Mechanisms of chronic airway obstruction in smokers

Abstract

Studies over the past few decades have showed a clear association between cigarette smoking and the development of chronic airway obstruction. Yet, only a minority of smokers is affected so that in many, even heavy, smokers, pulmonary function remains within normal limits. While carcinogens have been well characterized, there is only limited information about the constituents of cigarette smoke responsible for inducing chronic airway obstruction. In addition, the associated risks factors for airway obstruction in smokers have not been totally identified. The present paper is a review of the recently accumulated facts concerning the intimate action of cigarette smoke at the level of large and small airways and lung parenchyma. The role of classical inflammatory cells such as neutrophils and alveolar macrophages is reviewed, but emphasis is put on recent evidence indicating the involvement of CD8 + T-lymphocytes and possibly eosinophils in the genesis of the structural changes leading to airways obstruction. The mechanisms by which airway inflammation and remodelling cause airway narrowing and airflow limitation are discussed, along with the associated loss of lung elasticity secondary to destructive emphysema. Other biological, epidemiological, physiopathological, and clinical aspects are analyzed, stressing such fundamental aspects as the defence mechanisms, the morpho-functional correlations, the identification of susceptible smokers, and the early detection of airway obstruction, both in specialized laboratories and in primary care.

Chronic obstructive pulmonary disease: current burden and future projections

“…Many Bayesian studies use 70% or 80% credible intervals (which are lower than the 95% confidence interval levels used in frequentist analyses in recognition that certain prior knowledge about the data, as well as statistical uncertainty, are reflected in the results) and the 90% bounds presented here may be more stringent than required for planning purposes [65]. disease development have not been definitively characterised [66]. Repeating the analyses presented here using annual tobacco consumption by sex lagged 20 or 40 yrs, as the period effect did not improve predictions and resulted in an unrealistic widening of credible intervals, particularly in females [67].…”

Distal Airways in Mice Exposed to Cigarette Smoke

“…The correlation of small airway narrowing, whether it be from infiltrating inflammatory cells, airway remodeling, or untethering of alveolar attachments, and physiologic impairments suggests a direct contribution of the small airways to the functional deterioration seen in COPD (45,46). Studies have detected increased levels of oxidant markers in biological samples from patients with COPD, and oxidative stress has been associated with airway narrowing (47,48).…”

MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production

“…IT HAS BEEN GENERALLY ACCEPTED that cigarette smoking is clearly associated with the development of chronic airway obstruction (5,6,20,37) and is responsible for 80 -90% of cases of chronic obstructive pulmonary disease (COPD) in the United States (34). However, only 15-20% of heavy smokers develop clinically significant airflow obstruction, so, even in many heavy smokers, pulmonary function remains within normal limits.…”