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PubMed1987

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.

Adolescent↗

PubMed2000

The clinical course of bronchiolitis associated with acute otitis media.

BACKGROUND: Acute otitis media (AOM) is the most common bacterial co-infection of viral bronchiolitis. AIMS: To evaluate the influence of AOM on the clinical course of bronchiolitis. SUBJECTS: 150 children younger than 24 months old, diagnosed with bronchiolitis, hospitalised between December 1997 and May 1999. METHODS: Body temperature, respiratory rate, oxygen saturation, and the need for oxygen supplementation were recorded on admission and daily throughout hospitalisation. Complete blood count, erythrocyte sedimentation rate, and assay for respiratory syncytial virus were performed on admission. All children were examined daily for the appearance of AOM. The clinical course of children with bronchiolitis and AOM was compared to those without AOM. RESULTS: AOM was diagnosed in 79/150 (53%) children with bronchiolitis. Most were diagnosed within the first two days of hospitalisation. No significant difference was found in the clinical and laboratory findings on admission and on daily follow up between children with and without AOM. CONCLUSIONS: This 2.5 year prospective study showed no difference in the course of bronchiolitis, whether an ear infection was present or not.

Acute Disease↗

PubMed2000

Implementation of evidence-based management of acute bronchiolitis.

OBJECTIVE: Implementation of clinical guidelines is frequently delayed well beyond their dissemination and the publication of clinical evidence. The recently published Australian guidelines for the management of acute viral bronchiolitis (AVB) have been evaluated by assessing the current practice of Australian paediatricians. METHODS: Questionnaire survey of all Australian paediatricians and a review of the literature. RESULTS: Of a total of 891 questionnaires, 555 (62%) were returned. Of the respondents, 373 (67%) treated children with AVB and, of these, 232 (67%) treated 10-50 children per year. A wide variation in management practice for both outpatient and inpatient treatment of AVB was identified. Up to 70% of paediatricians who treated AVB indicated using pharmaceutical agents in their outpatient management (88% in inpatient management), most using these agents 'sometimes' or in high-risk children. Paediatric respiratory physicians tended to use bronchodilators less frequently than general paediatricians. Compared with many countries in Europe, few Australian paediatricians routinely use supplementary drugs in the inpatient managenment of AVB; in particular, bronchodilators (61 vs 7%) and corticosteroids (11 vs 1%) are used far less often. A review of the literature demonstrated that pharmaceutical agents do not influence the course of AVB. CONCLUSIONS: Despite a lack of evidence for their efficacy and the recommendation of the Australian guidelines, pharmaceutical agents are frequently used in the management of AVB by paediatricians in Australia, although far less than reported in a recently published European survey. Guidelines alone are not sufficient to implement change and there is a need for more specific strategies to ensure that children receive appropriate management for this common condition.

Acute Disease↗

PubMed1999

Prevention of chronic postbronchiolitis airway sequelae with IFN-gamma treatment in rats.

After viral bronchiolitis at an early age, Brown Norway (BN) rats develop chronic airway dysfunction consisting of inflammation, remodeling, episodic reversible obstruction, and hyperresponsiveness. We hypothesized that supplementation of interferon gamma (IFN-gamma) during viral illness would alter the inflammatory response and attenuate the postviral sequelae. Weanling rats were treated daily with aerosolized interferon gamma (IFN-gamma), from 2 d prior through 7 d after inoculation, and compared with saline-treated infected rats and with noninfected control rats. The IFN-gamma treatment had no significant effect on viral titers, growth retardation, or total bronchoalveolar leukocytes, but there was a slight decrease in lung interleukin-4 (IL-4) mRNA (p = 0.015) during the first week. Despite having minimal effects on the acute illness, the IFN-gamma had marked effects on postviral sequelae, the IFN-gamma group having less bronchiolar inflammation (p = 0.025) and fibrosis (p = 0.01), and lacking abnormalities in pulmonary resistance (p = 0.028) and dynamic compliance (p = 0.006) compared with the untreated postviral group. We conclude that IFN-gamma modulated the inflammatory response to viral illness, such that acute airway injury did not evolve into chronic airway dysfunction. If similar processes contribute to the development of human asthma, it may be possible to interrupt the progression of airway dysfunction with an early immunomodulatory intervention.

