Statistical analyses Unless otherwise noted, all data are presented as means �� se for n experiments. Differences between means were tested for statistical significance using paired or unpaired selleckchem t tests when the variances were homogeneously distributed, or the case of nonhomogeneity of variance, the Wilcoxon rank-sum or Mann-Whitney U tests were used as appropriate. From such comparisons, differences yielding values of P �� 0.05 were judged to be significant. HBECs derived from ��3 donors were used per experiment, and experiments using cell lines were repeated on 3 separate occasions. All analyses were conducted using Instat software (GraphPad, San Diego, CA, USA). RESULTS Mucus dehydration and altered ion transport in chronic smokers Mucin hypersecretion frequently occurs with chronic CS exposure and chronic inflammation (30).

However, little is known about the hydration state of mucus following chronic smoke exposure. Accordingly, mucus samples were collected from 2- to 3-mm-diameter airways from smokers’ lungs that were harvested at the time of surgery, and wet-dry ratios were obtained immediately after extraction of mucus from the lungs. From these samples, percentage solids values of 10.0 �� 0.7% were measured (n=8 donors; see Table 1). Mucus was also sampled from the trachea of these lungs, and this was similarly dehydrated (11.3��0.5%; n=8 donors). Mucus plugging was not observed in the lungs of nonsmokers. However, during postsurgery transplantation of these lungs to our research center, the proximal end of the trachea was sealed, and because of normal mucociliary transport, mucus accumulated at this site.

Direct sampling revealed that this mucus was significantly less dehydrated than that from smokers (4.6��1.0%; n=5 donors; P = 0.003). Table 1. Subject demographics for smokers vs. control participants Adequate mucus hydration requires regulated ion transport activity, including sufficient CFTR function. However, little is known about ion transport rates in chronic smokers. Cantin et al. (5) recently reported that chronic smokers display abnormal ion transport characteristics that mimic aspects of CF airways. In particular, the researchers reported that chronic smokers lacked CFTR-dependent Cl? transport. In agreement with these studies, we found that the low Cl?/isoproterenol (ISO) transepithelial NPD response, which corresponds to activation of CFTR, was significantly Drug_discovery decreased in the nasal epithelia of chronic smokers compared to nonsmoking controls (Fig. 1A). Figure 1. In vivo assessments of whole CS action on CFTR function. A) In vivo NPD measured in nonsmoking control subjects (open bars; n=8) and chronic smokers (solid bars; n=4). Bar graphs show basal NPD and the responses to cumulative mucosal superfusion with …