Experienced interventional bronchoscopists treating emphysema patients with BLVR procedures agree that collateral ventilation is a cardinal issue determining treatment outcome. Atelectasis promotes more marked volume reduction, and therefore lobar exclusion is the treatment of choice in patients with negative collateral ventilation (Fig. 32.3).

In 2009, Aljuri and Freitag [16] introduced a new method to estimate collateral ventilation. The concepts described by these investigators have been employed to develop the Chartis™ Pulmonary Assessment System, which measures airway resistance and collateral ventilation in lung compartments. For that, a catheter with a compliant balloon component at the distal tip is inserted into the lung. The balloon is inflated and blocks the airway, so that the air flowing from the target compartment into the environment must pass through the Chartis catheter (Fig. 32.4).

The Chartis console displays airway flow, pressure, and resistance [16]. Collateral ventilation occurs through:

In patients with emphysema, in whom airway resistance is increased, collateral resistance is lower. This was demonstrated by Hogg et al. [17], who measured the resistance of CV in excised normal and emphysematous lungs. In normal lungs, the resistance of collateral channels was 260–330 cmH₂O (25–324 kPa), whereas this was 5–20 cmH₂O (0.5–2.0 kPa) in emphysematous lungs. Therefore, airflow is increased approximately 30 times through collateral channels in an emphysematous vs. a normal lung [18].

Although collateral ventilation was initially thought to be strictly an intralobar phenomenon, interlobar ventilation (i.e., between the lobes) also occurs across incomplete lung fissures. Probably due to the same mechanism, the flow between different lobes is higher in patients with emphysema [17–19].

Fissure integrity has emerged as a focus of much interest for BLVR. In embryos, the visceral pleura is formed at around 7 weeks of gestational age, and invaginations start to separate the lobar bronchi. This gives rise to lobar fissures and the formation of lung lobes. However, if the pleura fails to cover the entire lobe, it can be assumed that the fissures will be incomplete near the lung hilum [20]. The right major fissure has been shown to be more often incomplete (48 vs. 43% for the left-side major fissure 43%, p < 0.05). Minor fissures are convex superiorly with an anterolateral apex and have been reported to be incomplete in 63% of the cases [21].

In another study, Manoj et al. describe the variations in lung fissure patterns in the general population of India (Fig. 32.5). One hundred lungs were meticulously dissected (right lung, 50; left lung, 50). The number of fissures, whether complete, incomplete, or absent, and the presence of accessory fissures were noted. In the right lung, horizontal fissure was absent in four (8%) and incomplete in 14 (28%) cases. Oblique fissure was absent in two (4%) lungs and incomplete in seven (14%). Accessory fissures were present in 19 specimens (38%). In the left lung, the oblique fissure was absent in two (4%) lungs and was incomplete in 16 (18%) lungs. Accessory fissures were present in 16 (32%) [22].

Knowledge regarding the occurrence of fissure variability in a particular population might help radiologists and clinicians make a correct diagnosis and help surgeons plan, execute, and modify their surgical procedures. However, definitive studies regarding the role of fissure integrity in lung volume reduction following BLVR are still lacking.

Interlobar CV might be an important predictor of EBV treatment outcome, as BLVR therapy is based on complete atelectasis of a lobe. Most probably, incomplete fissures are responsible for interlobar collateral flow. There is no literature regarding the mechanism of CV in incomplete fissures between lobes. It can be assumed that the mechanism of collateral flow between lobes is the same as within a lobe. The collapse of emphysematous lobes, despite occlusion of their bronchi, is attributed to the low collateral resistance in emphysema. Collateral resistance is often less than airway resistance in these patients, and collateral channels frequently cross incomplete interlobar fissures [23]. Gas may thereby continue to enter these lung regions at rates exceeding their rate of absorption. A technique to predict which patients or which lobes have high collateral resistance and are likely to become atelectatic could guide patient selection and procedural planning [24].

In a retrospective study [25], our group has shown that target lobe volume reduction is possible with lung fissure integrity ≥75%. Patients with fissure integrity >90% are likely to achieve a clinically relevant target lobe volume reduction with EBV treatment. Patients with fissure integrity between 75 and 90% should undergo further evaluation of interlobar ventilation (Chartis™), as previously noted [25–27]. The overall accuracy of a 75% fissure integrity cutoff point was 87.2% for a 350 mL reduction in target lobe volume. Patients with fissure integrity <75% are not likely to achieve any clinically relevant target lobe volume reduction with BLVR-EBV.

