Diagnostic and Therapeutic Bronchoscopy Ro Steven Tharratt* and Andrew Chan Division of Pulmonary and Critical Care Medicine, University of California, Davis Medical Center, Sacramento CA 95817

~NTRODUCTION

No procedure, except the radiologic examination, has shaped the practice of pulmonary medicine as much as bronchoscopy. From the initial translaryngeal passage of rigid tubes by Gustav Killian (I) in the late 1800s, and through the introduction of flexible fiberbronchoscopy by Shigeto Ikeda (2) in the early 1970s to the exciting techniques of bronchoalveolar lavage and bronchoscopic laser therapy, bronchoscopy, with the history, physical examination, and radiographic evaluation, remains a cornerstone in the m a n a g e m e n t of patients presenting with complaints referable to the pulmonary system. Because of the close relationship between pulmonary medicine and clinical allergy, patients may be referred to either specialist with the tentative diagnosis of an allergic disorder. Since "all that wheezes is not asthma," occasional patients will need further diagnostic evaluation to either confirm the diagnosis of asthma or to correctly diagnose conditions presenting as pseudoasthma. Since the indications for bronchoscopy in allergic disorders are few, most allergists are not trained in bronchoscopy. This discussion wilt provide an overview of the capabilities and limitations ofbronchoscopy, and highlight those indications with particular interest to allergists. *Author to whom all correspondence and reprint requests should be addressed. Clinical Reviews in Allergy, vol. 8

Ed: M. Eric Gershwin

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The Humana Press Inc.

Tharratt and Chan

292 OVERVIEW OF THE PROCEDURE

Most diagnostic bronchoscopy is performed with the flexible fiberoptic i n s t r u m e n t and is undertaken utilizing topical anesthesia. Light intravenous sedation is a usual adjunct; we prefer to utilize conscious sedation in the majority of our diagnostic and therapeutic procedures. Bronchoscopy is usually performed in a procedure suite with capabilities for continuous EKG and oximetry monitoring. A trained assistant is required for patient monitoring and for assistance in specimen collection. Bronchoscopic equipment is portable and can be brought to the bedside in an intensive care unit or an emergency department, if needed (3). The fiberoptic instrument can be introduced into the patient via nasal, oral, or tracheostomy routes, depending on the condition of the patient and preference of the operator (I). Rigid bronchoscopy is usually performed in an operating suite since general anesthesia is often utilized for patient comfort. Most rigid bronchoscopies performed by pulmonary physicians are therapeutic in nature, often for foreign body removal, stricture dilation, control of hemorrhage, or laser resections. Bronchoscopy usually has diagnostic or therapeutic indications; occasionally a case is both diagnostic and therapeutic. Common indications are shown in Tables i and 2. There are no absolute prohibitions to bronchoscopy, although uncontrolled hemodynamic instability or bronchospasm makes all but emergency therapeutic bronchoscopic procedures contraindicated (1,4). Uncontrolled bleeding tendencies and positive pressure mechanical ventilation are relative contraindications to transbronchoscopic biopsy procedures (5). Morbidity and mortality are quite low with flexible bronchoscopy in trained hands approximating 0oland 0.01%, respectively (1,6, 7)~

DIAGNOSTIC USES OF FmBEROPTICBRONCHOSCOPY The majority of bronchoscopies today are performed for diagnestic purposes (8). The flexible bronchoscope provides an expanded viewing capability, usually easily visualizing the upper lobes and often providing visualization of fourth generation bronchi~ The rigid bronchoscope is more often utitized if a therapeutic procedure is also needed, such as localizing the source of massive hemoptysis, or removing a foreign body.

293

Sronchoscopy Table 1 Diagnostic Indications for Bronchoscopy Biopsy of visible bronchial Biopsy of distal

lesions

localized lesions under fluoroscopic guidance

Brushing of central

and distal

lesions

for cytologic

analysis

Transbronchial

needle biopsy for localized parabronchial

"Bronchoscopic

staging n of endobronchial

Localization of occult carcinoma

Culture and stains Use of p r o t e c t e d material

of aspirated brush

Transbronchoscopic

Diagnostic b r o n c h o a l v e o l a r

Visualization

carcinoma

(in situ) utilizing p h o t o f l u o r e s c e n c e

secretions and bronchial

catheters

lung biopsy

to

obtain

washings

"uncontaminated"

lavage

of the source of hemptysis

Visualization

of broncholiths

(cough, wheeze~

tubes

central

airways

for inhalation

Survey central

airways

for bronchial disruption

Transbronchoscopic

atelectasis)

and foreign bodies

Confirm correct placement of endotrachial

instillation

injury

of bronchographic media

Table 2 Therapeutic Indications for Bronchoscopy Intrabronchial

foreign body removal

Aspiration

of

mucus

Therapeutic

lavage

plugs

**

causing

atelectasis

in status asthmaticus

(rare)

Nd-YAG laser resection of obstructing bronchial masses Photodynamic

Instrumental

**

therapy of carcinoma

Placement of catheters

Tamponade

culture

for diffuse lung disease

Evaluation of v a r i o u s pulmonary signs

Survey

disease

for endobronchial b r a c h y r a d i a t i o n

dilation of bronchial

of massive hemoptysis

strictures

**

** U s u a l l y requires the rigid bronchoscope

**

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~tAGNOSIS AND STAGING OF BRONCHOGENtCCARCINOMAS The yield of these diagnostic procedures are highest for endobronchial carcinomas especially if they are located centrally, and therefore, visible bronchoscopically, tn such cases, brush biopsies (performed with a small device t h a t resembles a bottle brush) and forceps biopsies will positively identify the presence of tumor in 85-97% of cases in skilled hands (10,11). Lower yields are obtained in tumors that are predominantly submucosai. The minute tissue samples obtained with the biopsy forceps are often insufficient to reach the submucosal nests of tumor cells seen in small cell carcinoma. Tumors presenting in this manner can often be sampled with transbroncho.scopic needle biopsies (TBNB) (12). This technique utilizes either an 18-gage plastic or 19-gage stainless steel needle to pierce the bronchial wall and aspirate material for cytologic analysis. TBNB allows parabronchial lymph nodes and masses to be sampled. Computed tomographic scans of the chest enhance the ability of the bronchoscopist to correctly place the needle and maximizes sampling accuracy. The sensitivity of TBNB approximates 75%, and the specificity approaches 100% (13). Bronchoalveolar lavage (BAL), a technique in which saline solution is lavaged via the instrument channel through a bronchoscope that is wedged in a bronchopulmonary subsegment, provides a sampling of the cellular constituents of the alveolar space. Cytologic analysis of BAL fluid can be useful in the diagnosis of bronchoalveolar carcinomas. In addition to direct biopsy of visible mucosal abnormalities and masses, the biopsy forceps may be directed toward the periphery of the lung beyond direct vision. Referred to as transbronchoscopic lung biopsies (TBLB) (14,15), these biopsies sample the peribronchial lymphatic spaces and peribronchial alveoli. These biopsies are often positive in cases of lymphangitic spread of m a n y carcinomas (16), and are often successful in the biopsying of peripheral nodular masses, especially if performed with fluoroscopic localization. The usual diagnostic procedures in the setting of a clinical history suspicious for bronchogenic carcinoma include conducting a thorough systematic examination of the tracheobronchial tree, washing, brushing and biopsying any mucosal abnormalities or endobronchial masses, and performing BAL and/or transbronchoscopic biopsies, often under fluoroscopic guidance, in subsegments t h a t

