Bronchiectasis

Key words: bronchiectasis; bronchoscopy; COPD; hemoptysis; polyps

Pulmonary clinicians are often faced with management problems for which there are no answers at hand, either because there is no literature that gives definite answers, because there are conflicting data in the literature, or because the circumstances surrounding the clinical cases are unusual enough to prevent the application of existing scientific knowledge. When faced with these problems, clinicians are forced to make decisions based on a logical extension of their scientific knowledge into uncharted clinical waters. They are forced to make judgments based on the conviction of their speculations and on prior experiences.

This clinical conference addresses difficult management problems without singularly correct decisions. Its object is not necessarily to seek consensus. Defining the exact issues, formulating rationales for decision making, and committing to the decisions themselves are all equally important in this presentation. This is a real case in which the decisions were made by the "treating pulmonologist" without input from the other participants. The "Responses of Pulmonary Experts" are given only with the knowledge of the case presentation up to the moment at which each expert gives his or her decision and without the knowledge of any of the other opinions rendered. The last "Commentary" opinions are given only with the knowledge of the case presentation and the remarks of the treating pulmonologist but without the knowledge of any of the other opinions rendered. Although the opinions in the "Commentary" section are the last in the sequence of this presentation, they are not necessarily offered as definitive solutions to the problems posed in the case. The reader is the ultimate arbiter in this presentation of decision-making alternatives.

CASE REPORT

A 70-year-old Persian man with a history of right lower lobe pneumonia at age 3 years had another occurrence of right lower lobe pneumonia in March 1992. After this, while receiving therapy with oral antibiotics for 4 months for the same case of pneumonia, he developed worsening shortness of breath and right lower lobe pleuritic chest pain. At the end of June 1992, he developed temperatures up to 38 [degrees] C, which continued for the next 3 weeks and were associated with a daily expectoration of 1 tablespoon of yellow sputum with streaky hemoptysis. He was given therapy with cefaclor po on July 19, which decreased his fever. He had a history of having smoked two packs per day for 40 years up until 10 years earlier.

On examination on July 20, 1992, the patient appeared to be a well-developed, well-nourished, white man with a cough. His BP was 145/73 mm Hg, his heart rate was 107 beats/min, his respiratory rate was 32 breaths/min, and his oral temperature was 36.5 [degrees] C. A chest examination revealed decreased breath sounds and inspiratory crackles at the right base, but there were no wheezes, either diffusely or localized. The results of cardiac, head, neck, abdominal, and extremity examinations were unremarkable. A chest radiograph performed on July 20, 1992, is seen in Figure 1. The measurement of arterial blood gas levels on room air revealed the following: pH, 7.46; PC[O.sub.2], 29 mm Hg; and P[O.sub.2], 91 mm Hg. The hemoglobin level was 12.6 g/dL, hematocrit was 36.6%, and the WBC count was 9,900 cells/[micro]L.

[FIGURE 1 OMITTED]

The impression of the admitting pulmonologist (JS) was that the patient had severe bronchiectasis of the right lower lobe with new hemoptysis, shortness of breath, and borderline lung function. The possibility of pneumonia in the right lower lobe also was entertained. The patient was admitted to the hospital for IV antibiotic therapy, receiving ceftazidime and clindamycin. Thereafter, his condition showed improvement in the hospital with the breaking of his fever, the cessation of hemoptysis, and a reduction in sputum volume. The patient underwent fiberoptic flexible bronchoscopy on July 23, which revealed bronchiectasis of the major airways, especially in the right lower lobe. The probable site of bleeding was determined to be the right lower lobe, where the mucosa was seen to be very boggy, but no active bleeding, no fresh blood, and no secretions were seen. An examination of the right middle lobe bronchus revealed the presence of two polyps (Fig 2), which were described as smooth, pink, conical in shape, perpendicular to the bronchial wall, twice as long as they were wide, and reaching slightly more than half-way across the lumen.