Lung hyperinflation leads to exercise intolerance and greatly hurts quality of life. Lung emphysema encompasses a broad vicious cycle in which social isolation, depression, limb weakness, breathlessness, and a disturbed chest wall mechanics contribute to increase mortality. In a large 4-year follow-up study of patients with mild-to-severe emphysema, IC/TLC ≤ 0.25 was associated with a twofold increase in mortality vs. IC/TLC ≤ 0.25. We conclude that IC/TLC is an independent risk factor for mortality in subjects with chronic obstructive pulmonary disease. We propose that this ratio be considered in the assessment of patients with COPD [28].

In emphysema, heart performance is greatly compromised by lung hyperinflation. In 2010, Barr et al. [29], using MRI, showed that a 10% worsening of emphysema on CT scans was sufficient to reduce LV diastolic volume, LV mass, stroke volume, and cardiac output. The same was observed for the increase in airway obstruction (FEV₁/FVC).

Gerard Criner has recently proposed the notion of “Less Lung Means More Heart,” shedding light on the contribution of the heart for the severity of symptoms and the loss of quality of life in lung emphysema [30].

The first endoscopic approach for emphysema treatment was proposed by Crenshaw. In 1966, that author described a technique in which diluted sodium hydroxide was bronchoscopically applied as sclerosing agent to promote retraction of emphysema bullae. Despite the marked improvement obtained with two patients, with one being able to resume work, there is no record of this experience having been pursued further [31].

Also pioneer was the work of Watanabe et al., who proposed the use of an endoscopically delivered cork-like device, the spigot. One of the major limitations of the method was the occurrence of obstructive pneumonia and pneumothorax, possibly resulting from hyperinflation due to collateral ventilation. Therefore, the Watanabe Spigot had limited clinical application. Other therapeutic options include fibrin sealant, extra anatomical airway, vapor, and coils [32].

Concerning lung volume reduction surgery (LVRS) , the uncertainties related to the outcomes, and the high associated morbidity and mortality have limited the use of this major surgical procedure [24]. In the NETT, almost 30% of the participating patients faced major pulmonary complications, including the need for reintubation and tracheostomy and the need for ventilatory support for more than 2 days or pneumonia within 30 days of operation. In turn, about 20% of the sample developed cardiovascular problems, such as arrhythmia requiring chemical or electrophysiological treatment, myocardial infarction, or pulmonary embolus [33]. Advancing age, declining FEV₁, and declining D_LCO were predictors of major cardiac morbidity, as well as the use of oral corticosteroids at the time of surgery and non-upper lobe predominant pattern of emphysema. Conversely, there is good evidence that patients with upper lobe emphysema and poor exercise capacity benefit from LVRS [34].

It is well recognized that the NETT played a major role in advancing the development of minimally invasive endoscopic modalities such as BLVR. The framework of this prospective randomized clinical trial provided the foundation for the search of alternative methods of lung volume reduction that could produce clinically significant results and translate into improved lung function and exercise capacity.

In 2001, our team was invited to participate in a phase II trial set up by endobronchial valve manufacturer Emphasys Medical. We implanted the first EBV in the Americas in the morning of June 4, 2002 (Fig. 32.6).

This was a challenging premiere because treatment strategy in this 75-year-old male was right upper lobe (RUL) exclusion with three classic EBVs. Complete atelectasis was achieved almost immediately (Fig. 32.7).

After 48 h, minor chest pain and respiratory discomfort evolved to a large ipsilateral pneumothorax on chest X-ray requiring the insertion of a 32F chest tube. This measure however was unsuccessful in re-expanding the RUL, since a massive air leak indicated that a large bulla was probably torn apart. Removal of the valve located in the anterior segment (B3) naturally allowed pulmonary re-expansion, followed by an uneventful recovery (Fig. 32.8).

