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PubMed2004

Eosinophil activation and cysteinyl leukotriene production in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: It has been suggested that acute infantile bronchiolitis associated with respiratory syncytial virus (RSV) may share some pathogenic features with atopic asthma in that virus-specific IgE is produced and cysteinyl leukotrienes (cLTs) and eosinophil cationic protein (ECP) have been detected in airway secretions. ECP is a specific marker of eosinophil activation although leukotrienes can be released from a variety of cells including mast cells, eosinophils and monocytes. OBJECTIVE: To test the association between eosinophil activation and cysteinyl leukotriene production in the upper airway secretions of infants with RSV positive (RSV+ve) bronchiolitis. METHODS: Nasal lavage samples were performed in 78 infants (0.0-11.5 months) admitted to hospital with RSV+ve bronchiolitis soon after admission (0-48 h). Leukotriene C4 (LTC4) was assayed by enzyme immunoassay (EIA) and eosinophil cationic protein (ECP) by fluoroimmunoassay (FIA). RESULTS: LTC4 was detectable in 51 and ECP in 57 of 78 samples with a significant positive relationship between LTC4 and ECP (r=0.557, P<0.001). CONCLUSION: In the majority of our subjects with RSV+ve bronchiolitis ECP and LTC4 were detectable in upper airway secretions and were significantly associated with each other. In this clinical setting much of the detected LTC4 within upper airway secretions is likely to originate from the eosinophil, an observation that may have implications for clinical management and for delineation of the underlying mechanisms associated with this illness.

Blood Proteins↗
PubMed1998

Porcine-derived surfactant treatment of severe bronchiolitis.

BACKGROUND: It is hypothesized that surfactant treatment helps to improve severe bronchiolitis by restoring surfactant system activity. This study aims to assess the effect of surfactant on gas exchange, peak inspiratory pressure and duration of mechanical ventilation and intensive care unit (ICU) stay in children with severe bronchiolitis. METHODS: Twenty children with bronchiolitis requiring mechanical ventilation were randomly assigned to one of two groups (10 patients each). Group A was treated with continuous positive pressure ventilation (CPPV) plus surfactant. Group B was treated with CPPV only. Porcine-derived surfactant, 50 mg/kg body weight, was instilled into the trachea. Arterial tension of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, arterial tension of carbon dioxide (PaCO2), and peak inspiratory pressure (PIP) were assessed. Heart rate and non-invasive arterial blood pressure were monitored. The duration of CPPV and the length of ICU stay were also recorded. Finally, the incidence of complications and the survival rate were assessed. RESULTS: In group A, the PaO2/FiO2 ratio significantly improved from 1 h and a reduction in PaCO2 was noted from 12 h. A reduction of PIP was observed from 3 h. The duration of CPPV and the length of ICU stay were reduced in group A. No complications were reported in either group and all children survived. CONCLUSIONS: Surfactant treatment of severe bronchiolitis appeared to improve gas exchange, reduce PIP and shorten CPPV and ICU stay. However, these initial results must be confirmed by a larger and more rigorously controlled study.

Analysis of Variance↗
PubMed1997

Effect of oral and inhaled salbutamol in infants with bronchiolitis.

The response of bronchiolitis to bronchodilator drugs is controversial. The present study was designed to evaluate the efficacy of oral or metered dose inhaler (MDI) salbutamol using a coffee cup as a spacer device in bronchiolitis. In the trial, 31 hospitalized patients between 6 and 24 months of age, who exhibited the first episode of acute bronchiolitis without any other predisposing illness such as cystic fibrosis, congenital heart disease etc., were randomly assigned to receive oral salbutamol (n = 11, 0.1 mg/kg per dose, four times a day), or MDI salbutamol (n = 12, 200 micrograms per dose, every 3 h) or formed the control group without any bronchodilator therapy (n = 8). All of the patients were given supplemental oxygen as needed and adequate hydration was maintained. The patients were evaluated with clinical symptom scores. There were no differences in the beneficial or side effects of salbutamol, or the number of days in hospital between the treatment groups and the control group. It was concluded that there is no beneficial effect in using bronchodilators in infants with bronchiolitis. Supplemental oxygen and maintenance of normal hydration may be adequate.

