© 2005 American Thoracic Society doi: 10.1164/rccm.2412005
Collateral Ventilation, the Bane of Bronchoscopic Volume ReductionDivision of Pulmonary and Critical Care Johns Hopkins Medical Institutions Baltimore, Maryland Various bronchoscopic treatments for emphysema are being explored in animal models and patients (1–5). The concept guiding these approaches is that atelectasis of emphysematous lung regions can reduce lung volume without the need to remove tissue. These techniques may render moot much of our understanding of the effectiveness and costs of surgical lung volume reduction, because both risks and benefits will differ. However, one feature both surgical and bronchoscopic approaches should share is the mechanism of improvement. Then, along comes a study that challenges even that assumption. In this issue (pp. 453–460), Hopkinson and colleagues describe 19 patients with severe emphysema whom they studied before and after bronchoscopic lung volume reduction (BLVR) with one-way valves (1). The valve is designed to allow secretions or gas to be expelled from the occluded segments, but to prevent air from entering. Valves were placed unilaterally in segmental bronchi leading to the most severely affected lung regions. This study is noteworthy in several respects. It is one of the largest series in this evolving field. It also may be the most exhaustive investigation anywhere in the lung volume reduction literature. Before and after treatment, subjects underwent computed tomography and studies of pulmonary function, blood gases, cardiopulmonary exercise variables, generic and respiratory quality of life, lung compliance, maximal respiratory muscle strength, transdiaphragmatic pressure during phrenic nerve stimulation, and pleural pressure during exercise. This constitutes a remarkably comprehensive, multidimensional evaluation of the effects of BLVR, and is a tribute to the motivation of both investigators and subjects. Finally, among myriad available outcome variables, the authors chose to define "responders" based on improvement in exercise time. This exemplifies another advance in the field, in that improvement in pulmonary function has been supplanted by more patient-centered goals. The impressive strengths of the article are nearly its undoing, because the study generates an enormous array of data that defy facile presentation or interpretation. I wish to comment on just two findings that challenge simple notions of why BLVR might work. The first finding is that only a minority of subjects (five) developed atelectasis visible on computed tomographic scan. This confirms similar results from another recently published study of the same device (3). Four of these five patients improved their exercise capacity (responders defined as > 30% and 60-second increases in exercise time at constant workload). The second finding was that one-third of the patients with no atelectasis nevertheless still responded. Thus, a study seemingly designed to answer all conceivable questions succeeded in raising at least two more: Why did so few patients develop atelectasis, and why did some of the others increase exercise time? I agree with the authors' explanation that atelectasis was prevented in the majority of patients by collateral ventilation. Collateral resistance is reduced in emphysema, and may be substantially lower than airway resistance (6). Fissures are often incomplete, allowing collateral ventilation to traverse lobes. These capacious collateral channels are being used in another investigational bronchoscopic treatment for emphysema, which creates auxiliary airways to function as "back doors" from emphysematous regions (7). It is axiomatic that absorptive atelectasis could not develop in patients after the occlusive valves were placed if occluded regions received more ventilation than the rate of gas absorption. Collateral channels were the only pathways available for such ventilation. The extent of collateral ventilation may have also been the factor that differentiated patients whose exercise capacity improved despite an absence of atelectasis. Exercise is typically limited by dynamic hyperinflation in chronic obstructive pulmonary disease (8, 9), and improvement in indices of dynamic hyperinflation correlated in the current study with improvements in exercise time after BLVR (1). In patients with relatively low-resistance collateral channels, the regions subtended by the occluded bronchi may still have hyperinflated with exercise, obviating a benefit. In patients with somewhat higher resistance collateral channels, however, dynamic hyperinflation of those occluded units may have been reduced and isotime ventilation directed toward more normal lung units. Finally, in patients with still higher collateral resistance, atelectasis occurred and lung mechanics improved through the same mechanisms as after surgical lung volume reduction. Thus, a characteristic that is probably a continuous variable (collateral resistance) channeled patients into dichotomous categories (atelectatic or not, and responder or not).
Because of the potential improvement in dynamic hyperinflation, the authors emphasize that atelectasis is not essential for this procedure to be beneficial. I would emphasize that, although unessential, atelectasis is nevertheless highly desirable. Patients with atelectasis were more likely to improve (4 of 5 vs. 5 of 14, p = 0.1 by Several techniques could be feasible for the measurement of collateral resistance. Resistance can be measured directly via a wedged bronchoscope (6). With selected bronchi occluded, collateral resistance may be inferred from the distribution of inhaled gas during a single breath using xenon and ventilation scintigraphy or hyperpolarized helium and magnetic resonance imaging (10). To test the hypothesis that patients with the least residual collateral flow after segmental occlusion will have the greatest improvement, measurements could be made retrospectively in patients who have already had bronchial valves implanted, or prospectively in new subjects after the targeted regions are occluded temporarily. The findings from such studies may guide patient selection or suggest modifications of the BLVR procedure to better isolate the occluded segments, or to target segments that are intrinsically better isolated. Dr. Hopkinson and colleagues are to be congratulated for raising the standard of patient evaluation for emphysema treatment. The rich dataset they provide will generate many more hypotheses and follow-up studies and should speed progress in the field. I have just one more suggestion: "bronchoscopic lung volume reduction" apparently needs a new name. FOOTNOTES Conflict of Interest Statement: H.E.F. does not have a financial relationship with a commercial entity that has an interest in the subject of the manuscript. REFERENCES
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2 testing) and mean improvements in lung function and exercise were substantial (32% increase in FEV1, 129% increase in exercise duration). In contrast, all mean changes in the group who failed to collapse occluded segments were minimal (see Table E4 in the online supplement to the article). Selecting patients for surgical volume reduction involves determining if their characteristics enhance the likelihood of a good outcome. A characteristic that is irrelevant for surgical selection may be cardinal for BLVR selection: measurement of collateral resistance.