Bronchoscopy

295

correspond to areas of radiographic abnormalities. A detailed inspection of the hypopharynx, pyriform sinuses, valleculae, and vocal cords is standard procedure in all diagnostic bronchoscopies (4). The staging of bronchogenic carcinoma has important clinical considerations in the comprehensive management of lung cancer. The current treatment of nonsmall ceil carcinoma is primarily surgicat, and since radiotherapy and chemotherapy, have limited value in increasing survival. Bronchoscopic techniques of staging are complementary to radiologic and surgical procedures in evaluating the patient for the advisability of definitive surgical therapy. Random biopsies of a grossly normal appearing main carina may reveal submucosal involvement with tumor in as many as 10%, especially if the tumor is originating in the right mainstem or right upper lobe (4,17) TBNB may also be useful in the staging setting (18). An exciting area of diagnostic/therapeutic bronchoscopy involves early diagnosis of radiographically occult lung cancer~ This unusual presentation of bronchogenic carcinoma may occur when sputum cytologies reveal neoplastic exfoliated cells, and radiographs and bronschoscopy do not reveal a lesion. Such occult carcinomas referred to as "carcinoma in situ" or Stage O carcinoma can present a diagnostic challenge. Current techniques of diagnosis involve a so-called "tong" bronchoscopy (19). Usually conducted under general anesthesia, the examination requires each bronchial subsegment to be brushed, washed, and biopsied in an attempt to localize the segment involved. Care is taken to accurately label each specimen. If the cytological and/or histological studies from a segment are positive for maiignancy, a second bronchoscopy is done, repeating the sampling of the possibly involved segment. Two positive samples from the same subsegment on separate occasions are usually required to confirm the localization. A potential alternative to this tedious procedure involves photodynamic laser therapy (20,21). A class of compounds known as hematoporphryin derivatives (HpD) exist that are avidly retained by neoplastic cells. When illuminated by laser light generated by an argon laser in the blue wavelength (405 nm), these compounds fluoresce and emit a yellow-red light that can be quantitated. This technique allows the direction of biopsies to areas that show no or only subtle changes to the naked eye, and improves the localization of stage O carcinomas. This technique can also be therapeutic by altering the wavelength of lazed light (see therapeutic section).

296

Tharratt and Chan ~SE OF ~RONCHOSCOPY IN THE DIAGNOSIS

OF PULMONARY ~NFECTtONS Another major diagnostic application for bronchoscopy is the diagnosis of pulmonary infections. Bronchial washings and aspirates can be cultured for aerobic bacteria, fungi, viruses, and mycobacterial organisms. Various staining techniques can rapidty and accurately identify organisms such as acid-fast mycobacteria, Legionella pneumophila, and parasitic organisms, such as, Pneumocystis carinii (22), amebic trophozoites, and nematode larvae. Limitations to the utility of the culture techniques liein the fact that whereas the tracheobronchial tree is normally nearly sterile, the bronchoscope must reach the bronchi via the nose or mouth, an area normally colonized with over 200 species of various flora. Identification of a nonnative organism recovered from the bronchial region, such as Pseudoraonas sp. does not usually present a problem in diagnosis, however, interpreting the clinical significance of a potential pathogen such as various Streptococcus species from a bronchial wash, can often be difficult. Further problems occur in the intensive care unit where the tracheobronchial tree of an intubated patient rapidly becomes colonized with gram-negative aerobic bacteria (23), and distinguishing between colonization and infection can be difficult. The use of a telescoping double brush with its end covered with a small carbowax plug (often referred to as a protected specimen brush or Bartlett brush) allows sampling of the bronchial environment with a minimum of extrabronchial contamination (24). Specimens suitable for anaerobic culture can also be obtained. The technique of use of these catheters requires meticulous attention to collection details and the use of quantitative cultures to obtain the maximum diagnostic yield from these brushes. Sensitivity and specificity range from 59-90% (22). The highest yields are obtained prior to the institution of any antibiotic therapy. Since it is unusual to perform bronchoscopy on any patient prior to the institution of empiric antibiotic therapy, these catheters do not often reach their full potential. The explosive development of bone marrow and solid organ transplant technology, together with the rapid emergence of the acquired immunodeficiency syndrome (A!DS), have resulted in the development of a large pool of immunocompromised hosts. Bronchoscopic techniques, including bronchoalveolar lavage, transbronchoscopic bi-

