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A study was conducted to evaluate the efficacy of combined use of epinephrine and dexamethasone in infants with bronchiolitis. Results indicated that a combined use of the two did effectively reduce the need for hospital admissions.

Byline: Gilles Cambonie (1,7), Christophe Milesi (1), Samir Jaber (2,6), Francis Amsallem (3), Eric Barbotte (4), Jean-Charles Picaud (1), Stefan Matecki (5,6) Keywords: Bronchiolitis; Continuous positive airway pressure; Infant; Respiratory effort; Respiratory syncytial virus infections; Respiratory therapy Abstract: Objective To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis. Design Prospective study. Setting The paediatric intensive care unit of a university hospital. Patients Twelve infants less than 3 months of age, with severe respiratory distress. Interventions Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients. Measurements and results The respiratory distress score decreased after nCPAP, particularly accessory muscles' use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes.sub.insp, two indices of inspiratory effort, were reduced by 54 (+-4)% and 59 (+-5)%. PTPgas.sub.exp, an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP. Conclusions In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms. Author Affiliation: (1) Pediatric Intensive Care Unit, CHU Montpellier, 34000, Montpellier, France (2) Intensive Care Unit and Transplantation Department, CHU Montpellier, 34000, Montpellier, France (3) Pediatric Pulmonology Unit, CHU Montpellier, 34000, Montpellier, France (4) Department of Medical Information, CHU Montpellier, 34000, Montpellier, France (5) Physiological Department, CHU Montpellier, 34000, Montpellier, France (6) INSERM ERI 25, Muscle and Pathologies, University Montpellier I, 34000, Montpellier, France (7) Unite de Reanimation-Pediatrique, CHU de Montpellier, Hopital Arnaud de Villeneuve, 371 Avenue du Doyen G. Giraud, 34295, Montpellier Cedex 5, France Article History: Registration Date: 24/06/2008 Received Date: 19/01/2008 Accepted Date: 15/06/2008 Online Date: 08/07/2008 Article note: This work was carried out in the Paediatric Intensive Care Unit, Hopital Arnaud de Villeneuve, CHU Montpellier, 34000 Montpellier, France.

Byline: Michel E. Berner (1), Sylviane Hanquinet (2), Peter C. Rimensberger (3) Keywords: Respiratory syncytial virus; High frequency oscillatory ventilation; Bronchiolitis; Respiratory failure; Hypercapnia Abstract: Objective To describe the time course of high frequency oscillatory ventilation (HFOV) in respiratory syncytial virus (RSV) bronchiolitis. Design Retrospective charts review. Setting A tertiary paediatric intensive care unit. Patients and participants Infants with respiratory failure due to RSV infection. Intervention HFOV. Measurements and results Pattern of lung disease, ventilatory settings, blood gases, infant's vital parameters, sedation and analgesia during the periods of conventional mechanical ventilation (CMV, 6 infants), after initiation of HFOV (HFOVi, 9 infants), in the middle of its course (HFOVm), at the end (HFOVe) and after extubation (Post-Extub) were compared. All infants showed a predominant overexpanded lung pattern. Mean airway pressure was raised from a mean (SD) 12.5 (2.0) during CMV to 18.9 (2.7) cm[H.sub.2]O during HFOVi (P < 0.05), then decreased to 11.1(1.3) at HFOVe (P < 0.05). Mean FiO.sub.2 was reduced from 0.68 (0.18) (CMV) to 0.59 (0.14) (HFOVi) then to 0.29 (0.06) (P < 0.05) at HFOVe and mean peak to peak pressure from 44.9 (12.4) cm[H.sub.2]O (HFOVi) to 21.1 (7.7) P < 0.05 (HFOVe) while mean (SD) PaCO.sub.2 showed a trend to decrease from 72 (22) (CMV) to 47 (8) mmHg (HFVOe) and mean infants respiratory rate a trend to increase from 20 (11) (HFOVi) to 34 (14) (HFOVe) breaths/min. With usual doses of sedatives and opiates, no infant was paralysed and all were extubated to CPAP or supplemental oxygen after a mean of 120 h. Conclusion RSV induced respiratory failure with hypercapnia can be managed with HFOV using high mean airway pressure and large pressure swings while preserving spontaneous breathing. Author Affiliation: (1) Neonatology and Paediatric Intensive Care Service, Geneva University Hospitals and University of Geneva, Geneva, Switzerland (2) Paediatric Radiology Unit, Geneva University Hospitals and University of Geneva, Geneva, Switzerland (3) Neonatology and Paediatric Intensive Care Service, Geneva University Hospitals and University of Geneva, Geneva, Switzerland Article History: Registration Date: 07/05/2008 Received Date: 21/06/2007 Accepted Date: 06/12/2007 Online Date: 24/05/2008 Article note: This article is discussed in the editorial available at doi: 10.1007/s00134-008-1152-2.