Administration, Inhalation↗
PubMed2004

Additive effects of dexamethasone in nebulized salbutamol or L-epinephrine treated infants with acute bronchiolitis.

BACKGROUND: Although it is the most common lower respiratory infection of infancy, the optimal treatment for acute bronchiolitis is still controversial. The aim of this study was to compare the early and late effects of nebulized L-epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators alone in outpatients with acute bronchiolitis. METHODS: A total of 69 infants aged 2-21 months who were admitted to the Pediatrics Department of the Faculty of Medicine, Mersin University, with acute bronchiolitis were included in a randomized, placebo-controlled, prospective trial study. Patients were assigned to receive either nebulized L-epinephrine (3 mg) or salbutamol (0.15 mg/kg) and 15 min later, either dexamethasone 0.6 mg/kg or placebo (PLA), intramuscularly, in a double-blind randomized fashion. The study groups were: epinephrine + dexamethasone group (group 1, n=23), salbutamol + dexamethasone group (group 2, n=23), epinephrine + placebo group (group 3, n=11), and salbutamol + placebo group (group 4, n=12). The outcome measures were heart rate, respiratory rate and Respiratory Distress Assessment Instrument (RDAI) score determined at 30, 60, 90 and 120 min, 24 h, and 5 days after the first therapy. Patients were then followed-up during the subsequent 2 months for the prevalance of respiratory complaints regarding bronchial hyperreactivity. RESULTS: There were no significant differences between the outcome variables of the four groups within the first 120 min and at 24 hours, or between the rates of requirement of a second dose of the same bronchodilator. However, fifth day RDAI score values of both DEX groups were significantly lower than that of SAL + PLA group (P=0.000 and P=0.01, respectively). The fifth day score value of group 1 was also significantly better than that value of EPI + PLA group but not different from group 2. CONCLUSIONS: A single dose of intramuscular dexamethasone added to nebulized L-epinephrine, or salbutamol therapies resulted in better outcome measures than bronchodilators alone in the late phase (fifth day) of mild to moderate degree bronchiolitis attack. However, effects of EPI + DEX combination was not different from SAL + DEX combination.

Acute Disease↗
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↗
PubMed2005

Teenage asthma after severe infantile bronchiolitis or pneumonia.

OBJECTIVE: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. METHODS: In 1981-1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n = 81) or pneumonia (n = 46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. RESULTS: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non-RSV infection group. Early asthma-predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis. CONCLUSION: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.

Adolescent↗
PubMed1982

Sleep apnoea in acute bronchiolitis.

Three- to 4-hour polygraphic sleep studies were carried out in 16 infants aged between 1 and 6 months during and after recovery from acute bronchiolitis. During bronchiolitis 35% of total sleep time was active sleep compared with 31% after recovery. Respiration rate was increased during bronchiolitis and was higher in active sleep and quiet sleep irrespective of the stage of the illness. Apnoeic pauses were invariably shorter than 15 seconds, the mean duration for active sleep and quiet sleep being similar during infection and after recovery. Apnoeic episodes were central in type and generally initiated by a sign or body movements. Preapnoea heart rate was significantly higher than during or after apnoea. Apnoea index (the percentage of time the baby spends apnoeic), apnoea attack rate (the number of episodes of apnoea per unit time), and apnoea percentage (the distribution of episodes of apnoea while in a given sleep state) were increased significantly in quiet sleep during the index illness. Transcutaneous oxygen tension was significantly reduced during the course of infection, but comparable values were obtained in active sleep and quiet sleep during initial and recovery periods. These results show that the main changes in respiration pattern during the course of acute bronchiolitis occur in quiet sleep.

Acute Disease↗
PubMed1996

Surfactant abnormalities in infants with severe viral bronchiolitis.

