Severe respiratory disease caused by human respiratory syncytial virus impairs language learning during early infancy.

Human respiratory syncytial virus infection is a leading cause of pediatric morbidity and mortality. A previous murine study showed that during severe acute respiratory infections the virus invades the central nervous system, and that infected animals evolve with long-lasting learning difficulties associated with long-term potentiation impairment in their hippocampus. We hypothesized here that human infants who presented a severe episode of respiratory syncytial virus infection before 6 months of age would develop long-term learning difficulties. We measured the acquisition of the native phoneme repertoire during the first year, a milestone in early human development, comprising a reduction in the sensitivity to the irrelevant nonnative phonetic information and an increase in the sensitivity to the information relevant for the native one. We found that infants with a history of severe respiratory infection by the human respiratory syncytial virus presented poor distinction of native and nonnative phonetic contrasts at 6 months of age, and remained atypically sensitive to nonnative contrasts at 12 months, which associated with weak communicative abilities. Our results uncover previously unknown long-term language learning difficulties associated with a single episode of severe respiratory infection by the human respiratory syncytial virus, which could relate to memory impairments.

Contribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus.

The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.

Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/ß mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.

Host response to respiratory syncytial virus infection.

PURPOSE OF REVIEW: Respiratory syncytial virus (RSV) infection is the leading cause of bronchiolitis and hospitalization in young infants and causes 100, 000-200, 000 deaths annually. There is still no licensed vaccine against RSV infection and the therapeutic options are mainly supportive. Despite almost six decades of research, important knowledge gaps remain with respect to the characterization of immune mechanisms responsible for protection and pathogenesis, as well as to the identification of risk factors that predict the severity of infection. RECENT FINDINGS: Observations made in mouse models and young children suggest that the early innate immune response plays a major role in the pathogenesis of bronchiolitis due to RSV infection. Recent studies have improved our understanding of the role of the adaptive immune response mediated by TH1, TH2, TH17, regulatory T cells, and CD8 T cells in the pathogenesis and resolution of RSV infection. Moreover, investigations performed in the last years have made important contributions to our knowledge of the immune response in young children, the principal risk group for severe disease. SUMMARY: A comprehensive understanding of how the protective and deleterious immune response during the course of RSV infection is induced in young children remains a challenge over the coming years.

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.

Respiratory syncytial virus infection in Guatemala, 2007-2012.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute respiratory illness (ARI). Little is known about RSV disease among older children and adults in Central America. METHODS: Prospective surveillance for ARI among hospital patients and clinic patients was conducted in Guatemala during 2007-2012. Nasopharyngeal and oropharyngeal swab specimens were tested for RSV, using real-time reverse-transcription polymerase chain reaction. RESULTS: Of 6287 hospitalizations and 2565 clinic visits for ARI, 24% and 12%, respectively, yielded RSV-positive test results. The incidence of RSV-positive hospitalization for ARI was 5.8 cases/10 000 persons per year and was highest among infants aged <6 months (208 cases/10 000 persons per year); among adults, the greatest incidence was observed among those aged ≥ 65 years (2.9 cases/10 000 persons per year). The incidence of RSV-positive clinic visitation for ARI was 32 cases/10 000 persons per year and was highest among infants aged 6-23 months (186 cases/10 000 persons per year). Among RSV-positive hospital patients with ARI, underlying cardiovascular disease was associated with death, moribund discharge, intensive care unit admission, or mechanical ventilation (odds ratio, 4.1; 95% confidence interval, 1.9-8.8). The case-fatality proportion among RSV-positive hospital patients with ARI was higher for those aged ≥ 5 years than for those aged <5 years (13% vs 3%; P < .001). CONCLUSIONS: The incidences of RSV-associated hospitalization and clinic visitation for ARI were highest among young children, but a substantial burden of ARI due to RSV was observed among older children and adults.

Neural-endocrine mechanisms of respiratory syncytial virus-associated asthma in a rat model.

