Introduction
Since its discovery in 1876, bronchoscopy has served a fundamental role in the diagnosis and management of pulmonary disease. Over the past few decades, the therapeutic capabilities of bronchoscopy have evolved dramatically. Indeed, technologies such as laser therapy, argon plasma coagulation, cryotherapy, brachytherapy, and endobronchial stenting have revolutionized the management of malignant and nonmalignant central airway disease, ushering in a new age of interventional pulmonology. More recently, there has been increased interest in the direct application of medications to the airways utilizing a bronchoscopic approach. This chapter discusses the endoscopic application of medication to a variety of malignant and nonmalignant thoracic diseases.
Malignant Thoracic Disease
Transbronchial Needle Injections
Despite widespread anti-tobacco campaigns and lung cancer screening initiatives, lung cancer remains the leading cause of cancer death in the United States with a projected mortality of over 147,000 deaths in 2019 alone. The majority of lung cancers are non–small cell lung cancer (NSCLC), many of which are advanced at the time of initial presentation. Given the significant morbidity and mortality associated with lung cancer, early diagnosis is of paramount importance. In the late 1970s, Ko-Pen Wang developed flexible transbronchial needle aspiration (TBNA) through a fiberoptic bronchoscope, allowing for endoscopic tissue sampling with possible rapid on-site evaluation (ROSE) of histopathologic specimens. The use of TBNA for the diagnosis and staging of lung cancer significantly increased after the introduction of endobronchial ultrasonography (EBUS). EBUS allows for direct visualization of the lesion being biopsied, not only increasing the diagnostic yield of the procedure but also rendering the procedure safer by allowing operators to visualize advancement and retraction of the needle in real time. Today EBUS-guided TBNA has become an integral component in the diagnosis of thoracic malignancy and mediastinal lymph node staging, providing a minimally invasive alternative to mediastinoscopy and video-assisted thoracoscopic surgery as a means by which to diagnose and stage lung cancer. EBUS-TBNA has also previously been shown to reduce the time to diagnosis of lung cancer, allowing for earlier initiation of therapy, as well as expedited care coordination between patients, oncologists, pulmonologists, and surgeons.
Given the impressive diagnostic capabilities of TBNA, especially in conjunction with EBUS, there has been growing interest in the role of transbronchial needle injections (TBNI) as a therapeutic modality. This is particularly relevant to lung cancer. Treatment of NSCLC is based on cancer staging, with advanced stages (II–IV) typically requiring radiation and/or chemotherapeutic agents. Among patients diagnosed with lung cancer, approximately 20%–30% will develop some degree of malignant airway obstruction. These obstructive lesions can be associated with progressively worsening dyspnea, resulting in a diminished quality of life. Malignant airway obstructions may also give way to such complications as hemoptysis, postobstructive pneumonia, and, in severe cases, respiratory failure. In these situations, rapid, safe, and effective recanalization of the airway is imperative.
In contrast to intravenous therapies, TBNI allows for localized delivery of (oftentimes cytotoxic) medications into these lesions, not only potentially minimizing the systemic toxicities associated with these agents but also increasing the intratumoral concentrations of the drugs. In the 1980s, TBNI (without EBUS) was used to deliver ethanol into endobronchial tumors with the goal of alleviating central airway obstruction and minimizing tumoral bleeding. Fujisawa et al. injected 0.5–3 mL of 99.5% ethanol into the tumors of 13 patients with tracheobronchial tumors invading the central airway to potentiate tissue necrosis, allowing pieces of the necrotic tumor to be debrided with forceps in order to improve airway patency. Sawa et al. performed a similar intervention, injecting 4.5 mL (on average) of 99% ethanol into the endobronchial lesions of eight patients utilizing an endoscopic video information system to assess for leakage of ethanol beyond the tumor margins.
In addition to ethanol, chemotherapeutic agents have also been directly injected into intra- and extraluminal tumors endoscopically. When chemotherapy is administered via TBNI, the procedure is termed endobronchial intratumoral chemotherapy (EITC). One of the first descriptions of EITC came from Celikoglu et al. in Turkey. This study was designed to evaluate EITC as a potential palliative intervention for individuals with lung cancer (primarily squamous cell carcinoma) that was not amenable to surgery. Ninety-three patients with inoperable cancers and evidence of more than 50% exophytic obstruction of at least one major airway were enrolled. Of these patients, 68 carried a diagnosis of previously untreated bronchogenic carcinoma (with plans to initiate systemic chemotherapy and radiation following treatment with intratumoral injections), whereas 25 had a history of cancer that had recurred despite prior treatment with chemotherapy and/or radiation. Utilizing a flexible bronchoscope and 23-gauge (G) flexible needle (Olympus Corp, Tokyo, Japan), the authors injected 1–3 mL each of 50 mg/mL 5-fluorouracil, 1 mg/mL mitomycin, 5 mg/mL methotrexate, 10 mg/mL bleomycin, and 2 mg/mL mitoxantrone into different sites on the tumor. Injections took place over the course of one to six sessions. Following the treatment, the authors noted a reduction in tumor size and improvement in airway obstruction in 81 patients, 39 of whom experienced a more than 50% relative increase in the luminal diameter of their airways. The authors did report postprocedural fevers in a small percentage of the patients, though no significant adverse events were noted.
