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[beta]-Adrenergic agonists ([beta]-agonists) are commonly used to treat respiratory syncytial virus (RSV) bronchiolitis but are generally ineffective for unknown reasons. We have previously shown that RSV strain A2 inhibits bronchoalveolar epithelial responses to [beta]-agonists in a BALB/c mouse model by inducing heterologous keratinocyte cytokine (KC)/CXCR2-mediated desensitization of epithelial [[beta].sub.2]-adrenergic receptors. The aim of the current study was to determine whether RSV also induces airway insensitivity to [beta]-agonists. Total lung resistance (R) was measured in anesthetized female BALB/c mice undergoing mechanical ventilation on a flexiVent computer-controlled piston ventilator. Data were analyzed using the single-compartment model. Infection with RSV A2 did not induce airway hyperresponsiveness to increasing doses of the nebulized cholinergic agonist methacholine (MCh) at any time point after RSV infection. Prenebulization with the [beta]-agonist terbutaline (100 [micro]M) significantly attenuated bronchoconstrictive responses to 20 and 50 mg/ml MCh in uninfected mice and in mice infected with RSV 4-8 days postinfection (d.p.i.). However, in mice infected with replication-competent, but not UV-inactivated, RSV for 2 days, significant terbutaline insensitivity was found. Terbutaline insensitivity at 2 d.p.i, could be reversed by systemic preinfection treatment with neutralizing anti-CXCR2 antibodies, which reduced bronchoalveolar lavage (BAL) neutrophil counts but did not alter viral replication, BAL KC levels, or lung edema. Terbutaline insensitivity was also reversed by postinfection nebulization with neutralizing anti-KC or anti-CXCR2 antibodies and could be replicated in normal, uninfected mice by nebulization with recombinant KC. These data suggest that KC/CXCR2-mediated airway insensitivity to [beta]-agonists may underlie the modest utility of these drugs as bronchodilators in therapy for acute RSV bronchiolitis. CXCL8; CXCR2; keratinocyte cytokine; airway hyperresponsiveness doi:10.1152/ajplung.00363.2009.

Continuing Education This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives: 1. Describe the pathophysiology of [...]

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. Respiratory syncytial virus (RSV) infection is the foremost cause of serious lower respiratory tract infection in young children and infants. Because higher rates of hospitalization for bronchiolitis and pneumonia have been noted in high-altitude regions, we hypothesized that physiologic responses to altitude would predispose children to more severe illness from RSV infection. This study examined the effect of residential altitude on hospitalizations for RSV infection in Colorado from 1998 through 2002. METHODS. A geographic information system was used to assemble data for altitude and demographic variables by zip code-tabulation areas. Data then were linked with hospital discharge data for RSV infections. Poisson regression models were developed to explore correlations between hospitalization rates and residential altitude, after adjustment for socioeconomic differences in the underlying population. RESULTS. RSV-associated hospitalizations averaged 15.9 per 1000 infants who were younger than 1 year and 1.8 per 1000 children who were 1 to 4 years of age per season. A multivariate analysis suggested that the rate of hospitalization for RSV-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes increased 25% among infants who were younger than 1 year and 53% among children who were 1 to 4 years of age for every 1000-m increase in altitude. The risk for RSV-associated hospitalization was highest at elevations above 2500 m. CONCLUSIONS. High altitude above 2500 m is a modest predictor for RSV-associated hospitalization. Practitioners in these regions should consider additional efforts to educate parents about RSV infection and its prevention and the importance of early treatment. Key Words environmental factors, epidemiology, hospitalization rates, respiratory syncytial virus, risk factors Abbreviations RSV--respiratory syncytial virus CHA--Colorado Health and Hospital Association ICD-9-CM--Intemotional Classification of Diseases, Ninth Revision, Clinical Modification ZCTA--zip code-tabulation area GIS--geographic information systems RR--rate ratio, RESPIRATORY SYNCYTIAL VIRUS (RSV) infection is the foremost cause of bronchiolitis and pneumonia in infants and young children, causing > 100 000 hospitalizations annually in the United States. (1) A [...]

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 [...]

An 18-month-old boy was admitted to a hospital with chronic cough, wheezing, fever, nasal discharge and rapid breathing. He had a history of a brain tumor for which he was receiving chemotherapy. A chest X-ray revealed signs of a viral lung infection. Samples of nasal discharge on three separate occasions over a 2-month period had revealed the presence of parainfluenza virus type 3, which is common in infants but does not usually become chronic. Chemotherapy may have suppressed this boy's immune system. A lung biopsy confirmed the diagnosis. He was treated with intravenous ribavirin.

