Objectives

1. Describe the subspecialty of interventional pulmonology and site guidelines for training.
2. Describe the most current diagnostic and therapeutic modalities utilized in interventional pulmonology over the past 5 years.
3. Understand general indications and contraindications for specific procedures in interventional pulmonology.
4. Understand the potential application of these modalities for early detection of lung carcinoma.

Abbreviations

AB = autofluorescence bronchoscopy; EBUS = endobronchial ultrasound; FB = flexible bronchoscopy; IP = interventional pulmonology; PDT = percutaneous dilatational tracheostomy; RB = rigid bronchoscopy; WLB = white light bronchoscopy

Defining Interventional Pulmonology

The historic beginning of interventional pulmonology (IP) originated with rigid bronchoscopy (RB) in 1897.¹ The mid-1960s heralded the introduction of flexible bronchoscopy (FB), providing access to the more distal airways.² The subsequent 4 decades have led to further development and application of technologies that are complementary to each other - for both diagnosis and treatment of a wide spectrum of pulmonary diseases, specifically malignant diseases. IP is defined by interventions that extend beyond routine FB or thoracentesis. Procedures in IP include: FB (standard and ultrathin), RB, tracheobronchial stenting, balloon bronchoplasty, cryotherapy, electrocautery, argon plasma coagulation, Nd:YAG laser, photodynamic therapy, brachytherapy, endobronchial ultrasound (EBUS), autofluorescence bronchoscopy (AB), pleuroscopy, percutaneous pleural catheter placement, and percutaneous dilatational tracheostomy (PDT). We will review some aspects of IP, new innovations, and proposed applications of a number of these modalities.

Previously reported surveys by the American College of Chest Physicians³ (1991) and the American Association for Bronchology^3.1 (2000) indicated that only 6 to 8% of pulmonologists perform RB. Many pulmonologists have now begun to seek additional training in IP through national and international workshops, as well as through additional 1-year clinical fellowships. This trend appears to be partly due to the increasing incidence and prevalence of lung cancer worldwide and to the need for multidisciplinary approaches for earlier detection, curative therapies, and palliative interventions. With this renewed interest in training comes the need to develop guidelines for standardization of training, as well as for maintaining competency in IP procedures. The American Thoracic Society/European Respiratory Society and the American College of Chest Physicians have begun to develop some initial recommendations addressing these issues. It remains to be seen what will be deemed essential to establish basic competency in clinical situations that require multimodalities of interventional pulmonary therapies. ^3.2,4 Additionally, the role of a virtual bronchoscopy simulator for FB is being evaluated as a potential standardized training tool.⁵

This review will focus on the past 5 years of IP and describe the basic technologies and the role of this technology in screening, detection, and treatment of pulmonary diseases. Earlier detection of both primary and recurrent lung carcinoma is a driving force for further defining the role of EBUS and AB. Each has a potential complementary role to FB with radiographic imaging, such as CT and positron emission tomography. High collimation CT scanning with computer-generated multiplanar views, volume-rendered like three-dimensional virtual bronchoscopic images, allow precise length and diameter measurements of tracheobronchial disease for stent selection of the airways⁶ (Figs 1-4).

Figure 1. Volume rendered CT image of the tracheobronchial tree demonstrating left mainstem bronchial stenosis.

Figure 2.   Oblique coronal CT images demonstrating left mainstem bronchial stenosis.

Figure 3. Three-dimensional virtual bronchoscopic image of ( LMSB stenosis).   Note reverse orientation of view on CT as compared with flexible bronchoscopy view.

Figure 4.   FB view of LMSB stenosis.

