Weak link in the lung

Abstract

The transition from peripheral airway disease to COPD is characterized by three sequential stages: stage I, during which the closing volume (CV) eventually exceeds the FRC; stage II, during which tidal expiratory flow limitation (EFL) is eventually exhibited; and stage III, during which dynamic hyperinflation (DH) progressively increases leading to dyspnoea and exercise limitation. Smoking is a condition which accelerates the age-related impairment of lung function. Indeed, McCarthy et al.1 who studied 35 smokers with FEV and FEV/FVC within normal limits, found that in almost all instances CV was higher than predicted normal both sitting and supine. More importantly, while in all 66 control non-smokers whose age was less than 65 years the FRC exceeded the CV in the sitting position, this was not the case in eight of the 35 smokers. In the supine position, the age-corrected prevalence of peripheral airway closure during tidal breathing was even higher in the smokers. Thus, during stage I the extent of peripheral airway closure increases progressively in smokers until tidal EFL is present not only supine but also sitting. Tidal FL implies sequential closure of the peripheral airways during expiration and reopening during inspiration, with concurrent risk of peripheral airway injury, which is characterized by denuded epithelium in the respiratory and membranous bronchioles. Furthermore, there is rupture of the airway-alveolar attachments.2–4 Thus, the peripheral airways represent a weak link in the lung because airway closure in the tidal volume range is a common phenomenon reflecting either a decreased FRC (e.g. obesity, left heart failure) or an increased CV (e.g. smoking, asthma). The smoking-related increase of CV accelerates the age-related decrease of maximal flow (Vmax) at low lung volume.5 Indeed, such a pattern is exhibited by all COPD patients and is due to the combined effect of age and smoke on gas trapping. As a result of gas trapping the RV increases. Peripheral airway closure is usually found in the dependent lung zones where the transpulmonary pressure is lowest. Thus, airway closure is a regional phenomenon, whose extent and location varies with body posture. Most normal subjects do not exhibit tidal EFL even during maximal exercise. In contrast, in many COPD patients EFL may be present even at rest.6 Two main mechanisms promote the occurrence of tidal EFL, namely a reduction of available flow and/or an increase in ventilatory requirements. Since smoking causes a progressive reduction of Vmax in the tidal volume range of susceptible subjects, tidal EFL eventually occurs even in the sitting position. Tidal EFL implies heterogeneous sequential dynamic compression of the peripheral airways during expiration and re-expansion during inspiration, with concurrent risk of peripheral airway injury.7 During stage II, both tidal EFL and peripheral airway closure may concur in eliciting airway injury. In stage II, EFL during tidal breathing occurs initially at local levels but it eventually extends to all pulmonary airways, that is, the tidal expiratory flow rates are maximal even during quiet breathing. Thus, during stage II, EFL progresses from a local to a generalized phenomenon. Both promote DH because, in order to generate an adequate pulmonary ventilation, subjects with tidal EFL must breathe at a higher volume than the relaxed FRC. In normal individuals at rest, the end-expiratory lung volume (FRC) corresponds to the relaxation volume (Vr) of the respiratory system, that is, the lung volume at which the elastic recoil pressure of the respiratory system is zero. Pulmonary hyperinflation, which is defined as an increase in FRC above the predicted normal range, maybe due to increased Vr as a result of loss of lung recoil (e.g. emphysema) or dynamic pulmonary hyperinflation, which is said to be present when the FRC exceeds Vr. DH exists when the duration of expiration is insufficient to allow the lungs to deflate to Vr before the next inspiration. This may occur when expiratory flow is impeded (e.g. increased airway resistance) and/or expiratory time is shortened (e.g. increased breathing frequency). In COPD patients DH is common and is mainly due to tidal EFL.6 It is the main factor causing dyspnoea and exercise limitation.8