[Severe bronchiolitis. Epidemiology and clinical course of 284 patients]. / Bronquiolitis grave. Epidemiología y evolución de 284 pacientes.

INTRODUCTION: Bronchiolitis is the leading cause of hospital admission and a frequent cause of pediatric intensive care unit (PICU) admission among infants during the winter months. The objective of this study was to analyze the characteristics and clinical course of patients admitted to the PICU for bronchiolitis. PATIENTS AND METHOD: We performed a descriptive, observational study by clinical chart review of all patients admitted to the PICU for severe bronchiolitis from November 1994 to March 2006. RESULTS: A total of 284 patients were included. Most were admitted during December and January and 74% had respiratory syncytial virus (RSV) infection. At least one risk factor for severe disease was present in 68% of the patients: the most frequent risk factor was age < 6 weeks (45%), followed by prematurity (30%). Mechanical ventilation was required in 64 of the 284 patients (24%). Mortality was 1.8% and was associated with chronic pre-existing illness (p < 0.001). The factors associated with a greater risk of mechanical ventilation and a longer PICU stay were the association of two or more risk factors (42/284; 15%), the presence of apnea (73/284; 25.7%), and images of pulmonary consolidation or atelectasis on admission chest X-ray (157/284; 55%). CONCLUSIONS: Most patients admitted for severe bronchiolitis to the PICU are healthy infants whose principal risk factor is young age. The main predictors of severe clinical course during PICU stay are the association of two or more risk factors, the presence of apnea, and pulmonary consolidation on admission chest X-ray. Bronchiolitis-associated mortality is low and is associated with pre-existing chronic illness.

Ribavirin and cysteinyl leukotriene-1 receptor blockade as treatment for severe bronchiolitis.

In this work we have evaluated the clinical responses of pneumovirus-infected mice to combination therapy with the antiviral agent, ribavirin, and the CysLT1 cysteinyl leukotriene receptor antagonist, montelukast. We observed substantial virus replication in our mouse model of pneumovirus infection and significant accumulation of cysteinyl leukotrienes in lung tissue, the latter detected at levels that correlate directly with granulocyte recruitment to the airways. While administration of the nucleoside analog, ribavirin, reduced virus replication approximately 2,000-fold, the clinical outcomes as measured by morbidity and mortality, in response to ribavirin monotherapy were indistinguishable from those of the no-treatment controls. Similarly, montelukast therapy alone did not reduce granulocyte recruitment nor did it improve the clinical outcome. However, combined therapy with ribavirin and montelukast resulted in a significant reduction in morbidity and a substantial reduction in mortality (50% survival at t = 14 days and onward, compared to 10-20% survival in response to montelukast alone or to ribavirin alone, respectively, p < 0.01). These findings define further the independent contributions made by virus replication and by the ensuing inflammatory response to the detrimental sequelae of pneumovirus infection in vivo.

Small-airways disease in recipients of allogeneic bone marrow transplants. An analysis of 11 cases and a review of the literature.

In a retrospective review of 116 consecutive allogeneic bone marrow transplants (BMT), severe obstructive airways disease was identified in 11 patients. Lung pathology demonstrated bronchiolitis in 9 patients and physiologic studies showed small-airways disease consistent with bronchiolitis in the other 2. None of the 5 patients with associated infection survived, while 3 of the 6 patients without an identified pathogen stabilized or improved. Analysis of the 11 cases presented and all 25 cases reported in the literature (1982 to 1985) supports the conclusion that graft-versus-host disease is a major risk factor for bronchiolitis in BMT recipients. Among the proposed mechanisms for the development of bronchiolitis after allogeneic BMT, the 2 most likely are graft-versus-host disease directly causing bronchiolitis, and increased immunosuppressive therapy given for graft-versus-host disease predisposing to viral bronchiolitis. The available evidence would suggest that it is prudent to obtain serial pulmonary function tests even in asymptomatic patients post-BMT, and particularly in those with chronic graft-versus-host disease, in the hope that early detection will allow for early intervention that will arrest or reverse the progression of the obstructive airways disease.

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.

Complications of pediatric laryngotracheal reconstruction: prevention strategies.