Endobronchial Ultrasound

Accurately distinguishing paratracheal, parabronchial, and other mediastinal sites of pathologic findings have long been difficult with chest radiograph, CT, and FB. The development of a miniature ultrasound probe with a piezoelectric crystal for the airway now allows identification of lymph nodes, vasculature, and the layers of the airway by the emission of sound waves as a gray-scale image. There are variations in the type of probe, including those with and without a balloon tip device. Radial probes offer a 360-degree cross-sectional view, while linear probes offer a 180-degree sagittal view. Generally, the ultrasound device consists of a 20-MHz probe used with a saline solution-filled balloon tip catheter. Circumferential contact of the balloon transducer to the bronchial wall is essential to create a 360-degree cross-sectional view of the airway and adjacent mediastinal structures. The 2.5-mm ultrasound catheter is passed through the working channel of the FB to the area of interest. Saline solution is introduced into the balloon. The image-depth range varies from 1.5 to 12 cm, and the image diameter is 3 to 9 cm, depending on the probe utilized. It is important to note that image quality is significantly reduced with increasing depth. While the probe without the balloon allows for passage into the more narrow distal airways, the resulting view is limited by restricted surface contact. It is also important to note that as the bronchoscopist moves from the trachea to the more distal airways, spatial and anatomic orientation becomes more difficult. It is vital that the bronchoscopist be very familiar with the basic anatomy of the airways, as well as recognize their ultrasonographic appearance.^7-11 The central airway consists of seven layers¹² (Fig 5). These 1-mm layers include: the mucosa, submucosa, cartilaginous inner and outer layers, actual cartilage, external fibroelastic connective tissue, and loose connective tissue. The trachea may pose an imaging challenge, and creating an adequate seal with the small balloon probe is sometimes difficult. Results from one study indicated that all of the false-negative results in attempting mucosal and submucosal disease identification were noted due to inadequacy of the seal in the trachea.^7-11,13 Images with EBUS are obtained in "real-time" mode. The probe is subsequently removed, and the needle biopsy is obtained by utilizing endobronchial landmarks identified during the initial inspection with EBUS. A convex-probe EBUS now allows simultaneous localization of lymph nodes while performing needle biopsy with direct visualization.

Figure 5.   Endobronchial ultrasound - basic anatomy. With permission, Olympus/Dr. Heinrich Becker.

With the known limitations of CT for accurately staging lung carcinoma, the role of EBUS continues to evolve. EBUS has been studied in the following areas: differentiating between airway infiltration and airway compression by tumor; enhancing the diagnostic yield of transbronchial needle aspiration independent of size or location of the adenopathy (average nodal size of 1.7 cm with a sensitivity of 86% and confirmed diagnosis of carcinoma of 72%); detection of mediastinal and hilar disease with EBUS alone in 92% and with EBUS and CT in 100%; distinguishing direct invasion of pulmonary vasculature with an accuracy of 92%; and determination of depth of invasion of early bronchogenic squamous cell carcinoma with a sensitivity of 85.7% and specificity of 67%.^8-11,13 In 2004, EBUS was found to improve diagnostic yield from 58 to 84% in all nodal stations, with exception to the subcarinal region when compared to standard transbronchial needle aspiration. EBUS may also improve the diagnostic sensitivity and specificity of AB. Another study has assessed EBUS in the evaluation of peripheral pulmonary nodules. The authors suggest that the ultrasonographic pattern may distinguish between benign and malignant disease. A homogeneous pattern appears to correlate with benign disease, whereas, a hyperechoic or heterogeneous pattern suggests malignant disease. The sensitivity and specificity of these patterns cannot substitute the need for a tissue diagnosis.¹⁴

In general, accepted indications for EBUS include: assistance for more accurate staging of malignancy by determination of the depth of tumor invasion in tracheobronchial disease; depth of hilar disease invasion of the pulmonary vasculature; and disease involvement to paratracheal/parabronchial sites. EBUS may assist with the diagnostic yield of transbronchial needle aspiration; assess the extent of disease to assist in selecting the most appropriate therapy, such as stent placement, electrocautery, laser, and photodynamic therapy vs surgery; assess interval response to therapy; and identify and characterize peripheral pulmonary lesions. It is clear that successful use of EBUS is related to operator experience and understanding the normal anatomic relationships of the airways and mediastinal structures. The method appears to be well tolerated by the patient and cost effective. The method adds approximately 10 min to a standard FB and is safe. Contraindications to EBUS are the same as   standard FB.

Autofluorescence Bronchoscopy

The basic underlying principle of AB is fluorescence spectroscopy. It is a diagnostic tool that improves visualization of the tracheobronchial mucosa and, in so doing, identifies dysplasia and carcinoma in situ better than standard white light bronchoscopy (WLB). Mucosa and submucosa of the airways contain fluorochromes and chromophores. Fluorochromes and chromophores are identified as collagen, nicotinamide adenine dinucleotide, porphyrins, and flavins. When excited by the absorption of light energy at short wavelengths (380 to 440 nm), initially absorbed energy is allowed to be emitted at a longer wavelength (475-800 nm), creating an observable fluorescent light. Another description includes the situation when components in the airway are excited by the blue portion (400-450 nm) of the visible spectrum - the result is a green fluorescent appearance, made possible by a filter or image processor limiting the observed light wavelength. The normal tracheobronchial mucosa appears green, while the abnormal mucosa as seen in dysplasia and carcinoma in situ appears reddish-brown. This seems to result from an approximate 10-fold reduction in fluorescence (Fig 6). Theoretically, the cause of reduction is multifactorial and includes epithelial thickening, reduced fluorophores, tumor hyperemia, and tumor matrix redox changes.^15-19 False-positive results can be seen with bronchoscopic trauma, acute bronchitis, asthma, mucous gland hyperplasia, prior biopsies, photodynamic therapy, and scarring.