[FIGURE 2 OMITTED]

RESPONSES OF THE PULMONARY EXPERTS

Dr. Jim Harrell, San Diego, CA

Editor's note: Dr. Harrell directs the University of California San Diego Pulmonary Special Care Unit, which he established in 1971 and in which he currently performs > 2,000 flexible and rigid bronchoscopies per year.

In reviewing the radiograph of this case (Fig 1), it appears that the patient has a possible calcified granuloma in the right chest. The appearance of the right-middle and right-lower lobes seems to be a combination of atelectasis, possible bronchiectasis, and multiple air-fluid levels. Since the fissure is pulled downward, the lesion that may be calcified probably is not in the middle lobe. In evaluating this patient, a CT scan would have been helpful both to assess the damage to the middle and lower lobes and also to see whether there were any other calcified lesions around the orifice of the middle lobe. Once I could see whether there was any calcium near the middle lobe, I would personally repeat the bronchoscopy in the patient. The provided photographs (Fig 2), although interesting, do not allow the detail that a personal bronchoscopic examination could give. It would be important to palpate these lesions with the bronchoscope to see how firm they are and also to examine in detail the mucosa and the base of the lesion. I do not think that these are truly what I would call pedunculated lesions. They have more the appearance of submucosal lesions that invaginate into the airway. Truly pedunculated lesions that I have seen in the right middle lobe area include papillomas, lipomas, and carcinoid lesions. It is unusual to have two such lesions, unless the bronchus is surrounded with a carcinoma with two invaginations of carcinomatous tissue coming into the bronchus. This patient had been a smoker, and there is significant risk of carcinoma. Lymph nodes are located in this area, which can cause a right middle lobe syndrome, and calcified lymph nodes can erode into the orifice and either be covered by mucosa or, if they create a hole in the mucosa, can be covered with granulation tissue. At times, interestingly enough, granulation tissue may be secondarily infected with agents such as Aspergillus, Actinomyces, Coccidioides, or tuberculosis. (1) Tracheopathia osteoplastica (2) can affect the entire airway, and I have seen such lesions that were similar in appearance to those of the patient in this case. However, in patients with tracheopathia osteoplastica, the lesions are generally seen throughout the tracheobronchial tree, including the distal airways. Rarely may endobronchial endochondromas appear like the lesions in this case.

In the present case, I would like to know the status of the bronchus around this lesion and whether there is infiltration, edema, or friability. Nevertheless, I would not hesitate to perform a biopsy of both lesions. If an answer were not achieved with flexible bronchoscopy, a cupped-forceps biopsy could certainly be performed with a rigid bronchoscope. If malignancy were the diagnosis for the lesions, the patient would need to be staged, have pulmonary function testing, and be evaluated for resection. If there is an underlying calcified lymph node, right middle lobe resection should be considered. If calcified nodes erode through an airway, they continue to cause problems. In the event that the patient is not an operative candidate, and the lesion is not calcified, careful laser resection of the polyps may be considered. However, this patient's lesions are more distal than those considered to be ideal for laser resection. If the lesions are malignant and the patient is not an operative candidate, he may then be considered for external beam radiation and/or endobronchial irradiation or brachytherapy. I think this patient has destroyed middle and lower lobes and would probably benefit from surgical resection (assuming he remains a candidate for surgery by the usual medical criteria and has adequate pulmonary function).

In discussing true polyps of the airway, both lipomas and true polypoid carcinomas can be resected successfully by laser therapy. (3) Single papillomas can be resected, but in the long term papillomas do have a chance of malignant degeneration. (4) True malignant polypoid lesions of the airway are very rare. In nonsurgical candidates, these lesions could be resected with the laser and then considered for external beam irradiation or, in very specific selected cases, for brachytherapy by fractionated endobronchial treatments.

