Human rhinovirus infection during naturally occurring COPD exacerbations.

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.

Dose response of continuous positive airway pressure on nasal symptoms, obstruction and inflammation in vivo and in vitro.

Obstructive sleep apnoea is a common condition associated with cardiovascular risk. Continuous positive airway pressure (CPAP) is an effective treatment but is associated with nasal side-effects, which hinder compliance and may result from inflammation. We investigated whether CPAP was pro-inflammatory to human subjects in vivo, and to cultured bronchial epithelial cells in vitro. In vivo, we further investigated whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms and changes in nasal mucociliary clearance. In vitro, CPAP resulted in cytokine release from cultured BEAS-2B cells in a time- and dose (pressure)-dependent manner. In vivo, CPAP resulted in dose-dependent upregulation of nasal inflammatory markers associated with the development of nasal symptoms, and reduced mucociliary clearance. CPAP also upregulated selected markers of systemic inflammation. CPAP results in dose-dependent release of inflammatory cytokines from human epithelial cells in vitro and in vivo. In vivo responses were associated with systemic inflammation, reductions in nasal mucociliary function and the development of nasal symptoms. This emphasises the need for novel strategies to reduce nasal inflammation and therefore aid compliance.

Intersession repeatability of a novel nasal lavage technique.

This study describes a novel nasal lavage method using a pediatric tracheostomy tube and examines intersession repeatability for several clinically and technically relevant parameters. Fourteen healthy subjects were included in this study. Both nasal cavities were washed using a standard amount of saline solution (7 mL) via a pediatric tracheostomy tube, and the 2 samples were pooled for measurement of cytokine concentrations and cell count. Recovery volume was also recorded. For each subject, measurements were repeated on 5 consecutive days. Intersession repeatability of recovery volume, cell count, and cytokine concentrations interleukin (IL)-6 and IL-8 were expressed in terms of mean coefficient of variation, intraclass correlation coefficient, and interitem correlations. Intraclass correlation coefficients and interitem correlation coefficients indicated almost perfect agreement for cell count and IL-8 concentrations. Recovery volume and IL-6 concentrations were more variable. The mean coefficient of variation was low for cell count (2%), IL-8 concentration (3%), and recovery volume (3%), whereas the mean percentage recovery was high (87%). This newly developed nasal lavage technique is repeatable over successive sessions for cytokine concentrations and cell counts in nasal secretions of healthy subjects. This method might be valuable in the study of inflammatory conditions involving the upper respiratory tract.

Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozone.

BACKGROUND: Ozone is a photochemical oxidant pollutant that is an important public health hazard. Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood. OBJECTIVE: Because the epidermal growth factor receptor (EGFR) is a central regulator of epithelial function, we tested the hypothesis that nasal epithelial cells respond to ozone-induced oxidant stress by modulating expression of the EGFR and its ligands, EGF and transforming growth factor-alpha (TGF-alpha). METHODS: Normal volunteers were exposed to air or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF-alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF-alpha; mediator release was measured by ELISA and cellular EGFR expression by immunoblotting and fluorescence-activated cell sorting analysis. RESULTS: Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P <.05) increased in the nasal biopsy specimens after ozone exposure, and there was a significant positive correlation between EGFR expression and the increase in neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR expression, even though IL-8 release was enhanced. In contrast, exposure to TNF-alpha caused EGFR levels to increase significantly. CONCLUSION: These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha.