Expiratory flow limitation (EFL) during tidal breathing is a major determinant of dynamic hyperinflation and exercise limitation in chronic obstructive pulmonary disease (COPD). Current methods of detecting this are either invasive or unsuited to following changes breath-by-breath. It was hypothesised that tidal flow limitation would substantially reduce the total respiratory system reactance (X_rs) during expiration, and that this reduction could be used to reliably detect if EFL was present.To test this, 5‐Hz forced oscillations were applied at the mouth in seven healthy subjects and 15 COPD patients (mean±sd forced expiratory volume in one second was 36.8±11.5 % predicted) during quiet breathing. COPD breaths were analysed (n=206) and classified as flow-limited if flow decreased as alveolar pressure increased, indeterminate if flow decreased at constant alveolar pressure, or nonflow-limited.Of these, 85 breaths were flow-limited, 80 were not and 41 were indeterminate. Among other indices, mean inspiratory minus mean expiratory X_rs(ΔX_rs) and minimum expiratory X_rs(X_exp,min) identified flow-limited breaths with 100% specificity and sensitivity using a threshold between 2.53–3.12 cmH₂O·s·L⁻¹(ΔX_rs) and −7.38– −6.76 cmH₂O·s·L⁻¹(X_exp,min) representing 6.0% and 3.9% of the total range of values respectively. No flow-limited breaths were seen in the normal subjects by either method.Within-breath respiratory system reactance provides an accurate, reliable and noninvasive technique to detect expiratory flow limitation in patients with chronic obstructive pulmonary disease.

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a "multilevel cycle" responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of "multilevel cycle" helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.