Dr. Praveen Mathur, Indianapolis, IN

After this patient has recovered from the current crisis of bronchiectasis and respiratory failure, I would be interested in the diagnosis of these endobronchial polyps. I would obtain a high-resolution CT scan not only to look for the bronchiectasis, but also to look at the right middle lobe with fine cuts to see whether there were any extensions of these polyps beyond the endobronchial tree. I would also be interested in any hilar or mediastinal lymphadenopathy since this patient has risk factors for lung malignancy due to his long smoking history. Next, I would obtain pulmonary function tests and blood gas measurements to establish the safety of performing fiberoptic bronchoscopy, which I would then repeat myself.

During fiberoptic bronchoscopy, several options would be considered in order to diagnose the condition of these endobronchial polyps, including the use of an endobronchial biopsy and/or a transbronchial needle biopsy that directly aspirated a specimen from the polyp. (5) With white-light bronchoscopy, malignancy can be confidently diagnosed in certain lesions; however, diagnoses of severe dysplasia or carcinoma in situ are very difficult to be certain about. Due to this potential uncertainty and the fact that this patient is at high risk for malignancy, at our institution we would perform autofluorescence bronchoscopy to help us define the lesion. (6) In addition, if endobronchial ultrasound were available, this technique could define any bronchial wall involvement by the polyp as well as any lymphadenopathy. (7) My preliminary impression or speculation, as I look at the photograph of the polyp provided (Fig 2), is that this may be a benign lesion.

With the involvement of a pathologist and cytologist who are devoted to the investigation of lung pathology, there is a high likelihood that the diagnosis will be obtained. Certainly, the endobronchial biopsy may obtain only a very superficial specimen. But the possibility of obtaining a cytologic diagnosis is improved considerably by penetrating the lesion with a transbronchial needle and by having an on-site pathologist investigate the specimen (as is done at our institution). There would be a considerable risk if there was an attempt to excise this lesion totally with fiberoptic bronchoscopy as opposed to laser therapy or cryotherapy; however, the use of laser and cryotherapy may distort the pathologic specimen.

If this lesion was malignant and the patient was at our institution, he would be seen in the multidisciplinary thoracic oncology clinic and appropriate therapy would be based on the staging of the lesion. (8) The option of surgery would depend on pulmonary function, cardiac status, and the general physiologic well-being of the patient. If the patient were deemed not to be a surgical candidate, several endoscopic options would be available, depending on local expertise and the availability of equipment. These include the use of the Nd-YAG laser (which is the "gold standard"), a potassium titanyl phosphate (KTP) laser used with rigid bronchoscopy (preferred), (9) and other ablation techniques such as cryotherapy, electrocautery, intraluminal radiation (brachytherapy), and argon plasma coagulation, for which a fiberoptic bronchoscope could be used. (10,11) If the CT scan and bronchoscopy findings suggest that the lesion is localized and superficial, then consideration should be given to the use of photodynamic therapy or brachytherapy with the goal of attempting to cure the lesion. (11,12)

If this lesion happens to be benign, it is unlikely to be the cause of the bronchiectasis but is probably responsible for the hemoptysis. In this case, I would consider endoscopic ablation. A variety of endoscopic options are available, and the decision about which one to use should be based on the expertise of the physician and the institution. These options are the same as those used for malignant endobronchial lesions and would provide similar results. (9-12) However, the success of cryotherapy would depend on the composition of the benign lesion, since certain benign lesions are cryoresistant, such as chondromas or hamartomas. (10,11)

