily controller medication, as discussed below.
Intermittent preventative inhaled glucocorticoid is continued for up to 10 days. Fluticasone propionate 750 mcg inhaled twice daily and budesonide 1 mg nebulized twice daily have both been studied in this setting and appear to decrease asthma-type symptoms and need for oral glucocorticoid therapy. It is unclear if this therapy is effective if started after the onset of wheezing in the setting of a URI. Intermittent high-dose inhaled glucocorticoid therapy is generally well tolerated, although slight deficits in growth have been reported in some children. (See 'Intermittent preventive therapy' above.)
•Daily controller therapy for children with frequent or severe episodes – For young children with all of the following, we recommend daily controller therapy (Grade 1B) (see 'Daily controller therapy' above):
-Four or more episodes of wheezing in the past year, and
-Each episode lasted more than one day and affected sleep, and
-Other risk factors for persistent asthma (eg, family or personal history of atopic disease, wheezing outside the setting of a viral URI) are present
We also suggest daily controller therapy for young children who continue to experience severe or recurrent episodes of wheezing despite intermittent high-dose inhaled glucocorticoid therapy and those who are at risk for severe episodes, including children with any of the following (Grade 2C):
-Intermittent (ie, less than four per year) but severe exacerbations
-Frequent need for quick-relief medications (more than two days per week for a period of more than four weeks)
-Two severe exacerbations less than six weeks apart
-Two or more exacerbations requiring systemic glucocorticoid therapy within six months
For daily controller therapy, we suggest a standard dose of an inhaled glucocorticoid (table 3 and table 1) rather than high- or low-dose inhaled glucocorticoid or other agents (eg, montelukast) (Grade 2C). However, daily montelukast is a reasonable alternative for patients who do not tolerate daily inhaled glucocorticoids. Daily inhaled glucocorticoid therapy may result in modest decline in growth velocity. Thus, growth should be monitored regularly in all children receiving this therapy. (See 'Daily controller therapy' above and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Sujani Kakumanu, MD, who contributed to earlier versions of this topic review.
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