pulmicort and Respiratory-Syncytial-Virus-Infections

To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis.. A multicentre randomised double blind placebo controlled trial.. Infants admitted to hospital with their first episode of RSV positive bronchiolitis.. 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.. 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.. 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).. There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Topics: Acute Disease; Administration, Topical; Anti-Inflammatory Agents; Bronchiolitis, Viral; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Follow-Up Studies; Glucocorticoids; Hospitalization; Humans; Infant; Male; Nebulizers and Vaporizers; Respiratory Syncytial Virus Infections

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper-reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 microg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 microg twice per day for two months. Follow-up consisted of out-patient check-ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchiolitis; Bronchodilator Agents; Budesonide; Disease Management; Female; Humans; Infant; Infant, Newborn; Male; Outcome Assessment, Health Care; Respiratory Syncytial Virus Infections

Topics: Acute Disease; Administration, Topical; Anti-Inflammatory Agents; Bronchiolitis, Viral; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Glucocorticoids; Hospitalization; Humans; Infant; Male; Nebulizers and Vaporizers; Respiratory Syncytial Virus Infections

To evaluate the influence of early antiinflammatory therapy in the development of asthma 3 years after hospitalization for wheezing in infancy. In addition, the effects of allergic sensitization and respiratory syncytial virus (RSV) infection on the development of asthma were investigated.. A randomized, controlled follow-up study in a university hospital that provides primary hospital care for all pediatric patients in a defined area.. Eighty-nine infants under 2 years of age who had been hospitalized for infection associated with wheezing and followed up for 3 years.. Early antiinflammatory therapy was given for 16 weeks; 29 patients received cromolyn sodium and 31 received budesonide. Twenty-nine control patients received no therapy.. Clinical diagnosis of current asthma, defined as having at least 3 episodes of physician-diagnosed wheezing and either a wheezing episode during the preceding year or ongoing antiinflammatory medication for asthma.. Fourteen (48%) patients in the former cromolyn group, 15 (48%) in the former budesonide group, and 16 (55%) in the control group had current asthma. The significant predictors of asthma were age over 12 months (risk ratio [RR] 4.1; 95% confidence interval [CI] = 1.59-10.35), history of wheezing (RR 6.8; CI = 1.35-34.43), and atopic dermatitis on study entry (RR 3.4; CI = 1.17-9.39). Skin prick test positivity at the age of 16 months significantly predicted asthma (RR 9.5; CI = 2.45-36.72). In addition, all of the 18 (20%) children sensitized with furred pet developed asthma. RSV identification (RR 0.3; CI = 0.08-0.80) and early furred pet contact at home (RR 0.3; CI 0.10-0.79) were associated with the decreased occurrence of asthma.. Antiinflammatory therapy for 4 months has no influence on the occurrence of asthma 3 years after wheezing in infancy. Early sensitization to indoor allergens, especially to pets, and atopic dermatitis predict subsequent development of asthma. RSV infection in wheezing infants may have a better outcome than other infections.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Comorbidity; Cromolyn Sodium; Dermatitis, Atopic; Disease Progression; Female; Finland; Follow-Up Studies; Food Hypersensitivity; Hospitalization; Humans; Infant; Male; Prospective Studies; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Risk Factors

Respiratory syncytial virus (RSV) results in acute wheezing in infants and is frequently associated with recurrent wheezing. Although RSV-induced wheezing clinically resembles that of asthma, corticosteroids are not equivalently effective in RSV-associated wheezing. The study sought to determine the mechanisms of RSV-induced wheezing by establishing an in vitro model of RSV-infected human bronchial epithelial cells (16-HBEC).. Leukotriene C4 synthase (LTC4 S) messenger RNA (mRNA) expression in 16-HBEC was detected using fluorescence quantitative polymerase chain reaction, and the relative level of LTC4 S mRNA was expressed as quotient cycle threshold (qCt) based on the threshold cycle number value compared with that of β-actin. Cysteinyl leukotrienes (CysLT) in culture supernatant were measured by enzyme-linked immunosorbent assay. RSV-infected 16-HBEC was incubated with gradient concentration of budesonide (BUD) to assess its effects on LTC4 S expression and CysLT secretion.. RSV infection resulted in increased LTC4 S mRNA expression between 48 and 96 h post-infection. High level of CysLT was detected in the supernatant of RSV-infected 16-HBEC. BUD at concentrations of 10(-10) to 10(-5) mol/L did not significantly alter LTC4 S mRNA expression.. RSV infection upregulated LTC4 S expression in HBEC leading to increased CysLT secretion. Such induction was not attenuated by BUD, suggesting that CysLT might contribute to the pathogenesis of RSV-induced wheezing.