Bronchoscopy

297

opsy, and protected specimen brush catheter sampling have significantly reduced the number of open lung biopsies required to diagnose opportunistic pathogens in these patients. The overall success with bronchoscopic diagnosis of infiltrates in the immunecompromised patient is approx 66% (25). The sensitivity of BAL in diagnosis of Pneumocystis carinii pneumonia in patients with AIDS approximates 85% (26). The addition of transbronchoscopic biopsies to a diagnostic bronchoscopy in the immunocomproraised patient improves the diagnosis of malignancy from 40% to approx 70% but only minimally increases the yield in the diagnosis of infectious process~ This increase in yield must be balanced with a higher risk of complications as these patients are usually critically ill and often on mechanical ventilation. Open lung biopsy is an alternative, albeit an invasive alternative.

Nonneoplastic, Nonhffective Indications Patients presenting with diffuse pulmonary abnormalities compose a heterogeneous group. A majority of the patients successfully diagnosed by bronchoscopy will have malignant or infectious processes. Transbronchoscopic biopsies can reliably diagnose sarcoid by finding noncaseating granulomas (27). Primary alveolar protenosis is also occasionally diagnosed by TBLB (16), as is Histiocytosis X by electron microscopic visualization of burbeck bodies in the Langerhans cells. The diagnostic yield in other interstitial processes, especially the interstitial fibroses, is less. This is owing to the fact that the majority of interstitial processes are patchy, and the number of alveoli sampled with transbronchoscopic lung biopsy is often too small to rely on for diagnostic certainty (28). These patients will usually undergo bronchoscopy to "rule out" infective and neoplastic processes prior to an open lung biopsy that is usually required to reach a diagnosis. Bronchoalveolar lavage holds promise in the evaluation of interstitial processes although the clinical utility of the procedure has not been established. A detailed discussion of the utility and limitations of BAL by Martin and Cross can be found elsewhere in this issue. Minor hemoptysis, somewhat arbitrarily defined as hemoptysis less than I00 cc in I h, less than 600 cc in 24 h, and not producing airway obstruction, is a frightening sign to most patients who usually rapidly seek medical attention. Although in the majority of cases in the United States today hemoptysis is secondary to chronic bronchitis, hemoptyMs can also be the first sign ofa bronchogenic carcinoma

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even with a normal chest radiograph. Bronchoscopy is frequently utilized to localize the bleeding segment and "rule out" a neoplastic etiology. The decision to employ bronchoscopy must be made on an individual basis based in part on the results of a complete history and physical examination. Emergent bronchoscopy is rarely indicated in these patients; a delay of 12-24 h will only result in a small reduction in the likelihood that the bleeding site will be localized, and is more than made up for by having the full bronchoscopic staff available in the event of a major hemorrhage. Major hemoptysis will be discussed in the section of therapeutic indications.

Other Diagnostic Indications Bronchoscopic examination may be indicated if airway damage is suspected. Traumatic airway injury may include inhalation injury after burns (29), bronchial tears after chest trauma from decelerating force injury (30), or subglottic injury after prolonged tracheal intubation (4). Bronchoscopy can confirm the position of endotracheal tubes, and is most useful intraoperatively to place and confirm the correct positioning of double lumen bronchial catheters (31). In the intensive care setting, a chest radiograph is usually a more cost effective confirmatory study for correct tube positioning.

Diagnostic Bronchoscopy in Asthma and Pseudoasthma Diagnostic bronchoscopy is sometimes indicated in wheezing patients to delineate cause(s) of the "pseudoasthma syndromes." These conditions often mimic asthmatic conditions but have markedly different treatments. A foreign body that generates a localized wheeze is an example ofa pseudoasthmatic condition. Some clinical circumstances suggesting pseudoasthma are listed in Table 3. Occasional patients with allergic bronchopulmonary aspergillosis (ABPA) will show Aspergillis spo in bronchoscopic cultures and have hyphal elements in smears of bronchial plugs removed at bronchoscopy; these may help fix the diagnosis of ABPA in a patient with an appropriate history (32).

