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PubMed1988

Neonatal viral bronchiolitis and pneumonia induces bronchiolar hypoplasia and alveolar dysplasia in rats.

The objective of this research was to determine the effects of viral bronchiolitis and pneumonia on postnatal bronchiolar and alveolar growth. Neonatal (5-day-old) and weanling (25-day-old) outbred rats were infected with parainfluenza type 1 (Sendai) virus and were studied from 0 to 110 days after inoculation by scanning and transmission electron microscopy, by light microscopic morphometry, and by analysis of airway corrosion casts. Viral infection induced necrotizing bronchiolitis and interstitial pneumonia in both age groups of rats. Viral infection had a much more marked effect on neonatal rats in the proliferative stage of lung growth than on weanlings in the equilibrated stage of lung growth. Viral infection in neonatal rats resulted in delayed or impaired growth of secondary septa into alveolar saccules. The impaired septal ingrowth was multifocal and predominantly centriacinar in distribution and was associated with alveolar enlargement and significant decreases (14 to 26%, p less than 0.01) in alveolar surface density. Total alveolar surface area in rats inoculated with virus as neonates was 22% lower (p less than 0.05) that that in control animals by 110 days after inoculation. Alveolar septa in these rats inoculated as neonates had enlarged interalveolar pores and defects compatible with mild alveolar emphysema. Airway corrosion casts prepared at 30 and 90 days after neonatal viral inoculation had terminal bronchioles that were 11 and 20% smaller in diameter (p less than 0.02), respectively, than those from age-matched control rats. The density of attachments of alveolar septa to bronchiolar walls in viral-inoculated rats at these times was significantly decreased (p less than 0.001). Viral-infected rats had elevated respiratory resistance (p less than 0.005) and decreased dynamic compliance (p less than 0.02) at 39 days after inoculation. The results indicate that viral bronchiolitis and pneumonia during early life in rats induces abnormal alveolar development and bronchiolar hypoplasia that are associated with abnormalities in pulmonary function. Continued postnatal lung growth does not compensate for early virus-induced abnormalities in alveolar and bronchiolar growth.

Animals↗
PubMed1985

Continuing respiratory problems three and a half years after acute viral bronchiolitis.

We reviewed the clinical progress of 81 children as part of a prospective study three and a half years after admission to hospital with acute viral bronchiolitis in infancy. Fifty six (69%) reported episodes of lower respiratory symptoms continuing over the preceding year, 25 (31%) had symptoms lasting for longer than two weeks on two or more occasions, 14 (17%) had symptoms for more than 100 days, and six (7%) required readmission to hospital with acute respiratory illness. Two years previously, these percentages had been 82%, 36%, 33%, and 13% respectively. Forty six (57%) children were said to be improving or to have become asymptomatic, but eight (10%) were deteriorating. There was no difference in the personal or family history of atopy, nor in the rate of skin test positivity between those with and without continuing symptoms, suggesting that atopy does not play an important role in the persistence of symptoms. Less than half the symptomatic children had received bronchodilator treatment during the preceding 12 months.

Acute Disease↗
PubMed1990

Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Adenoviridae Infections↗
PubMed2000

Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.

OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Acute Disease↗
PubMed1999

Previously healthy infants may have increased risk of aspiration during respiratory syncytial viral bronchiolitis.

OBJECTIVE: Respiratory illnesses may cause feeding difficulties in infants. We studied the safety of oral feeding during respiratory syncytial viral (RSV) bronchiolitis in previously healthy infants. METHODS: Twelve previously healthy infants (3-12 months) with RSV bronchiolitis underwent barium swallow studies during the acute phase of illness. Those with abnormal studies underwent repeat studies 2 to 4 weeks later. RESULTS: The initial barium studies revealed aspiration in 3 infants. All repeat studies, performed 2 to 4 weeks later, were normal. CONCLUSIONS: Even previously healthy infants may be at risk of aspiration during RSV bronchiolitis.