A follow-up study was performed by Celikoglu using 5-fluorouracil monotherapy intratumorally for the palliative management of severe airway obstruction. The authors again studied patients with severe obstruction of at least one major airway. Among the 65 patients enrolled, the mean degree of luminal patency pretreatment was 22%; 56 patients experienced anatomic improvement of their airway obstruction with an average luminal patency of 58.5% following flexible bronchoscopic injection of 0.5–1 g of 50 mg/mL 5-fluorouracil with a 23-G TBNA needle. Again, no significant side effects were noted.
In addition to 5-fluorouracil, there are data to support the use of other chemotherapeutic agents. Additional studies have been done demonstrating the safety and efficacy of intratumoral injections of paclitaxel, carboplatin, and cisplatin, with many recent studies utilizing the latter. Drugs are selected based on their pharmacologic profile with regard to both safety and biometabolism. From a safety standpoint, chemotherapeutic agents selected for EITC must be directly cytotoxic but should not induce necrosis in the healthy tissues that are adjacent to the malignant lesions. Additionally, in terms of metabolism, the drugs must not require systemic metabolism in order to be effective. Though the optimal dose of cisplatin remains unclear, computational modeling studies have shown that lower cumulative doses may be achieved by performing multiple small, spaced injections of cisplatin as opposed to a larger bolus injection into the tumor center. More research must be done to determine which chemotherapeutic agents and dosages are most appropriate, as well as the optimal number of injections and their location. Additionally, more longitudinal follow-up data of patients who have undergone TBNI must also be conducted in order to determine the appropriate duration of therapy and the long-term implications of this therapeutic intervention.
EBUS-Guided TBNI
More recently, EBUS has been employed to help bolster the safety of EITC. Khan et al. described the first use of EBUS-guided TBNI in 2014, in which the authors utilized EBUS-guided TBNI to inject cisplatin into an endobronchial lesion in a patient with previously treated, recurrent squamous cell carcinoma ( Fig. 11.1 ). They noted that EBUS allows not only for direct visualization of drug injection into the tumor but also for the use of Doppler ultrasonography, which minimizes the risk that the needle could be inserted into a highly vascularized region.
Endobronchial Balloon Drug Delivery Catheter
TBNI used in conjunction with a flexible or rigid bronchoscope can lead to logistical difficulties for injection into lesions located perpendicular to the airway wall. Classic TBNI into airway walls may also lead to deep penetration of medication with the risk of airway dehiscence. A novel endobronchial balloon drug delivery catheter (Blowfish Catheter, Mercator MedSystems, Inc., CA, USA) was recently developed that is able to be passed down a flexible bronchoscope. Once deployed through the working channel of a bronchoscope, the distal balloon is inflated and extrudes a 34-G microneedle perpendicular to the catheter ( Fig. 11.2 ). Medications can then be injected through this needle into the tumor and bronchial wall directly into the submucosa and bronchial adventitia, but not past the cartilaginous layer. Porcine studies showed that the Blowfish catheter was able to circumferentially inject medication into 60% of the airway wall per injection. This catheter was studied in a multicenter human safety and feasibility pilot looking at the efficacy of injections of a cumulative dose of 1.5 mg of paclitaxel in 19 patients with NSCLC and malignant central airway obstruction ( Fig. 11.3 ). All patients underwent rigid bronchoscopy with recanalization of their airways with successful injection of paclitaxel using the Blowfish microinjection catheter. This required an average of 3.4 injections per patient. The authors noted significantly less airway stenosis following the intervention and reported no significant adverse events. None of the patients enrolled in the study required further interventions in the 6-week follow-up period. No patients required airway stenting.
