Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second -6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEVI values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P < 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness.

To test the hypothesis that rhinovirus (RV)-induced immune responses influence the outcome of RV infections, we inoculated 22 subjects with allergic rhinitis or asthma with RV16. Nasal secretions and induced sputum were repeatedly sampled over the next 14 d. RV16 infection increased nasal granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-8, which was accompanied by neutrophilia in blood and nasal secretions. Nasal G-CSF correlated closely with increased blood neutrophils (r(s) = 0.69, p < 0.005), whereas nasal neutrophils correlated with both G-CSF (r(s) = 0.87, p < 0.001) and IL-8 (r(s) = 0.75, p < 0.001). Although similar relationships were present in sputum, changes in sputum neutrophils and G-CSF with RV16 infection were relatively modest. In addition, virus-induced changes in the sputum interferon-gamma-to-IL-5 messenger RNA ratio were inversely related to both peak cold symptoms (r(s) = -0.60, p < 0.005) and the time to viral clearance (undetectable picornavirus RNA). These results indicate that airway IL-8 and G-CSF are closely associated with virus-induced neutrophilic inflammation during an experimental RV infection in atopic volunteers. In addition, the balance of airway T-helper cell type 1 (Th1)- and Th2-like cytokines induced by RV infection may help determine the clinical outcome of common cold infections, raising the possibility that the individual subject's immune response, rather than atopic status per se, is important in this regard.

A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above ∼44°N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health. aerobiology | allergies | global warming

Background Detection of either viral or bacterial pathogens is associated with wheezing in children, however the influence of both bacteria and virus on illness symptoms has not been described. Objective We evaluated bacterial detection during peak RV season in children with and without asthma to determine if an association exists between bacterial infection and the severity of RV illnesses. Methods 308 children (166 with asthma, 142 without asthma) ages 4–12 years provided five consecutive weekly nasal samples during September, and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were performed on all nasal samples. Results Detection rates were 53%, 17% and 11% for H. influenzae, S. pneumoniae and M. catarrhalis, respectively, with detection of RV increasing the risk of detecting bacteria within the same sample (OR 2.0, 95% CI 1.4–2.7, p<0.0001) or the following week (OR 1.6 (1.1–2.4), p=0.02). In the absence of RV, S. pneumoniae was associated with increased cold symptoms (mean 2.7 (95% CI 2.0–3.5) vs. 1.8 (1.5–2.2), p=0.006) and moderate asthma exacerbations (18% (12%–27%) vs. 9.2% (6.7%–12%), p=0.006). In the presence of RV, S. pneumoniae was associated with increased moderate asthma exacerbations (22% (16%–29%) vs. 15% (11%–20%), p=0.01). Furthermore, M. catarrhalis detected alongside RV increased the likelihood of experiencing cold and/or asthma symptoms compared to isolated detection of RV (OR 2.0 (1.0–4.1), p=0.04). Regardless of RV status, H. influenzae was not associated with respiratory symptoms. Conclusion RV infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M. catarrhalis and S. pneumoniae contribute to the severity of respiratory illnesses, including exacerbations of asthma.

IL-5 is a key cytokine for eosinophil maturation, recruitment, activation, and possibly the development of inflammation in asthma. High concentrations of IL-5 are present in the airway after Ag challenge, but the responsiveness of airway eosinophils to IL-5 is not well characterized. The objectives of this study were to establish, following airway Ag challenge: 1) the expression of membrane (m)IL-5Rα on bronchoalveolar lavage (BAL) eosinophils; 2) the responsiveness of these cells to exogenous IL-5; and 3) the presence of soluble (s)IL-5Rα in BAL fluid. To accomplish these goals, blood and BAL eosinophils were obtained from atopic subjects 48 h after segmental bronchoprovocation with Ag. There was a striking reduction in mIL-5Rα on airway eosinophils compared with circulating cells. Furthermore, sIL-5Rα concentrations were elevated in BAL fluid, but steady state levels of sIL-5Rα mRNA were not increased in BAL compared with blood eosinophils. Finally, BAL eosinophils were refractory to IL-5 for ex vivo degranulation, suggesting that the reduction in mIL-5Rα on BAL eosinophils may regulate IL-5-mediated eosinophil functions. Together, the loss of mIL-5Rα, the presence of sIL-5Rα, and the blunted functional response (degranulation) of eosinophils to IL-5 suggest that when eosinophils are recruited to the airway, regulation of their functions becomes IL-5 independent. These observations provide a potential explanation for the inability of anti-IL-5 therapy to suppress airway hyperresponsiveness to inhaled Ag, despite a reduction in eosinophil recruitment.