Hospitalization For Bronchiolitis Research Articles

Genetic Susceptibility to the Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Is MHC Dependent

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity, resulting in hospitalization for bronchiolitis in some infected infants that is associated with wheeze in later life. Genetic factors are known to affect the severity of the sequelae after RSV infection, but the complexity of the temporal and genetic effects makes it difficult to analyze this response in studies in man. Therefore, we developed a murine genetic model to analyze the sequelae occurring after RSV infection in early life. Haplotype-based genetic analysis of interstrain differences in severity identified the MHC as an important genetic determinant. This was confirmed by analysis of responses in congenic mice with different MHC haplotypes. We also found that susceptible strains had high CD8 levels during secondary infection. Analysis of first filial generation, second filial generation, and back-cross progeny produced by intercrossing resistant (H-2(k), C3H/HeN) and sensitive (H-2(b), BALB/c) strains indicated that susceptibility to sequelae after RSV infection was dominantly inherited but also segregated in a non-MHC-dependent manner. Thus, MHC haplotype and its effect on CD8 cell response is an important determinant of the outcome of neonatal RSV infection.

300 Recurrent Wheezing in Third Year Among Children Born at 32 Weeks Gestation: Relationship Respiratory Syncytial Virus During First Year

Background: Respiratory syncytial virus (RSV) is responsible for 50-80% of bronchiolitis hospitalizations and the leading cause of hospitalization in children < 1 year. Objective: To quantify the relationship between recurrent wheezing (RW) in year three and documented RSV infection, prematurity, and neonatal oxygen exposure. Design/methods: Participants were 71,102 children born at ≥ 32 weeks gestational age (GA)who were members of an integrated health care delivery system in Northern California for 9 months in their first and third years. The principal exposures were laboratory-confirmed, medically-attended RSV infection during year one, and receipt of supplemental oxygen during birth hospitalization. The outcome was RW in year three. Results: Rate of RW was 16.23% among premature infants with RSV infection and 6.22% among those without. Infants having an RSV outpatient encounter (adjusted odds ratio [AOR] 2.07, 95% CI, 1.61-2.67), uncomplicated hospitalization (AOR 4.66, 95% CI, 3.55-6.12), or prolonged hospitalization (AOR 3.42, 95% CI, 2.01-5.82) were at increased risk for RW compared to infants without RSV infection. GA of 34-36 weeks was associated with increased risk for RW (AOR 1.23, 95% CI 1.071.41) compared to 38-40 weeks, while GA of 41 weeks was protective (AOR 0.90, 95% CI, 0.81-0.99). Supplemental oxygen exposure was associated with increased risk at all levels. The 3 most important predictors were infant sex, family's asthma history, and RSV infection. Conclusions: Laboratory-confirmed, medically-attended RSV infection, prematurity, and exposure to supplemental oxygen during the neonatal period have independent associations with the development of third year RW. The study was sponsored by MedImmune.

Child nutrition and lower respiratory tract disease burden in New Zealand: A global context for a national perspective

To consider the contribution of malnutrition to acute lower respiratory infection (ALRI) disease burden in children <5 years old in New Zealand (NZ). The contribution of maternal and child malnutrition to ALRI disease burden in early childhood globally was described. A literature review was conducted to describe the nutritional status and ALRI disease burden of NZ children <5 years old. The four key nutritional risk factors for ALRI disease burden globally are macronutrient undernutrition, low birthweight, zinc deficiency and suboptimal breastfeeding. In addition, maternal nutritional status and vitamin D deficiency are potentially important nutritional determinants of ALRI disease burden. Relative to other developed countries, NZ has a large ALRI disease burden in pre-school-aged children. Pneumonia and bronchiolitis hospitalisation rates are two to four times greater than other developed countries. The ALRI disease burden varies with ethnicity, being highest in Pacific, intermediate in Maori and lowest in European children. Three of the four key nutritional risk factors for global ALRI disease burden--low birthweight, zinc deficiency and suboptimal breastfeeding--are potential contributors to ALRI disease burden in NZ. In addition to these factors, vitamin D deficiency during early childhood and maternal vitamin D deficiency are also potentially important particularly with respect to the larger disease burden in Pacific and Maori children. The contribution of malnutrition to ALRI disease burden in NZ requires greater clarification. Such clarification is necessary to inform the development of nutritional policy, which seeks to improve early child health.