A retrospective chart review was performed to quantify the postoperative complications and outcomes of 82 consecutive cases of laryngotracheal reconstruction (LTR) and cricotracheal resection (CTR) performed at a pediatric tertiary care hospital over the last 9 years. Six cases of respiratory syncytial virus (RSV) bronchiolitis and 8 cases of cervical pseudomonal wound abscess (PWA) were identified in a total of 12 patients. All of these infections occurred after single-stage LTR or CTR. Both RSV bronchiolitis and PWA were associated with significantly more unexpected days of intubation and admission to the intensive care unit, as well as higher rates of failure of LTR. Ossification of the cricoid cartilage, grade IV subglottic stenosis, and untreated gastroesophageal reflux disease (GERD) were also associated with restenosis. Trisomy 21 did not significantly influence the success rate of pediatric LTR. Both RSV bronchiolitis and PWA are potentially preventable complications of pediatric LTR and CTR. We propose strategies to prevent these infections. We also advocate the treatment of GERD during the healing phase of LTR.

Predictors of severity and mortality in children hospitalized with respiratory syncytial virus infection in a tropical region.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the leading causes of acute lower respiratory infection (ALRI) in infants and young children. Although ALRI is a major public health problem in developing countries located in tropical areas, studies about RSV epidemiology in these regions are scarce. METHODS: In a retrospective cohort study, we investigated the epidemiology and predictive variables that reflect disease severity and mortality in young children hospitalized with ALRI due to RSV in Colombia, South-America, during a 2-year period (2009-2011). RESULTS: Of a total of 6,344 children with a diagnosis of ALRI, we selected 2,147 (33.8%) that were positive for RSV. After controlling for pre-existing conditions, we found that independent predictors of severe disease in our population included age <6 months (RR 2.01; CI 95% 1.70-2.38; P < 0.001), prematurity (RR 1.61; CI 95% 1.20-2.17; P = 0.001), congenital heart disease (RR 2.03; CI 95% 1.16-3.54; P = 0.013), and mixed RSV-adenovirus infection (RR 2.09; CI 95% 1.60-2.73; P < 0.001). Multivariate analysis identified that cancer (RR 31.60; CI 95% 5.97-167.13; P < 0.001) is a predictor of mortality in our RSV-infected pediatric population independently of age and other co-morbidities. CONCLUSIONS: RSV is an important cause of ALRI in infants and young children living in tropical regions, especially during the rainy season. The identified predictors of severe disease and mortality should be taken into account when planning interventions to reduce the burden of ALRI in young children living in these regions.

Severe respiratory syncytial virus bronchiolitis in children: from short mechanical ventilation to extracorporeal membrane oxygenation.

UNLABELLED: The objective of this study was to describe the characteristics of children who required mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) support for respiratory syncytial virus (RSV) bronchiolitis, and to identify risk factors associated with disease severity assessed by duration of MV, mortality and need for ECMO. Ventilated children under 1 year of age admitted for bronchiolitis were retrospectively studied over the 8-year period 1996-2003. The study population included 151 children. Of these, 38.4% were born prematurely and 8.6% had bronchopulmonary dysplasia (BPD). The mean age at initiation of MV was 61 days (+/-63 days). Infants were ventilated for a mean of 7.8 days (+/-7.5 days). Multivariate analysis revealed that prolonged duration of MV (>6 days, median value) was significantly associated with low gestational age ( P =0.02 for the group <32 weeks), requirement of neonatal oxygen supplementation ( P =0.03), BPD ( P =0.02) and positive tracheal aspiration culture ( P =0.004), in particular for Haemophilus influenzae ( P =0.03). Fourteen infants required ECMO with a mean period of MV before ECMO of 3.9 days (+/-4.5 days). Amongst these infants, the frequency of BPD was significantly higher as compared with the others ( P =0.001). Four infants died (survival rate 71.4%). The mean duration of ECMO for survivors was 12.1 days (+/-3.3 days). CONCLUSION: The data suggest that gestational age, requirement of neonatal oxygen supplementation, bronchopulmonary dysplasia and tracheal colonisation with Haemophilus influenzae are correlated with prolonged mechanical ventilation in children with bronchiolitis. Only bronchopulmonary dysplasia was associated with a need for extracorporeal membrane oxygenation that may provide lifesaving support in infants refractory to conventional management.

Use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: the national experience, 1983 to 1988.