COMMENTS BY THE TREATING PULMONOLOGIST

Dr. Jeff Schnader, Dayton, OH

This small case posed a great dilemma for me since I had never before (and have never since) seen a case of apparently benign, noninfected, single or multiple endobronchial polyps, nor have I ever heard of this problem discussed even in the most fleeting or casual way in any conference I have ever attended. Oddly enough, although polyps of the GI tract are common, benign polyps of the bronchial tree (which, as we are all aware, is an embryologic bud of the GI tract) are notably rare. (13,14) When I asked my pulmonary colleagues, both locally and around the country, what their experience with this problem was, only one had ever seen a case, and only one other had ever heard of similar cases presented. The benign endobronchial polyp was first described in 1930 by Patterson (15) who called it a "neoplasm." However, since the term neoplasm refers to lesions that grow excessively after cessation of the stimuli that evoked the growth (16) and that are "purposeless, prey on the host and [are] autonomous," (17) then benign polyps do not seem to fit this definition. This may have led to early misunderstandings concerning the nature of benign polyps, which may have led to an overeagerness by clinicians to excise them rather than to treat them conservatively and observe. Other early reports (18-20) exist, generally in the surgical literature. Often, the polyps described in these reports are referred to as "inflammatory," and their etiologies have been attributed to asthma, (21-23) a foreign body, (24-25) thermal inhalational injury, (26,27) titanium tetrachloride, (28) smoke injury or inhalation, (27,29) and chronic bronchial infection, (30,31) the category into which the current case falls.

When first confronted with this case, I decided that the presence of multiple (in this case two) polyps was against this being a carcinomatous process. (22) Second, I reflected on what might be the difference between benign and malignant characteristics of a polyp on visual inspection. I thought that the appearance of these polyps was decidedly benign. They were smooth, pink, conical-shaped, had a relatively narrow base, were covered with what appeared to be normal-looking mucosa, and had no erythema, ulceration, nodularity, necrosis, or associated visible vascular abnormality. Parenthetically, their appearance also suggested that they were themselves uninflamed and were not the source of the hemoptysis. Third, I decided to perform a biopsy of the polyp. When I had performed a biopsy on the more proximal polyp, it dodged and sprang away from the forceps with that resilience or elasticity (or compliance) that I have experientially associated with more healthy tissue, very unlike neoplasia. The histology of the polyp revealed squamous metaplasia, which is the most frequent pathologic description of benign polyps that I have encountered in the literature. (13,29,30) I noted that in the case of my patient, the polyps were located in the right lung near a chronic locus of infection and bronchiectasis. I speculated that epithelial growth possibly was related to the release of mediators (perhaps growth factors) by the body's defense system, induced by an ongoing infectious process of at least 4 months' (or perhaps longer) duration. Last, I considered that my patient was an older man who had an 80 pack-year smoking history with possible severe impairment of his lung function, and this made me reluctant to jump to a surgical solution to his problems.

Although the treatment for polyps that appear to be ulcerated, granulomatous, virally papillomatous, grossly infected, or grossly cancerous might seem obvious, the management of either single or multiple benign-appearing polyps is unclear from the literature, and possibly even controversial. Eppinga et al (32) stated outright, in 1988, that "surgical resection is the chosen treatment" mostly based on the rationale that benign polyps are "often indistinguishable from malignant tumors." More recently however, other clinicians have found (22,24,25,29) that these polyps may regress and even disappear with medical treatment (ie, inhaled steroids). In one case, a polyp that had been present for 6 years was treated with inhaled steroids and disappeared within 1 year. (22) I found nothing in the literature describing a benign polyp transforming into a malignant lesion. In fact, there is very little published on the natural course of these lesions (eg, whether or not they are precancerous and whether or not they grow or regress spontaneously) or on whether surgical excision might be truly beneficial.

Initially, I was not totally familiar with the literature. My decision, after a discussion with the patient in which I stated the rarity of his condition and our community's lack of knowledge of the natural history of the benign polyp, was to observe his polyps over time and treat them with an agent that could possibly reverse the inflammation. I treated him with long-term antibiotic therapy, at first IV in the hospital and then by mouth, inhaled triamcinolone, and the avoidance of surgery. Pulmonary function testing was performed. I decided to impose a "2-year rule," whereby if I could document a lack of growth or change in the appearance of the polyps and the associated segment of airway for > 2 years, I would consider this proof of their benign nature, much as I would an intrapulmonary nodule. And since the only way I could visualize the polyps was to perform a bronchoscopy on the patient, I observed the patient's condition with serial bronchoscopies, much as I would a nodule with serial radiographs or CT scans. Repeat bronchoscopy was performed in October 1992, February 1993, January 1994 (during an occurrence of hemoptysis; Fig 3), and December 1994 (again during an occurrence of hemoptysis). There were never any changes in the polyps, and although there was no disappearance or regression of the polyps, I considered their stability to be strong evidence (if not proof) of their benign nature.