Viral respiratory tract infections and asthma: The course ahead

Inquiries into the relationships between viral respiratory tract illnesses and the inception and exacerbation of asthma are being facilitated by recent advances in research approaches and technology. In this article we identify important knowledge gaps and future research questions, and we discuss how new investigational tools, including improved respiratory tract virus detection techniques, will permit current and future researchers to define these relationships and the host, virus, developmental, and environmental mechanisms that regulate them. A better understanding of these processes should facilitate the development of improved strategies for the prevention and treatment of virus-induced wheezing illnesses and asthma exacerbations and, possibly, the ultimate goal of discovering effective approaches for the primary prevention of asthma.

Factors indicative of long-term survival after lung transplantation: A review of 836 10-year survivors

Despite 20 years of lung transplantation (LTx), factors influencing long-term survival remain largely unknown. The United Network for Organ Sharing (UNOS) data set provides an opportunity to examine long-term LTx survivors. We conducted a case-control study embedded within the prospectively collected UNOS LTx cohort to identify 836 adults from 1987 to 1997 who survived >or=10 years after first LTx. LTx patients within the same era and surviving 1 to 5 years served as controls. Multivariable logistic regression with incorporation of spline terms evaluated the odds of being a 10-year survivor. Two separate models were constructed. Model A incorporated pre-operative, operative, and donor-specific factors. Model B incorporated the factors used in Model A with post-operative covariates. Additional outcomes evaluated included hospitalizations for infection, rejection, and bronchiolitis obliterans. Of 4,818 LTx patients from 1987 to 1997, 836 (17.3%) survived >or=10 years with a mean follow-up of 148.8 +/- 21.6 months. Mean follow-up for 1,657 controls was 34.0 +/- 13.9 months. The distribution of 10-year survivors by disease was cystic fibrosis, 170 (20%); chronic obstructive pulmonary disease, 254 (30%); and idiopathic pulmonary fibrosis, 92 (11%). On multivariable logistic regression, significant factors influencing 10-year survival included age <or=35 years (odds ratio [OR] 1.07, 95% confidence interval [CI], 1.03-1.11; p = 0.01), bilateral LTx (OR. 1.71; 95% CI, 1.25-2.34; p = 0.001), and hospitalizations for infections (OR, 1.40; 95% CI, 1.27-1.54; p < 0.001) and for rejection (OR, 0.55; 95% CI, 0.48-0.65; p < 0.001). Examination of a cohort of long-term LTx survivors in the UNOS data set indicates that bilateral LTx and fewer hospitalizations for rejection may portend improved long-term survival after LTx.

Recurrent wheezing after respiratory syncytial virus or non‐respiratory syncytial virus bronchiolitis in infancy: a 3‐year follow‐up

Recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non-RSV bronchiolitis. We identified retrospectively all children <2 years of age who were admitted to Turku University Hospital because of bronchiolitis in the months of August-December during 1988-2001. The primary outcome was recurrent wheezing that required long-term asthma medication. Data on asthma medications of the individual children were derived from the Social Insurance Institution of Finland. Within the first year after hospitalization, 36 of 217 (16.6%) children with non-RSV bronchiolitis developed recurrent wheezing, compared with five of 199 (2.5%) children with RSV bronchiolitis [relative risk (RR) 6.6; 95% confidence interval (CI) 2.6-16.5]. The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years (RR 2.9; 95% CI 1.7-5.1) and 3 years (RR 3.4; 95% CI 2.0-5.7) after hospitalization. The increased risk of recurrent wheezing in children with non-RSV-associated bronchiolitis was observed both in boys and girls at all time points of the 3-year follow-up, and it was not explained by the age difference between the RSV and non-RSV groups or any confounding seasonal factors. Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis.