Byline: Etienne Javouhey (1), Audrey Barats (2), Nathalie Richard (1), Didier Stamm (1), Daniel Floret (1) Keywords: Bronchiolitis; Non-invasive ventilation; Pulmonary infection; Children; Duration of ventilation Abstract: Objective To report our experience of non-invasive ventilation (NIV) as primary ventilatory support strategy in infants admitted for severe bronchiolitis. Design and setting Retrospective study in a paediatric intensive care unit of an university hospital. Patients Infants aged less than 12 months, admitted for bronchiolitis during 2003--2004 and 2004--2005 winter epidemics. Intervention NIV was used as the primary ventilatory support during the second winter (NIV period), whereas invasive ventilation (IV) was the only support employed during the first winter (IV period). NIV consisted in either continuous positive airway pressure (CPAP from 5 to 10 cm[H.sub.2]O) or bilevel positive airway pressure (inspiratory pressure from 12 to 18 cm[H.sub.2]O) with a nasal mask. Results During the IV period, 53 infants were included, compared to 27 during the NIV period. The two groups did not differ in age or in number of premature births. Children in NIV group had less apnoea on admission. The intubation rate was reduced during NIV period (p < 0.001). No children had ventilator-associated pneumonia (VAP) during NIV period compared to nine during IV period (p < 0.05). In the NIV group, 10 infants (37%) required supplemental oxygen for more than 8 days compared to 33 children (65%) in IV group (p < 0.05). The length of hospital stay and the duration of ventilation were similar. Conclusions In this retrospective study, the use of NIV decreased the rate of ventilator associated pneumonia and reduced the duration of oxygen requirement without prolonging the hospital stay. Author Affiliation: (1) Service de Reanimation Pediatrique Hopital Femme Mere Enfant, Groupement Hospitalier Est, 59 Boulevard Pinel, Hospices Civils de Lyon, Universite Lyon 1, 69677, Bron Cedex, France (2) Service de pediatrie 2, Hopital Hautepierre, avenue Moliere, 67200, Strasbourg, France Article History: Registration Date: 07/05/2008 Received Date: 02/03/2007 Accepted Date: 22/12/2007 Online Date: 24/05/2008 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-008-1152-2. This work was accepted for a poster presentation in the XXXIVdeg congres de la Societe de Reanimation de Langue Francaise (SRLF). Paris-la Defense, 18--20 janvier 2006 (Reanimation vol 14, suppl 1, SP126) and for an oral presentation in the 8th European Conference in Paediatric and Neonatal Ventilation, 29 Mars--01 Avril 2006, Montreux, Switzerland. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1150-4) contains supplementary material, which is available to authorized users.

The development of chronic allograft rejection is based on the hypothesis that cumulative, time-dependent tissue injury eventually leads to a fibrotic response. In this issue of the JCI, Babu and colleagues found that alloimmune-mediated microvascular loss precedes tissue damage in murine orthotopic tracheal allografts (see the related article beginning on page 3774). The concept that injury to the endothelium may precede airway fibrosis suggests that interventions to maintain vascular integrity may be important, especially in the case of lung transplantation. Further, for all solid organ allografts, it is possible that the key to long-term allograft survival is physiological vascular repair at early times following transplantation., Clues to mechanisms underlying long-term allograft survival The major obstacle to the long-term survival of lung transplant recipients is the development of the bronchiolitis obliterans syndrome (BOS), which typically occurs [...]

Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role [...]