Figure 6.   Autofluorescence bronchoscopy and white light bronchoscopy demonstrating mucosal lesion.

Available AB systems vary, primarily, with regard to the technology utilized to create the excitation needed to invoke visible fluorescence. The xenon filter light (System D-Light AF, Karl Storz Endoscopy of America; Culver City, CA) is currently the only available system in the United States. It requires a specific bronchoscope with the filter as part of the eyepiece to filter out the blue light. The helium-cadmium laser light and a charged-coupled device camera (LIFE-Laser Induced Autofluorescence-Lung-System, Xillix Technologies Corp; Richmond, BC, Canada) has been the device used in most published AB studies. A modified version of this system (Onco-Life, Xillix Technologies Corp; Richmond, BC, Canada) will feature adaptability to the standard FB. Studies report the sensitivities of detecting dysplasia and carcinoma in situ to be 25 to 52% in WLB and 67 to 86% in AB. These are considered "relative sensitivities," as biopsy specimens from apparently normal areas have occasionally been positive for premalignant changes.^15-19 It is also suggested that utilizing both techniques in tandem may further improve sensitivity and specificity. Given that approximately 75% of carcinomas in situ are superficial and flat, it is not surprising that lesions 5 mm or smaller go undetected with WLB.¹⁵ An additional tool is available with AB to screen high-risk patients for primary or recurrent malignancy.¹⁸ At the present time, high-risk patients may be defined as having the following: a diagnosis of COPD; tobacco use > 30 pack-years; prior malignancy; positive sputum cytologic results; staging of current malignancy (head, neck, lung, or bladder) or negative findings on chest radiograph with a high clinical suspicion for malignancy; and follow-up assessment in patients with prior curative resection for lung carcinoma. With large multicenter lung cancer screening programs in progress and aimed at better defining the high-risk patient and the best utilization of AB technology, AB may be routinely performed with WLB in the future. Determining a standard method for interval reassessment after diagnosis and initial treatment in patients with an abnormal findings on AB will also be necessary. AB adds very little time to conventional bronchoscopy, does not require photosensitization, and may offer the patient more treatment options because of the earlier disease detection.

Rigid Bronchoscopy

While the majority of all the interventional tools listed earlier in this lesson can be applied via FB, with the exception of silicone tracheobronchial stent deployment, RB has some specific advantages. RB establishes a controlled airway and a large conduit for: therapeutic intervention in the setting of significant airway hemorrhage, improved visualization, timeliness in foreign body retrieval, and access for larger biopsy sampling. General anesthesia ensures a motionless field and patient comfort during RB. Both RB and FB are complementary in managing complex airway diseases.

General indications for RB include the following: foreign body retrieval; massive hemoptysis; central airway obstruction from benign or malignant neoplasms; tumor ablation; laser therapy; airway dilatation; airway stenting; and tracheal stenosis. Contraindications to RB include the following: unstable cardiac disease; uncorrectable coagulopathy; maxillofacial trauma; cervical spine instability; refractory hypoxemia; and an inadequately trained team member.

Complications as a direct result of RB are extremely rare at 0.1 to 1.8%. Potential complications include: cardiovascular instability; hypoxemia; tracheobronchial perforation; esophageal perforation; laryngeal edema; laryngospasm; bronchospasm; vocal cord injury; dental trauma; pneumothorax; and severe bleeding. The expected mortality rate is 0.4 to 1%. Mathisen and Grillo²⁰ and Cavaliere and colleagues^21,22 report successful recanalization in up to 90% of cases with central airway obstruction due to tumor. Symptoms of cough, dyspnea, and hemoptysis were significantly reduced with associated improvement in quality of life. RB continues to have a vital role in the management of this patient population.