The Need for Validation of Statistical Methods for Estimating Respiratory Virus-Attributable Hospitalization

Public policy regarding influenza has been based largely on the burden of hospitalization estimated through ecologic studies applying increasingly sophisticated statistical methods to administrative databases. None are known to have been validated by observational studies. The authors illustrated how 6 commonly applied statistical methods estimate virus-attributable hospitalization of children 6-23 months of age and compared the estimates with results obtained from a prospective study using virologic assessment. The proportions of pneumonia and influenza and of bronchiolitis hospitalizations attributable to respiratory syncytial virus and/or influenza were derived by using Serfling regression, periseason differences, Poisson regression with log link, negative binomial regression with identity link, and a Box-Jenkins transfer function. No method provided accurate or consistent estimates for both viruses and outcomes. Virus-attributable hospitalization estimates varied widely between statistical methods and between seasons, with greater between-season variation for admissions attributed to influenza compared with respiratory syncytial virus. Sophistication of statistical methods may have been interpreted as assurance that results are more accurate. Without validation against epidemiologic data, with viral etiology confirmed in individual patients, the accuracy of statistical methods in ecologic studies is simply not known. Until these methods are validated, their methodological limitations should be made explicit and proxy estimates used cautiously in guiding public policy.

Infant exposure to fine particulate matter and traffic and risk of hospitalization for RSV bronchiolitis in a region with lower ambient air pollution

Few studies investigate the impact of air pollution on the leading cause of infant morbidity, acute bronchiolitis. We investigated the influence of PM 2.5 and other metrics of traffic-derived air pollution exposure using a matched case–control dataset derived from 1997 to 2003 birth and infant hospitalization records from the Puget Sound Region, Washington State. Mean daily PM 2.5 exposure for 7, 30, 60 and lifetime days before case bronchiolitis hospitalization date were derived from community monitors. A regional land use regression model of NO 2 was applied to characterize subject's exposure in the month prior to case hospitalization and lifetime average before hospitalization. Subject's residential proximity within 150 m of highways, major roadways, and truck routes was also assigned. We evaluated 2604 (83%) cases and 23,354 (85%) controls with information allowing adjustment for mother's education, mother's smoking during pregnancy, and infant race/ethnicity. Effect estimates derived from conditional logistic regression revealed very modest increased risk and were not statistically significant for any of the exposure metrics in fully adjusted models. Overall, risk estimates were stronger when restricted to bronchiolitis cases attributed to respiratory syncytial virus (RSV) versus unspecified and for longer exposure windows. The adjusted odds ratio (OR adj) and 95% confidence interval per 10 mcg/m 3 increase in lifetime PM 2.5 was 1.14, 0.88–1.46 for RSV bronchiolitis hospitalization. This risk was also elevated for infants who resided within 150 m of a highway (OR adj 1.17, 0.95–1.44). This study supports a developing hypothesis that there may be a modest increased risk of bronchiolitis attributable to chronic traffic-derived particulate matter exposure particularly for infants born just before or during peak RSV season. Future studies are needed that can investigate threshold effects and capture larger variability in spatial contrasts among populations of infants.

Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand

This study assessed risk factors for respiratory syncytial virus (RSV) hospitalization and disease severity in Wellington, New Zealand. During the southern hemisphere winter months of 2003--2005, 230 infants aged < 24 months hospitalized with bronchiolitis were recruited. RSV was indentified in 141 (61%) infants. Comparison with data from all live hospital births from the same region (2003--2005) revealed three independent risk factors for RSV hospitalization: birth between February and July [adjusted risk ratio (aRR) 1.62, 95% confidence interval (CI) 1.5-2.29], gestation <37 weeks (aRR 2.29, 95% CI 1.48-3.56) and Māori ethnicity (aRR 3.64, 95% CI 2.27-5.85), or Pacific ethnicity (aRR 3.60, 95% CI 2.14-6.06). The high risk for Māori and Pacific infants was only partially accounted for by other known risk factors. This work highlights the importance of RSV disease in indigenous and minority populations, and identifies the need for further research to develop public health measures that can reduce health disparities.

Index of Suspicion

Index of Suspicion

Late Onset of Spontaneous Pneumothorax Complicating Acute Bronchiolitis in a 5-Month-Old Infant

The literature contains only a few reported cases of spontaneous pneumothorax complicating acute bronchiolitis in infants. We present a case of a 5-month-old infant with a presentation of spontaneous pneumothorax 7 days after hospitalization for acute bronchiolitis. The characteristics of this particular manifestation are discussed.