Airway Resistance↗

PubMedDate not supplied

[Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis].

OBJECTIVE: To assess interleukin-2 concentrations in nasopharyngeal secretion of children (0-24 months) with acute respiratory syncytial virus bronchiolitis, within the first 12 hours of hospital admission, and compare the levels of IL-2 with the severity of the illness. METHODS: Prospective study performed between June and August 1999. The study included 62 patients, previously healthy, hospitalized with acute viral bronchiolitis characterized by recent prodromes of coryza and/or nasal obstruction, which evolved to at least two of the following signs: respiratory dysfunction, tachypnea, wheezing or rales, and detection of respiratory syncytial virus in nasopharyngeal aspirate. The nasopharyngeal specimens were collected within 12 hours of hospital admission. The interleukin-2 levels were obtained by enzyme immunoassay. Severity of illness was assessed through oxygen saturation by pulse oximetry, Modified Clinical Score System, time of supplemental oxygen required, length of hospital stay, and mechanical ventilation. Spearman's correlation and Kruskal-Wallis test were used to compared these variables in relation to the median of interleukin-2. The chi-square test was used for categorical analysis of interleukin-2. RESULTS: The mean age of patients was 2.2 (1.3-4) months. Males comprised 54% of cases. Hemoglobin oxygen saturation by pulse oximetry at hospital admission was below 95% in 66.1% of patients. The mean time of supplemental oxygen use was 4.7 days (+/-3.54). The mean length of hospital stay was 4.25 days (+/-1.76). Mechanical ventilation was used in 4.8% of patients. The values of interleukin-2 in nasopharyngeal aspirates varied from 0 to 40,256 ng/ml with median of 86 ng/ml (4.4 - 457.3). The study showed no statistical difference between levels of IL-2 and severity of illness. CONCLUSIONS: The interleukin-2 levels showed a heterogeneous behavior. We found no association between interleukin-2 levels in nasopharyngeal secretion and respiratory syncytial virus bronchiolitis.

Acute Disease↗

PubMed1996

Respiratory syncytial virus bronchiolitis: clinical aspects and epidemiology.

Sixty to ninety percent of the clinical syndrome of bronchiolitis is caused by respiratory syncytial virus (RSV) infection. RSV epidemiology has several unusual characteristics. RSV infects nearly all infants in the first year of life, with a peak incidence of hospitalized infants with bronchiolitis between 2-6 months of age. It is the only virus that causes most severe disease during the first month of life, i.e. at a time when maternal antibodies are present. Lower respiratory tract infections caused by RSV are limited to children younger than 3 yrs but symptomatic infection with RSV occurs throughout life. Infants with cardiac disease as well as infants with bronchopulmonary dysplasia are especially prone to develop severe RSV bronchiolitis. Apnoea is a complication that occurs in infants younger than 3 months and after a history of apnoea of prematurity. Nosocomial infection is a major health problem. Hospital staff may spread the infection by becoming infected and shedding the virus, or by carrying contaminated secretions between patients. Classical teaching has been that the prevalence of wheeze is high after acute viral bronchiolitis in infancy, but recent data suggest that infants with already lower maximal expiratory flows at functional residual capacity are more prone to develop wheeze at the time of RSV bronchiolitis.

Bronchiolitis, Viral↗

PubMed1996

Treatment of parainfluenza virus type 3 bronchiolitis and pneumonia in a cotton rat model using topical antibody and glucocorticosteroid.