OBJECTIVE. Our goal was to determine whether maternal asthma and maternal smoking during pregnancy are associated with the incidence and severity of clinically significant bronchiolitis in term, otherwise healthy infants without the confounding factors of small lung size or underlying cardiac or pulmonary disease. PATIENTS AND METHODS. We conducted a population-based retrospective cohort study of term, non-low birth weight infants enrolled in the Tennessee Medicaid Program from 1995 to 2003. The cohort of infants was followed through the first year of life to determine the incidence and severity of bronchiolitis as determined by health care visits and prolonged hospitalization. RESULTS. A total of 101 245 infants were included. Overall, 20% of infants had [greater than or equal to] 1 health care visit for bronchiolitis. Compared with infants with neither factor, the risk of bronchiolitis was increased in infants with maternal smoking only, maternal asthma only, or both. Infants with maternal asthma only or with both maternal smoking and asthma had the highest risks for emergency department visits and hospitalizations. Infants with a mother with asthma had the highest risk of a hospitalization >3 days, followed by infants with both maternal asthma and smoking, and maternal smoking only. CONCLUSIONS. Maternal asthma and maternal smoking during pregnancy are independently associated with the development of bronchiolitis in term, non-low birth weight infants without preexisting cardiac or pulmonary disease. The risk of bronchiolitis among infants with mothers who both have asthma and smoke during pregnancy is ~50% greater than that of infants with neither risk factor. Efforts to decrease the illness associated with these 2 risk factors will lead to decreased morbidity from bronchiolitis, the leading cause of hospitalization for severe lower respiratory tract infections during infancy. Key Words bronchiolitis, risk factors, infant, smoking, asthma, BRONCHIOLITIS, CAUSED BY viruses such as respiratory syncytial virus (RSV) and rhinovirus, is the leading cause of lower respiratory tract infections in infants. (1-4) Bronchiolitis results in significant morbidity in [...]

OBJECTIVES. Although bronchiolitis is the leading cause of hospitalization for infants, there are limited data describing the epidemiology of bronchiolitis hospitalizations, and the associated cost is unknown. Our objective was to determine nationally representative estimates of the frequency of bronchiolitis hospitalizations and its associated costs. PATIENTS AND METHODS. We analyzed the 2002 Health Care Utilization Project-National Inpatient Sample, a federal, stratified random survey of hospital discharges. For admissions age RESULTS. In 2002, an estimated 149 000 patients were hospitalized with bronchiolitis. Frequency of hospitalizations was higher among children age < 1 year of age, male gender, and nonwhite race. Mean length of stay was 3.3 days. Total annual costs for bronchiolitis-related hospitalizations were $543 million, with a mean cost of $3799 per hospitalization. Mean cost of bronchiolitis with a codiagnosis of pneumonia was $6191. In a multivariate analysis controlling for 3 confounding factors (including length of stay), cost per hospitalization was higher for children [greater than or equal to]1 year and lower for those in the South versus Northeast. CONCLUSIONS. Bronchiolitis admissions cost more than $500 million annually. A codiagnosis of bronchiolitis and pneumonia almost doubles the cost of the hospitalization. Inpatient health care costs of bronchiolitis are higher than estimated previously and highlight the need for initiatives to safely reduce bronchiolitis hospitalizations and thereby decrease health care costs. Key Words bronchiolitis, cost, HCUP, Bronchiolitis is the leading cause of hospitalization for infants Estimating bronchiolitis hospitalization costs from RSV-related bronchiolitis may underestimate the true cost of bronchiolitis hospitalizations. Although RSV infection is the most [...]

Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection. It is the most common lower respiratory infection in this age group. It is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, increased mucus production, and bronchospasm. The American Academy of Pediatrics convened a committee composed of primary care physicians and specialists in the fields of pulmonology, infectious disease, emergency medicine, epidemiology, and medical informatics. The committee partnered with the Agency for Healthcare Research and Quality and the RTI International-University of North Carolina Evidence-Based Practice Center to develop a comprehensive review of the evidence-based literature related to the diagnosis, management, and prevention of bronchiolitis. The resulting evidence report and other sources of data were used to formulate clinical practice guideline recommendations. This guideline addresses the diagnosis of bronchiolitis as well as various therapeutic interventions including bronchodilators, corticosteroids, antiviral and antibacterial agents, hydration, chest physiotherapy, and oxygen. Recommendations are made for prevention of respiratory syncytial virus infection with palivizumab and the control of nosocomial spread of infection. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent comprehensive peer review before it was approved by the American Academy of Pediatrics. This clinical practice guideline is not intended as a sole source of guidance in the management of children with bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It is not intended to replace clinical judgment or establish a protocol for the care of all children with this condition. These recommendations may not provide the only appropriate approach to the management of children with bronchiolitis. Key Word bronchiolitis Abbreviations CAM--complementary and alternative medicine LRTI--lower respiratory tract infection AHRQ--Agency for Healthcare Research and Quality RSV--respiratory syncytial virus AAP--American Academy of Pediatrics AAEP--American Academy of Family Physicians RCT--randomized, controlled trial CLD--chronic neonatal lung disease SBI--serious bacterial infection UTI--urinary tract infection AOM--acute otitis media Sp[O.sub.2]--oxyhemoglobin saturation LRTD--lower respiratory tract disease, INTRODUCTION THIS GUIDELINE EXAMINES the published evidence on diagnosis and acute management of the child with bronchiolitis in both outpatient and hospital settings, including the roles of supportive therapy, oxygen, [...]