To determine whether abnormalities of pulmonary surfactant occur in infants with acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid from 12 infants with severe bronchiolitis and eight infants without lung disease. Compared with controls, the bronchiolitis group showed deficiency of surfactant protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v 1060 micrograms/ml) which resolved as the disease improved. Surfactant functional activity was also impaired (minimum surface tension 22 v 17 mN/m). These findings indicate that surfactant abnormalities occur in bronchiolitis, and may represent one of the pathophysiological mechanisms causing airway obstruction.

Acute Disease↗
PubMed1999

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.

Acute Disease↗
PubMed1981

Atopy does not predispose to RSV bronchiolitis or postbronchiolitic wheezing.

Twenty-six 8-year-old children who had had respiratory syncytial virus (RSV) bronchiolitis in infancy and their paired controls underwent skin and blood tests to assess the role of immunodeficiency and atopy in the pathogenesis of RSV bronchiolitis and the wheezing that may follow it. There was no difference between patients and controls in prevalence of atopy; positive results of prick tests to common antigens; eosinophil counts; yeast opsonisation defect; C2 deficiency; IgG, IgA, IgM, and IgE concentrations; or IgE antibody to dermatophagoides, timothy-grass pollen, and cat fur. Those of the children who had had RSV bronchiolitis and who continued to wheeze had a slightly higher mean eosinophil count and levels of IgE antibody to dermatophagoides than those who did not wheeze. Exercise-induced bronchial lability, though higher in patients than controls, did not correlate significantly with eosinophil counts or IgE concentrations. The genetic factors predisposing to RSV bronchiolitis and postbronchiolitic wheezing may differ from those predisposing to atopic asthma, though exclusive breast feeding may protect against both.

Bronchiolitis, Viral↗
PubMed2000

Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families.

BACKGROUND: Respiratory syncytial virus (RSV) infects nearly all children by the end of their second winter. Why some develop bronchiolitis is poorly understood; it is not known whether there is a genetic component. The pathological features include neutrophil infiltration and high levels of interleukin 8 (IL-8), a potent neutrophil chemoattractant. METHODS: Common genetic variants of the promoter region of the IL-8 gene were identified by sequencing DNA from 36 healthy individuals. Genetic correlates of IL-8 production were assessed using whole blood from 50 healthy subjects. To investigate genetic correlates of disease severity 117 nuclear families were recruited in which a child had required hospital admission for RSV bronchiolitis. RESULTS: A common single nucleotide polymorphism (allele frequency 0.44) was identified 251 bp upstream of the IL-8 transcription start site. The IL8-251A allele tended to be associated with increased IL-8 production by lipopolysaccharide stimulated whole blood (p=0.07). Using the transmission disequilibrium test, the frequency of this allele was significantly increased in infants with bronchiolitis (transmission = 62% (95% confidence interval (CI) 53 to 71), p=0.014) and particularly in those without known risk factors (transmission = 78% (95% CI 62 to 93), p=0.004). CONCLUSION: Disease severity following RSV infection appears to be determined by a genetic factor close to the IL-8 gene. Further analysis of this effect may elucidate causal processes in the pathogenesis of RSV bronchiolitis.

Alleles↗
PubMed2006

High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTI). Viral LRTI is a risk factor for bacterial superinfection, having an escalating incidence with increasing severity of respiratory illness. A study was undertaken to determine the incidence of pulmonary bacterial co-infection in infants and children with severe RSV bronchiolitis, using paediatric intensive care unit (PICU) admission as a surrogate marker of severity, and to study the impact of the co-infection on morbidity and mortality. METHODS: A prospective microbiological analysis was made of lower airways secretions on all RSV positive bronchiolitis patients on admission to the PICU during three consecutive RSV seasons. RESULTS: One hundred and sixty five children (median age 1.6 months, IQR 0.5-4.6) admitted to the PICU with RSV bronchiolitis were enrolled in the study. Seventy (42.4%) had lower airway secretions positive for bacteria: 36 (21.8%) were co-infected and 34 (20.6%) had low bacterial growth/possible co-infection. All were mechanically ventilated (median 5.0 days, IQR 3.0-7.3). Those with bacterial co-infection required ventilatory support for longer than those with only RSV (p<0.01). White cell count, neutrophil count, and C-reactive protein did not differentiate between the groups. Seventy four children (45%) received antibiotics prior to intubation. Sex, co-morbidity, origin, prior antibiotics, time on preceding antibiotics, admission oxygen, and ventilation index were not predictive of positive bacterial cultures. There were 12 deaths (6.6%), five of which were related to RSV. CONCLUSIONS: Up to 40% of children with severe RSV bronchiolitis requiring admission to the PICU were infected with bacteria in their lower airways and were at increased risk for bacterial pneumonia.