Gene Therapy
There are very early and preliminary studies of tumor suppressor gene therapy delivered via TBNI. The most common genetic anomaly associated with lung cancer is a mutation in the p53 tumor suppressor gene. In the 1990s, Roth et al. used TBNI to administer wild-type copies of p53 via a retroviral vector into the endobronchial lesions of four patients with recurrent NSCLC. The authors reported regression of the tumor mass in three patients on subsequent bronchoscopic examinations, with follow-up biopsies revealing no viable tumor (though patients did experience progression of disease elsewhere). More recently multiple studies have been performed using recombinant adenoviral vectors. Weill et al. administered adenoviral-mediated p53 gene ( Adp53 ) through TBNI to 12 patients with endobronchial NSCLC associated with a known p53 mutation; they noted significant improvement in airway obstruction in half of the patients. The authors reported minimal toxicity associated with the therapy. It is important to note that in this cohort 5 of the 12 patients received Adp53 alone, whereas 7 received Adp53 in conjunction with cisplatin; of these subgroups, only one of the patients who received Adp53 alone experienced significant improvement in endobronchial obstruction, whereas 5 of the 7 in the Adp53 /cisplatin group experienced improvement. An additional study looked at the coadministration of Adp53 and cisplatin in 24 patients with NSCLC; 17 patients had disappearance of their endobronchial lesions posttreatment for at least 4 weeks based on imaging and/or physical examination, whereas 2 patients demonstrated partial response.
Beyond cisplatin, other therapies have been administered alongside p53 . Schuler et al. studied the concurrent administration of intratumoral injections of adenovirus-mediated wild-type p53 genes with either carboplatin/paclitaxel or cisplatin/vinorelbine. Ultimately the authors did not detect a difference in response rates between those who received chemotherapy and p53 versus those who received chemotherapy alone. They did note, however, that local tumor regression appeared to be more significant among those who received cisplatin/vinorelbine and p53 relative to those who received carboplatin/paclitaxel and p53 .
The impact of tumor suppressor gene injections has also been considered in the setting of radiation therapy. Swisher et al. studied patients with nonmetastatic NSCLC who were ineligible for chemotherapy or surgical intervention. Patients were given intratumoral injections of Adp53 in the setting of also receiving radiation therapy (at 60 Gy) over 6 weeks. After several months, the biopsies of 12 of 19 patients revealed no viable tumor.
All of these studies are fairly preliminary and lack the sample size to either prove or disprove efficacy of various agents delivered bronchoscopically. As such, the data should be viewed as exploratory, the main emphasis here being that bronchoscopy as a platform for delivery of drugs and other therapeutic agents is starting to be explored. In this context, it is important for the interventional bronchoscopist to understand the available data, the limitations of these data, and the procedural aspects of bronchoscopic drug delivery in case it is needed.
Nonmalignant Thoracic Disease
Postintubation or Tracheostomy Laryngotracheal Stenosis
In addition to lung cancer, there are a variety of nonmalignant airway-centric pathologies that may benefit from endobronchially administered medications. One such disorder, benign laryngotracheal stenosis, is most commonly seen in patients who have previously required endotracheal intubation and/or tracheostomy for a prolonged period of time (typically greater than 7–10 days ). Other risk factors for developing laryngotracheal stenosis include a history of difficult or emergency intubation, placement of an oversized endotracheal tube, or excessively high cuff pressures. Symptoms of laryngotracheal stenosis may take weeks to months after extubation or decannulation to manifest. Patients will often complain of subacute, progressive dyspnea, as well as wheezing that is refractory to treatment with bronchodilators. Laryngotracheal stenoses can be subdivided into simple versus complex stenoses. Simple lesions are defined as those impacting a short region (less than 1 cm long) of the airway without evidence of tracheomalacia. In contrast, complex lesions are those involving extensive areas (greater than 1 cm in length) of stenosis and/or cartilaginous involvement and tracheomalacia. Simple stenoses are typically amenable to a bronchoscopic intervention, usually consisting of radial incision (e.g., with an electrocautery knife) followed by balloon dilation. Complex stenoses may require multiple, repeated interventions including deployment of airway stents, argon plasma coagulation, cryotherapy, balloon dilation, or eventually surgical resection.
Recently, the use of mitomycin C in the management of benign laryngotracheal stenosis has been gaining popularity. Mitomycin C is an antineoplastic agent that derives from Streptomyces caespitosus . It has historically been used in the treatment of a variety of cancers, including breast cancer, colorectal cancer, gastric cancer, and NSCLC, and its use as an antiproliferative agent in the treatment of diseases like glaucoma is well established in the ophthalmology literature. Dalar et al. reported on the use of topical 0.2 mg/mL mitomycin C in a limited number of patients with simple and complex tracheal stenoses ( Fig. 11.4 ). The authors noted that mitomycin appeared to delay time to consecutive stent dilations in patients with complex stenoses and decreased the need for repeated dilations in patients with simple stenoses. Though there are not yet any randomized controlled trials studying the impact of mitomycin C on this condition, Perepelitsyn and Shapshay performed a retrospective cohort study comparing the efficacy of carbon dioxide laser incisions combined with bronchoscopic dilatation alone versus steroid injections versus topical application of mitomycin C. They reported symptomatic improvement in the group that received topical mitomycin C. There are also some data to suggest that two applications of mitomycin C, spaced approximately 1 month apart, can help to postpone (but not prevent) episodes of restenosis. Additional research must be done to further explore these results and determine the optimal dosing frequency of topical mitomycin C in these patients.
