ated the feasibility of using an ultrathin bronchoscope, VBN, and 2Duoroscopy with the addition of CBCT in 40 patients. The target was unable to be localized with conventional C-Armuoroscopy, but it was seen in all 40 patients with CBCT. They categorized the biopsy location into three categories: inside lesion, outside lesion, and indeterminate with goals of a CBCT target-forceps sign. The overall diagnostic yield was 90.0%. Diagnostic yield for CBCT targetforceps sign was 100%, 0%, and 75%, respectively [98]. Park et al. concluded that the only contributing factor that increases diagnostic yield is the forceps’ position assessed by CBCT [94].

Therapeutic Procedures Via FB

Therapeutic bronchoscopy refers mainly to managing central airway obstruction (CAO), which may be intrinsic, extrinsic, or combined. This entitles mechanical and non-mechanical tumor debulking in malignant and benign diseases, tracheobronchial dilatation of stenosis, deployment of airway stents, extraction and removal of foreign bodies, and management of hemoptysis. It also includes newer therapeutic applications like endobronchial valve placement for prolonged air leak post lobectomy or endoscopic lung volume reduction interventions in selected emphysema patients.

Therapeutic bronchoscopic interventions, to a certain degree, can be accomplished via the exible bronchoscope (Fig. 2.10a–c).

However, the bronchoscopist must be competent and experienced with the use of rigid bronchoscopy and ready to use it when intervening on complex central airway obstruction. The rigid bronchoscope remains the tool of choice recommended by most experts in the feld when treating CAO [15, 99].

In this chapter, we will outline a brief summary of some available interventional therapeutic

modalities that can be implemented for use withexible bronchoscopy.

LASER Bronchoscopy

The majority of publications on LASER bronchoscopy report the use of neodymium-doped yttrium aluminum garnet (Nd:YAG) LASER [100, 101]. Other LASERs like CO2, Nd:YAP neodymium doped yttrium aluminum perovskite (Nd:YAP), Holmium:YAG, and diode LASERs are utilized in bronchoscopic interventions.

In LASER therapy, the heat energy from the LASER light is used to coagulate and vaporize the endobronchial lesion.

It is recommended to set LASER at low power (40 W) to coagulate the target lesion in anticipation to prevent bleeding.

The LASER fber is introduced through the working channel of the FB. The LASER fber tip should be at least 4 mm away from both the target lesion and the bronchoscope distal end. The inspired FiO2 should be lowered to 40% or less, and frequent suctioning should be used to minimize the risk of endobronchial fre [102].

Then coagulation followed by mechanical resection with the exible forceps can occur. In general, LASER treatments performed using aexible bronchoscope are long and require a signifcant amount of patience. The exible bronchoscope is not useful in severe obstruction or critical situations; they are better handled with the rigid bronchoscope [17]. Small lesions such as granulomas are easily treated with LASER application via exible bronchoscopy.

LASER is very effective in restoring airway patency, with symptomatic improvement in around 70–80% of patients [100, 101, 103]. Complications related to LASER application include massive hemoptysis (1%), pneumothorax (0.4%), pneumomediastinum (0.2%), and endobronchial fre and peri-procedural death (2–3%) [101, 103, 104].

Fig. 2.10  (a) Right main stem obstruction with squamous cell carcinoma causing post-obstructive pneumonia and severe hypoxemia. (b) The endobronchial component

of the tumor resected via a exible bronchoscope in an already intubated patient. (c) The resected tumor

Electrocautery

Electrocautery is used to treat central airway obstructions from benign or malignant tumors of the airway [105]. It also acts through coagulation and vaporization. The electrical probe can be used to treat superfcial lesions, while the snare can be applied to polypoid tumors protruding into the airway lumen. Similar to LASER, electrocautery is contraindicated when the obstruction arises from extrinsic compression without an intraluminal component [106].

Palliation of malignant obstructions using electrocautery is effective, with a rate of restoration of airway patency and symptomatic relief similar to LASER debulking (69–94%) [107–109].

Complications are similar to those of LASER application, with massive hemoptysis being the most concerning. Suggested settings to avoid fre during the procedure are: FiO2 equal to or less than 40% and low power (20–30 W).

Argon Plasma Coagulation (APC)

APC is a non-contact mode of electrocautery that causes coagulation and vaporization. It is performed to treat exophytic endobronchial tumors and has good results treating bleeding tumors. APC can also be applied to other benign lesions compromising the airway, such as granulomas resulting from airway stents.

APC shows good results in central airway obstruction, with a partial or complete restoration of airway patency in 66% of patients. It has a reported success rate of 99% when treating hemoptysis [110].

Complications related to APC are airway perforation and gas embolism [35].

Cryotherapy

Cryotherapy refers to the use of extreme cold to destroy abnormal or diseased tissue. The cryoprobe is inserted through the working channel of the exible bronchoscope, and cycles of freezing and thawing are applied to the target, causing

delayed necrosis. Repeat bronchoscopy is performed three to seven days after the application to remove necrotic tissue. Cryotherapy does not open the airway rapidly, and it is not utilized in critical airway obstruction since its application generates edema that may worsen the degree of the obstruction.

