Rhinovirus-induced airway inflammation in asthma: effect of treatment with inhaled corticosteroids before and during experimental infection.

Asthma exacerbations are frequently linked to rhinovirus infections. However, the associated inflammatory pathways are poorly understood, and treatment of exacerbations is often unsatisfactory. In the present study we investigated whether antiinflammatory treatment with inhaled corticosteroids prevents any rhinovirus-induced worsening of lower airway inflammation. To that end, we selected 25 atopic patients with mild asthma who underwent experimental rhinovirus 16 (RV16) infection, while receiving double-blind, placebo-controlled treatment with the inhaled corticosteroid budesonide (800 microg twice a day) throughout the study period, starting 2 wk before infection. We assessed inflammatory cell numbers in the bronchial mucosa as obtained by bronchial biopsies 2 d before and 6 d after RV16 infection, and analyzed those in relation to cold symptoms, changes in blood leukocyte counts, airway obstruction, and airway hyperresponsiveness. RV16 colds induced an increase in CD3(+) cells in the lamina propria (p = 0.03) and tended to decrease the numbers of epithelial eosinophils (p = 0.06) in both groups analyzed as a whole. The T cell accumulation was positively associated with cold symptoms. Budesonide pretreatment improved airway hyperresponsiveness (p = 0.02) and eosinophilic airways inflammation (p = 0.04). Yet it did not significantly affect the RV16-associated changes in the numbers of any of the inflammatory cell types. We conclude that RV16 infection by itself induces only subtle worsening of airway inflammation in asthma, which is not improved (or worsened) by inhaled corticosteroids. The latter finding is in keeping with the limited protection of inhaled corticosteroids against acute asthma exacerbations.

Experimental rhinovirus 16 infection increases intercellular adhesion molecule-1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment.

BACKGROUND: Rhinovirus infections in airway epithelial cells in vitro have been shown to upregulate intercellular adhesion molecule-1 (ICAM-1) expression. Epithelial ICAM-1, in its dual role as the major rhinovirus receptor and as adhesion molecule for inflammatory cells may be involved in the pathogenesis of rhinovirus-induced exacerbations of asthma. OBJECTIVE: We aimed to investigate the effect of experimental rhinovirus 16 (RV16) infection on ICAM-1 expression in bronchial mucosal biopsies in asthma. In addition, the effect of 2 weeks pretreatment with inhaled budesonide (800 microg b.d.) on RV16-associated changes in ICAM-1 expression was studied. METHODS: The study had a parallel, placebo-controlled design in 25 steroid-naive nonsmoking atopic asthmatic subjects. After 2 weeks budesonide (BUD) or placebo (PLAC) pretreatment bronchoscopy was performed 2 days before (day -2) and 6 days after (day 6) RV16 inoculation (on days 0 and 1). Immunohistochemical staining for ICAM-1 was performed on snap-frozen bronchial biopsies. ICAM-1 staining intensity on the basal epithelial cells was scored semiquantitatively from 1 (weak) to 3 (intense). Similarly, epithelial intactness was noted (1 = basal cells only, 2 = basal and parabasal cells, 3 = intact epithelium). RESULTS: ICAM-1 scores were not significantly different between the groups at day -2 (P > or = 0.08). Subsequent RV16 infection was associated with a trend towards an increase in ICAM-1 expression in the BUD-group (P = 0.07), whereas the increase was significant in the PLAC-group (P = 0.03). However, the increase was not significantly different between the groups (P = 0.74). Epithelial intactness score was not different between the groups before RV16 infection (P > or = 0.07), and no significant changes were observed in either group (P > or = 0.59). Moreover, ICAM-1 score did not correlate significantly with epithelium score in either group, at any time-point (P > or = 0.27). CONCLUSION: We conclude that an RV16 common cold in atopic asthmatic subjects is associated with increased ICAM-1 expression in the bronchial epithelium, which is not related to epithelial intactness. Glucocorticoid treatment does not appear to prevent the RV16-associated increased ICAM-1 expression. This suggests that other treatment modalities are required to protect against the spreading of infection during rhinovirus-induced exacerbations in asthma.

Success and safety of sputum induction in the clinical setting.

It has previously been reported that sputum induction is successful and safe in the clinical research setting. The authors examined the success and safety of sputum induction in routine clinical practice in patients with asthma or chronic airflow limitation of varying severity. Records of 304 patients with asthma and 25 with smoking related chronic airflow limitation were examined retrospectively. All had sputum induced as part of their routine clinical evaluation. When the baseline post salbutamol forced expiratory volume in one second (FEV1) was > or =70% predicted, the inductions consisted of inhalation of an aerosol of 3%, 4% and 5% saline, each given for 7 min. If the FEV1 was <70%, or there were other reasons for concern, the inductions were initiated with normal saline for shorter periods. Inhalations were discontinued when sputum was obtained or when there was a fall in FEV1 > or =20%. Success was identified by obtaining nonsquamous total and differential cell counts containing macrophages, and safety by the fall in FEV1. The overall success was 93%. The procedure was safe even amongst patients with an FEV1 of <60% and <1 L. Of 77 patients with an FEV1 between 40-59%, 8% fell by > or =20% and of 35 patients with an FEV1 <40%, 6% fell by 20%. Carefully standardized sputum induction can be successful and safe in patients with asthma or chronic airflow limitation in clinical practice, even when moderate or severe airflow limitation is present.

Diagnosis of left-ventricular dysfunction from induced sputum examination.

We have shown that the examination of induced sputum for haemosiderin-laden macrophages is sensitive and specific for detecting raised left-sided filling pressures associated with left-ventricular dysfunction.