Beyond randomized controlled trials: a "real life" experience of respiratory syncytial virus infection prevention in infancy with and without palivizumab

A population-based study of the impact of palivizumab on confirmed Respiratory Syncytial Virus (RSV) hospitalizations over a 7-year period within and between two similar health regions . Clinicians in Calgary implemented palivizumab prophylaxis for high-risk infants during the last four RSV seasons; clinicians in Edmonton did not. The two cities are part of a unified health care system and similar sociodemographics. Infants <36 weeks (wk) of gestational age (GA) were identified. RSV prophylaxis data and RSV-hospitalizations for high-risk infants eligible for prophylaxis were reviewed, as well as that of moderate-risk infants (33-35 weeks GA) for whom RSV prophylaxis was not given a high priority in the recommendations published by the Canadian Paediatric Society (CPS). Prevalence of RSV hospitalization before and after palivizumab was determined (1995-1998 and 1999-2002, respectively). There were 411 high-risk infants eligible for palivizumab prior to its provision (Pre) and 496 during the prophylaxis program (Post) in Calgary. There were 401 Pre and 425 Post in Edmonton, where no such prophylaxis program was implemented. In Calgary where palivizumab was offered (Post), RSV hospitalization was significantly reduced: 7.3% Pre versus 3.0% Post (OR, 2.53, 95% CI, 1.34, 4.76). No reduction was observed in Edmonton where palivizumab was not offered: 5.0% Pre versus 7.1% Post (OR, 1.45, 95% CI, 0.81, 2.59; P = 0.212). RSV hospitalizations did not change for moderate-risk infants not receiving palivizumab in Calgary (OR, 1.26, 95% CI, 0.75, 2.12; P = 0.389). An RSV prevention program with palivizumab for high-risk infants reduced RSV hospitalizations, providing "real life" evidence of the benefits of this prophylaxis strategy. Further research is required to determine if specific sub-sets of moderate-risk infants would also benefit from an RSV prophylaxis program with palivizumab.     

Impact of palivizumab on admission to the ICU for respiratory syncytial virus bronchiolitis: a national survey

STUDY OBJECTIVES: To assess the effect of palivizumab licensing for respiratory syncytial virus (RSV) prophylaxis on national pediatric ICU (PICU) admissions and on the need for mechanical ventilation due to RSV bronchiolitis in Israel. DESIGN: Prospective national surveillance survey. SETTING: All PICUs in Israel.Patients or participants: All patients admitted to a PICU because of acute bronchiolitis in two consecutive RSV seasons (November 2000 to April 2001 and November 2001 to April 2002). METHODS: Data on demographic and epidemiologic factors and RSV prophylaxis status were collected for every infant with bronchiolitis who was admitted to a PICU in Israel in the year before and after issuance of the Israel Ministry of Health recommendation for palivizumab prophylaxis (January 2001). RESULTS: One hundred five patients were admitted to a PICU because of RSV bronchiolitis in the year before the recommendations were issued, and 123 patients were admitted in the year after they were issued. Mechanical ventilation was required by 33 and 42 children, respectively. Gestational age was > 32 weeks in 92.9% and 83.9% of the admitted patients, respectively, and 89% and 91% of the patients, respectively, were free of chronic lung disease (CLD). In both periods, 83% of the children who were admitted to a PICU did not meet the American Academy of Pediatrics criteria for RSV prophylaxis. CONCLUSIONS: Most of the children with severe RSV bronchiolitis needing PICU admission from 2000 to 2002 born at term did not have CLD and were not candidates for RSV prophylaxis according to the current recommendations.     

Palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from The Palivizumab Outcomes Registry

The objective of the Registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (RSV) disease by describing the patterns and scope of usage of palivizumab in a cross section of US infants. RSV hospitalization outcomes were also described. The Palivizumab (Synagis, MedImmune, Inc., 25 West Watkins Mill Road, Gaithersburg, MD 20878) Outcomes Registry was a prospective multicenter survey conducted at 63 sites. Demographics, injection history, and RSV hospitalization outcomes were collected on 2,116 infants receiving palivizumab. Infants were enrolled in the Registry between September 1, 2000-March 1, 2001, at the time of their first injection. Infants born at less than 32 weeks of gestation accounted for 47% of infants enrolled, and those between 32-35 weeks accounted for 45%; approximately 8% were greater than 35 weeks of gestation. Lower RSV hospitalization rates were observed in infants who had greater adherence to regularly scheduled injections. Nearly one-half of all hospitalizations occurred within the first and second injection intervals, suggesting the importance of early RSV protection. The confirmed RSV hospitalization rate of all infants in the Registry was 2.9%; the rate was 5.8% in infants with chronic lung disease of infancy, and 2.1% in premature infants without chronic lung disease. In conclusion, these data support the continued effectiveness of palivizumab prophylaxis for severe RSV lower respiratory tract disease in a large cohort of high-risk infants from geographically diverse pediatric offices and clinics. The Palivizumab Outcomes Registry provides an opportunity to assess palivizumab utilization and clinical effectiveness in the US.     

Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective

Background

Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. In children with congenital heart disease (CHD), it is associated with significant morbidity and mortality. Palivizumab is a monoclonal antibody that reduces the number of RSV-associated hospitalizations in children with CHD. We sought to assess cost savings and cost-effectiveness of palivizumab in children < 2 years old with hemodynamically significant CHD in a provincially administered RSV prophylaxis program.

Methods

A cohort of children who received palivizumab (N = 292) from 2003-2007 was compared to a historical cohort of children (N = 412) from 1998-2003 who met the eligibility criteria for palivizumab prior to initiation of the prophylaxis program. Direct and indirect costs and benefits were determined.

Results

The direct and indirect costs in the historical cohort were $838 per patient season compared to $9130 per patient season in the palivizumab cohort. Risk of admission was reduced by 42%, and days in hospital were reduced by 83%. The incremental cost of the RSV prophylaxis program was $8292 per patient for 1 RSV season. The incremental cost to prevent 1 day of hospitalization was $15,514. The cost of palivizumab accounted for 87.9% of the cost of prophylaxis.

Conclusions

Palivizumab is clinically effective; however, the cost was exceptionally high relative to the outcomes in this population. Given the financial constraints in a public health care setting, more strict criteria for patient selection or reduced drug costs would improve the cost-effectiveness of RSV prophylaxis.     

Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.

OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).     

A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice

Respiratory syncytial virus (RSV) is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies.The present article reviews the epidemiology of RSV infection and the short- and long-term impact of disease in high-risk infants and special populations. Prevention strategies and treatment are discussed based on the existing scientific evidence, and future challenges in the management of RSV infection are addressed.     

Surveillance of clinical isolates of respiratory syncytial virus for palivizumab (Synagis)-resistant mutants

Premature infants and those with chronic lung disease or congenital heart disease are at high risk of severe respiratory syncytial virus (RSV) disease. Palivizumab (Synagis), a humanized anti-RSV monoclonal antibody, has been used extensively since 1998 to prevent severe RSV disease in high-risk infants. To monitor for possible palivizumab-resistant mutants, an immunofluorescence binding assay that predicts palivizumab neutralization of RSV was developed. RSV isolates were collected at 8 US sites from 458 infants hospitalized for RSV disease (1998-2002). Palivizumab bound to all 371 RSV isolates able to be evaluated, including 25 from active-palivizumab recipients. The palivizumab epitope appears to be highly conserved, even in infants receiving prophylaxis with palivizumab.     

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections,and association between respiratory syncytial virus infection risk factors and disease severity

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants.Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection.The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.     

Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis

Background

Evidence on the effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is lacking.

Methods

We utilized Medicaid Extract files from 27 states from 1999 to 2006 linked to the National Cystic Fibrosis Registry to establish a cohort of children 0–2 years with CF diagnosis. Eligible children entered the cohort after CF diagnosis and after RSV season onset, and were followed until season end, second birthday, death, or hospitalizations for reasons other then the study outcome. Two outcomes were examined: hospitalization for RSV infections (RSV‐ha), or hospitalization for acute respiratory infections (ARI‐ha). Palivizumab exposure was defined based on pharmacy or procedure claims as current (claim date plus 30 days), former (day 31–60 after a claim), and no exposure (days before the first or >60 days after any claim). Both outcomes were examined in a Cox regression model, adjusting for RSV risk factors and CF severity via exposure propensity score.

Results

The matched cohort included 1,974 infants (2,875 infant seasons), who experienced 32 RSV‐ha and 212 ARI‐ha (3.9 and 26.2/1,000 season months, respectively). Compared to periods of no use, the adjusted hazard ratio for current use was 0.57 (95% confidence interval [CI]: 0.20–1.60) for RSV‐related hospitalization and 0.85 (95% CI: 0.59–1.21) for ARI‐related hospitalization. Each month of increasing age reduced the ARI‐ha by 5.8%.