Bronchiolitis, Viral↗
PubMedDate not supplied

[Exogenous surfactant treatment for severe acute viral bronchiolitis: case report]

OBJECTIVE: To describe the possible clinical and laboratory effects of exogenous surfactant instillation into the tracheal tube of a child with severe acute bronchiolitis undergoing mechanical ventilation. CASE REPORT: a 2-month-old girl with clinical diagnosis of acute viral bronchiolitis underwent mechanical ventilation. She required high positive inspiratory peak pressure (35 to 45 cmH(2)O) and high inspiratory fraction of oxygen (FiO(2) = 0.9), but showed no clinical response or improvement in the arterial blood gas analysis. An exogenous surfactant (Exosurf(R), Glaxo - 50 mg/kg) was used to facilitate the use of a less aggressive ventilatory strategy. RESULTS: Four hours after surfactant administration, it was possible to reduce the positive peak inspiratory pressure (PIP) from 35 to 30 cmH(2)O, and FiO(2) from 0.9 to 0.6; and to increase the positive end-expiratory pressure (PEEP) from 6 to 9 cmH(2)O. During this period the paO(2)/FiO(2) ratio increased from 120 to 266. At the end of 24 hours, FiO(2) could be reduced to 0.4. DISCUSSION: Surfactant inactivation may be a decisive factor in the unfavorable evolution of some severe cases of acute bronchiolitis. The tracheal instillation of exogenous surfactant, in these cases, allows us to adopt less aggressive ventilatory strategies, and promotes rapid clinical responses.

Journal Article↗
PubMed2005

Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis.

BACKGROUND: The involvement of neutrophil-mediated inflammation may play an important role in the pathogenesis of acute respiratory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre-alpha-/inter-alpha-trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated. METHODS: Serum UTI concentrations in infants admitted with RSV bronchiolitis, other viral infections, bacterial pneumonia and control subjects were measured by means of one-step sandwich-type enzyme immunoassay. RESULTS: Serum UTI concentrations in 25 patients on admission were significantly higher than the 15 infantile control values (mean +/- SEM, 22.126 +/- 2.317 and 6.701 +/- 0.719 U/mL, respectively; P < 0.0001). The elevated levels returned to baseline values with improvement in the respiratory symptoms. Higher levels of serum UTI with RSV infection were consistently associated with clinical symptoms and artificial ventilation. Serum NE concentrations of patients were elevated in some patients but not significantly different from controls in the patients who showed only upper respiratory symptoms with RSV infections. CONCLUSION: The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.

Bronchiolitis↗
PubMed1990

Acute and long-term effects of viral bronchiolitis in infancy.

About 1% of infants are admitted to hospital with acute bronchiolitis; 85% of cases are caused by infection with Respiratory Syncytial Virus (RSV). The pathophysiological changes during the acute illness are inflammatory obstruction in the small airways with submucosal cellular infiltration, epithelial necrosis and mucous plugging; FRC increases and dynamic compliance falls. Failure to respond to bronchodilator drugs suggests that muscle spasm contributes relatively little to the airway narrowing. Affected infants become increasingly dyspnoeic and hypoxic for 3-4 days then spontaneously improve. After an attack of acute bronchiolitis up to 75% of children have recurrent lower respiratory tract symptoms, many continue to have hyperinflated lungs and bronchial hyperresponsiveness. In the majority, symptoms of cough and wheezing have subsided by the time they start school, but abnormalities of small airway function are detectable at least 13 years later. Children with a genetic predisposition to atopy do not appear to have an increased risk of developing bronchiolitis. Evidence of genetic predisposition to bronchial hyperresponsiveness in those with persistent wheezing is controversial. There is little to suggest that neonatal lung damage or an adverse home environment are important factors in determining susceptibility to post-bronchiolitis wheezing. IgE antibodies to RSV, and leukotriene C4, are found more frequently in the respiratory secretions of infants who wheeze during and after bronchiolitis than in those who do not. The possibility of viral-induced alteration of the immune response at the time of infection needs further investigation.

Bronchial Provocation Tests↗
PubMed1992

[From acute viral bronchiolitis in infancy to asthma in childhood].