[FIGURE 3 OMITTED]

Hospital Course: During bronchoscopy, the top of the most proximal polyp was removed with a forceps for histologic examination. Histologic and cytologic testing of the bronchial washings were negative for neoplasm. A report on the histology stated, "Fragments of bronchopulmonary tissue showing foci of metaplastic epithelium. No granulomas or fungi seen." The results of special stains for fungi and acid-fast bacilli were negative. Cultures of endobronchial secretions were negative for all organisms.

The patient was maintained on IV antibiotic therapy and eventually was placed on a regimen of oral clindamycin, 300 mg tid, and cefixime, 400 mg every morning. He began receiving triamcinolone, 8 puffs bid by oral inhalation. He did well on this regimen initially and was observed by serial bronchoscopy for confirmation of the stability of the polyps and for the localization of occasional bouts of hemoptysis. His course was characterized by an obstruction of the airflow, which was reversible to some degree, and by several bouts of bacterial lung infection requiring hospitalization for IV antibiotic therapy and steroid therapy for wheezing. The patient was last seen by the author (JS) in January 1995 when he was relatively well. The polyps never changed.

COMMENTARY

Dr. Paul Kvale, Detroit, MI

Benign polyps, either single or multiple, are extremely rare. I have never encountered one in nearly 30 years of active bronchoscopy practice. (I estimate my total volume of bronchoscopies at about 8,000 to 10,000 procedures.) For 18 years, I have actively solicited referrals for interventional bronchoscopy (laser-assisted debulking of tumors, for example). Pulmonary physicians, thoracic surgeons, and otolaryngologists have referred patients to me whom they believed had benign bronchial polyps, but on each occasion a different etiology was proven by a more extensive biopsy and pathologic evaluation. I think it is nearly impossible to state that a lesion is a benign polyp from its gross endoscopic appearance.

Endobronchial polypoid lesions that have been thought to represent benign polyps in my practice have included true neoplasms such as carcinoid, adenoid cystic carcinoma, and mucoepidermoid carcinoma. Most of the time there is little doubt that the polypoid lesion in question is a neoplasm. However, sometimes the vascular appearance of the tumor stimulates the bronchoscopist not to biopsy the lesion because of concern that the bleeding might be excessive. On other occasions, the tissue taken with the small forceps used with flexible bronchoscopes does not provide a specimen that the pathologist can properly characterize as a malignancy. (In these circumstances, skills with a rigid bronchoscope are invaluable, so that larger and deeper biopsies can be performed.) There are other rare malignant neoplasms that might be confused with a benign polyp, such as a chondrosareoma or paraganglionoma.

Polypoid lesions other than malignant neoplasms can be confused with benign polyps. Squamous epithelial papillomata are rarely single, and they have an appearance that resembles tapioca pudding. When such papillomata are confused with another entity, they are more often thought to be a carcinoma than benign polyps. Tracheopathia osteoplastica has a polypoid appearance, but it is a condition that never involves the membranous portion of the airway, only the cartilages; it is almost always confined to the trachea, mainstem bronchi, and the intermediate bronchus. The localization to the cartilages plus its extremely hard consistency, which makes biopsy difficult, is diagnostic. Granular cell myoblastoma can be single or multiple in the airways and would be managed much as this case was, expectantly or by removal if it were associated with recurring infections in the affected lobe. Endobronchial amyloidosis is a rare entity that is not seen by most bronchoscopists in a lifetime of practice. It tends to be diffuse within the airway, but it may be localized and resemble one or several polyps. Polypoid growths may cover an underlying broncholith. Endobronchial hamartoma is an unusual finding, and it certainly could be confused with a simple benign polyp. A final example from my own practice this year was localized invagination of benign mucosa, causing the appearance of a polyp in a patient with emphysema. The stability of the membranous portion of the airway at the origin of the lower lobe bronchus was more pronounced than in the rest of the airways, giving rise to the appearance of a localized benign polyp.