Granulomatosis With Polyangiitis
Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) is a form of small-vessel, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. According to the American College of Rheumatology, there are four criteria used to diagnosis the disease:
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Abnormal urinary sediment
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Abnormal chest imaging findings
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The presence of oral ulcers or nasal discharge
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The presence of granulomas on biopsy.
From a pulmonary standpoint, GPA can have a wide variety of manifestations, including (potentially cavitary) lung nodules, ground-glass opacities in the setting of alveolar hemorrhage, airway stenoses, and mucosal ulcerations. The disease is typically managed with systemic immunosuppressive therapy and avoidance of airway manipulation, as this can lead to worsening inflammation and further stenosis in the future. However, central airway involvement can be the primary derangement in a small proportion of patients and may progress even with appropriate systemic therapy; this situation may necessitate endoscopic intervention.
Upper respiratory tract involvement is relatively common in GPA, particularly involving the subglottic region of the trachea. Indeed, 16% of patients with active disease develop subglottic stenosis, which can be life-threatening. Multiple studies have suggested a role for endoscopic glucocorticoid injections, performed in conjunction with bronchoscopic dilation. Additionally, prior research has demonstrated that patients may develop subglottic stenosis while receiving systemic immunosuppression, suggesting that immunosuppressive therapy may not always be sufficient to prevent/manage this complication. Hoffman et al. performed intralesional long-acting corticosteroid injections and dilatations in 21 patients with GPA complicated by subglottic stenosis. In this study, 40 mg/mL of methylprednisolone acetate was injected into the submucosa of the stenotic region using a 20-G laryngeal needle in a four-quadrant distribution. They noted that patients with no prior airway scarring required an average of 2.4 procedures approximately 12 months apart in order to maintain patency of the subglottic region. In contrast, patients with evidence of airway scarring (from prior procedures) required an average of 4.1 procedures approximately 7 months apart in order to maintain regional patency. Based on their findings, the authors suggest that steroid injections and dilatation are a reasonable therapeutic modality for patients with subglottic stenosis and GPA not responsive to systemic therapy.
Sarcoidosis
Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas. Though presentations of sarcoidosis can vary significantly based on the affected organ systems, the respiratory system is impacted in more than 90% of cases. Pulmonary manifestations of sarcoidosis include bilateral hilar adenopathy, pulmonary micronodules, ground-glass opacities, and, in advanced disease, fibrosis. Airway involvement of the disease is typically indicative of the presence of endobronchial mucosal granulomas, causing scarring and stenosis. The resulting narrowing of the airway can be detected radiographically and bronchoscopically and often leads to symptoms of dyspnea and wheezing. On imaging, extensive involvement of the small airways can result in evidence of air-trapping on expiratory films.
Corticosteroids are among the most commonly used therapies for active sarcoidosis. When endobronchial airway involvement occurs in sarcoidosis, intraluminal injections of corticosteroids (including dexamethasone and triamcinolone ) may be of benefit, although data on efficacy are limited. Butler et al. performed a retrospective chart review of 10 patients with laryngeal involvement from sarcoidosis. Among these patients, six had sarcoidosis that was limited to the larynx, whereas four had other systemic manifestations; two patients had symptoms that were so severe that they required emergency tracheostomy. All had received high doses of systemic corticosteroids prior to intervention. Patients underwent multiple steroid injections into the base of each lesion, using 40–120 mg of 40 mg/mL methylprednisolone acetate, as well as laser photoreduction using a carbon dioxide laser. They completed anywhere from one to four sessions. The authors reported significant improvement in the patients’ Medical Research Council (MRC) dyspnea scales following treatment, as well as a significant reduction in systemic steroid usage.
There may also be a role for topical mitomycin C in the management of sarcoidosis of the airway. In a case report describing a woman with endobronchial involvement of her sarcoidosis who had failed systemic steroid therapy, balloon dilation, and the application of topical 0.4 mg/mL mitomycin C resulted in transient improvement in the patient’s symptoms. More research must be done on the potential role of mitomycin C in the management of sarcoidosis involving the airways.