Bronchiolitis and wheezy bronchitis are frequently associated with viral infection of the respiratory tract in infants. They play an important role in the natural history of chronic obstructive airway disease, not only in children, but also in adults. The risk of early recurrent wheezing and subsequent asthma or chronic bronchitis (with anatomical sequelae such as obliterans bronchiolitis) is significant. The precise pathogenic mechanisms of virus-induced wheezing and its sequelae are not clear. Whether airway hyperreactivity is inherited and airway hyperreactivity is present prior to, or is the result of bronchiolitis is not clear. Nevertheless the evidence for viral trigger of wheezing and long-term pulmonary sequelae must be considered and prevention must be undertaken at the first episode.

Acute Disease↗
PubMed1996

[Viral bronchiolitis and pneumopathies in infants].

Acute bronchiolitis is the most common severe lower-respiratory-tract infection of infancy. Although signs and symptoms may become severe, most viral respiratory infections are self-limited and improvement occurs within a few days. Patients hospitalized with bronchiolitis usually require supportive therapy, including oxygen and fluids, and may require mechanical ventilation. A trial of aerosolized beta 2-agonist is warranted in patients with bronchiolitis. Systemic corticosteroids have not been proved efficacious. Inhaled corticosteroids may be useful in reducing the severity of chronic wheezing that may follow acute bronchiolitis. Ribavirin may be considered in patients with severe disease of those at high risk for severe disease.

Acute Disease↗
PubMedDate not supplied

Bronchodilator response during acute viral bronchiolitis in infancy.

Bronchodilator responsiveness was assessed by measuring specific respiratory conductance before and after inhalation of aerosolized bronchodilator in 50 infants who had acute bronchiolitis due to respiratory syncytial virus infection. Thirty per cent of the infants showed an improvement in specific conductance. Responders could not be differentiated from nonresponders by family histories of atopy, eosinophil counts, or immunoglobulin levels in blood and nasal secretions. Eighty-three per cent of the families and 54% of the mothers of the infants were smokers. Babies of smoking mothers had lower specific conductances than did those of nonsmoking mothers but showed no differences in bronchodilator response. The clinical significance of this bronchodilator-responsive sub-group has yet to be defined.

Acute Disease↗
PubMed1998

A comparison of IL-2 levels in nasopharyngeal and endotracheal aspirates of babies with respiratory syncytial viral bronchiolitis.

BACKGROUND: Cytokines such as IL-2 are thought to be important in the pathogenesis of respiratory tract inflammation. Cytokine levels in nasopharyngeal aspirates (NPAs) have been used as a measure of respiratory inflammation in children with viral infections, but it is unclear whether they reflect levels in the lower respiratory tract. OBJECTIVE: We sought to assess the correlation between IL-2 levels in the nasopharyngeal and endotracheal secretions of children intubated with respiratory syncytial virus (RSV)-positive bronchiolitis. METHODS: NPA and endotracheal aspirates were collected concurrently from intubated infants with RSV-positive bronchiolitis. IL-2 levels were assayed by ELISA, and the results were compared according to collection site. RESULTS: Nine paired specimens were collected. IL-2 levels ranged from 31 pg/mL to 8040 pg/mL. No significant difference was found in the geometric mean IL-2 values from the 2 collection sites. The intraclass correlation coefficient between NPA IL-2 levels and endotracheal aspirate IL-2 levels was 0.83. CONCLUSION: IL-2 levels in NPAs are comparable with those in the lower respiratory tracts of infants with RSV-positive bronchiolitis. NPA cytokine levels provide a simple and useful means of assessing respiratory tract inflammation.

Bronchiolitis, Viral↗
PubMed2006

T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis.