Introduction

This Supplement includes the proceedings of a symposium held on January 30, 2007, to address issues relating to the seasonality of respiratory syncytial virus (RSV) disease. RSV infects more than 90% of all children within their first 2 years of life resulting in >125,000 hospitalizations annually and representing the single most common cause of hospitalization among infants in the United States. Despite the frequency of RSV infection, mortality among hospitalized patients appears to be <500 deaths annually, due largely to the increasing sophistication of supportive respiratory care provided in pediatric intensive care units. Long-term complications associated with severe RSV disease early in life include recurrent wheezing, reactive airway disease, and abnormalities in pulmonary function testing. Whether prevention of severe RSV disease or actual RSV infection early in life will reduce such long-term complications is unknown. Annual RSV outbreaks in countries with temperate climates primarily continue between late fall through early spring. Data from virology laboratories, compiled by the Center for Disease Control and Prevention have demonstrated that Southern regions of the United States experience the earliest onset and the longest season relative to other areas of the country. Midwestern states typically experience the latest onset as well as the shortest RSV season. The onset and duration of the RSV season in the West and Northeast regions typically fall between that noted in the South and the Midwest. Bronchiolitis outbreaks are correlated closely with RSV detection and prospective studies have found that most hospitalizations for bronchiolitis are caused by RSV. However, within this overall national paradigm of RSV circulation, there may be considerable variation in season onset and offset from year to year and from one location to another. Approximately 3% of all infants in the first 12 months of life will be hospitalized because of RSV infection and most of these infants will be previously healthy, term infants. Development of a vaccine offers the best hope for ultimate control of this disease, but serious scientific and societal obstacles must be overcome before this becomes a reality. In the absence of a useful antiviral agent for treatment or chemoprophylaxis, passive immunoprophylaxis remains the most important means of lowering hospitalization rates and reducing the burden of RSV disease in infants. However, immunoprophylaxis is costly and the most efficient use of resources necessitates its judicious use. Increasing the cost-effectiveness of immunoprophylaxis can be accomplished by restricting its use to infants with the highest risk for severe RSV disease and by concentrating its use to times of most active RSV circulation. The intention of this supplement is to review and refine RSV epidemiology in the United States, to describe 3 areas of the country where RSV circulation differs from national trends, and to address variation in RSV epidemiology that may have clinical impact. The first article by Welliver provides a provocative treatise on meteorological conditions which may influence patterns of RSV circulation. Then, Henrickson and Hall describe the advantages and disadvantages of standard diagnostic techniques and contrast them with newer molecular methods for diagnosis of RSV infection. The article by Panozzo et al, updates results from the National Respiratory and Enteric Virus Surveillance System tracking seasonal and geographic RSV trends within the United States. Singleton et al, describe their observations and thoughts on seasonal variation of RSV hospitalizations in the Yukon-Kuskokwim Delta region of Alaska. Next, Fergie and Purcell describe their experience with RSV hospitalizations in Corpus Christi and San Antonio, Texas. Light then presents observations on RSV hospitalizations from 3 hospitals in Miami and contrasts that experience with the data from Florida as a whole. The supplement concludes with thoughts on how differing definitions of RSV seasonality and how seasonal and geographic variation might be incorporated into decisions regarding immunoprophylaxis so as to better reflect patterns of RSV circulation.

Vitamin D status is not associated with the risk of hospitalization for acute bronchiolitis in early childhood

The association between vitamin D status and susceptibility to acute lower respiratory tract infection (ALRI) was studied in young Canadian children. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in patients aged 1-25 months admitted to hospital with uncomplicated ALRI (primarily viral bronchiolitis) as well as in healthy, similarly aged patients without a history of hospitalization for ALRI (controls). Serum 25(OH)D concentrations were similar among cases and controls (77.0 versus 77.2 nmol l(-1); P=0.960), and there was no case-control difference in the prevalence of vitamin D insufficiency using two thresholds (<40 nmol l(-1): 4.7 versus 1.5%, P=0.365; <80 nmol l(-1): 51.6 versus 56.9%, P=0.598). Vitamin D status was not associated with the risk of hospitalization for ALRI in this population.