Therapeutic Indications for Bronchoscopy The division between diagnostic and therapeutic bronchoscopy is nebulous at best. A diagnostic indication such as complete atelectasis of the left lung may become therapeutic when the obstructing mucus plug is removed from the left main bronchus. Advances in

Bronchoscopy

299 Table 3 Clinical Circumstances Suggesting Pseudoasthma

Atypical history for asthma Dyspnea disproportionately

great for the degree of wheezing

History suggestive of foreign body

inhalation

Physical signs other than wheezing Stridor Wheezing loud over the neck and faint over the lungs Masses palpable

in the neck

Abnormal chest radiograph

bronchoscopic techniques and equipment have led to an explosion in therapeutic indications,and the development ofinterventionalbronchoscopy. The early bronchoscopies performed by Gustav Killian were for therapeutic indications, i.e., foreign body removal. Therapeutic bronchoseopy usually involves placing or removing substances in the airways. Foreign body removal continues to be a significant indication for bronchoscopy. Aspiration of foreign bodies is seen predominantly in the pediatric population with a peak incidence between the ages of one and three years; the period of time when children are "oral explorers" (33). The usual aspirated objects include seeds, and nuts, especially peanuts; less commonly seen are small nonvegetable objects or pieces of toys (34). Foreign body aspirations in adults are usually associated with altered states of consciousness secondary to alcohol and/or drugs. Patients with psychiatric disorders and/or mental retardation are also at risk for foreign body aspiration. Foreign bodies are usually easily removed with the rigid bronchoscope; several special purpose forceps exist for extremely specialized tasks such as folding and sheathing the point of a straight pin (35). The rigid bronchoscope is usually chosen, especiallyin the pediatric population, because of its superior airway control and larger orifice for instrument manipulation; however, some bronchoscopists are skiiled at using the flexible scope to remove small objects utilizing forceps, tongs, and wire baskets. Morbidity and mortality, although small, are increased approx 100-fold compared to diagnostic bronchoscopy (1,35). Removal of"natural bodies," usually in the form of mucus plugs, can be accomplished with either the flexible or rigid bronchoscope. Removal of central obstructing plugs usually result in the reexpansion of distal lung parenchyma with improvement in oxygenation and gas exchange (36). Presence of a distal air bronchogram on a chest radiograph usually portends a poor response to bronchoscopic attempts at reexpansion (37).

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Tharratt and Chan

Massive hemoptysis is variously and somewhat arbitrarily defined as sufficient bleeding to obstruct the airway or 600 cd24 h (4). Massive hemoptysis is usually a spectac~ar medical emergency that almost always calls for rigid bronchoscopy. This maximizes the ability to maintain a patent airway, allows for rapid suctioning of blood while maintaining visualization, and allows the option of packing off the involved airway if needed. Other temporizing methods of controlling massive hemorrhage include blockage of the bleeding segment with a Fogarty catheter (38), or the infusion of thrombin or fibrinogen-thrombin solutions to achieve hemostasis (39). Definitive management is dependent on the etiology of the bleeding. Surgical resection and radiologic embolization of bronchial arteries are therapeutic options.

TREATMENT OF CENTRAL OBSTRUCTING LESIONS A small population of patients present with congenital or acquired central airway obstructions. The vast majority of the acquired lesions result from nonsmall cell carcinomas. These patients usually are not candidates for surgical resection of the tumor. Endobronchial resection of obstructing airway neoplasms using laser therapy can provide significant palliation from asyphixiation caused by airway obstruction, or death from postobstructive pneumonitis. For the majority of pulmonary indications, the Neodynium-Yittrium Aluminum Garnet (Nd-YAG) laser is used. Its wavelength in the near infrared (1064 nm) spectrum provides coagulation and desiccation at low powers, and vaporization at higher power settings. The cutting beam is not as precise as the carbon dioxide laser (and is rarely needed); coagulation of bleeding is markedly superior. The laser energy can also easily be carried via a quartz fiber passed through the instrument channel of the bronchoscope. Controversies exist over the optimal bronchoscope to use in these cases. The rigid bronchoscope offers all the advantages of foreign body removal; the skills of which are similar to laser resection, together with superior airway control in a nonflammable instrument. Advantages of the flexible bronchoscope include better access to the distal reaches of the main conducting airways (espedally the distal left mainstem bronchus). The flexible instrument is often the only way to resect high tracheal lesions when the distance beneath the