Anti-Bacterial Agents↗
PubMed1997

Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis.

BACKGROUND: Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. METHODS: A randomised double blind trial was conducted in children up to two years of age admitted to hospital with RSV bronchiolitis to compare prednisolone (1 mg/ kg/day orally for seven days) with placebo. Variables used for the efficacy analysis were a daily symptom score and the length of time in hospital in the non-ventilated patients, and the duration of mechanical ventilation and the length of time in hospital in the ventilated patients. RESULTS: Fifty four patients were included in the trial, 40 of whom were non-ventilated (20 in each group) and 14 were ventilated (seven in each group). During the first three days of treatment the symptom score decreased significantly faster in the prednisolone group than in the placebo group (mean (SE) decrease -1.2 (0.2) points/day versus -0.6 (0.2) points/day; mean (95% confidence interval (CI)) for difference = -0.6 (-0.1 to -1.2); p = 0.02). The mean duration of hospital stay of all 40 non-ventilated patients was not significantly different between the two groups. In the ventilated patients the duration of mechanical ventilation was not significantly different, but the length of time in hospital was six days shorter in the prednisolone group than in the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI) difference = 7.0 (1.8 to 10.2) days; p < 0.01). CONCLUSIONS: These results suggest that prednisolone may be effective in accelerating the clinical recovery of children admitted to hospital with RSV bronchiolitis.

Administration, Oral↗
PubMed1997

Obliterative bronchiolitis: individual CT signs of small airways disease and functional correlation.

PURPOSE: Individual features of small airways disease depicted at computed tomography (CT) were correlated with functional indexes in patients with obliterative bronchiolitis. MATERIALS AND METHODS: Fifteen patients (all women) who fulfilled the strict criteria for diagnosis of obliterative bronchiolitis underwent thin-section CT at full inspiration and at end expiration. The CT scans were scored by two observers for extent of decreased attenuation of the lung parenchyma; end-expiration CT signs of air trapping; and bronchial dilation, wall thickening, and mucous plugging. The functional importance of each CT sign was evaluated. RESULTS: Areas of decreased attenuation were present in all patients (median score at end expiration, 61%; range, 21%-83%). Bronchial wall thickening was identified in 13 of the 15 patients. Correlations of the extent of decreased attenuation and measures of air-flow obstruction were strongest between decreased attenuation at end expiration and air flow at low lung volumes (r(s) = -.70, P < .005). This relationship remained intact after correction for the severity of bronchial wall thickening. CONCLUSION: In patients with obliterative bronchiolitis, the extent of decreased attenuation at CT was most strongly related to depression of pulmonary function tests of the small airways. Decreased attenuation is the cardinal sign for further quantitative studies of obliterative bronchiolitis.

Adult↗
PubMed1999

Follicular bronchiolitis: thin-section CT and histologic findings.