OBJECTIVE. Hypoxia is a common reason for hospital admission in infants and children with acute bronchiolitis. No study has evaluated discharge from the emergency department (ED) on home oxygen. This study evaluated the feasibility and safety of ED discharge on home oxygen in the treatment of acute bronchiolitis. METHODS. This was a prospective, randomized trial of infants and children with acute bronchiolitis and hypoxia (room-air saturations of [less than or equal to] 7%) aged 2 to 24 months presenting to an urban, academic, tertiary care children&apos;s hospital ED from December 1998 to April 2001. Subjects received inpatient admission or home oxygen after an 8-hour observation period in the ED. We measured the failure to meet discharge criteria during the observation period, return for hospital admission, and incidence of serious complications. RESULTS. Ninety-two patients were enrolled. Fifty three (58%) were randomly assigned to home and 39 (42%) to inpatient admission. There were no differences between the groups in age, initial room-air saturation, and respiratory distress severity score. Of 53 patients, 37 (70%) randomly assigned to home oxygen completed the observation period and were discharged from the hospital. The remaining 16 patients were excluded from the study (6), resolved their oxygen requirement (5), or failed to meet the discharge criteria and were admitted (5). One discharged patient (2.7%) returned to the hospital and was admitted for a cyanotic spell at home after the 24-hour follow-up appointment. The patient had an uncomplicated hospital course with a length of stay of 45 hours. The remaining 36 patients (97%) were treated successfully as outpatients with home oxygen. Satisfaction with home oxygen was high from the caregiver and the primary care provider. CONCLUSIONS. Discharge from the ED on home oxygen after a period of observation is an option for patients with acute bronchiolitis. Secondary to the low incidence of complications, the safety of this practice will require a larger study. Key Words bronchiolitis, hypoxia, oxygen, home therapy, observation Abbreviations PCP--primary care provider ED--emergency department RDSS--respiratory distress severity score, BRONCHIOLITIS IS THE most common cause of hospital admission in children < 1 year of age. An estimated 80 000 to 120 000 children < 1 year of age are [...]

Bronchiolitis obliterans (BO) in children is a rare, inflammatory/fibrosing process involving the small airways that often results in progressive, irreversible obstructive pulmonary disease. Because treatment has focused mainly on supportive care and generally unsuccessful immunosuppression, children with BO experience significant morbidity and mortality. We report a case of biopsy-proven BO after bone marrow transplantation in a child who, after failed corticosteroid therapy, was treated with infliximab, a monoclonal antibody with binding specificity for human tumor necrosis factor-[alpha]. With initiation of treatment, her pulmonary symptoms and radiographic and spirometric evidence of BO resolved. Nine months later, she remains asymptomatic and shows no evidence of pulmonary decompensation. This case illustrates a successful treatment of BO with selective tumor necrosis factor-[alpha] blockade. Pediatrics 2005;116:767-770; bone marrow transplant, bronchiolitis obliterans, tumor necrosis factor-alpha., ABBREVIATIONS. BO, bronchiolitis obliterans; BMT, bone marrow transplantation; TNF-[alpha], tumor necrosis factor-[alpha]; GVHD, graft-versus-host disease; HRCT, high-resolution computed tomography; IVIG, intravenous immunoglobulin; RSV, respiratory syncytial virus; [FEV.sub.1], forced expiratory volume [...]