Conventional cryotherapy is indicated in malignant airway obstruction as a palliative method. A success rate of 61% has been reported in airway restoration and signifcant improvement of symptoms such as hemoptysis, cough, and dyspnea [111, 112]. Complications related to cryotherapy are hemoptysis, bronchospasm, cardiac arrhythmia, and death [113].

A newer modality of cryotherapy called cryoextraction or cryorecanalization can be considered a rapid airway restoration method since tumor pieces attached to the cryoprobe are removed immediately [14].

Photodynamic Therapy

It involves the administration of a photosensitizer substance (most commonly porfmer sodium) followed by its activation with LASER light of a given wavelength. This generates a photodynamic reaction that produces oxygen radicals that damage tumor cells, ultimately resulting in cellular death. Photodynamic therapy can be applied to early and advanced malignant lesions with good results [114].

Complications related to this procedure are photosensitivity (can last up to six weeks) and hemoptysis.

Airway Stent Placement

The exible bronchoscope can be used to deploy self-expandable metallic stents (SEMS) in the airway. Both bare and fully covered SEMS are commercially available.

The bare SEMS’ application is limited to malignant conditions. Long-term permanence inside the airway has been linked to severe complications such as erosion and perforation of the airway wall, excessive granulation tis-

sue, bacterial colonization, stent disruption, and fracture [115].

The Food and Drug Administration (FDA) released very clear recommendations regarding the use of metallic airway stents in 2005 [116]. Experts recommend avoiding bare metallic stents and considering other therapeutic strategies. Placement of a silicon stent can be performed in most patients via rigid bronchoscopy and represents a safer alternative [117].

However, post-surgical stenosis that follows lung transplant or tracheal resection can be an indication for metallic stents. Bronchial dehiscence after lung transplantation can present as a lifethreatening respiratory insuffciency, and deployment of a metallic stent can be life-saving and can favor healing, taking advantage of granulation tissue formation secondary to stent placement [118]. This indication is left to the team of experts managing lung-transplanted patients, not applicable to the general interventional bronchoscopy practice.

It is crucial to note that when bronchoscopists deploy a stent via exible bronchoscopy approach, they must be skilled and ready to perform rigid bronchoscopy if needed.

Endobronchial Valve Placement

Currently, two commercially FDA-approved valves for the treatment of emphysema exist.

•\ Zephyr Valve: This is a one-way silicone duckbill endobronchial valve attached to Nitinol self-expandable frame.

•\ Spiration Valve: This is an umbrella-shaped self-expanding one-way valve made of various metals, including a nickel-titanium frame. Distal anchors secure the valve against bronchial walls, with proximal struts keeping contact with the airway.

These valves can range in sizes, and depending on target airway size, they can be passed through a exible bronchoscope with a channel > 2.6 mm.

The uses for endobronchial valve (EBV) are growing but most commonly limited to severe

emphysema and a non-­surgical alternative to persistent air leaks.

Criner et al. studied patients with forced expiratory volume in the frst second (FEV1) between 15 and 45% of predicted, TLC greater than 100% predicted, residual volume (RV) equal or greater than 175% predicted, and diffusion capacity of carbon monoxide (DLCO) equal or greater than 20% predicted in the lung function improvement after bronchoscopic lung volume reduction with pulmonx endobronchial valves used in the treatment of emphysema (LIBERATE) study, and demonstrated that the Zephyr EBV provides meaningful benefts in the lung function where FEV1 improved 0.106 L, and 6-min-walk distance +39.31 m. Also, the study demonstrated improvement in quality of life for these severe emphysema patients with intact fssure or lack of collateral ventilation of the target lobe [119].

The effectiveness and safety of the Spiration valves were evaluated in a multicenter, open-­ label, randomized controlled trial evaluation of the spiration valve system for emphysema to improve lung function (EMPROVE), including patients with severe heterogeneous emphysema with somewhat similar inclusion criteria to the LIBERATE study.

The primary effectiveness endpoint was a mean change in FEV1 post-bronchodilator from baseline to 6 months between treatment and control groups; 12-month results were also reported.

Mean FEV1 showed statistically signifcant improvements in the treatment group at 6 and 12 months, respectively, of 0.10 and 0.099 L and in health status quality of life questionnaires [120].

Pneumothorax is the most common complication, with rates ranging 12–34% without affecting survival rates [121, 122].

EBV can be used for patients with air leaks who are refractory to conventional treatments and not good surgical candidates. A balloon occlusion device is often placed in the airway to assess if the air leak has improved. If it does improve, an EBV can be considered for placement. Fiorelli et al. and Gilbert et al. both showed improvement in air leaks with EBV placement [123, 124].

Large prospective trials are ongoing to continue to evaluate effcacy and safety profle.