How and why did this patient develop a benign polyp? I am tempted to speculate that the episode of right lower lobe pneumonia at age 3 years might have been related to the unrecognized aspiration of a foreign body. That age is the primary group at risk, since 75 to 90% of all foreign bodies found in pediatric population groups occur under the age of 3 years. (33-36) Boys more commonly aspirate foreign bodies than girls, in a ratio that varies from 1.2:1 to 2:1. (33,35,37,38) The right side is the locus of aspirated foreign bodies 56% of the time, (33) and the right lower lobe is a common location (28%) for a foreign body to become lodged in the airway. (39) The aspiration of foreign bodies can remain occult for years and can lead to an incorrect diagnosis of asthma, bronchitis, and chronic pneumonia. (40-42)

The patient's current problem is in the right lower and middle lobes, essentially the same location as the childhood episode of pneumonia. We are not told whether the patient had chronic lower respiratory symptoms during the interval between the childhood pneumonia and the current illness. His chest radiograph (Fig 1) and the CT scan of his chest (Fig 3) revealed findings that are characteristic for bronchiectasis. All of these phenomena are consistent with a foreign body that may have been undetected for decades. The polyp could have been a reactive process to a foreign body, (24,25,43) if one was ever present, and the patient may have expectorated the foreign body before the first bronchoscopy was performed. Alternatively, the polyp could have been a reactive process to the inflammation in that portion of the lung and airway that was chronically infected.

There are four possible management approaches that might be taken for a patient with a benign inflammatory polyp such as this patient had. First, the first would be simple observation. However, to simply observe such a patient implies that the biopsy specimen has been judged to be adequate for the pathologist to state unequivocally that the polyp is benign and not a more ominous process. Second, as this approach may require rigid bronchoscopy with larger cup-forceps biopsy, the polyp may end up being removed endoscopically in the process. Endoscopic removal of a polyp often can be done with the mechanical energy of the bronchoscope and forceps, particularly if a rigid bronchoscope is used. The removal of the polyp by endoscopic means could be facilitated by the use of a laser or by electrocautery, but a polyp this small seldom would require more than large cup forceps for it to be completely resected with a bronchoscope. Although bleeding might occur, rarely would I expect it to be so severe that cauterizing instruments would be needed for control. Third, to simply observe such a patient would be predicated on clinical circumstances in which there were no associated symptoms of chronic or recurring infection. Inflammatory polyps have been attributed to inhalation injuries, and therapy with systemic or aerosolized corticosteroids has been reported (22,24-26,28,29) to induce the regression of such polyps. Fourth and finally, if symptoms of chronic but localized infection cannot be adequately controlled by the use of steroid and/or antibiotic therapy, surgical resection of the affected lobe likely would relieve the symptoms and result in the removal of the offending polyp.

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* From the Pulmonary and Critical Care Section (Dr. Schnader), Department of Veterans Affairs Medical Center, Dayton, OH; the Department of Medicine (Dr. Harrell), University of California at San Diego, California; the Department of Medicine (Dr. Mathur), Indiana University School of Medicine, Indianapolis, IN; the Department of Medicine (Drs. Schnader and Koduri), Wright State University School of Medicine, Dayton, OH; and the Department of Medicine (Dr. Kvale), Wayne State University School of Medicine, Detroit, MI. Dr. Joseph is in private practice.

Manuscript received July 26, 2001; revision accepted August 16, 2001.

Correspondence to: Jeff Schnader, MD, CM, FCCP, Chief, Division of Pulmonary and Critical Care Medicine, Wright State University School of Medicine, Veterans Affairs Medical Center (111), 4100 West Third St, Dayton, OH 45428; e-mail: jeff.schnader@med.va.gov

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