In an effort to obtain data to provide the basis for the design of controlled clinical trials, we contacted all U.S. participants in the National ECMO Registry to assemble the national experience on the use of extracorporeal membrane oxygenation in respiratory syncytial virus bronchiolitis during the past 5 years. Twelve infants were treated at nine centers between 1983 and 1988. Eight had been born prematurely, and five had bronchopulmonary dysplasia. The mean age at onset of infection with respiratory syncytial virus was 108 +/- 102 days. The mean length of ventilator management before extracorporeal membrane oxygenation was 7.8 +/- 7.1 days. All infants had persistent hypoxemia with a mean arterial oxygen pressure of 39.2 +/- 11.7 torr (5.3 +/- 1.6 kPa) despite high ventilator pressures (mean airway pressure 19.7 +/- 6.4 cm H2O) and 100% inspired oxygen; six had air leak syndrome. Seven infants survived (58%). The mean duration of extracorporeal membrane oxygenation for survivors was 233 +/- 139 hours. Preexisting chronic lung disease did not predict a poor outcome: four of the five infants with bronchopulmonary dysplasia survived. Six of the survivors have subsequently achieved expected developmental milestones and one has slight motor delay. We conclude that, for infants with severe respiratory syncytial virus bronchiolitis whose condition deteriorates despite maximal ventilator management, extracorporeal membrane oxygenation may provide lifesaving support. The duration of successful treatment with this therapy may be longer than that for conventional neonatal indications, but excellent neurologic outcome may be expected in survivors.

Speculation on pathogenesis in death from respiratory syncytial virus infection.

The lungs of three infants, two with bronchiolitis and one with pneumonia, were examined by fluorescent antibody techniques for the distribution of respiratory syncytial (R.S.) virus, and also for the presence of human globulin. In bronchiolitis the lungs contained little virus, whereas in pneumonia virus was abundant and widespread; and, paradoxically, while in bronchiolitis human globulin had the same scanty distribution as virus it was absent in pneumonia. It is suggested that the essential process in bronchiolitis is a widespread type 1 allergic reaction dependent on a second encounter with R.S. virus antigen, whereas in R.S. virus pneumonia the mucosal necrosis and alveolar and interstitial inflammation are the result of direct virus damage to the lungs. The alternative explanation put forward is that the process may be a type 3 allergic reaction.

[Severe viral pneumonia. A radiological classification with prognostic value]. / Bronchopneumopathies virales graves classification radiographique, interet pour le pronostic.

In one year eighteen children were admitted to an intensive care unit with severe viral pneumonia. Four groups were identified by the appearance of the chest X-ray. Bronchiolitis was seen in eight patients, alveolitis in four, interstitial pneumonia in two and combined bronchiolitis and alveolitis in four. Three of the four children with alveolitis died and six of the twelve with bronchiolitis, alone or with alveolitis, had residual bronchial obstruction.

Admission to the intensive care unit for respiratory syncytial virus bronchiolitis: a national survey before palivizumab use.

OBJECTIVE: Preterm infants, especially those with chronic lung disease (CLD), are considered more susceptible to severe respiratory illness from respiratory syncytial virus (RSV) infection than healthy term infants, and are therefore targeted for prophylactic administration of immune globulins. The impact of this practice on the more severe cases of bronchiolitis (i.e., pediatric intensive care unit [PICU] admission, mechanical ventilation, mortality) has not been reported to date. The aim of this study was to evaluate PICU admissions, need for mechanical ventilation, and mortality attributable to RSV bronchiolitis in Israel before the introduction of RSV prophylaxis to the country. DESIGN AND SETTING: Prospective survey of 11 PICUs in Israel during the RSV season (November 2000-March 2001). PATIENTS: All patients admitted to the PICU because of bronchiolitis, and the subgroups who needed mechanical ventilation or who died, were analyzed for known risk factors, namely, prematurity, CLD, and chronic oxygen dependence. RESULTS: A total of 105 patients with RSV bronchiolitis met the inclusion criteria, of whom 33 were mechanically ventilated. Most of the patients (84% total admission, 88% ventilated) were born after 32 weeks' gestation, and 89% and 88%, respectively, did not have CLD. Only 16% and 9%, respectively, met any of the American Academy of Pediatrics criteria for RSV prophylaxis, such that 84% of the whole sample and 91% of the ventilated patients were not candidates for RSV prophylaxis. Five patients died, 2 of them with cyanotic heart disease. CONCLUSIONS: Most of the infants with severe RSV bronchiolitis were born at term and did not have CLD. The great majority of patients admitted to the PICU for bronchiolitis were not candidates for RSV prophylaxis. Administration of RSV prophylaxis to the predefined high-risk population could be expected to yield no significant change in PICU admissions or number of infants needing mechanical ventilation. New risk-stratified guidelines for RSV prophylaxis are needed.