Tobacco Update: Scientific Advances, Clinical PerspectivesCigarette Smoke-Induced Airway Inflammation as Sampled by the Expired Breath Condensate
Section snippets
Tobacco Smoking, Emphysema, and α1-Antitrypsin
Cigarette smoke is most rapidly destructive in that group of smokers who have reduced levels of α1 antitrypsin (α1-AT) in the blood: 30% of female and 18% of male smokers with serum α1-AT below 11 μmol/L were alive at 55 years of age, compared with 98% and 65% of nonsmokers with low α1-AT. The excess deaths were primarily caused by a striking emphysema that develops in the smokers (and only to a much smaller extent in nonsmokers) with low α1-AT, a condition that exists at a prevalence of 1 in
The Components of Tobacco Smoke That Cause Disease
We have seen that smoking can be devastating in to a particular group of smokers—those with aberrant α1-AT—and that the root cause is not only the free radicals present in cigarette smoke but also the ability of that smoke to recruit and activate leukocytes in the airways. The task of identifying how smoke causes airway inflammation is not identifying the causative agent, but ranking the likely candidates among the 3000 to 4000 identified chemicals that comprise cigarette smoke. Inorganic heavy
The Path to Tissue Injury
As cigarette smoke enters the lungs, particulate matter is trapped in the larger airways by the mucociliary escalator, which is well designed to clear the lung of foreign matter. The gas components of the smoke will continue on to the smaller airways and the alveoli, depending on their solubility. First to be exposed to the smoke are the epithelial cells lining the airways, cells that have the capacity to respond to insults with a wide variety of biologically active compounds. Some of the
Breath Condensate As a Sample of the Airway Surface Liquid
Water vapor in the airways is ordinarily thought to be simply the consequence of ambient air becoming saturated during inspiration, and so tending toward an equilibrium partial pressure, as do all the other molecules that have a finite vapor pressure, such as carbon dioxide, nitric oxide, and ammonia. At expiration, if the ambient air or impinging surface is cold enough, water molecules condense into the liquid phase, bringing with them the other components of the expired air in proportion to
Reactive Oxygen Species in Breath Condensate of Smokers
Cigarette smoke itself is highly reactive, containing large amounts of short-lived free radicals (including nitric oxide) as well as chemicals (such as quinones) that can react to form free radicals.21 As expected, short-term exposure to cigarette smoke directly reduces airway glutathione, the lung’s naturally occurring antioxidant. Consequently, the airways become more vulnerable to additional sources of oxidative stress, such as activated neutrophils. With time, smokers do adapt to these
Breath Condensate as a Research Tool
Breath condensate would seem to be a useful tool, allowing us to sample the airways in a noninvasive manner, because a subject need only breathe into a low resistance chilled circuit for 10 minutes to produce 1 or 2 milliliters of fluid. However, we do not understand how large molecules that have negligible vapor pressure can even be present in expired gas,33 let alone where they come from or the meaning of the observed concentrations. These 3 unsolved problems stand in the way of the general
Hypothesis: Breath Condensate Chemistry Arises from Bifurcations in the Distal Conducting Airways
I propose that the breath concentrate chemistry is a consequence of a long-standing paradox in the fluid economy of the lung, namely that airway surface liquid (ASL), which covers the airway surface, remains thin throughout the conducting airways, even though it continuously moves into a rapidly converging network of airways on its way out of the lung.35., 36.
ASL is composed of a periciliary fluid layer the height of the cilium capped by a viscoelastic mucous gel.37 The height of the
Summary
Questions about airway physiology and pathology are limited when only highly invasive techniques, such as bronchoscopy, bronchoalveolar lavage, and the study of tissue explants exist. These findings illustrate that it is now possible to do population studies and time-control studies to approach the signaling mechanisms that cause the inflammation associated with tobacco smoke and thus to better understand the subsequent pathophysiology of airway inflammation.
Acknowledgements
I thank Drs. Malcolm King and Jonathan Widdicombe for valuable discussions and their critical reading of an earlier version of the manuscript.
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This work was supported by ACT (A Comprehensive Tobacco Program) and the Mississippi chapter of the American Lung Association.