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A clinical pathway for bronchiolitis is effective in reducing readmission rates.

OBJECTIVE: To examine the use of a clinical pathway in the management of infants hospitalized with acute viral bronchiolitis. STUDY DESIGN: A clinical pathway with specific management and discharge criteria for the care of infants with bronchiolitis was developed from pathways used in tertiary care pediatric institutions in Australia. Two hundred and twenty-nine infants admitted to hospital with acute viral bronchiolitis and prospectively managed using a pathway protocol were compared with a retrospective analysis of 207 infants managed without a pathway in 3 regional and 1 tertiary care hospital. RESULTS: Readmission to hospital was significantly lower in the pathway group (P = .001), as was administration of supplemental fluids (P = .001) and use of steroids (P = .005). There were no differences between groups in demographic factors or clinical severity. The pathway had no overall effect on length of stay or time in oxygen. CONCLUSIONS: A clinical pathway specifying local practice guidelines and discharge criteria can reduce the risk of readmission to hospital, the use of inappropriate therapies, and help with discharge planning.

Acute Disease↗

Bronchiolitis and asthma: possible common pathogenetic pathways.

A discussion of possible mechanism for virus-induced wheezing in normal and asthmatic children is presented. Presently attractive theories for immune injury in viral bronchiolitis include those which depend on pathology induced by types 1, 3, and 4 of Gell and Coombs. The continuum of viral bronchiolitis with virus-induced wheezing in young children who are labeled "asthmatic" argues for some common mechanism of bronchiolar obstruction.

Asthma↗

Abnormal surfactant composition and activity in severe bronchiolitis.

A prospective study of infants under 1 y of age, ventilated for severe viral bronchiolitis, was carried out in four paediatric intensive care units in order to study surfactant activity and composition in this condition. Lung lavage fluid from 24 infants with bronchiolitis, 19 with bronchiolitis and sepsis or cardiac failure and 12 controls were analysed by the "click test" for surfactant activity and for phospholipids. Surfactant activity was present in all controls, but in only 2 of the 24 infants with bronchiolitis alone. The presence of phosphatidylglycerol correlated perfectly with the click test, suggesting that reduced activity is due to changes in surfactant lipid composition. In those with bronchiolitis plus coexisting disease, surfactant activity and phosphatidylglycerol were absent in only half. Surfactant activity and phosphatidylglycerol re-appeared by extubation. Severe viral bronchiolitis is associated with an absence of surfactant activity and PG, which resolves by clinical recovery. Infants with coexisting conditions are not always surfactant deficient. Surfactant administration is likely to be beneficial, but requires a selective approach.

Bronchiolitis↗

[Bronchiolitis treated with mechanical ventilation: prognosis factors and outcome in a series of 135 children].

UNLABELLED: Viral bronchiolitis is usually associated with favorable outcome as regard to mortality. Only few studies reported severe bronchiolitis requiring mechanical ventilation, and respiratory outcome is not well described. METHODS: Therefore, we conducted a retrospective study in a series of 135 children admitted in a single Pediatric Intensive Care Unit (PICU) over a four year period (1994-1998). All of them were admitted for viral bronchiolitis requiring mechanical ventilation. RESULTS: At admission, 83% of them were less than three months old. Prematurity at birth was present in 33,3%. Mortality was observed in four cases (2,9%), all premature babies with mechanical ventilation at birth. Univariate analysis showed as main factors associated to mortality: prematurity (P =0,056) and acute respiratory distress syndrome (P =0,017). Childhood asthma was observed in 40,4% of children without any associated factor wether at birth or in PICU related to such outcome. CONCLUSION: Bronchiolitis associated with mechanical ventilation is particularly observed in very young babies and prematurity is the main factor associated to mortality. Mechanical ventilation seems not to be associated with unfavorable respiratory outcome. Considering physiology and population, non invasive ventilation could be an effective alternative of mechanical ventilation.

Bronchiolitis↗

Haplotype mapping of the bronchiolitis susceptibility locus near IL8.

Susceptibility to viral bronchiolitis, the commonest cause of infant admissions to hospital in the industrialised world, is associated with polymorphism at the IL8 locus. Here we map the genomic boundaries of the disease association by case-control analysis and TDT in 580 affected UK infants. Markers for association mapping were chosen after determining patterns of linkage disequilibrium across the surrounding region of chromosome 4q, a 550-kb segment containing nine genes, extending from AFP to PPBP. The region has three major clusters of high linkage disequilibrium and is notable for its low haplotypic diversity. We exclude adjacent chemokine genes as the cause of the association, and identify a disease-associated haplotype that spans a 250-kb region from AFM to IL8. In between these two genes there is only one structural feature of interest, a novel gene RASSF6, which is predicted to encode a Ras effector protein.

Base Sequence↗

Bronchiolitis: assessment and evidence-based management.