Objective. To determine the incidence of preventable adverse events (AEs) and near misses (NMs) among infants hospitalized for bronchiolitis at a pediatric tertiary care hospital and the impact of these errors on hospital length of stay (LOS). Methods. We studied 143 infants with bronchiolitis, ages 0 to 12 months, admitted from December 2002 to April 2003. Using prospective chart review and staff reports, we captured medical errors and AEs. Each event was classified as a (1) preventable AE, (2) nonpreventable AE, (3) intercepted NM, (4) nonintercepted NM, or (5) error with little or no potential for harm. Results. Of 143 patients, 15 (10%) suffered an AE or NM. The incidence of preventable AEs was 10 per 100 admissions. We found a higher incidence of preventable AEs and NMs among critically ill patients (CIPs) compared with non-CIPs (68 vs 5 per 100 admissions, respectively), making the absolute risk of an AE or NM 14 times more likely in CIPs. Mean LOS was significantly longer for CIPs with at least 1 AE (9.1 + 8.8 days) than for CIPs without AEs (2.9 [+ or -] 1.5 days). Mean LOS was not significantly different between non-CIPs who did (3.8 [+ or -] 2.6 days) and did not (4.2 [+ or -] 5.0 days) experience an AE. Conclusions. Preventable AEs occur frequently among patients admitted for bronchiolitis, especially those who are critically ill. CIPs who suffer AEs during their hospitalization have longer hospital LOSs. Future studies should investigate error-prevention strategies with a focus on those patients with severe disease. Pediatrics 2005;116:603-608; adverse events, bronchiolitis, medical errors., ABBREVIATIONS. AE, adverse event; NM, near miss; LOS, length of stay; CIP, critically ill patient. Pediatric inpatients frequently suffer medical errors, which may cause severe harm. Although the numbers are [...]

Objectives. We know little about the variation in diagnosis and management of bronchiolitis. The objectives of this study were (1) to document variations in treatment and diagnostic approaches, lengths of stay (LOSs), and readmission rates and (2) to determine which potentially modifiable process of care measures are associated with longer LOSs and antibiotic usage. Methods. We used the Pediatric Health Information System, which includes demographic, diagnostic, and detailed patient-level data on 30 large children&apos;s hospitals. We examined infants who were younger than 1 year and hospitalized for bronchiolitis (October 2001-September 2003). Multivariate analysis of variance was used to determine whether the variance in the outcomes was hospital related after controlling for other covariates. Linear regression was used to model predictors of increased LOS. Logistic regression was used to model antibiotic usage. Analyses were stratified by age group ( Results. A total of 17397 patients were included in the analysis. The mean LOS was 2.97 days; 72% of patients received chest radiographs, 45% received antibiotics, and 25% received systemic steroids. The mean LOS varied considerably across hospitals (range: 2.40-3.90 days), and hospital remained a significant contributor to LOS variation after controlling for our covariates. Variations in the use of diagnostic tests and medications as well as readmission rates also existed and also remained significant after controlling for covariates. The factors associated with the greatest increases in LOS in the regression analyses included higher severity scores and use of antibiotics, bronchodilators, and corticosteroids. The strongest predictors of antibiotic use in the logistic regression analyses were higher severity scores and receipt of a blood or cerebrospinal fluid culture. Receiving a chest radiograph was a significant predictor of antibiotic use in older but not younger infants. Conclusions. Considerable, unexplained variation exists in the inpatient management of bronchiolitis. The development of national guidelines and controlled trials of new therapies and different management approaches are indicated. Pediatrics 2005;115:878-884; bronchiolitis, infants, quality of care., ABBREVIATIONS. LOS, length of stay; APR-DRG, All-Patient Refined Diagnosis Related Group; OR, odds ratio; CI, confidence interval. Most commonly caused by respiratory syncytial virus, bronchiolitis is a clinical syndrome characterized [...]

Byline: Michael Eisenhut (1), Kentigern Thorburn (1), Tageldin Ahmed (1) Keywords: Alanine aminotransferase; Aspartate aminotransferase; Hepatitis; Myocarditis; Disease severity; Respiratory syncytial virus Abstract: Objectives To compare disease severity as judged by duration of ventilation, inotrope use and mortality in children ventilated for respiratory syncytial virus (RSV)-positive lower respiratory tract infection (LRTI) with and without elevated transaminase levels and to determine the aetiology of elevated transaminase levels in this patient group. Design Prospective observational study. Setting Twenty-two-bed Paediatric Intensive Care Unit. Patients Forty-eight ventilated children with RSV-positive LRTI. Measurements and results Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured daily. In patients with elevated transaminase levels infection with the following viruses was investigated: hepatitis A, B and C viruses, cytomegalovirus, Epstein Barr virus, adenovirus, influenza virus, and parainfluenza viruses (types I, II, and III). Elevated transaminase levels were detected in 22 (46%) patients. The duration of mechanical ventilation (geometric mean 95% CI) was significantly (P Conclusions RSV disease in ventilated children was more severe if transaminase levels were elevated. Transaminase level elevation was due to hepatitis in the majority of patients. In patients with congenital heart disease we also detected myocardial involvement. Author Affiliation: (1) Paediatric Intensive Care Unit, Royal Liverpool Children's NHS Trust Alder Hey, Eaton Road, Liverpool, L12 2AP, UK Article History: Registration Date: 24/02/2004 Received Date: 20/01/2004 Accepted Date: 09/02/2004 Online Date: 13/03/2004