Tracheobronchial Stenting

Over 500,000 FBs are performed in the United States, and 15,000 tracheobronchial stents are deployed worldwide.³ The role of these stents is primarily to reestablish and preserve patency of either the proximal or distal airways, thereby relieving symptoms. Tracheobronchial stents may facilitate extubation in patients with large airway obstruction and in patients with acute respiratory failure and imminent asphyxiation.^23-16 Tracheobronchial stents are utilized in both benign and malignant disease.^{20,24,25,27-35} Metallic and silicone stents, as well as hybrid variations of the two, are available for use, and their properties should be known in order to make the most appropriate selection. A recent review by Saad and Mehta^33,36  gives one perspective on the importance of patient selection and the role of metallic stents deployed with FB. They describe their experience with metallic stent placement in the central airways for malignancy and note that in those mechanically ventilated patients, 87.5% could be successfully weaned and extubated. Indications for stent placement vary; however, the interventionalist should always ask the following questions prior to stent placement: (1) Is this a surgical disease? Should the underlying disease process be primarily addressed with definitive surgical intervention and a stent only be considered as a potential bridge or not considered at all, ie, in the case of benign tracheal stenosis? (2) Is this benign disease? (3) Will there ever be a need to remove the stent being placed? (4) Is the distal airway below the obstruction patent?

General guidelines for appropriate stent selection include the following: (1) central airway obstruction with significant symptoms; (2) anticipated slow response to therapy in setting of tumor; (3) rapidly growing tumor; (4) proximal vs distal disease; (5) benign vs malignant disease; (6) loss of cartilaginous support of central airways; and (7) external compression of airways.

Complications include the following: (1) migration; (2) infection/secretion plugging; (3) erosion/perforation; (4) granulation tissue; and (5) stent fracture and uncoiling.

Major stent types include the following: (1) metallic (balloon expanding vs self expanding: covered and uncovered): nickel and titanium alloy (nitinol); (2) silicone; (3) hybrid; and (4) "Y" stent/dynamic stent (silicone alone or with anterior tracheal steel struts).

Specific Features of Metallic vs Silicone

Characteristics of metallic stents include the following: migration is less common; easy to insert with FB with or without fluoroscopic guidance; conforms to smaller, distal, and more tortuous airways, when uncovered much more difficult to remove; and generally avoided in benign disease states. Characteristics of silicone stents include the following: easy to remove; higher incidence of secretion plugging; migration more common; and requires RB for deployment. Proposed new stent-related technologies include the following: (1) gene therapy delivery via tracheobronchial stents for site-specific therapies; (2) new delivery systems for polyurethane/silicone/metallic stents for FB; (3) new measurement devices for more accurately sizing stents; (4) custom-made stents tailored for individual patients; (5) wider variety of sizes with thinner stent walls to accommodate more distal airways; (6) beveled edges to improve mucociliary clearance; (7) variety of stent shapes to better fit "bottle-neck" stenosis; (8) bioabsorbable stent materials to reduce granulation; and (9) fully covered self-expanding nitinol stents.

Medical Pleuroscopy

Medical pleuroscopy classically involves entering the pleural space with a rigid 7-mm trocar, rigid telescopes placed under local anesthesia with IV analgesia, and sedation. Historically, this procedure gained popularity in the prechemotherapy era of tuberculosis; it was used to lyse adhesions and to promote collapse therapy with pneumothorax. Today, the most common indications include diagnosis and treatment for unexplained, persistent, pleural effusion, often having exudative characteristics. The procedure is carried out in an endoscopy suite with a spontaneously breathing patient under conscious sedation with midazolam and fentanyl. Blanc and colleagues 37 recently confirmed the utility of pleuroscopy in a series of 154 patients who underwent 168 procedures using local anesthesia, mild sedation, and rigid instruments. The authors compared the results of closed pleural biopsy with pleuroscopy in diagnosing pleural disease. In this series, pleuroscopy had an overall diagnostic accuracy of 93.3% with extremely low morbidity and mortality. The procedure resulted in a diagnosis in 43 of 90 patients who previously had nondiagnostic closed pleural biopsies.

Read³⁸ reported that when compared to a series of historical control patients who had undergone pleurodesis with chest tube drainage and doxycycline instillation, talc pleurodesis performed with pleuroscopy shortened the hospitalization of patients with malignant pleural effusion and the length of chest tube duration. Pleuroscopy is underutilized, but potentially a very helpful diagnostic and therapeutic tool. It offers a safe and effective way to fully assess the visceral and parietal pleura. Medical pleuroscopy has been found to be most helpful in diagnosing unexplained exudative pleural effusions (Fig 7); establishing the diagnosis of mesothelioma (Fig 8); assuring proper placement of the chest tube (Fig 9) and distributing talc for pleurodesis (Fig 10); and managing of recurrent pneumothorax (Fig 11). A survey of pulmonologists³⁹ revealed that many pulmonologists are inexperienced with this procedure, but that they recognize a need to expand the role of pleuroscopy in clinical practice.^39,40 A new flexible-rigid combination thoracoscope recently has been developed. This instrument has a handle, suction apparatus, and distal-flexible end. It is very similar to that of a flexible bronchoscope and may prove to be more acceptable than the classic rigid instrument.⁴¹ Additionally, "minithoracoscopy" has been described utilizing a 3.3-mm telescope and 3.8-mm trocars for small pleural effusions with and without loculations requiring further diagnostic evaluation.⁴² Training in conventional thoracoscopy is required. Some advantages of this might include: good visibility of the pleura, easy maneuverability, less anesthetic requirements, and less patient discomfort. Relative disadvantages might include: small biopsy sample size, 20% longer procedural time, and conversion to conventional thoracoscopy when required.