Viral bronchiolitis is the commonest cause of hospital admission in young infants. Respiratory syncytial virus is responsible for most cases of bronchiolitis. Secondary bacterial infection is rare and antibiotics are seldom necessary. Most children with bronchiolitis develop only mild illness and can be managed at home. Infants born prematurely, those with pre-existing cardiac or respiratory disease, and infants in the first three months of life are more likely to need hospital admission. On current evidence, nebulised adrenaline, inhaled and systemic corticosteroids, and inhaled bronchodilators do not have a role in the routine management of infants with bronchiolitis.

Antibodies, Monoclonal↗

Antileukotrienes in the treatment of asthma and allergic rhinitis.

OBJECTIVES: To compare leukotriene antagonists (LTA) to other groups of drugs used in asthma and allergic rhinitis treatment. SOURCES: MEDLINE, LILACS and Cochrane Library. KEYWORDS: leukotrienes, antileukotrienes, asthma treatment, allergic rhinitis treatment, asthma and allergic rhinitis. An attempt was made to group the main studies and reviews about this topic. SUMMARY OF THE FINDINGS: LTA are more efficient than placebo and enhance the effects of inhaled corticosteroids. The association of inhaled corticosteroids with long-acting Beta2 agonists is more efficient than the association of inhaled corticosteroids + LTA. Although use of LTA in acute asthma attacks and allergic rhinitis seems reasonable, more studies are needed to confirm this benefit. LTA reduce hospitalization time and the number of wheezing attacks in infants with acute viral bronchiolitis caused by respiratory syncytial virus, as well as recurrent wheezing after acute viral bronchiolitis. LTA are less efficient than intranasal corticosteroids for allergic rhinitis management. LTA are efficient in exercise-induced asthma, although they are not the first-line treatment. CONCLUSION: Controlled and randomized studies show that inhaled corticosteroids are the drugs of choice to treat persistent asthma and allergic rhinitis. There is not enough evidence to recommend the use of LTA as first-line drug (monotherapy) in children with asthma (level I). For children who cannot use inhaled corticosteroids, LTA may be a good alternative (level II).

Acute Disease↗

[Respiratory insufficiency in acute bronchiolitis in infancy].

Forty-one infants with acute viral bronchiolitis were hospitalized in our paediatric intensive care unit during the seven year period from 1980 to 1987. In 14 out of 27 evaluated patients, Respiratory Syncitial Virus (RSV) was detected in the nasal secretions. Twenty-three children required only supportive care and monitoring. Eighteen infants had to be ventilated because of respiratory failure. The major indication for mechanical ventilation was an arterial or capillary pCO2 of more than 64 mmHg; other criteria were repeated apnoea, respiratory acidosis, and clinical deterioration. In all cases the type of the mechanical ventilation was an intermittent mandatory ventilation (IMV) with flow and time cycled respirators; muscle relaxation was not required in any case. The average duration of mechanical ventilation was 40 hours. All the children recovered uneventfully. These data suggest that even the most severe cases of acute bronchiolotis can be treated successfully, and that the mortality rate of this disease entity can be reduced to zero.

Bronchiolitis, Viral↗

Unilateral hyperlucent lung: the case for investigation.

Seventeen children with unilateral hyperlucent lungs were referred for investigation. Of the 11 who had a referring diagnosis of possible Macleod's syndrome only two were shown to have post-viral bronchiolitis. Three of the 11 had conditions that required surgical treatment and a further two with brochiectasis were treated medically. To avoid confusion we suggest that Macleod's syndrome is reserved exclusively for children with post-viral bronchiolitis. Radioisotopic regional lung function studies were useful in the investigation of the subjects from three points of view. Firstly, they distinguished children with primary perfusion abnormalities and normal ventilation, secondly, they defined the extent of altered respiratory function, and thirdly, they were able to distinguish compensatory emphysema from congenital lobar emphysema. As bronchography and bronchoscopy may be hazardous in small children with poor respiratory reserve, such regional studies may be useful in indicating which patients do not require further invasive investigation.

Child↗

Reproducibility of forced expiratory flow and volume measurements in infants with bronchiolitis.

The end-tidal rapid thoracoabdominal compression (ETRTC) technique is an established method for lung function testing in infancy. Previous work in healthy infants, however, has shown that measurements with the newly developed raised volume rapid thoracoabdominal compression (RVRTC) technique are more reproducible than those with the ETRTC technique. So far, reproducibility of the two techniques has not been compared in infants with acute airway disease. Twenty-three infants with acute viral bronchiolitis underwent lung function assessment with both the ETRTC and the RVRTC technique. A series of 8-10 measurements with each technique was done in randomized order. Forced expired volumes at 0.5, 0.75, and 1 sec after chest compression (FEV(0.5), FEV(0.75), and FEV(1.0)) were measured with the RVRTC technique; maximum expiratory flow at functional residual capacity (V'(maxFRC)) was measured with the ETRTC technique. Group mean intrasubject coefficients of variation (CV) were 4.84% for FEV(0.5), 5.01% for FEV(0.75), 5.43% for FEV(1. 0), and 13.79% for V'(maxFRC), respectively. Differences between FEV parameters were statistically insignificant, whereas the difference between each FEV parameter and V'(maxFRC) was highly significant (P < 0.001). In infants with acute viral bronchiolitis, RVRTC measurements have significantly less intraindividual variability than flow rates assessed with the conventional ETRTC technique. This finding provides the basis for assessing disease course and effects of therapeutic interventions on an individual basis.