Lung function and bronchial hyper‐responsiveness 11 years after hospitalization for bronchiolitis

Aim: Atopic infants hospitalized for wheezing not caused by respiratory syncytial virus (RSV) carry the highest risk for later asthma. In the present paper, early risk factors for later lung function abnormalities and for bronchial hyper‐responsiveness (BHR) were evaluated in 81 children, hospitalized for bronchiolitis in infancy, at the median age of 12.3 years.Methods: The basic data, including data on atopy in children and viral aetiology of bronchiolitis, had been collected on entry to the study at less than 2 years of age. Lung function was studied by flow‐volume spirometry (FVS), and BHR by methacholine and exercise challenge tests 11.4 years after hospitalization during infancy.Results: RSV aetiology of bronchiolitis was associated with reduced forced vital capacity (FVC; 93.65% of predicted ± 11.05 vs. 99.57%± 12.59, p = 0.009). Early sensitization to inhalant allergens (OR 12.59, 95% CI 2.30–68.77) and maternal smoking during pregnancy (OR 4.58, 95% CI 1.28–16.39) were associated with BHR to exercise, and early atopic dermatitis (OR 3.48, 95% CI 1.09–11.10) was associated with BHR to methacholine.Conclusions: RSV bronchiolitis was associated with a restrictive pattern of lung function. Early atopy and maternal smoking during pregnancy may play a role in the development and persistence of BHR.

Wheezy Episodes as a Function of Time-Variant Exposure to Point Source of Air Pollution

ISEE-819 Objective: To assess risk of acute episodes of wheezy respiratory disease among children living around industrial refinery stacks as a function of hours of from-refinery wind exposure, and (separately) of daily exposure to stack-generated SO2. Materials and Methods: In previous work, we found that the 20,000 <15-year-old children who live within 3 km of a Montreal petroindustrial zone experience twice the annual background rate of hospitalizations for asthma, bronchiolitis, and other wheezy respiratory diseases. Based on electronic claims records of medical visits and hospitalizations from Quebec's universal health services system, we developed a 12-year file of health care contacts by day for the diagnoses of interest. Children's addresses, at the level of a city street block, were attached. Exposure assessment was based on (a) hours of wind blowing from the industrial site toward children's homes; (b) the difference in monitored SO2 at fixed sites down- minus up-wind of children's residences with respect to the zone; and (c) a plume model of daily residence-specific SO2 concentrations. We considered lagged exposure-to-disease scenarios of up to 5 days. Medical data were coupled to environmental measures through case-only designs, where SO2 concentration gradients related to the odds of cases occurring in the impacted versus distant sectors, and case-crossover designs where odds of acute case presentation were expressed by hours of off-sector winds, and separately as a function of residence-specific SO2 estimates in the hazard versus control periods. Results: Initial results indicate moderate impacts of time-variant exposure to both winds and to increasing SO2 levels on the odds of presentation for acute wheezy disease. Final results will be available by September. Conclusions: New epidemiologic methods allow for the assessment of time-variant exposure to point sources of pollution on the risk of acute episodes of respiratory disease.

Winter air pollution and infant bronchiolitis in Paris

Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens in infants and young children. It is not known why some previously healthy infants, when in contact with RSV, develop bronchiolitis whereas others have only mild symptoms. Our study aimed to evaluate the possible association between emergency hospital visits for bronchiolitis and air pollution in the Paris region during four winter seasons. We included children under the age of 3 years who attended emergency room services for bronchiolitis (following standardized definition) during the period 1997–2001. Two series of data from 34 hospitals, the daily number of emergency hospital consultations ( n=50 857) and the daily number of hospitalizations ( n=16 588) for bronchiolitis, were analyzed using alternative statistical methods; these were the generalized additive model (GAM) and case-crossover models. After adjustments for public holidays, holidays and meteorological variables the case-crossover model showed that PM 10, BS, SO 2 and NO 2 were positively associated with both consultations and hospitalizations. GAM models, adjusting for long-term trend, seasonality, holiday, public holiday, weekday and meteorological variables , gave similar results for SO 2 and PM 10. This study shows that air pollution may act as a trigger for the occurrence of acute severe bronchiolitis cases.