Conclusion

RSV hospitalization incidence was low suggesting either little contribution of the virus to respiratory infections in patients with CF or lack of RSV testing. Unadjusted and adjusted RSV‐hospitalization incidence rates suggested potentially positive effects of palivizumab, but results were inconclusive due to small event rates. Hospitalizations for acute respiratory illness with possible RSV contribution showed no association with palivizumab use, suggesting limited overall effect of palivizumab. Younger age greatly increased infection risk. Pediatr Pulmonol. 2013; 48:874–884. © 2012 Wiley Periodicals, Inc.

     

Effect of delayed palivizumab administration on respiratory syncytial virus infection-related hospitalisation: A retrospective,observational study

Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in infants and young children. Monthly administration of palivizumab during the RSV season is effective in preventing severe infections in children with comorbidities. However, determining the onset of the RSV season for starting palivizumab is often challenging. The present study aimed to evaluate the ideal timing to start palivizumab and its effect on hospitalization in the real world.We performed a retrospective, observational study to identify the relationship between the timing of the first dose of palivizumab administration and RSV-related hospitalization. Medical records from 2015 to 2019 were reviewed. We included patients who had indications for palivizumab as of July 1 in each year. We counted the proportion of children receiving palivizumab and the number of RSV infection-related hospitalizations each month. We also evaluated the differences in background and underlying disease between children with and without hospitalization.A total of 498 patients were included, and 105 (21.0%) completed the first dose in July when the RSV season usually begins in Japan. Twenty-three (4.6%) patients were hospitalized for RSV infection during the observation period, with 13 (56.5%) hospitalizations before their first dose of palivizumab. The remaining 10 patients were hospitalized after receiving 1 or more doses of palivizumab. Children living with siblings and children with cyanosis originating from congenital heart disease had a higher risk of RSV with odds ratios of 5.1 (95% confidence interval 1.48-17.6, P < .01) and 3.3 (95% confidence interval 1.33-7.94, P < .01), respectively.Delays in administering palivizumab at the beginning of the season increases the rate of RSV infection-related hospitalization. To maximize prophylactic effectiveness, administering the first dose as early as possible in the RSV season is crucial, with priority for cyanotic children or those with siblings.     

Prospective Population-based Study of RSV-related Intermediate Care and Intensive Care Unit Admissions in Switzerland over a 4-Year Period (2001–2005)

Abstract Objectives:   Respiratory syncytial virus (RSV) infections are a leading cause of hospital admissions in small children. A substantial proportion of these patients require medical and nursing care, which can only be provided in intermediate (IMC) or intensive care units (ICU). This article reports on all children aged < 3 years who required admission to IMC and/or ICU between October 1, 2001 and September 30, 2005 in Switzerland. Patients and Methods:   We prospectively collected data on all children aged < 3 years who were admitted to an IMC or ICU for an RSV-related illness. Using a detailed questionnaire, we collected information on risk factors, therapy requirements, length of stay in the IMC/ICU and hospital, and outcome. Results:   Of the 577 cases reported during the study period, 90 were excluded because the patients did not fulfill the inclusion criteria; data were incomplete in another 25 cases (5%). Therefore, a total of 462 verified cases were eligible for analysis. At the time of hospital admission, only 31 patients (11%) were older than 12 months. Since RSV infection was not the main reason for IMC/ICU admission in 52% of these patients, we chose to exclude this subgroup from further analyses. Among the 431 infants aged < 12 months, the majority (77%) were former near term or full term (NT/FT) infants with a gestational age ≥ 35 weeks without additional risk factors who were hospitalized at a median age of 1.5 months. Gestational age (GA) < 32 weeks, moderate to severe bronchopulmonary dysplasia (BPD), and congenital heart disease (CHD) were all associated with a significant risk increase for IMC/ICU admission (relative risk 14, 56, and 10, for GA ≤ 32 weeks, BPD, and CHD, respectively). Compared with NT/FT infants, high-risk infants were hospitalized at an older age (except for infants with CHD), required more invasive and longer respiratory support, and had longer stays in the IMC/ICU and hospital. Conclusions:   In Switzerland, RSV infections lead to the IMC/ICU admission of approximately 1%–2% of each annual birth cohort. Although prematurity, BPD, and CHD are significant risk factors, non-pharmacological preventive strategies should not be restricted to these high-risk patients but also target young NT/FT infants since they constitute 77% of infants requiring IMC/ICU admission.     