As part of this project, 19 patients were treated between June 2002 and October 2004. At that initial stage, we were able to show that treatment with EBV was safe and reversible, an advantage over other emerging bronchoscopic techniques. Nevertheless, it soon became clear that patient selection and the criteria to measure improvement required refinement.

Around 2004, classic EBV valves were replaced with a transcopic endobronchial valve model called Zephyr™ . The transcopic model added elegance and fluency to the procedure; the classic EBV model was delivered through a comparatively clumsy system, using a guide wire and a delivery case that was passed through a large orotracheal tube. The flexible bronchoscope only provides a visual field from above. Implantation of the classic EBV required more technical dexterity and was difficult especially in upper lobe apical segments. However, the crucial disadvantage was a high incidence of granuloma formation close to the tip of the valve, which often obstructed the valve itself [35].

In the early era of EBVs, there was some debate regarding the appropriateness of the name “bronchoscopic lung volume reduction surgery” as the best description for the procedure. We ourselves proposed the use of the term “transbronchoscopic pulmonary emphysema treatment” (TPET), based on the argument that the bronchoscope is only a means to deliver the treatment. The idea of TPET was also an attempt to prevent confusion with LVRS and an acknowledgment of the realization that volume reduction is often not obvious with BLVR. In this sense, it should also be noted that clinical improvement is often possible even in the absence of significant lung volume reduction. Nevertheless, the expression BLVR prevailed, and this is the current term used to describe the minimally invasive procedure through which EBVs are implanted in patients with emphysema [36–38].

Bronchoscopic lung volume reduction (BLVR) with one-way unidirectional EBVs is a minimally invasive, reversible treatment option that has been used to treat over 12,000 patients with emphysema around the world. Considering an average of three valves per patient, around 36,000 valves have been implanted in the world since 2004.¹ This is currently the most common BLVR modality.

One-way endobronchial valves operate by blocking airflow into diseased portions of the lung in which parenchyma disruption causes air trapping. By doing that, the valves induce dependent volume reduction and redirect airflow to less diseased lung areas. Diaphragm repositioning and improved respiratory mechanics are expected to diminished dyspnea and restore to a certain extent the ability to perform simple tasks of daily living, such as taking a shower, getting dressed, or walking short distances. The recovered ability to perform activities of daily living improves patient disposition. Collateral ventilation still seems to be the main factor complicating the likelihood of success [4].

As previously mentioned, the new EBV design (Zephyr™) introduced improvements for implantation, with the valve being totally compressed and loaded in a catheter with a diameter that is sufficiently small to be passed through a 2.8 mm bronchoscope operative channel. Also, the new valve design provided protection for the valve mechanism itself, facilitating grasping with the removal forceps when required. Our group was able to maintain a strict follow-up scheme in second half of the phase II Emphasys Medical trial. Mandatory flexible bronchoscopies at 30, 90, 180, and 365 days following the procedure allowed us to verify a significant reduction in granuloma formation with the Zephyr™ valve. Reversibility of the procedure was also improved with the transcopic valve. We were able to safely remove a valve more than 5 years after implantation in one case.

The Zephyr™ is available in three sizes, 4.0, 4.0LP, and 5.5, each delivered by a specific catheter (Table 32.1). There are separate delivery catheters and loader systems for each valve size. Each system is color coded: blue for the 4.0 and 4.0LP systems and green for the 5.5 system.

The valves are built with a nitinol frame that provides structural support and is covered by a silicone layer that prevents the inclusion of material in the mucosa. One-way airflow is controlled through a duckbill tip. The new model mimics airflow flexibility, decreasing friction, minimizing granuloma formation, and reducing valve migration/dislodgment. In summary, the newer model can be delivered directly through a 2.8 bronchoscope channel, streamlining the procedure. Valve mounting has also been greatly simplified.

The Zephyr^® 4.0-J EDC facilitates the introduction of valves in apical and intricate segmental or subsegmental bronchi, because the length in 4.0LP is 5.2 mm instead of 6.9 mm as normal 4.0 valve.

Rat tooth grasping forceps must be available to remove mismanaged valve delivery and positioning. For valve removal, the bronchoscope must be introduced through the mouth.

In brief, the ideal candidate for BLVR with EBV has:

Table 32.2 describes relative and absolute contraindications for valve treatment.