title: A systematic review of nicotine by inhalation: is there a role for the inhaled route?
abstract: BACKGROUND
  A considerable minority of adults remain addicted to smoking cigarettes despite substantial education and public health efforts. Nicotine replacement therapies have only modest long-term quit rates. The pulmonary route of nicotine delivery has advantages over other routes. However, there are regulatory and technical barriers to the development of pulmonary nicotine delivery devices, and hence, none are commercially available. Current knowledge about pulmonary nicotine delivery is scattered throughout the literature and other sources such as patent applications. This review draws together what is currently known about pulmonary nicotine delivery and identifies potential ways that deep lung delivery can be achieved with a simple portable device.
  
  
  OBJECTIVE
  To systematically review clinical trials of nicotine inhalers, determine whether they delivered nicotine via the lung, and identify ways that pulmonary delivery of medicinal nicotine might be achieved and the technical issues involved.
  
  
  METHODS
  Systematic search of Medline and Embase.
  
  
  RESULTS
  Thirty-eight trials met the inclusion criteria. Cough, reflex interruption of smooth inspiration, and throat scratch limited the usefulness of nicotine inhalers. The pharmacokinetic profiles of portable nicotine inhalers were inferior to smoking, but among commercially available products, electronic cigarettes are currently the most promising.
  
  
  CONCLUSIONS
  Pulmonary nicotine delivery might be maximized by use of nicotine salts, which have a more physiological pH than pure nicotine, by ensuring the mass of the particles is optimal for alveolar absorption, and by adding flavoring agents. Metered-dose inhalers potentially can deliver nicotine more efficiently than other nicotine products, facilitating smoking cessation and improving smokers' lives.
authors.affiliation: Department of Medicine, University of Otago, 23a Mein Street, Newtown, Wellington 6021, New Zealand. brent.caldwell@otago.ac.nz
authors.forename: Brent
authors.initials: B
authors.lastname: Caldwell
authors.forename: Walt
authors.initials: W
authors.lastname: Sumner
authors.forename: Julian
authors.initials: J
authors.lastname: Crane
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D005260:Female; D006801:Humans; D008168:Lung; D008297:Male; D036501:Metered Dose Inhalers; D009538:Nicotine / Q000008:administration & dosage*; D012907:Smoking / Q000628:therapy*; D016540:Smoking Cessation / Q000379:methods*; D062789:Tobacco Products
chemical_list: D009538:Nicotine