fluticasone and Respiratory-Syncytial-Virus-Infections

A double-blind randomized placebo-controlled trial was conducted to investigate the efficacy of 3 months' inhaled steroids delivered via a spacer device with face mask attachment to infants recovering from bronchiolitis. Forty-eight previously healthy infants recovering from their first documented episode of acute bronchiolitis were randomized to receive 150 microg fluticasone propionate (FP) b.i.d. or placebo delivered via the Babyhaler spacer. Longitudinal assessments were performed on seven occasions over 1 yr based on symptom diaries and health records, clinical examinations, overnight cough recordings and oxygen saturation readings. Lung function was measured 6 months after hospital discharge. Forty-three infants completed the trial (FP 21, placebo 22). There were no significant differences in the three objective end-points measured, recorded night cough, oxygen saturation and lung function test results. Symptom scores were low in both the FP and placebo groups with the absence of (0) or mild (1) symptoms > or =90% of the trial days. No statistical differences in symptom frequency, use of rescue respiratory medications or hospital admissions between treatment groups were found throughout the trial or follow-up periods. In conclusion, the use of inhaled fluticasone propionate in infants recovering from acute bronchiolitis cannot be recommended.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Bronchiolitis, Viral; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Nebulizers and Vaporizers; Respiratory Syncytial Virus Infections; Time Factors

Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors.

Topics: Androstadienes; Anti-Asthmatic Agents; Bacterial Adhesion; Bronchodilator Agents; Cell Line, Tumor; Cromolyn Sodium; Dexamethasone; Epithelial Cells; Fluticasone; Glucocorticoids; Haemophilus Infections; Haemophilus influenzae; Humans; Intercellular Adhesion Molecule-1; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses

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

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.. Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined.. The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal.. Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

Topics: Albuterol; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Respiratory Syncytial Virus Infections; Salmeterol Xinafoate

Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in infants, is an important trigger of asthma exacerbation, and stimulates chemokine production by human respiratory epithelial cells in vitro. We tested the effect of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS-2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque-forming unit/cell, and media were collected at 24 h intervals. Concentrations of IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at varying concentrations on RSV-induced chemokine release was determined. RSV stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h after virus inoculation. Significant but incomplete inhibition of RSV-stimulated increases for both chemokines was found when cultures were treated with FP at > or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no significant effect of FP on release of RSV itself from infected BEAS-2B cells. We conclude that a possible mechanism for the efficacy of inhaled corticosteroids in reducing the frequency or severity of asthma exacerbations is inhibition of virus-induced chemokine production by airway cells.

Topics: Androstadienes; Anti-Inflammatory Agents; Bronchi; Cell Line; Chemokine CCL5; Epithelial Cells; Fluticasone; Humans; Interleukin-8; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human