Analysis of Variance↗

Canine parainfluenza type 2 bronchiolitis increases histamine responsiveness in beagle puppies.

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Distinct types of lung disease caused by functional subsets of antiviral T cells.

T cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups of T cells have not been defined. To test the activities of T cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of RS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of RS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8+ cells; F-specific cells, a mixture of cytolytic CD8+ cells and CD4+ cells with a T helper 1 cell (Th1) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4+, with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G- and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.

Animals↗

Contribution of airway closure to chronic postbronchiolitis airway dysfunction in rats.

Genetically susceptible Brown Norway rats develop a chronic asthmalike syndrome after recovering from viral bronchiolitis at an early age. We hypothesized that airway closure is an important mechanism of airflow obstruction in postbronchiolitis rats. Rats were studied 8-12 wk after inoculation with Sendai virus or sterile vehicle at 3-4 wk of age. Under light pentobarbital anesthesia, rats were instrumented with an orotracheal catheter and an esophageal pressure monitor and placed in a total body plethysmograph. Lung volumes and forced-expiratory maneuvers were measured using the Boyle's law method and software-controlled valving of positive and negative pressures to elicit lung inflations and rapid deflations; pulmonary resistance was measured during spontaneous tidal breathing; and quasi-static pressure-volume curves were obtained with passive inflations and deflations in fully anesthetized, paralyzed rats. Compared with controls, the postbronchiolitis rats had elevated pulmonary resistance and reduced forced-expiratory volume in 0.2 s. Most of the reduced forced-expiratory volume in 0.2 s was associated with reduced forced vital capacity, indicating premature airway closure as a prominent mechanism. The reduced airflow in postbronchiolitis rats was highly dependent on lung volume, being nearly normal at 70% lung capacity, but sevenfold less than normal at 30% lung capacity. Increased respiratory system hysteresis between functional reserve capacity and total lung capacity was evidence for increased airway closure at normal end-expiratory lung volumes in postbronchiolitis rats. We conclude that airway instability and closure is a prominent mechanism of the chronic airway dysfunction in rats that have recovered from viral bronchiolitis at an early age.

Airway Resistance↗

Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR) both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease. RESULTS: Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27) and the highly downregulated gene Charcot-Leyden crystal protein (CLC) to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray. CONCLUSION: The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity.

Acute Disease↗

Respiratory status and allergy after bronchiolitis.

As part of a long term prospective study, 73 children who had been admitted to hospital with viral bronchiolitis as infants, were reviewed 5.5 years later and compared with a carefully matched control group. In the postbronchiolitis group, there was a highly significant increase in respiratory symptoms including wheezing (42.5% v 15.0%, relative risk = 2.8). Although atopy in the family was not significantly increased in the index group, personal atopy was more prevalent. However, personal atopy was not significantly more prevalent in the symptomatic postbronchiolitis, compared with those who were symptom free, and so did not account for the high prevalence of postbronchiolitis wheezing in this cohort. In addition, in a stepwise logistic regressional model, bronchiolitis remained a significant predictor of wheezing after adjusting for potential confounding variables, including atopy. Bronchial responsiveness to histamine was significantly increased in the index group. However, no significant relationship of positive tests to wheezing could be demonstrated, and a high rate of positive responses was noted in the controls.

Bronchiolitis, Viral↗

Atopy and pulmonary function abnormalities in children with a history of acute bronchiolitis.

To assess the relationship between acute viral bronchiolitis and subsequent development of asthma, we studied retrospectively 97 index children, aged between 9 and 14 years, and 52 controls. The bronchiolitis group showed significantly lower values for mean expiratory flow at 50% of vital capacity (MEF50) higher incidence of atopy, and were more sensitive to methacholine than were controls, even if they had not shown recurrent wheezing episodes. It is suggested that an increased incidence of atopy, bronchial hyperresponsiveness, and reduced expiratory flows may be detectable in children with a history of acute bronchiolitis, regardless of the fact that they did not develop subsequent clinical symptoms suggestive of bronchial asthma.

Acute Disease↗

Recovery of the ciliated epithelium following acute bronchiolitis in infancy.

BACKGROUND: Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo. METHODS: Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0-6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants. RESULTS: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure. CONCLUSION: Ciliary loss and epithelial abnormalities persist on average for 13-17 weeks following acute bronchiolitis in infancy.

Acute Disease↗