We examined the underlying neural-endocrine mechanisms of asthma associated with respiratory syncytial virus infection. Thirty Sprague-Dawley rats were randomly divided into control group, respiratory syncytial virus (RSV) group, and anti-nerve growth factor (NGF) IgG group. An RSV infection model was established by nasal drip once a week. In the anti-NGF antibody intervention group, each rat was given an intraperitoneal injection of anti-NGF IgG 3 h before RSV infection. Optical microscopy and transmission electron microscopy were used to observe the structural changes in adrenal medulla cells. Changes in adrenaline and norepinephrine in serum were detected by ELISA. NGF expression was assayed by immunohistochemistry. Expression differences in synaptophysin mRNA were detected by RT-PCR. Transmission electron microscopy displayed widened adrenal medulla intercellular spaces, reduced chromaffin particle concentration, and increased mitochondria in the RSV infection group. At the same time, NGF expression was increased in the RSV infection group significantly. In addition, the adrenaline concentration was significantly decreased compared with the control and anti-NGF antibody groups. Synaptophysin mRNA expression was significantly increased in the RSV infection and anti-NGF antibody groups. However, compared with the RSV infection group, synaptophysin mRNA expression was significantly decreased in the anti-NGF antibody group. We conclude that RSV infection could induce adrenal medulla cell differentiation to nerve cells by over-expression of NGF, resulting in the decreased endocrine function found in asthma progression.

The epidemiology and clinical characteristics of respiratory syncytial virus infection in children at a public pediatric referral hospital in Mexico.

OBJECTIVES: The aim of this study was to determine the epidemiological and clinical characteristics of children with respiratory syncytial virus (RSV) treated at a public referral children's hospital in Mexico. METHODS: We reviewed RSV infection in patients aged 0-18 years who were treated at Hospital Infantil from January 2004 to December 2008. RESULTS: During the 5 years, 2797 samples were tested for respiratory viruses; 356 samples were positive for any virus, including 266 (74.7%) positive for RSV. Complete clinical information was available for 205 RSV patients. The mean age was 22 months, and 33.7% of the infections were nosocomially acquired. Hospitalization occurred in 187 children. Of 14 deaths, nine were directly attributed to RSV infection. During the study, RSV infections were seen throughout the year, predominating in the colder months. Of the 205 patients, 79.0% (162/205) had an underlying disease. Congenital heart disease was found in 30.2% (49/162), including three children (33.3%) who died of RSV. Thirty-three patients (16.1%) with RSV required mechanical ventilation. None of the children with RSV received palivizumab or ribavirin. CONCLUSIONS: RSV caused high hospitalization rates and admission to intensive care units, especially among those with underlying illnesses and young infants. The data presented here will be useful for strategies to improve outcomes in children at risk of complications.

Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-alpha, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença / Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

C5 modulates airway hyperreactivity and pulmonary eosinophilia during enhanced respiratory syncytial virus disease by decreasing C3a receptor expression.

Enhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes. Mice with a targeted disruption of complement component C5 affected by the enhanced disease displayed enhanced airway reactivity, lung eosinophilia, and mucus production compared to wild-type mice and C5-deficient mice reconstituted with C5. C3aR expression in bronchial epithelial and smooth muscle cells in the lungs of C5-deficient mice was enhanced compared to that in wild-type and reconstituted rodents. Treatment of C5-deficient mice with a C3aR antagonist significantly attenuated airway reactivity, eosinophilia, and mucus production. These results indicate that C5 plays a crucial role in modulating the enhanced-disease phenotype, by affecting expression of C3aR in the lungs. These findings reveal a novel autoregulatory mechanism for the complement cascade that affects the innate and adaptive immune responses.

Infección por virus sincicial respiratorio en recién nacidos / Respiratory syncytial virus infections in newborns

El virus sincicial respiratorio es el principal patógeno causante de bronquiolitis en el lactante pequeño.En recién nacidos,las descripciones de la enfermedad son menos frecuentes.Objetivo.Describir las características clínicas y epidemiológicas de la infección por virus sincicial respiratorio en recién nacidos sanos y establecer factores predictores en el momento de la hospitalización que se relaciones con la gravedad de la enfermedad.Población.Se incluyeron todos los recién nacidos de término internados en la Unidad de Neonatología del Hospital Nacional de Pediatría J.P Garrahan entre abril y septiembre de 1999 con infección respiratoria aguda por virus sincicial respiratorio.Resultados.Ingresaron 26 pacientes al estudio,80 por ciento de ellos recibía leche humana y el 77 por ciento de los casos existía un medio epidemiológico positivo,la edad media al ingresar fue de 23 días.La evolución referida de los síntomas fue de 12 a 120 hs y en 15 pacientes(58 por ciento)se habían efectuado consultas previas.La dificultad alimentaria fue el síntoma más frecuente,seguido por tos y rinorrea,en el 20 por ciento se detectaron apneas.Al ingreso,todos menos uno estaba taquipneicos:la frecuencia respiratoria promedio fue de 70 ñ15 por minuto y en 16 recién nacidos(61 por ciento) se constato hipoxemia.La Rx de tóraz inicial fue patológica en la mayoría:en 24 pacientes se observaban signos de atrapamiento aéreo.La bronquiolitis fue la forma clínica más frecuente.Nueve recién nacidos(35 por ciento)ingresaron a asistencia respiratoria mecánica y 16(60 por ciento)recibieron oxigenoterapia.El promedio de internación fue de 11 días(entre 3 y 22)y no se registraron muertes.Conclusión.La infección respiratoria por virus sincicial respiratoria ocasiona importante morbilidad,aún en recién nacidos previamente sanos,que requieren cuidado intensivo y asistencia respiratoria en un alto porcentaje.La media de la frecuencia respiratoria inicial fue significativamente mayor en los que requirieron ventilación mecánica