Exposure to immunosuppressive environmental contaminants is a possible contributing factor to increased occurrence of viral respiratory diseases. The objective of this study was to test the hypothesis that the trichothecene mycotoxin T-2 toxin (T-2), a frequent food contaminant, alters host resistance to lung infection by reovirus, a model respiratory virus. Balb/c mice (4 week old) were treated intraperitoneally with T-2 toxin (1.75 mg/kg bw) or saline vehicle and then intranasally instilled 2 h later with 10(7) plaque forming unit (PFU) of reovirus, strain Lang (T1/L) or saline vehicle. At 10 days post-instillation (PI), both virus plaque-forming responses and reovirus L2 gene expression were 10-fold higher in lungs of T-2-treated mice compared to controls. No-effect and lowest-effect levels for T-2-induced suppression of reovirus clearance were 20 and 200 microg/kg bw, respectively. Respiratory reovirus infection resulted in a mild bronchiolitis with minimal alveolitis, which was markedly exacerbated by T-2 pretreatment. Reovirus exposure induced marked increases in total cells, neutrophils and lymphocytes at 3 and 7 days PI in bronchial alveolar lavage fluid (BALF) whereas macrophages were increased only at 7 days PI. Although prior T-2 exposure attenuated total cell and macrophage counts in BALF of control and infected mice at 3 days PI, the toxin potentiated total cell, macrophage, neutrophil and lymphocyte counts in infected mice at 7 days PI. At 3 days PI, T-2 suppressed reovirus-induced IFN-gamma elevation in BALF, but enhanced production of IL-6 and MCP-1. T-2 pretreatment also suppressed reovirus-specific mucosal IgA responses in lung and enteric tract, but potentiated serum IgA and IgG responses. Taken together, T-2 increased lung viral burden, bronchopneumonia and pulmonary cellular infiltration in reovirus-infected mice. These effects might be attributable to reduced alveolar macrophage levels as well as modulated cytokine and mucosal Ig responses.

Animals↗
PubMed1990

Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness.

The objectives of this study were to determine the kinetics of Sendai virus-induced increases in bronchiolar mast cells and to determine whether virus-induced increases in bronchiolar mast cells were associated with increased airway responsiveness to methacholine and with altered allergic inflammatory responses to antigen stimulation. Mast cell density in intrapulmonary airways was measured in outbred CD (Crl:CDBR) rats by use of morphometric techniques at 7, 15, 30, 60, and 90 days after viral or sham inoculation. Density of bronchiolar mast cells was higher in virus-inoculated rats than in control rats at 30, 60, and 90 days after inoculation (P less than 0.01), but not at 7 or 15 days after inoculation. Total pulmonary mast cell numbers were increased in virus-inoculated rats at 30 days after inoculation. Rats at 42 days after viral inoculation had over a threefold increase in sensitivity to the concentration of nebulized metbacholine that would stimulate a 50% increase in respiratory resistance. Virus-inoculated rats sensitized to ovalbumin had over a 10-fold increase (P less than 0.02) in pulmonary neutrophils that were recovered by bronchoalveolar lavage at 4 hours after ovalbumin aerosol challenge. Virus-inoculated rats at this time also had higher densities of neutrophils in bronchiolar walls than allergen-exposed control rats. The results indicate that Sendai virus induces increases in numbers of bronchiolar mast cells at times from 30 to 90 days after inoculation, and that mast cell increases are associated with airway hyperresponsiveness to methacholine and heightened allergic airway inflammatory reactions.

Animals↗
PubMed2001

Benefits of thickened feeds in previously healthy infants with respiratory syncytial viral bronchiolitis.

Infants with respiratory syncytial virus (RSV) bronchiolitis have an increased risk of aspiration. The optimal feeding strategy for these patients has not been described. Fifteen previously healthy and clinically stable infants with RSV bronchiolitis underwent video-fluoroscopy studies to assess swallowing using thin barium. Those with abnormal studies underwent a repeat study, using barium that was thickened with rice cereal. Nine of 15 infants had abnormal studies with thin barium. Laryngeal or tracheal penetration with thin barium was seen in 3 and 2 infants, respectively, but not with thickened barium. Aspiration of thin barium was seen in 4 infants, but it corrected in 3 of these 4 infants with thickened barium. Thickened feeds provide a simple, safe, and cost-effective intervention to improve swallowing dysfunction and prevent aspiration in infants with RSV bronchiolitis.

Barium↗