Figure 7.   Intrathoracic view via pleuroscopy.

Figure 8.   Pleural inspection in patient with mesothelioma.

Figure 9.   Chest radiograph with chest tube placement after pleuroscopy.

Figure 10.   Talc for pleurodesis.

Pleural Catheter for Malignant Pleural Effusions

An alternative strategy to malignant pleural effusion management, with or without trapped lung, is with a chronic indwelling 15.5F silicone catheter with a polyester cuff (Pleurx catheter, Denver Biomedical; Golden, CO). This catheter is tunneled subcutaneously into the pleural space in the outpatient setting with an attached external plastic bottle. It allows the patient or caregiver to drain the effusion as needed. This is a beneficial option for those patients who may not be a candidate for pleuroscopy, nor desire a more invasive approach. This technique has been compared with tube thoracostomy and pleurodesis with doxycycline and was found to have comparable results in terms of dyspnea relief, efficacy of pleurodesis, and safety.^42.1 Comparatively, patients undergoing the indwelling catheter placement had reduced hospital stays: a median of 1 day vs 7 days. The complication rate for this procedure has been reported as 7% in some studies and included infection, return of pleural fluid, clogging from tumor overgrowth, or catheter malfunction. Contraindications to the use of this catheter include: uncorrectable coagulopathy, pleural space infection, chylous effusion, multiloculated pleural effusion in the pleural space, radiographic evidence of greater than a 2-cm mediastinal shift to the ipsilateral side of the effusion (Denver Biomedical PleurX Catheter Company Instruction Manual, page 3).   The procedure should be considered a feasible alternative for patients when they have an overall poor prognosis, symptomatic palliation is desired, trapped lung is coexistent, and the patient would not be a candidate for medical pleuroscopy with pleurodesis.

Percutaneous Dilatational Tracheostomy

PDT has become an increasingly utilized bedside procedure in intensivists' hands for establishing a secure long-term airway. The indications for PDT are identical to that of the traditional surgical tracheostomy, including: optimization of pulmonary toilet, anticipated prolonged weaning from mechanical ventilation, patient comfort while reestablishing oral nutrition and speech, and bypassing upper airway obstruction. The additional benefits of the bedside PDT include: patient safety by eliminating the need to transport a mechanically ventilated patient to the operating room, cost effectiveness with less personnel, equipment needs, and timeliness.⁴³

Appropriate patient selection, patient preparation, and an experienced procedure team are always the cornerstones of a successful procedure. When comparing PDT to traditional surgical tracheostomy, the postoperative complications are comparable. There are some published absolute and relative contraindications for PDT; however, clinical judgment will guide the experienced operator. Traditional contraindications include: uncorrectable coagulopathy, active infection over the anterior neck, and children who are less than 15 years of age.⁴⁴ Relative contraindications include: morbid obesity, emergent need for airway access, gross anatomic distortion of the neck, prior neck surgery or tracheostomy, high positive end-expiratory pressure >15 cm H₂0 or Fio₂>70%, and hemodynamic instability.

Complications are divided into immediate perioperative and early/late postoperative. Perioperative complications include: bleeding, accidental extubation, hypoxemia, hypercapnia, arrhythmia, subcutaneous emphysema, pneumothorax/pneumomediastinum, posterolateral tracheal wall laceration, and paratracheal insertion of the tracheostomy tube. Early postoperative complications include: bleeding, infection, and premature decannulation of the tracheostomy tube. Late postoperative complications include: tracheal stenosis, tracheal granulation tissue, tracheomalacia, tracheoesophageal fistula, tracheoinnominate artery fistula, and scar at tracheostomy site.

There are a number of PDT kits available that utilize a modified Seldinger technique with either sequential dilators or a single dilator system. The use of FB to assess the airway via the original endotracheal tube at short intervals throughout the procedure may be done safely and does not significantly increase the procedure time. It provides an additional means to verify the airway again via the newly placed tracheostomy tube, as well as provide immediate pulmonary toilet.

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