Byline: S. Romero (1), E. Barroso (1), J. Gil (1), I. Aranda (2), S. Alonso (3), E. Garcia-Pachon (4) Keywords: Bronchiolitis; Flock worker&apos;s lung; Follicular bronchiolitis; Interstitial lung disease; Lung biopsy Abstract: The purpose of this study was to review our experience with patients who had a definitive diagnosis of follicular bronchiolitis (FB), and to describe in detail the clinical and pathological findings, looking for common clinical aspects that may help to identify this entity. Ours is a community 750 bed teaching hospital that acts as a tertiary referral center for several subspecialties, including thoracic surgery. Six patients with a morphological diagnosis of FB, defined by the presence of coalescent germinal centers adjacent to airways, were included. Lung biopsy was obtained by thoracotomy in all patients (2 women and 4 men, mean age 53 years). In one patient FB was associated with advanced AIDS, and in another with prolonged exposure to polyethylene-flock. In 4 patients no condition previously associated with FB was found. Five patients had a history of repeated respiratory infections, 3 patients complained of dyspnea and none had peripheral blood eosinophilia. After a mean follow-up of 25 months, 2 patients responded well to steroid therapy 3 patients suffered symptomatic exacerbations that required an increase in the steroid dose and 1 patient was not treated with steroids. The most important contribution of this series is the description of a subset of patients with FB who were not associated with other processes. These patients present relatively homogeneous clinical and pathological pictures that do not differ greatly from secondary forms. Author Affiliation: (1) Servicios de Neumologia, Hospital General Universitario de Alicante, Spain (2) Anatomia Patologica, Hospital General Universitario de Alicante, Spain (3) Radiologia, Hospital General Universitario de Alicante, Spain (4) Seccion de Neumologia, Hospital Vega Baja, Orihuela-Alicante, Spain Article History: Registration Date: 01/01/2003 Accepted Date: 10/06/2003

Aim: To examine over time, the cellular response within the lungs of infants ventilated with respiratory syncytial virus (RSV) bronchiolitis and to compare this response in infants born at term [...]

Byline: Louis Bont (1), Jan L. Kimpen (1) Keywords: Respiratory syncytial virus Artificial respiration Review Pathogenesis Immunity Abstract: Respiratory syncytial virus (RSV) bronchiolitis resulting in respiratory insufficiency is frequently encountered during the winter season in paediatric intensive care units. This review evaluates potential determinants described in severe RSV bronchiolitis with special attention to the role of immaturity of immune responses during infancy. Pre-existent cardiac or pulmonary compromises have been documented as clinical risk factors for severe RSV bronchiolitis. In addition to this group of infants with pre-morbidity, a large proportion of mechanically ventilated RSV bronchiolitis patients are previously healthy full-term infants or premature neonates without predisposing risk factors. In general, infants at this early age have maturation-related deficient cellular immunity. Several studies show an association between decreased cellular immunity and severe RSV bronchiolitis, indeed suggesting that a maturation-related defect of the cellular immune system facilitates severe RSV. In addition, low virus-specific antibody titres prior to RSV bronchiolitis have been shown to be a risk factor for severe RSV bronchiolitis. A low level of cellular and humoral immunity would explain that higher viral titres are found in infants with most severe illness. In conclusion, immaturity of the physiological functions in healthy pre-term infants and neonates, in particular the immune system, appears to be an important factor in the pathogenesis of RSV bronchiolitis resulting in mechanical ventilation. Author Affiliation: (1) Wilhelmina Children's Hospital, University Medical Center, POB 85090, 3508 AB Utrecht, The Netherlands Article History: Received Date: 07/03/2001 Accepted Date: 28/01/2002 Article note: Electronic Publication

