title: Effect of inhaled endotoxin on mucociliary clearance and airway inflammation in mild smokers and nonsmokers.
abstract: BACKGROUND
  In healthy nonsmokers, inhaled endotoxin [lipopolysaccharide (LPS)] challenge induces airway neutrophilia and modifies innate immune responses, but the effect on mucociliary clearance (MCC), a key host defense response, is unknown. Although smokers are chronically exposed to LPS through inhaled tobacco smoke, the acute effect of inhaled LPS on both MCC and airway inflammation is also unknown. The purpose of this study was to determine the effect of inhaled LPS on MCC in nonsmokers and mild smokers with normal pulmonary function.
  
  
  METHODS
  We performed an open-label inhalational challenge with 20,000 endotoxin units in healthy adult nonsmokers (n=18) and young adult, mild smokers (n=12). At 4 hr post LPS challenge, we measured MCC over a period of 2 hr, followed by sputum induction to assess markers of airway inflammation.
  
  
  RESULTS
  No significant changes in spirometry occurred in either group following LPS challenge. Following LPS, MCC was significantly (p<0.05) slowed in nonsmokers, but not in smokers [MCC=10±9% (challenge) vs. 15±8% (baseline), MCC=14±9% (challenge) vs. 16±10% (baseline), respectively]. Both groups showed a significant (p<0.05) increase in sputum neutrophils 6 hr post LPS challenge versus baseline. Although there was no correlation between the increased neutrophilia and depressed MCC post LPS in the nonsmokers, baseline neutrophil concentration predicted the LPS-induced decrease in MCC in the nonsmokers, i.e., lower baseline neutrophil concentration was associated with greater depression in MCC with LPS challenge (p<0.05).
  
  
  CONCLUSIONS
  These data show that a mild exposure to endotoxin acutely slows MCC in healthy nonsmokers. MCC in mild smokers is unaffected by mild endotoxin challenge, likely due to preexisting effects of cigarette smoke on their airway epithelium.
authors.affiliation: 1 Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina (UNC) at Chapel Hill , NC.
authors.forename: William D
authors.initials: WD
authors.lastname: Bennett
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.forename: Martha
authors.initials: M
authors.lastname: Almond
authors.forename: Margaret
authors.initials: M
authors.lastname: Herbst
authors.forename: Kirby L
authors.initials: KL
authors.lastname: Zeman
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D004731:Endotoxins / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009657:North Carolina; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects*; D013147:Spirometry; D013997:Time Factors; D055815:Young Adult
chemical_list: D004731:Endotoxins
keywords: airway inflammation; endotoxin; lipopolysaccharide; mucociliary clearance