Although many new treatments have been introduced, respiratory papillomatosis remains incurable
Papillomatosis is generally thought to be viral in origin.1 Respiratory tract papillomas, rare in adults, are derived from surface epithelium at mucosal junctions.2 It is even less common to find tracheobronchial papillomatosis without laryngeal involvement, since it spreads through aspiration of viral particles from the larynx.3
These tumors are composed of fibrovascular connective tissue covered by stratified squamous epithelium.4 Histologically, these tumors are usually benign, although malignant transformations have been documented.5 The papilloma lesions can be seen through direct bronchoscopy, virtual bronchoscopy,6 and radiography.7
Treatment of papillomatosis is difficult. The neodynium:yttrium-aluminum-garnet (Nd:YAG) laser8 is effective in giving the patient relief by clearing the airways, but can spread the virus even farther down the respiratory tract. Other treatments include photodynamic therapy9,10; argon plasma coagulation,11 sometimes used after attempts with the Nd:YAG laser have failed; and interferon.12 Cryosurgery13 and radiation therapy,14 although controversial as their effectiveness is under question, have also had some success.
Lesions in the trachea that cause audible wheezing are the earliest sign of papillomatosis.15 Other symptoms include stridor, hemoptysis, dyspnea, and cough.3 Secondary changes that may occur are empyema, pneumonia, lung abscess, obstructive emphysema, atelectasis, and bronchiectasis. If the lesions are untreated, the patient will become increasingly dyspneic, and the condition will eventually result in death.4
In 1983, a 44-year-old man with a smoking history of more than 70 pack-years presented to the airway management clinic at the University of Iowa Hospitals and Clinics (UIHC), Iowa City, with a diagnosis of chronic obstructive pulmonary disease and hypertension. He had a history of chronic cough and nocturnal wheezing, but denied hemoptysis or voice changes. A physical examination confirmed hypertension, and auscultation of his chest revealed right-sided inspiratory and expiratory wheezes, bilateral basilar rales, and generalized coarse breath sounds. A chest radiograph showed no infiltrate, but a prominent hilum. Pulmonary function testing yielded a prebronchodilator forced vital capacity (FVC) of 3 L and a forced expiratory volume in 1 second (FEV1) of 1.35 L. Postbronchodilator results were 3.3 L for FVC and 1.5 L for FEV1.
The patient was treated using 60 mg of prednisone at a tapered dosage for 2 weeks. His symptoms did not improve, and his pulmonary function testing results did not change. The patient was followed locally by his general practitioner until 1993, when bronchoscopy revealed a mass in the mid trachea and left upper lobe. Histologic analysis showed it to be a squamous papilloma. The patient complained of increasing dyspnea, increased productive cough, and occasional hemoptysis.
He was lost to follow-up for 3 years and presented to a local hospital with night sweats, poor appetite, a 30-lb weight loss, and episodes of paroxysmal nocturnal dyspnea. A chest radiograph revealed a 5- to 6-cm mass in the posterior segment of the left lingula. Pulmonary function testing results were 4.96 L for FVC and 0.99 L for FEV1. An arterial sample taken while the patient breathed 40%yielded a pH of 7.35, a Pao2 of 46 mm Hg, and a Paco2 of 55 mm Hg.
In February 1996, the patient was again seen at the pulmonary clinic. A chest CT study performed without contrast revealed a 4x5x6-cm mass in the posterior basal segment of the left lower lobe that was encasing the bronchi to the posterior and lateral basal segment. The distal trachea and right main stem bronchus were narrowed by a mediastinal mass that was encroaching on the airway. There were large cavitary lesions within both lower lobes and emphysematous changes within the lung parenchyma.
The patient was scheduled for the first of approximately 14 Nd:YAG laser bronchoscopy procedures performed to resect endotracheal papillomas. The laser was used through a rigid bronchoscope. The tracheal lumen was reduced to approximately 200of normal (Figure 1a, page 81). The right main bronchus was narrowed to just a slit (Figure 2a, page 81). The tracheal tumor was treated by laser using an initial setting of 30 W of power for 5-second pulses. This was later increased to 40 W for 5-second pulses–in order to get better penetration of the laser and, therefore, cover less area–as the tracheal papillomas were removed (Figure 1b, page 81).
Figure 2b (page 81) shows the right main bronchus now visible after clearance of the tumor. There was an extensive tumor in the airways, and to facilitate subsequent laser procedures, three-dimensional computer-generated images were used to further define the airway anatomy (Figure 3, page 81). At the end of the procedures, the patient had a tracheal lumen of approximately 808of normal size and a right main stem bronchus that was approximately 50 of normal size (with residual papillomas). Repeated laser procedures at intervals of approximately 3 months were required to maintain airway patency.
In July 1996, after undergoing six laser resections, the patient began treatment with 200 mg of acyclovir three times daily, interferon injections every other day, and an experimental drug, Indole-3-carbinol. Pulmonary function testing results in August 1996 were 3.07 L for FVC and 0.68 L for FEV1 before bronchodilator administration and 3.39 L for FVC and 0.9 L for FEV1 after bronchodilation.
On presentation to the clinic in November 1996, the patient, now 57 years old, had a 100-pack-year history of smoking. Chest radiography revealed an unchanged left perihilar mass, numerous cystic lesions, and postobstructive atelectasis in the lingula.
By July 1997, the patient had worsening dyspnea. A chest CT study now revealed a 10×8-cm necrotic left lower lobe mass that extended posteriorly from the left hilum. Further weight loss and absent breath sounds in the left lower lobe posteriorly were noted when the patient returned to the clinic 1 month later. A malignant transformation of papillomatosis into squamous cell carcinoma was diagnosed upon bron-chcoscopy.
Despite radiation therapy and chemotherapy, the carcinoma metastasized to the liver. The patient’s last hospital admission, in September 1997, was related to the complications and adverse effects of chemotherapy. A chest CT study revealed extension of the lung tumor, with chest wall invasion. The patient died in October 1997.
Despite the viral etiology of papillomatosis, this patient had no laryngeal involvement. Perhaps this viral strain was subtly different from those found in other documented cases. Malignant changes rarely occur in papillomatosis. The fact that this patient continued to smoke probably contributed to his carcinoma. ND:YAG laser therapy did provide relief for this patient, although earlier intervention would have been beneficial. Although many new treatment modalities have been introduced, respiratory papillomatosis remains incurable, and its management goal remains symptomatic palliative relief. N
Shana Stalkfleet, RRT, RCP, is a staff respiratory therapist at the University of Iowa Hospitals and Clinics (UIHC), Iowa City. Lori Dvorak, RRT, RCP, is a staff respiratory therapist at Rapid City Regional Hospital, Rapid City, SD. Geoffrey McLennan, MD, is director of bronchoscopic services at UIHC.
The authors would like to thank Eric Hoffman, PhD, and Janice Cook-Granroth, of the Division of Physiologic Imaging, University of Iowa, for production of the image in Figure 3.
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