The Clinical Significance of Collateral Ventilation

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Abstract

<p class="first" id="d2602630e130">Oxygen delivery and carbon dioxide removal being critical to cell survival, mammals have developed collateral vascular and ventilation systems to ensure tissue viability. Collateral ventilation, defined as ventilation of alveoli via pathways that bypass normal airways, is present in humans and many other species. The presence of collateral ventilation can be beneficial in certain disease states, whereas its relative absence can predispose to other diseases. These well defined anatomical pathways contribute little to ventilation in normal humans, but modulate ventilation perfusion imbalance in a variety of diseases, including obstructive diseases, such as asthma and emphysema. These pathways can be affected by pharmaceuticals and inhaled gas compositions. The middle lobe and lingula, constrained by their isolated, segmental anatomy, have reduced collateral ventilation, which predisposes them to disease. Recently, attempts to improve the quality of life of patients with emphysema, by performing nonsurgical lung volume reduction via use of endobronchial valves, have led to mixed results, because the role of collateral ventilation in the success or failure of the procedure was not initially appreciated. This review describes the anatomical pathways of collateral ventilation, their physiology and relationship to disease states, their modulatory effects on gas exchange, treatment considerations, and their effect on diagnostic procedures. </p>

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A randomized study of endobronchial valves for advanced emphysema.

Kevin L Kovitz, Geoffrey McLennan, … (2010)

Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

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Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation.

Karin Klooster, Nick ten Hacken, Jorine E Hartman … (2015)

Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. To date, the benefits have been modest but have been hypothesized to be much larger in patients without interlobar collateral ventilation than in those with collateral ventilation.

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Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

PL Shah, D-J Slebos, PFG Cardoso … (2011)

Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. Broncus Technologies. Copyright © 2011 Elsevier Ltd. All rights reserved.