Topics: Anti-Inflammatory Agents; Asthma; Bronchi; Budesonide; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Epithelial Cells; Glutathione Transferase; Humans; In Vitro Techniques; Receptors, Leukotriene; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; RNA, Messenger; Time Factors

Airway viral infections provoke exacerbations of asthma and chronic obstructive pulmonary disease. B7-H1 is a costimulatory molecule that is implicated in an escape mechanism of viruses from host immune systems. This escape may be associated with the persistence of viral infection and lead to exacerbation of underlying diseases. We have shown that an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1 on airway epithelial cells, an effect which was corticosteroid-resistant. We investigated the effects of corticosteroids plus long-acting β(2)-agonists (LABAs; fluticasone/salmeterol or budesonide/formoterol) on the expression of B7-H1.. BEAS-2B cells and primary airway epithelial cells were stimulated with poly IC or respiratory syncytial virus. The expression of B7-H1 was assessed by flow cytometry.. Poly IC upregulated the expression of B7-H1, which was suppressed by high-concentration corticosteroids but not by LABAs. The upregulation was suppressed by very low-concentration corticosteroids when used in combination with LABAs. Their combination also suppressed the virus-induced upregulation of B7-H1. Poly IC stimulation induced the nuclear translocation of nuclear factor ĸB (NF-ĸB). Inhibitors of NF-ĸB activation prevented the poly IC-induced upregulation of B7-H1. Low-concentration corticosteroids in combination with LABAs enhanced the de novo induction of IĸBα, the endogenous inhibitor of NF-ĸB activation.. Fluticasone/salmeterol or budesonide/formoterol attenuate the virus-associated upregulation of B7-H1 on airway epithelial cells via suppression of NF-ĸB activation.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; B7-H1 Antigen; Budesonide; Cell Line; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; I-kappa B Proteins; NF-kappa B; NF-KappaB Inhibitor alpha; Poly I-C; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Up-Regulation

Neurotrophic factors and receptors are upregulated in the respiratory tract of humans and rodents infected by the respiratory syncytial virus, leading to airway inflammation and hyperreactivity. The contribution of neurotrophic pathways to the recruitment of immuno-inflammatory cells and their response to anti-inflammatory therapy remains unclear. We sought to determine whether selective nerve growth factor inhibition prevents the immuno-inflammatory response against infection, and explored the effect of inhaled corticosteroids on virus-induced neurotrophic upregulation and the consequent recruitment of immuno-inflammatory cells into the airways. We tried to inhibit the recruitment of lymphocytes and monocytes into the airways of infected weanling rats using immunologic inhibition of nerve growth factor with a specific blocking antibody, or chemical inhibition of receptor tyrosine kinase with K252a. The anti-inflammatory activity of inhaled corticosteroids was studied in infected rats treated with budesonide, fluticasone, or vehicle. Immunological or chemical inhibition of nerve growth factor or its high-affinity receptor tyrosine kinase pathway inhibited the recruitment of inflammatory cells triggered by nociceptive irritation of infected rat airways, thereby reducing local and systemic immuno-inflammatory responses against the virus. Neurotrophic upregulation in infected airways was not affected by inhaled corticosteroids. As a logical consequence, these commonly used drugs were also unable to stop the recruitment of immune and inflammatory effector cells into infected airways. Overexpression of neurotrophic factors and receptors in airways infected by respiratory syncytial virus is critical for the development of airway inflammation and hyperreactivity, which is resistant to the anti-inflammatory effect of inhaled corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Animals; Body Weight; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Budesonide; Carbazoles; Drug Resistance; Enzyme Inhibitors; Female; Fluticasone; Indole Alkaloids; Male; Nerve Growth Factors; Pneumonia; Rats; Rats, Inbred F344; Receptor Protein-Tyrosine Kinases; Respiratory Syncytial Virus Infections; Steroids; Up-Regulation

Topics: Administration, Inhalation; Asthma; Bronchiolitis; Bronchodilator Agents; Budesonide; Humans; Infant; Respiratory Sounds; Respiratory Syncytial Virus Infections

The aim of the study was to assess the effect of inhaled corticosteroids on subsequent respiratory symptoms and asthma in infants hospitalized for respiratory syncytial virus infection (RSV). The study included 188 children below 12 mo of age, hospitalized because of RSV infection. During the winter of 1994/95 only selected children (13%) were given inhaled corticosteroids following discharge from the hospital. The following winter (1995/96), almost all children (86%) were given this treatment for 6-8 wk. Outcomes of the two different treatment regimens were compared by questionnaire 19-24 mo after discharge. Children hospitalized and treated during the winter of 1995/96 developed asthma (12% vs. 24%) and other severe symptoms of the respiratory tract less often than infants treated the year before. The frequency of children with less severe symptoms did not differ between the two treatment periods.. The results indicate that inhalation of corticosteroids for 6-8 wk may reduce subsequent asthma and severe respiratory morbidity in infants hospitalized for RSV infection.

Topics: Administration, Inhalation; Asthma; Budesonide; Female; Glucocorticoids; Humans; Infant; Male; Morbidity; Nebulizers and Vaporizers; Patient Discharge; Respiratory Syncytial Virus Infections; Treatment Outcome