Treatment of parainfluenza virus type 3 bronchiolitis and pneumonia in the cotton rat using topical IgG cleared infectious virus within 24 h but did not reduce pulmonary pathology. Treatment with topical triamcinolone acetonide dramatically reduced pathology but increased virus titers >10-fold. Combined therapy, however, demonstrated both favorable effects. Animals treated 3,4, and 5 days after infection showed a rebound of lung lesions to levels of untreated animals without reappearance of virus, but treatment through 8 days resulted in virus-free lungs without rebound of lesions. There was no difference in response to rechallenge 21 days after the original infection between treated and untreated animals. Combined antiviral and antiinflammatory therapy looks promising for viral bronchiolitis and pneumonia, but further questions relating to mechanism of action and to range of infections that can be treated in this fashion will need to be answered in animal models.

Administration, Intranasal↗

PubMed2002

Persistence of viral RNA in 2 rat strains differing in susceptibility to postbronchiolitis airway dysfunction.

After viral bronchiolitis at an early age, a chronic asthma-like syndrome develops in BN, but not F344, rats. We hypothesized that the BN strain is less effective at clearing virus from the involved tissues. Weanling BN and F344 rats were inoculated with Sendai virus, and lung and peribronchial lymph nodes were harvested from each strain at 5 to 84 days after infection; control tissues were obtained from noninfected rats. Lung viral titers were similar for the 2 strains, with no infectious virus detectable by day 10. However, viral RNA was detected consistently by means of RT-PCR analyses in lungs and lymph nodes of both strains from days 10 to 27 and was still present at day 84 in some of the tissues from each strain. In contrast, there were strain-related differences in immune responses because IL-13 levels remained increased in the lung secretions of BN rats at 4 weeks after inoculation. Thus although Sendai virus could persist for at least 3 months after an acute infection in rats, this did not differ with strain. The persistent increase in IL-13 suggests instead that the strain-related variability in virus-associated airway pathology might be determined by the host response to infection rather than by the intensity or duration of infection.

Animals↗

PubMed1987

Effect of ipratropium bromide on respiratory mechanics in infants with acute bronchiolitis.

The effect of nebulized ipratropium bromide in 14 infants (mean age: 20 weeks, range: 4-41) with acute respiratory syncytial virus bronchiolitis was examined. A modified rapid chest compression technique was used to obtain partial expiratory flow-volume curves and maximum flow at functional residual capacity. Passive respiratory mechanics were assessed by brief occlusion at end inspiration. Thoracic gas volume was measured in a body plethysmograph. No significant difference was found in forced and passive respiratory mechanics pre- and post-ipratropium bromide. No subgroups could be identified. These results do not support the use of ipratropium bromide in acute viral bronchiolitis.

Acute Disease↗

PubMed2005

Dexamethasone inhalations in RSV bronchiolitis: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis. STUDY DESIGN: A double-blind, placebo-controlled study compared nebulization of dexamethasone versus nebulization of 0.9% saline. Both groups were treated with epinephrine nebulizations. Follow-up continued for 3 mo. PATIENTS AND METHODS: Sixty-one infants with bronchiolitis aged 3 to 12 mo were included. They were randomly allocated to nebulizations with 0.25 mg dexamethasone every 6 h (group 1) or an equivalent amount of normal saline (group 2). RESULTS: No statistically significant differences with respect to clinical score, oxygen saturation, or IV fluid requirement between the groups were noted. Using Kaplan-Meyer's method, the cumulative proportion of in-hospital stay was significantly lower in group 1 compared with group 2, mainly in days 5 and 6 post-hospitalization (p<0.038). A subgroup of prematurely born children in group 1 had a shorter hospitalization period (6.5+/-1.7 d) compared with group 2 children (9.1+/-1.9) (p<0.018). Follow-up revealed similar wheeze and hospitalization rates in the two groups. CONCLUSION: Inhaled dexamethasone may reduce the length of hospitalization among infants with acute viral bronchiolitis, especially among those born prematurely.

Administration, Inhalation↗

PubMed2006

High-frequency oscillatory ventilation in an infant with cystic fibrosis and bronchiolitis.

Infants with cystic fibrosis (CF) may develop severe respiratory compromise related to viral lower respiratory tract infections due to impaired mucous clearance and plugging of small airways. Consequently air trapping may lead to lung hyperinflation, impaired gas exchange, and respiratory failure. We describe the case of an infant with newly diagnosed CF who developed severe hypercarbic respiratory failure in the setting of viral bronchiolitis successfully treated with high-frequency oscillatory ventilation (HFOV).

Bronchiolitis↗

PubMed2004

Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis.

BACKGROUND: Viral bronchiolitis is the leading cause of respiratory failure among infants in the United States. Currently, the mainstay of treatment is supportive care. The effectiveness of treatments used for mechanically ventilated infants with bronchiolitis is unclear. OBJECTIVE: To evaluate the strength of the evidence supporting the use of currently available treatments for critically ill infants with bronchiolitis. DATA SOURCE: We searched PubMed, citations of relevant articles, personal files, and conference proceedings, and we contacted experts in the field. STUDY SELECTION: Randomized, controlled trials evaluating any therapy for bronchiolitis that included children in an intensive care unit. DATA EXTRACTION: Two reviewers independently extracted data and assessed methodologic quality. DATA SYNTHESIS: A total of 2,319 citations were screened, and 16 randomized, controlled trials were included. There were three trials of surfactant, three of ribavirin, three of immune globulin, three of systemic corticosteroids, and one each of vitamin A, interferon, erythropoietin, and heliox. A meta-analysis of the three surfactant studies showed a strong trend toward a decrease in duration of mechanical ventilation of 2.58 days (95% confidence interval, -5.34 to 0.18 days; p =.07) and a significant decrease of 3.3 intensive care unit days (95% confidence interval, -6.38 to -0.23 days; p =.04). A meta-analysis of the three systemic corticosteroid studies showed no overall effect on duration of mechanical ventilation when all three trials were combined (-0.62 day; 95% confidence interval, -2.78 to 1.53 days; p =.57). We identified one published meta-analysis of three ribavirin studies showing a significant decrease in ventilator days with ribavirin (-1.2 days; 95% confidence interval, -0.2 to -3.4 days; p =.2). CONCLUSIONS: Currently, there are no clearly effective interventions available to improve the outcome of critically ill infants with bronchiolitis. Surfactant seems to be a promising intervention, and corticosteroids or ribavirin may also be beneficial.

Bronchiolitis↗

PubMed2005

Levels of Th1 and Th2 cytokines in children with post-infectious bronchiolitis obliterans.

BACKGROUND: Post-infectious bronchiolitis obliterans (BO) is a chronic obstructive airway disease associated with inflammation and fibrosis of the small airways; it is more common in children who have had acute viral bronchiolitis. No previous studies have reported the immune response of BO. Unbalanced Th1/Th2 immune response might be one of the risk factors for developing this illness. AIM: To compare the production of interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 in peripheral blood mononuclear cell cultures in children with BO and in healthy children. METHODS: From March 2003 to October 2003, children with BO and healthy children were selected from the paediatric outpatient clinics in our centre. Peripheral blood was collected and mononuclear cells were separated and cultured (96 hours) with 1% phytohaemagglutinin stimulation. The supernatant was stored and cytokine levels were measured through ELISA. RESULTS: IFN-gamma, IL-4 and IL-10 levels were not significantly different between the groups studied. Family history of atopy was significantly associated with subjects with BO (p=0.02). CONCLUSIONS: Our results suggest that unbalanced peripheral blood Th1/Th2 immune response of children with post-infectious BO might not be associated with its pathophysiology. Further studies are required to better understand the role of risk factors, including viral genotype, viral load or tissue repair abnormalities in the development of post-infectious BO.

Acute Disease↗

PubMed1999

Epidemiologic evidence of increased airway reactivity in children with a history of bronchiolitis.