Respiratory syncytial virus infection in a Sicilian pediatric population: risk factors, epidemiology, and severity.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTIs) in young children worldwide. This study evaluated the epidemiological and clinical patterns of RSV infection in infants hospitalized for LRTIs in Sicily. Over a 7-month period (October 1, 2005 to April 30, 2006), all children <2 years of age hospitalized for LRTIs were evaluated and tested for respiratory viruses. Logistic regression was used to identify the risk factors associated with RSV infection and with more severe disease. One hundred sixty-four children were enrolled and 40.9% were found to be RSV(+). The epidemic peak of RSV occurred in April, and no cases were observed in October, November, and December. RSV Infections had the highest incidence in children <3 months of age (54.7%). The likelihood to be RSV(+) rather than RSV(-) was lower for female gender and children >6 months old, with a gestational age (GA) of >36 weeks, with a birth weight of >2.50 g, with previous hospitalizations due to LRTI, with smokers in the household, and with a history of breast-feeding (p < 0.05 for each). RSV infection was associated with a higher likelihood to be admitted to neonatal intensive care units and to longer hospitalizations (p = 0.061). The collected data show that, in Sicily, RSV is an important cause of LRTIs in infants and a variety of factors, such as gender, chronological age at hospitalization, GA, birth weight, and exposure to tobacco smoke and breast-feeding may affect the prevalence of RSV-related lower respiratory tract disease and, possibly, the risk of developing asthma-like symptoms during the school years.     

Readmission with respiratory syncytial virus (RSV) infection among graduates from a neonatal intensive care unit

We evaluated the incidence of readmission with respiratory syncytial virus (RSV) infection among the graduates of a regional Neonatal Intensive Care Unit (NICU), and characterized those who were rehospitalized. These data were used as a predictive tool to estimate the number of babies likely to suffer readmission with RSV for the year 2000 cohort. Using the published efficacies of palivizumab, the costs and benefits of protecting this cohort were assessed. Retrospective analysis of 2,507 NICU inpatient records from January 1, 1994-December 31, 1999 from the Royal Maternity Hospital, Belfast, were compared with data on positive RSV samples from 1,790 patients between January 1, 1995-December 31, 1999 from the Northern Ireland Regional Virus Laboratory.The analysis yielded 136 (7.6%) ex-NICU patients among the positive RSV samples over this 5-year period. Characteristic seasonal peaks of RSV infection with interseasonal variability were observed. Of those readmitted, 86.9% were hospitalized with RSV before their first birthday. A calculated readmission rate of 5.4% for all NICU graduates, and 6.4% for those 相似文献   

Early ribavarin treatment of bronchiolitis: effect on long-term respiratory morbidity

BACKGROUND: The mortality rate from respiratory syncytial virus (RSV) bronchiolitis has significantly reduced over the last decade. A major concern now is the long-term respiratory morbidity following RSV bronchiolitis. METHODS: In this prospective study, we randomly assigned 49 previously healthy infants with severe RSV bronchiolitis, early in the course of illness (< 5 days duration), to receive either conservative treatment (n = 21) or additional ribavirin treatment (n = 24). Both groups were closely matched for age and clinical characteristics. RESULTS: During a prospective, closely monitored, 1-year follow-up period, the group treated with ribavirin had significantly fewer episodes (2.7 +/- 2.3 episodes vs 6.4 +/- 4.2 episodes per patient per year) and reduced severity of reactive airway disease (0.08 episodes vs 1.09 episodes of moderate-to-severe illness per patient per year) and respiratory illness-related hospitalization (25 hospital days vs 90 hospital days per 100 patients per year). CONCLUSIONS: Early ribavirin treatment of RSV bronchiolitis in previously healthy infants resulted in reduction of incidence and severity of reactive airway disease as well as respiratory illness-related hospitalization.     

Rehospitalisations for respiratory disease and respiratory syncytial virus infection in preterm infants of 29-36 weeks gestational age

BACKGROUND: To evaluate rates of rehospitalisation due to respiratory illness in preterm infants of 29-36 weeks gestation without chronic lung disease. PATIENTS AND METHODS: Retrospective single centre cohort study including infants from 1998 to 1999 with follow-up over two respiratory syncytial virus (RSV) seasons. RESULTS: Of 435 infants included 61 infants (14%) experienced 78 rehospitalisations. The overall RSV attack rate was 4.4% over two consecutive RSV seasons for infants below 6 months of age at onset of RSV season (7.7 and 1.1%, respectively, p=0.015), with significant differences between infants of 29-32 and 33-36 weeks gestational age (10.5% vs. 2.3%, p=0.008). None of the infants needed mechanical ventilation or admission to the intensive care unit. Infants with RSV infection were younger of age (mean 4.2 vs. 8.2 months; p=0.015), had longer stays at the hospital (11.5 vs. 7.0 days; p=0.006), and more severe courses of disease (score 3.0 vs. 1.8; p<0.001). Additional risk factors for RSV infection were multiple gestation (OR 5.5; CI 95% 1.439-21.028) and congenital heart disease (OR 4.2; CI 95% 1.005-17.669). CONCLUSION: The total burden of respiratory disease and RSV infection in this population was low. A lower gestational age, multiple gestation, and congenital heart disease were associated with increased risk of RSV infection.     