The role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis was investigated. The procedure involved the examination of lowerrespiratory specimens from lung transplant recipients with evolving and established obliterative bronchiolitis for the presence of PDGF protein and transcripts. The results showed that there is a direct correlation between the progression of the disease and the levels of PDGF. The results demonstrate a possible role for PDGF in fibroproliferative changes during obliterative bronchiolitis.

Acute bronchiolitis, inflammation of the bronchioles, is the most common infection of the lower respiratory tract in infants in North America and Europe. It is caused by the respiratory syncytial virus (RSV) and occurs as outbreaks in winter and spring. Although acute bronchiolitis also occurs in developing countries in the tropics, there is limited knowledge about its causes and epidemiology in tropical regions of the world. Previous studies have shown that RSV infection was prevalent between July and October and caused 20 to 60 percent of cases of acute bronchiolitis. The clinical features and causes of acute bronchiolitis in tropical South India were assessed in 328 children under 5 years of age with acute lower respiratory infections. One hundred and fourteen children were diagnosed with acute bronchiolitis, including 87 children less than a year old and 107 less than 2 years old. Tachypnea, a respiratory rate greater than 50 breaths per minute, developed in 95 percent of the children; subcostal retraction or abnormal movement of the chest during respiration was observed in 93 percent. Pneumonia was present in 30 of 88 children who had chest X-rays; pneumonia could not be diagnosed by clinical signs and symptoms alone. Viruses were detected in 81 children, including 65 patients with RSV and 12 patients with parainfluenza viruses. In South India, acute bronchiolitis tended to occur in outbreaks between August and November, and coincided with RSV outbreaks. These findings suggest that bronchiolitis is a viral rather than bacterial disease. Eight children died, including five infants with pneumonia and three with other complications. All of the children who died had been treated with antibiotics. In caring for infants and children with bronchiolitis, X-ray findings should be considered before antibiotics are prescribed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Respiratory syncytial virus (RSV) is responsible for many cases of bronchiolitis in children, many of whom are hospitalized. Bronchiolitis is a lung disease. Between 1980 and 1996, about 1.65 million young children were hospitalized for bronchiolitis. Admission rates for bronchiolitis more than doubled during this time, from 12.9 per 1,000 children to 31.2 per 1,000. Between 50,000 to 80,000 hospitalizations each year among children less than one year old were due to bronchiolitis caused by RSV.

People who work at microwave popcorn factories are at risk of developing a lung disease called bronchiolitis obliterans, particularly if they work near the vats where the oil and flavorings are mixed. This mixing process creates airborne particles that can be inhaled. Eight people at one factory of 560 employees developed this lung disease, which was a rate 5 to 11 times higher than expected for an occupational lung disease. Four of the patients were mixers.

Objective. The hospitalization rate for bronchiolitis of any cause among US children younger than 1 year is estimated at 31.2 per 1000. No data exist on respiratory syncytial virus (RSV)-specific hospitalization rates among high-risk Native Americans other than Alaska Natives, for whom the incidence of RSV hospitalization was estimated at 150 per 1000 among infants younger than 1 year. We aimed to estimate RSV hospitalization rates among Navajo and White Mountain Apache children younger than 2 years. Methods. We conducted prospective population-level hospital-based surveillance to determine RSV hospitalization rates among Navajo and White Mountain Apache children younger than 2 years. From 1997 to 2000, all children who were admitted for acute lower respiratory tract infection between October 1 and March 31 had a nasopharyngeal aspirate obtained and tested for RSV by commercial enzyme immunoassay kits. We reviewed charts of children who tested positive for RSV antigen to determine disease severity. Results. During 3 RSV seasons (1997-2000), 51.3% of 1837 admissions for acute lower respiratory tract infection among children younger than 2 years were attributed to RSV infection. The overall seasonal RSV hospitalization rate among children younger than 2 years was 63.6 per 1000 and 91.3 per 1000 among children younger than 1 year. In a univariate analysis, predictors of severity included age Conclusions. Navajo and White Mountain Apache children are at high risk for RSV disease requiring hospitalization. A lower threshold for hospitalization or underlying chronic conditions that predispose to severe RSV disease do not seem to explain high RSV hospitalization rates in this population. Pediatrics 2002;110(2). URL: http://www.pediatrics.org/cgi/content/full/110/2/ e20; respiratory syncytial virus, American Indian, hospitalization, lower respiratory tract infection, bronchiolitis, surveillance.