PURPOSE: To evaluate the thin-section computed tomographic (CT) findings of follicular bronchiolitis and compare them with the histologic findings. MATERIALS AND METHODS: Thin-section CT scans obtained in 12 patients (age range, 24-77 years; mean age, 47 years) with follicular bronchiolitis proved at open lung biopsy were reviewed by two observers. Underlying conditions included rheumatoid arthritis (n = 8), mixed collagen vascular disorders (n = 2), autoimmune disorder (n = 1), and acquired immunodeficiency syndrome (n = 1). All patients had thin-section CT scans (1.0-1.5-mm collimation, 11 patients; 3.0-mm collimation, one patient; high-spatial-frequency reconstruction algorithm) obtained at 10-mm intervals through the chest. RESULTS: The main CT findings included bilateral centrilobular (n = 12) and peribronchial (n = 5) nodules. All 12 patients had nodules smaller than 3 mm in diameter; six patients also had nodules 3-12 mm in diameter. Areas of ground-glass opacity were present in nine (75%) patients. Histologically, all patients had lymphoid hyperplasia along the bronchioles; eight had peribronchiolar lymphocytic infiltration. CONCLUSION: The cardinal CT feature of follicular bronchiolitis consists of small centrilobular nodules variably associated with peribronchial nodules and areas of ground-glass opacity.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Bronchiolitis obliterans in a case of juvenile rheumatoid arthritis presented with pneumomediastinum.

We present a case of bronchiolitis obliterans associated with juvenile rheumatoid arthritis in whom pneumomediastinum was the presenting manifestation. Diagnosis of bronchiolitis obliterans was made on the basis of the clinical history, pulmonary function tests and high-resolution computerized tomography scan findings. Pneumomediastinum resolved in a few days following high-dose nasal oxygen. This case shows that bronchiolitis obliterans can occur in patients with juvenile rheumatoid arthritis. Complicating pneumomediastinum in such cases should be considered as an indication of underlying bronchiolitis obliterans.

Adult↗
PubMed1996

Seasonal variation in sudden infant death syndrome and bronchiolitis--a common mechanism?

The purpose of this study was to compare epidemiologic features of sudden infant death syndrome (SIDS) and bronchiolitis and to apply statistical examination in order to examine the hypothesis that similar mechanisms could be at work in both conditions. The setting was Scotland from 1982 through 1990. We compared 1,211 deaths from SIDS with 10,058 hospital admissions for bronchiolitis in infancy. The comparisons included age, sex ratio, and seasonality. The sex ratios were similar (SIDS [M:F]:1.61:1; bronchiolitis: 1.63:1), but age distribution was different (chi 2 = 104.6, p < 0.001). When monthly rates throughout the year were compared using correlation of residuals from average season variation and by autocorrelation of residual series, no significant relationships were found between the two conditions (r2 = 0.0004). Once the seasonal pattern common to both conditions was accounted for, SIDS was not autocorrelated between months whereas bronchiolitis exhibited a high level of autocorrelation indicating an epidemic pattern for the latter but not for the former. While a common seasonal variation may indicate some shared etiologic factors associated with winter season, the two conditions do not appear to be closely related. The hypothesis that a common host susceptibility is at work is not supported. Further investigations of seasonal influences are warranted.

Age Distribution↗
PubMed2002

Association of rhinovirus infection with increased disease severity in acute bronchiolitis.

Respiratory syncytial virus (RSV) is the major pathogen responsible for acute bronchiolitis in infancy. However, evaluation of the relative importance of rhinovirus or multiple viral infections has been hampered by the lack of sensitive diagnostic methodologies. Therefore, in this study we used the reverse transcription-polymerase chain reaction for 11 respiratory pathogens to assess the etiology in infants with acute bronchiolitis and correlate it with clinical characteristics of the disease. Viruses were detected in 73.7% of patients. RSV was identified in 72.4% of virologically confirmed cases, rhinovirus in 29%, whereas multiple infections represented 19.5% of cases, most of which (69%) were combinations of rhinovirus with RSV. In a logistic regression model controlling for age, sex, birth weight, presence of fever, and day of disease on admission, the presence of rhinovirus was found to increase by approximately five-fold, the risk for severe disease. Multiple pathogens had a similar trend in the univariate analysis, which was eliminated in the multivariate model. Multiple virus cases were admitted to the hospital later in the course of their disease than unique pathogen cases, suggesting successive infections. In conclusion, rhinovirus is second only to RSV as a causative agent of bronchiolitis and is associated with more severe disease. The presence of more than one pathogen may influence the natural history of acute bronchiolitis.

Analysis of Variance↗