Management approaches to intermittent wheezing in young children

To review the recently published studies addressing various treatment approaches for episodic wheezing in young children. A landmark study demonstrated that short courses of oral corticosteroids initiated at the first sign of an upper respiratory tract infection decreased wheezing episode frequency and severity. Since then, alternative treatment strategies have been investigated. Montelukast decreased short-term daytime cough and delayed exacerbations following hospitalization for respiratory syncytial virus bronchiolitis, and led to fewer exacerbations without decreasing oral corticosteroids use among children with intermittent asthma. Preschool children with frequent wheezing at high risk for asthma receiving daily inhaled corticosteroids experienced lower rates of exacerbations requiring oral corticosteroids. Episodic use of inhaled corticosteroids, initiated at the early signs of an upper respiratory infection, led to modest reduction in symptoms, but not oral corticosteroid use. Among young children with 'preasthma', inhaled corticosteroids initiated after 3 days of wheezing did not affect the frequency or severity of wheezing episodes. Evidence for the preferred treatment strategies for intermittent wheezing in young children remains incomplete. Most of the studies represent heterogeneous populations and lack adequate statistical power to evaluate relevant outcomes. Based on the evidence, there is rationale for further investigation of several management strategies, including corticosteroids and/or leukotriene receptor antagonists administered daily or episodically.

Clinical and therapeutic variables influencing hospitalisation for bronchiolitis in a community-based paediatric group practice

To examine the effect of different clinical characteristics and different treatments on the hospitalisation of infants with bronchiolitis seen in an outpatient clinic setting. The medical records of infants under 2 years of age who presented with a first episode of wheezing over a two-year period were reviewed retrospectively. Hospitalisation within ten days of evaluation was used as the primary outcome measure. Data from 320 patients were included. 17% were hospitalised. Age was lower in the hospitalised patients (4.9 months vs. 7.1, p<0.001). Hospitalisation was higher in RSV-positive versus RSV-negative patients (38% vs. 10%, p<0.001) and was higher in those children who had been exposed to tobacco smoke versus those who hadn't (24% vs. 12%, p<0.01). Treatment with oral corticosteroids was associated with fewer hospitalisations in those patients with a family history of asthma or allergic rhinitis (9.7% vs. 24%, p=0.02) and in RSV-negative patients (2.5% vs. 16.7%, p<0.05). Early treatment of bronchiolitis with oral corticosteroid in an outpatient clinic setting was associated with lower hospitalisation rates in patients with a family history of asthma or allergic rhinitis and in RSV-negative patients.

Does blood eosinophilia in wheezing infants predict later asthma? A prospective 18–20-year follow-up

Although eosinophilia in wheezing infants predicts subsequent wheezing, it is not known how long the association persists. Our aim was to evaluate the connection between blood eosinophilia in infancy and later wheezing/asthma until adulthood, with special attention paid to infection-induced changes in blood eosinophils. We have prospectively followed up 83 infants until adulthood after hospitalization for bronchiolitis in 1981-1982. Blood eosinophils were determined in a counting chamber on admission and on convalescence 4-6 weeks later. Data on recurrent wheezing and asthma were registered prospectively at five follow-ups until the age of 18-20 years. The median (25th-75th percentile) eosinophil count was 0.100 x 10E9/L (0.028-0.321) on admission and 0.231 x 10E9/L (0.119-0.368) on convalescence. Eosinophils during bronchiolitis or infection-induced changes in eosinophils were not associated with subsequent wheezing/asthma at any age during the follow-up. The result was similar in univariate and multivariate analyses. Respiratory syncytial virus (RSV) bronchiolitis patients had lower eosinophils on admission than non-RSV cases, but the changes induced by RSV or other infection did not differ significantly. In univariate analyses, elevated eosinophils on convalescence predicted later wheezing until 3-4 years of age. In multivariate analysis, adjusted for RSV etiology, age on admission, and histories of earlier wheezing and atopy, elevated eosinophils on convalescence predicted increased asthma risk at 2-3 years (OR, 2.26; 95% CI, 1.29-3.95), at 3-4 years (OR, 2.24; 95% CI, 1.27-3.95), and at 8.5-10 years (OR, 2.16; 95% CI, 1.01-4.64). Eosinophilia outside, but not during, infection predicted recurrent wheezing until preschool and early school years but not thereafter.

Recombinant Human Deoxyribonuclease in Infants With Respiratory Syncytial Virus Bronchiolitis

Background:Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase).Methods:In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions.Results:There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95%confidence interval, 0.96 to 1.33);for the duration of supplemental oxygen, the ratio was 1.28 (95%confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions.Conclusions:Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.