Impact of human metapneumovirus and respiratory syncytial virus co-infection in severe bronchiolitis

We have previously shown high rates of co-infection with Respiratory Syncytial Virus (RSV) and human Metapneumovirus (hMPV) in infants with severe bronchiolitis at our institution in 2000-2002, and that co-infection was associated with increased disease severity. In this study, we have attempted to identify differences in intubated infants with severe RSV infection with and without hMPV co-infection. Here we show that RSV+/hMPV+ were clinically symptomatic for longer than RSV+/hMPV- infants, but that no differences in airway total cell concentration, differential cell count or cytokine/chemokine concentrations were detectable.     

Three monthly doses of palivizumab are not adequate for 5-month protection: A population pharmacokinetic analysis

Recent guidelines in British Columbia, Canada have suggested that the use of a maximum of 3 monthly doses of palivizumab 15 mg/kg intramuscularly for RSV immunoprophylaxis of high risk infants born prior to the RSV season is adequate to provide protection against severe RSV disease for a 5-month RSV season. Efficacy was established, however, with 2 large, randomized controlled clinical studies using 5 monthly doses of immunoprophylaxis. To evaluate the differences in expected palivizumab exposures between the 2 dosing regimens (3 vs 5 monthly doses across a 5-month period), we used a population pharmacokinetic (PK) model that was developed using palivizumab PK data collected from 22 clinical studies with a total of 1800 subjects. This model adequately described observed palivizumab concentrations from the different pediatric studies and was subsequently used to simulate expected palivizumab serum concentrations for 3 monthly doses compared with 5 monthly doses in children younger than 24 months with chronic lung disease of prematurity and infants younger than 6 months postnatal age who were born at ≤35 weeks gestational age. Results from the population PK model indicated lower serum concentrations of palivizumab during the fourth and fifth months, after an abbreviated 3-monthly–dose regimen when compared with the mean trough concentrations seen with the 5-monthly–dose regimen studied in the pivotal clinical trials in premature infants. Specifically, during the fourth and fifth months, 52% and 85%, respectively, would have levels below the lowest concentration (fifth percentile) in those receiving the 5-monthly-dose regimen. Simulations using this model did not support a 3-monthly–dose regimen to protect against severe RSV disease during the typical 5-month season.     

Risk factors for recurrent wheezing following acute bronchiolitis: a 12-month follow-up

The objective of this study was to identify wheezing recurrences and related risk factors in two groups of infants with bronchiolitis: respiratory syncytial virus (RSV)+ and RSV- as determined by RSV enzyme immunoassay. A 1-year prospective cohort study was conducted with infants younger than 2 years old. Follow-up was made monthly, by a clinical visit and/or by telephone, checking the number of wheezing episodes per month and possible related risk factors. There were 96 subjects enrolled, of whom 77 reached complete follow-up: 36 were RSV+ (46.8%), and 41 were RSV- (53.2%). In the RSV+ group, there were 17 males (47%), vs. RSV- with 30 males (73%) (P < 0.05); 22 RSV+ (61%) were admitted to hospital, vs.14 RSV- (34%) (P < 0.05). Mean age was not significantly different in both groups. The mean number of recurrences was 3.36 episodes/infant/year in the RSV+ and 2.34 in the RSV- group (P = 0.06). Crude relative risk (RR) for a new recurrence of an obstructive episode was 1.33 (95% CI, 0.99-1.79). After adjustment for several potential confounders, the RR was 1.41 (95% CI, 1.03-1.93). Hospitalization stay was longer in the RSV+ than the RSV- group (P < 0.05). In the RSV+ group, patients who had been hospitalized showed more recurrences (4.18) than those with outpatient treatment (2.07) (P < 0.05); this difference did not exist in the RSV- group. The related risk factors for recurrent wheeze in the RSV- group were male gender, number of siblings, and daycare attendance (P < 0.05). In the RSV+ group, the risk of recurrent wheeze was only increased by admission to hospital during the acute bronchiolitis episode (P < 0.05). We speculate that there may be a higher rate of increased airway reactivity and/or preexisting diminished lung function in RSV+ infants requiring hospitalization for their initial illness. In conclusion, RSV-proven bronchiolitis, particularly in those infants who are hospitalized, is associated with a higher recurrence of wheezing episodes in the subsequent 12 months. Other factors appear to account for recurrent wheeze in the RSV- group.