Estado nutricional y evolución clínica de lactantes chilenos hospitalizados con infección por virus respiratorio sincicial (VRS) / Nutritional status and clinical evolution of hospitalized Chilean infants with infection by respiratory syncytial virus (RSV)

Respiratory syncycial virus (RSV) is the first cause of acute lower respiratory tract infection in Chilean infants. A significant impact of nutrition on clinical course of these infections has been described. In order to analyze the association between nutritional status (NS) and clinical course of infants hospitalized with acute lower respiratory tract infection due to RSV, 130 infants (mean age 5.8 +/- 4.9 m) without chronic diseases, admitted to hospital with confirmed RSV infection, were studied. Clinical course of disease was assessed (hospitalization days and days with oxygen therapy) according to nutritional status on admission (weight/length (W/L), ratio, arm muscle area, lymphocyte count and albumin), antropometrics changes, and hospital dietary intake. On admission prevalence of malnutrition by W/L (z score) was 1, 14 overweight and 8 were obese. Median value of hospitalization days was 5 d (2-29 d) and days receiving oxygen was 3 d (0-19 d). Longer admission were observed in fasted patients than in those who were fed everyday (Wilcoxon and Log-rank test, 8 d vs 5 d; P < 0.01). Obese children (Wilcoxon and Log-rank test, 5 d vs. 3d in normal patients; P < 0.05), and patients not fed enterally (Wilcoxon and Log-rank test, 7 d vs. 3 d; P < 0.01) required oxygen for longer time. Fasting and severity of illness (Tal score) were correlated variables (X2 0.001). The multivariate analysis showed an association of Tal score and NS on admission, with days receiving oxygen therapy. We conclude that obesity is a risk factor for worse clinical course of acute lower respiratory tract infection in Chilean infants with RSV infection and without chronic disease.

Neural control mechanisms within airways: disruption by respiratory syncytial virus.

UNLABELLED: Among the factors influencing airway function are neural control mechanisms, including adrenergic, cholinergic, nonadrenergic noncholinergic inhibitory, and nonadrenergic noncholinergic excitatory pathways. Respiratory infections affect these pathways in ways that are not entirely clear. OBJECTIVE: To determine acute and chronic effects of respiratory syncytial virus infection on airway neural control mechanisms. STUDY DESIGN: Acute effects were studied in cotton rats, which received human respiratory syncytial virus or uninfected cell culture medium intranasally at 5 weeks of age. Chronic effects were studied in ferrets, which received human respiratory syncytial virus or uninfected cell culture medium intranasally during the first 10 days of life. The responsiveness of tracheal smooth muscle segments was studied in vitro 4 days after infection of cotton rats and when ferrets were 4, 8, and 24 weeks of age. RESULTS: Tracheal smooth muscle segments from cotton rats demonstrated significant increases in contractile responses to nerve stimulation (cholinergic responses). In the presence of neurokinin A, contractile responses increased (enhanced nonadrenergic noncholinergic excitatory response), and relaxation of airways by nerve stimulation (nonadrenergic noncholinergic inhibitory response) was severely impaired. Airway epithelium was also disrupted. These alterations favor airway obstruction and a hyper-responsive state. Contractile responses to nerve stimulation were increased in 4- and 8-week-old ferrets infected with human respiratory syncytial virus compared with ferrets in a control group, a difference that resolved by 24 weeks. Nonadrenergic noncholinergic inhibitory responses were absent in all 4-week-old ferrets and significantly decreased in 8-week-old ferrets infected with human respiratory syncytial virus. A significant difference persisted at 24 weeks of age. CONCLUSION: Human respiratory syncytial virus causes acute and chronic changes in neural control of airways in animal models. When infection occurs early in life, the alterations persist for long periods.

