We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.

R Re ep pe ea at ta ab bi il li it ty y o of f c ce el ll lu ul la ar r a an nd d s so ol lu ub bl le e m ma ar rk ke er rs s o of f i in nf fl la am mm ma at ti io on n i in n i in nd du uc ce ed d s sp pu ut tu um m f fr ro om m p pa at ti ie en nt ts s w wi it th h a as st th hm ma a ABSTRACT: Sputum induced by inhalation of nebulized hypertonic saline is increasingly used to monitor airways inflammation in asthma. The aim of this study was to assess the repeatability of measuring cellular and soluble markers of inflammation in whole sputum samples as obtained by sputum induction in patients both with mild and moderate-to-severe asthma. Twelve patients with mild, atopic asthma without inhaled steroid treatment and nine patients with moderate-to-severe, atopic asthma treated with inhaled steroids were studied on two separate days at least 2 days apart. Whole sputum samples, induced by inhalation of hypertonic (4.5%) saline, were homogenized, and analysed for differential cell counts and for concentrations of albumin, fibrinogen, inter- leukin-8 (IL-8), and eosinophil cationic protein (ECP). Repeatability was expressed as intraclass correlation coefficient (Ri), and as coefficient of repeatability (CR) in percentage cells or in doubling concentration.Samples from two patients with mild asthma contained more than 80% squamous cells and were excluded from analysis. The repeatability for cell differential counts in both groups combined was: for neutrophils, Ri=0.57 and CR=31.0; for eosinophils, Ri=0.85 and CR=12.4; and for lymphocytes, Ri=0.76 and CR=6.9. The repeatability of the fluid phase measurements was: for albumin, Ri=0.71 and CR=3.2; for fibrinogen, Ri=0.88 and CR=2.8; for IL-8, Ri=0.66 and CR=2.2; and for ECP, Ri=0.82 and CR=1.1.We conclude that the repeatability of cellular and soluble markers of inflammation in induced sputum from patients with mild and moderate-to-severe asthma is satisfactory. Hence, induced sputum, processed by using the whole expectorated sample, seems to be a valuable method to monitor airway inflammation in asthma.

SUMMARYA number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10

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Some patients with severe asthma are difficult to control and suffer from frequent exacerbations, whereas others remain stable with anti-inflammatory therapy. To investigate mechanisms of exacerbations, we compared 13 patients 20 to 51 yr of age (11 female, two male) with difficult-to-control asthma (two or more exacerbations during the previous year) and 15 patients 20 to 47 yr of age (13 female, two male) with severe but stable asthma (no exacerbations) after matching for sex, age, atopy, lung function, airway responsiveness, and medication. Exacerbations were induced by double-blind, controlled tapering of inhaled corticosteroids (fluticasone propionate) at weekly intervals. FEV1, airway responsiveness for methacholine (PC20MCh) and hypertonic saline (HYP slope), eosinophils and soluble markers (ECP, albumin, IL-6, IL-8) in induced sputum were assessed at baseline and during exacerbation (peak flow < 60% of personal best), or after 5 wk if no exacerbation occurred. Steroid tapering caused a decrease (mean +/- SEM) in FEV1 (12.1 +/- 3.1% pred; p = 0.045), PC20MCh (2.1 +/- 0.4 doubling dose; p = 0.004) and HYP slope (1.7 +/- 0.3 doubling dose; p = 0.001), and an increase in sputum eosinophils (10 +/- 3%; p = 0.008) and soluble markers for the two groups combined, without significant differences between the groups. Patients with difficult-to-control asthma had more exacerbations than did the stable asthmatics during both steroid tapering (7 versus 2; p = 0.022) and corticosteroid treatment (6 versus 0; p = 0.003). Exacerbations during steroid treatment in the patients with difficult-to-control asthma were associated with a decrease in FEV1 and PC20MCh, but not in HYP slope or increase in sputum eosinophils. We conclude that tapering of inhaled corticosteroids induces a rapid, reversible flare-up of eosinophilic airway inflammation. Patients with difficult-to-control asthma may develop exacerbations despite treatment with inhaled corticosteroids, which appear to have an eosinophil-independent mechanism. This implies that assessment of the nature of exacerbations may contribute to improved treatment for these patients.