B~nchoscopy

301

vocal cords will not allow placement of the rigid ventilating bronchoscope. Based on our experience with both instruments in 200 cases, proficiency with both bronchoscopes appears to provide the greatest versatility and maximum safety margin (9). We begin virtually all of our laser resections utilizing the rigid bronchoscope, and use the flexible bronchoscope passed through the rigid bronchoscope, if needed, for parts of the resection. In addition to the diagnostic uses ofhematopyrphyrin derivatives discussed earlier, HpD may have therapeutic capabilities. By adjusting the dye laser to emit light in the red wavelength (630nm), tumor fixed HpD can be stimulated into an unstable state that generates intracellular singlet oxygen (40). This compound is rapidly toxic to the cell. The exact role of this laser in the palliation of nonsmall cell cancer is being examined in a large mutticenter prospective trial. Other "second generation" photosensitizers are being developed that may prove to have advantages over the currently available compounds. Radiation therapy is commonly employed in the treatment of nonsmail cell carcinoma of the lung. Limiting factors in the delivery of therapeutic teleradiotherapy are the relative radiosensivities of structures in the radiation field, especially the tung and spinal cord. Fractionating of the radiation dose, the use of oblique beams and local boosting of the tumor are all techniques used to minimize radiation damage to surrounding structures. The development ofendobronchial brachyradiotherapy may prove advantageous as one part of a multimodality approach to the palliation of lung cancer. Brachyradiotherapy (brachy = close) utilizes a radioactive source placed in close proximity to the tissue of interest. It differs from implantation of radioactive sources, such as gold 84 seeds, in that the radioactive source is removed after the radiation dose is given. In practice, a hollow catheter is placed via bronchoscopic guidance to the area involved with tumor. This catheter exits via the trachea, hypopharynx and nose. A radioactive source, usually iridium 192, is placed into the catheter by hand or remote control. The wire then dwells at the tumor site for a time dependent on the activity of the radioactive source to provide the desired radiation dose. The source and catheter are then removed from the patient. There is little data available comparing this new mode of therapy with teleradiation. We currently use brachyradiation to potentiate the time an involved airway remains patent after removing the endobronchial portion of tumor with the Nd-YAG laser.

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Therapeutic lndications Specific to Ailergic Disorders The extreme therapeutic indication of bronchoscopy in allergic mediated diseases is seen in emergency bronchoscopy to remove central airway plugs in intractable status asthmaticus. Although this is an extremely high .risk procedure, it has been lifesaving in selected cases (4I). A similar condition exists in the relatively unusual condition of plastic bronchitis in children (42). Plastic bronchitis obstructs the central conducting airways with a mucoid material that conforms to the bronchial tree. Therapy has consisted of repeated bronchoscopies with bronchial irrigations.

CONCLUSIONS Bronchoscopy has evolved to play a pivotal role in the diagnosis and t r e a t m e n t of m a n y diseases and conditions. The further development of new techniques and equipment will only add to the importance of this diagnostic and therapeutic modality. The development of interventional bronchoscopy has led to a "rediscovery" of rigidbronchoscopy skills among pulmonary physicians. Am appreciation of the capabilities and limitations ofbronchoscopy allows all respiratory specialists to provide optimal management of patients suffering from pulmonary related disorders.

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Diagnostic and therapeutic bronchoscopy.

Diagnostic and Therapeutic Bronchoscopy Ro Steven Tharratt* and Andrew Chan Division of Pulmonary and Critical Care Medicine, University of California...
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