Pulmonary function changes in children after respiratory syncytial virus infection in infancy.

During the last 20 years, an association between respiratory syncytial virus (RSV) bronchiolitis or pneumonia in infants and abnormal pulmonary function later in childhood has been established. Study designs have varied considerably, but most investigators have used an observational approach in which children with early bronchiolitis or pneumonia are identified and pulmonary function is measured later in childhood. Decreased forced expiratory flows at mid-lung volumes and increased airway reactivity have been demonstrated consistently in most studies. Few studies, however, have addressed the issue of whether the early symptomatic RSV infection caused the subsequent abnormalities in pulmonary function. An atopic tendency does not appear to explain the underlying association between early RSV infection and subsequent abnormal pulmonary function. Evidence suggests that infants with symptomatic bronchiolitis have an underlying deficit in pulmonary function that might contribute to the abnormalities documented later in childhood. The issue of causation could be addressed by intervention studies in which RSV is prevented or treated and differences in pulmonary function are observed. Several small prospective studies of children enrolled in early controlled trials of ribavirin treatment of RSV lower respiratory tract infection have not consistently demonstrated differences between infants in treated and control groups. Larger studies of the effect of ribavirin treatment, immunoglobulin prophylaxis, or immunization (when it becomes available) on subsequent pulmonary function and airway hyperreactivity may resolve this important issue.

[Nutritional status and clinical evolution of hospitalized Chilean infants with infection by respiratory syncytial virus (RSV)]. / Estado nutricional y evolución clínica de lactantes chilenos hospitalizados con infección por virus respiratorio sincicial (VRS).

Respiratory syncycial virus (RSV) is the first cause of acute lower respiratory tract infection in Chilean infants. A significant impact of nutrition on clinical course of these infections has been described. In order to analyze the association between nutritional status (NS) and clinical course of infants hospitalized with acute lower respiratory tract infection due to RSV, 130 infants (mean age 5.8 +/- 4.9 m) without chronic diseases, admitted to hospital with confirmed RSV infection, were studied. Clinical course of disease was assessed (hospitalization days and days with oxygen therapy) according to nutritional status on admission (weight/length (W/L), ratio, arm muscle area, lymphocyte count and albumin), antropometrics changes, and hospital dietary intake. On admission prevalence of malnutrition by W/L (z score) was 1%, 14% overweight and 8% were obese. Median value of hospitalization days was 5 d (2-29 d) and days receiving oxygen was 3 d (0-19 d). Longer admission were observed in fasted patients than in those who were fed everyday (Wilcoxon and Log-rank test, 8 d vs 5 d; P < 0.01). Obese children (Wilcoxon and Log-rank test, 5 d vs. 3d in normal patients; P < 0.05), and patients not fed enterally (Wilcoxon and Log-rank test, 7 d vs. 3 d; P < 0.01) required oxygen for longer time. Fasting and severity of illness (Tal score) were correlated variables (X2 0.001). The multivariate analysis showed an association of Tal score and NS on admission, with days receiving oxygen therapy. We conclude that obesity is a risk factor for worse clinical course of acute lower respiratory tract infection in Chilean infants with RSV infection and without chronic disease.

Albuterol responsiveness in infants with respiratory failure caused by respiratory syncytial virus infection.

OBJECTIVE: To assess the bronchodilator effect of inhaled albuterol in the acute stage of severe respiratory syncytial virus (RSV) infection. DESIGN: Prospective, nonrandomized study of previously healthy infants who underwent intubation and whose lungs were ventilated because of respiratory failure caused by RSV infection. Ten infants with an endotracheal tube in place and without lung disease were matched for age and weight and served as normal control subjects. METHODS: Lung function tests, including respiratory mechanics by single-breath occlusion, small airway function by forced deflation, and lung volumes by nitrogen washout, were performed before and after inhalation of 900 micrograms albuterol by metered dose inhaler. Bronchodilator response was defined as a change of more than twice the coefficient of variation of repeated baseline measurements. RESULTS: Twenty-three infants (mean +/- SE age = 4.2 +/- 1.1 months) were studied, of whom 20 (87%) had obstructive small airway disease, and 3 (13%) had exclusively restrictive lung function profiles. Ten of the infants with obstructive disease (50%) did not benefit from albuterol, and 9 (45%) had small but significant improvements in lung function. Deterioration of lung function was documented in 1 patient after albuterol inhalation. CONCLUSION: Inhaled albuterol is of limited value as a bronchodilator in infants with RSV-induced respiratory failure and should be discontinued if a beneficial response cannot be observed.