Airway hyper-responsiveness, or hyper-reactivity, can be identified on clinical evaluation in a number of ways, including a history of wheezing, physician-diagnosed asthma, or the bronchial response to challenge with nonspecific stimuli such as methacholine or histamine. However, wheezing and the responses to these stimuli are not uniform within or across individuals, and in the general population there is a wide range of bronchial responsiveness that follows a normal distribution. Airway hyper-reactivity occurs in a number of settings, including acute viral bronchiolitis. Some, but not all, studies of children years after hospitalization during infancy for respiratory syncytial virus bronchiolitis or another lower respiratory tract infection demonstrate the presence of airway hyper-responsiveness. In contrast, infants studied who are <12 months of age do not have airway hyper-responsiveness after episodes of bronchiolitis. Discrepancies in the study results may reflect the bronchial challenge procedure used and the pulmonary function studies performed. Viral lower respiratory tract infections might alter immune responses to favor immunoglobulin E production, but the results of studies relating respiratory syncytial virus bronchiolitis with subsequent immunoglobulin E production again have been discrepant. Host and environmental factors such as exposure to tobacco smoke or a family history of atopy may be more important than viral lower respiratory tract infections as determinants of bronchial reactivity.

Adolescent↗

PubMedDate not supplied

[Lactate dehydrogenase isoenzymes and alveolar inflammation in acute severe bronchiolitis in infants].

The authors have tried to value in 17 children (age: 1-11 months) affected by a severe acute viral bronchiolitis, if the measurement of Lactate Dehydrogenase (LD) isoenzymes could have been used to reveal alveolar injury. In the 76.4% (13/17) of subjects areas of consolidation were demonstrated by chest's radiographic examination due either to atelectasis secondary to obstruction or to inflammation of the alveoli. These coincided with a significant increase respect to a check's group (18 children) of LD4 in 70.5% (12/17), LD3 in 35.2% (6/17) and LD5 in 29.4% (5/17) of children. The presence of an analogous electrophoretic pattern and macrophages degenerated in pulmonary alveolar proteinosis lavage effluent associated with increases in lymphocytes and mononuclear phagocytes in lung specimens from children dead for bronchiolitis help to understand the inflammatory origin of pathological modification of LD isoenzymes observed in this series of cases.

Acute Disease↗

PubMed1996

[Treatment of acute bronchiolitis in infants. Role of bronchodilators and steroids].

The management of infant bronchiolitis with bronchodilators and steroids is controversial. A literature review on this topic allows to determine the influence of these medications on the first episode of viral bronchiolitis. The effect of alpha and beta adrenergic drugs is undoubtful but it is not possible to anticipate a positive or negative response based on the age of the child nor on a family history of atopic disease. Systemic steroid therapy has no immediate effect but inhaled steroids may be tried during the recovery period to reduce short term morbidity.

Acute Disease↗

PubMedDate not supplied

Pathogenesis of severe acute respiratory infections in the developing world: respiratory syncytial virus and parainfluenza viruses.

Respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) are the most frequently isolated pathogens in infants and children with acute lower respiratory infection (LRI) in the developed world. Less information is available about their importance in LRI in the developing world, but they are probably important there also. The pathogenesis of viral bronchiolitis and pneumonia involves inoculation and early replication in the upper respiratory tract, followed by aspiration into the lower respiratory tract when both the mucosal and systemic immune systems are involved in a specific response. Both disease and recovery reflect processes of viral replication (with attendant cellular destruction) and of immune response (with attendant direct cellular destruction and release of pathogenic, along with beneficial, mediators). Factors predisposing to bacterial superinfection are poorly understood except in animal models. Conditions leading to heightened susceptibility to severe disease in the developed world are particularly common in the developing world. Increasing information on RSV and PIV infections in the developing world will likely point to their importance. Strategies for prevention of severe illnesses due to these viruses will follow from concepts elucidated through animal models and studies of infants in the developed world.

Acute Disease↗

PubMed2002

Interactions between respiratory tract infections and atopy in the aetiology of asthma.

The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context. The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy. Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli.

Adult↗