Objective. To assess the therapeutic effects of breathing a low-density gas mixture (heliox: 70% helium and 30% oxygen) in infants with bronchiolitis. Design. Prospective, interventional, comparative study. Setting. A pediatric intensive care unit (PICU) in a tertiary care, teaching hospital. Patients. Thirty-eight infants, 1 month to 2 years old, consecutively admitted to the PICU for treatment of moderate-to-severe acute respiratory syncytial virus bronchiolitis. Interventions. The first 19 patients were enrolled as the control group and received supportive care and nebulized epinephrine. In the next 19 patients, heliox therapy was added through a nonrebreather reservoir face mask. Measurements and Outcomes. Respiratory distress score, respiratory rate, heart rate, end-tidal C[O.sub.2] (etC[O.sub.2]), and pulse oximetry oxygen saturation (sat[O.sub.2]) values were recorded at baseline and at regular intervals. Data obtained during the first 4 hours were analyzed for comparison purposes. Demographic data, age, time elapsed from the start of the symptoms to the admission to PICU, length of stay in PICU (PICU-LOS), and duration of heliox therapy were also collected for each patient. Reductions in clinical scores and PICU-LOS were considered primary outcomes. Main Results. At baseline, the heliox and control groups had similar age (5.5 [+ or -] 3.1 vs 5.9 [+ or -] 3 months), previous length of course (47.3 [+ or -] 19.3 vs 45.4 [+ or -] 18.6 hours), clinical score (6.7 [+ or -] 1.1 vs 6.6 [+ or -] 1), heart rate (160 [+ or -] 24 vs 165 [+ or -] 20 beats per minute), respiratory rate (64 [+ or -] 7 vs 61 [+ or -] 7 respirations per minute), sat[O.sub.2] (91 [+ or -] 2.3 vs 91 [+ or -] 2.5%), and etC[O.sub.2] (34 [+ or -] 7 vs 33 [+ or -] 6 mm Hg). Clinical score, heart rate, respiratory rate, and sat[O.sub.2] improved during the study in both groups. After 1 hour, the improvement in clinical score was significantly higher in the heliox group than in the control group (3.6 [+ or -] 1.16 vs 5.5 [+ or -] 0.89), and these differences continued to be significant at the end of the observation period (2.39 [+ or -] 0.69 and 4.07 [+ or -] 0.96, respectively), with a total average decrease in the score of 4.2 points in the heliox group versus 2.5 points in the control group. Heart and respiratory rates were also significantly lower in the heliox group compared with the control group after 1 hour and stayed lower throughout the rest of the study period. No changes were noted either in sat[O.sub.2] between groups or in etC[O.sub.2] within or between groups throughout the study. Mean duration of heliox administration was 53 [+ or -] 24 hours (range: 24-112 hours) and no adverse effects were detected. PICU-LOS was significantly shorter in the heliox group (3.5 [+ or -] 1.1 days) than in the control group (5.4 [+ or -] 1.6 days). Conclusions. In infants with moderate-to-severe respiratory syncytial virus bronchiolitis, heliox therapy enhanced their clinical respiratory status, according to the marked improvement in their clinical scores and the reduction of the accompanying tachycardia and tachypnea. This beneficial response occurred within the first hour of its administration and was maintained as long as heliox therapy continued. In addition, PICU-LOS was reduced in heliox-treated patients. Long-term prospective studies are required to corroborate these findings and to establish the proper place of heliox in the therapeutic schedule of bronchiolitis. Pediatrics 2002;109:68-73; infant, helium-oxygen mixture, heliox, bronchiolitis, respiratory syncytial virus infections, airway obstruction, respiratory therapy, work of breathing, epinephrine, pediatrics. ABBREVIATIONS. RSV, respiratory syncytial virus, PICU, pediatric intensive care unit; M-WCAS, modified Wood&apos;s Clinical Asthma Score; 1pm, liters per minute; sat[O.sub.2], pulse oximetry oxygen saturation; etC[O.sub.2], end-tidal C[O.sub.2]; PICU-LOS, length of stay in pediatric intensive care unit., Since use of helium-oxygen mixtures (heliox) was proposed by Barach, (1,2) as a medical therapy for severe asthma and upper airway obstruction, several studies on its role in respiratory therapy [...]