Airway Obstruction in Severe COPD
Archie F. Wilson, MD, PhD, FCCP
Lung obstruction in emphysema patients is due to the reduction of airway support and the consequent dynamic collapse of airways, particularly during forced exhalation; in emphysema patients, intrinsic airway disease is not present and resistance is entirely expiratory. Severe COPD is a combination of emphysema with varying amounts of chronic bronchitis and bronchospasm. The primary treatment for chronic or recurrent bronchospasm is administration of anti-inflammatory drugs, specifically, inhaled corticosteroids. Attempts to identify significant responses to inhaled steroids in patients with moderate COPD have shown minor improvement in pulmonary function utilizing forced exhalation and in functional measures determined using such assessment tools as questionnaires or distance walked in 6 min. It is usually stated that patients with more severe, end-stage disease will not benefit from receiving inhaled corticosteroids. The possible reasons for such negative opinions about corticosteroids in patients with severe COPD include the following: (1) minimum or the wrong type of airway inflammation; (2) ineffective delivery of inhaled drugs to the sites of inflammation in the airway (eg, small distal airways); and (3) utilization of the wrong evaluation measures. However, (1) airway inflammation clearly plays a role in COPD, since oral corticosteroids are often the sole effective treatment for acute exacerbations of COPD. (2) The delivery of inhaled drugs to airways remains a major issue. The proper use of metered-dose inhalers is not intuitive, and, even with coaching, the coordination of activation with inhalation, the slow speed of inhalation, and end-expiratory breath holding are rarely achieved. Spacers, dry-powder inhalers, and breath-activated devices help with the coordination, but a too-rapid inhalation speed remains a common limitation. (3) The pulmonary function response to agents that increase airway diameter can be accurately assessed with the use of the body plethysmograph, but use of this tool is limited to specialized laboratories. Functional assessments such as the 6-min walking test may be faulty guides to the improvement of airway caliber in patients with COPD, since patients with severe COPD are limited by physical deconditioning and can greatly improve conditioning by pulmonary rehabilitation without change in pulmonary function (by all measures, including body plethysmography).1
In this issue of CHEST (see page 990), Nava and Compagnoni have taken another look at this problem and have attempted to find answers in a clinical situation in which steroid responsiveness would not be expected, ie, in patients with very advanced COPD (mean Paco2, 60 mm Hg; mean FEV1, 31% of predicted) who were receiving long-term ventilation. The authors utilized a ventilator tubing spacer (Aerovent; Monaghan Medical; Plattsburgh, NY) that delivered large amounts of inhaled corticosteroid (2,000 μg fluticasone per day for 5 days), and they assessed pulmonary function response primarily with ventilator measurements of pulmonary mechanics. They found that this treatment reduced mean (± SD) auto-positive end-expiratory pressure (auto-PEEP) from 4.3 ± 2.4 to 3.1 ± 1.7 cm H2O (suggestive but not significant), and pulmonary resistance from 19.0 ± 6.5 to 14.6 ± 6.0 cm H2O/L (significant). Since compliance and the component of pulmonary resistance due to viscoelastic (tissue) effects did not change significantly, they concluded that inspiratory (airway) resistance was reduced by inhaling high-dose corticosteroids for 5 days.
It should be noted that increased resistance in COPD is largely expiratory and that the pulmonary resistance measured by Nava and Compagnoni was inspiratory only. The presence of auto-PEEP implies inadequate time for expiration and, therefore, can be used as an indicator of expiratory resistance. However, auto-PEEP is also affected by respiratory rate, tidal volume, and inspiratory flow rate (ie, all the variables that affect expiratory time) and, hence, may be a poor indicator of expiratory resistance change. Auto-PEEP is decreased as more expiratory time is available. Auto-PEEP was not very high in the patients reported in this article and fell an insignificant amount.
What have we learned from this study? The following insights and suggestive observations emerge: (1) there seems to be some degree of reversible obstruction due to inflammation even in end-stage COPD patients; and (2) passive rather than active expiration may be desirable to determine the magnitude of changes in airway function (eg, Jubral et al2 have utilized measurements in nonintubated patients with a ventilator to obtain important information about the effects of lung volume reduction surgery on patients with COPD). This study does not demonstrate that administration of high-dose inhaled steroids is a desirable treatment for severe COPD, and it does not disprove the conclusions of many that inhaled steroids are not significantly beneficial in such patients; long-term, large-scale, placebo-controlled studies are needed to settle this issue. Rather, this study raises questions about the delivery of topical corticosteroids and other inhaled agents in patients with severe COPD and about the appropriate manner in which to study their potential benefits.