Idiopathic Laryngotracheal Stenosis
Idiopathic laryngotracheal stenosis is a rare inflammatory disorder that almost exclusively affects women, typically those who are pre- and perimenopausal. Patients generally present with exertional dyspnea, wheezing, and, occasionally, a change in the quality of their voice. As its name suggests, idiopathic laryngotracheal stenosis is a diagnosis of exclusion. As such, it is incumbent on the provider to rule out infectious, traumatic, and rheumatologic processes in order to make the diagnosis. Recently, derangements in estrogen and progesterone, as may be seen at the time of menopause, have been studied as possible contributors to the pathogenesis of this disorder.
Idiopathic laryngotracheal stenosis is characterized by stenosis within the upper airway, often impacting the subglottic region. Histopathologically there is evidence of fibrous inflammation in the lamina propria of the subglottis and proximal trachea. Traditionally this disorder has been managed surgically, with laryngotracheal or tracheal resection and reconstruction. Outcomes with this surgical approach have been favorable. One study described 73 patients who underwent operative intervention for idiopathic laryngotracheal stenosis; of this group, 19 patients described no difficulties in breathing or vocal quality postoperatively, 47 reported some difficulty projecting loudly after surgery, 5 reported some ongoing dyspnea or stridor, and 1 needed ongoing management with dilations.
Despite the efficacy of surgery, there has been increasing interest in the role of bronchoscopy for the management of this disorder, as extensive surgical resection may not be tolerated by a large subset of patients with this disease due to medical comorbidities. As with benign laryngotracheal stenoses, bronchoscopic interventions for idiopathic stenoses include balloon dilatation, laser as well as other thermal ablative therapies, stenting, and cryotherapy. Shabani et al. attempted endoscopic balloon dilation and steroid injection in 37 patients with subglottic stenosis due to idiopathic laryngotracheal stenosis. Of the 37 patients, 13 received steroid injections (triamcinolone or dexamethasone) for all procedures, whereas 4 received no concurrent steroid injections. Though the results did not reach statistical significance, the authors noted that the patients who received steroid injections tended to require fewer dilations (on average, approximately 4 vs. 7) with a longer time between dilations (on average, approximately 556 days as opposed to 283 days) than those who did not receive the steroid injections. Given the small sample size, more research must be done to determine the utility of concurrent steroid injections, as well as the optimal timing of these treatments.
Recurrent Respiratory Papillomatosis
Recurrent respiratory papillomatosis (RRP) is a benign disorder characterized by the development of numerous papillomatous, exophytic lesions throughout the respiratory tract. Very rarely there may also be parenchymal involvement of RRP, characterized by the presence of solid or cavitary pulmonary nodules. The disease is attributed to infection with human papillomavirus (HPV), most commonly subtypes 6 and 11, which together account for more than 90% of cases of RRP. There is general consensus that HPV 11 represents the more virulent strain, as patients afflicted with RRP due to HPV 11 typically are those who require more aggressive airway interventions (including tracheostomy) and have a higher risk of malignant transformation. RRP may affect children, who frequently contract HPV at the time of birth through vaginal delivery, though there is evidence that some children become infected through placental transmission of the virus. Adults may also contract HPV and develop RRP following orogenital sexual contact.
The traditional approach to management of RRP has focused on surgical debulking of the papillomas, typically using laser therapy, in order to restore airway patency. Still, given the recurring nature of the disease, frequent surgeries may be required, placing (oftentimes pediatric) patients at risk for laryngotracheal stenosis and scarring, burns, and fistulae formation. As a result, there has been increased focus on adjuvant therapies intended to minimize the need for repeated operative interventions. The use of intralesional cidofovir has been evaluated as a potential intervention to minimize the need for invasive procedures in this population. Cidofovir is an antiviral medication that inhibits viral DNA polymerases. Much of the data describing use of cidofovir come from case reports, with varying descriptions of the efficacy of the drug. Wierzbicka et al. noted complete remission in 18 of 32 patients with recurring papillomatous disease who underwent intralesional cidofovir injections (ranging from a total of one to seven injections, using 2–33 mL in total of 5 mg/mL cidofovir); importantly, the authors reported that one patient developed gastrointestinal symptoms following the procedure, whereas two more developed a transient transaminitis. Naiman et al. performed monthly intralesional injections of 5 mg/mL cidofovir in 26 patients (including adults and children). Repeat endoscopies were performed at 3 months to assess for ongoing disease burden and, if present, cidofovir injections were repeated at the time on the persisting papillomas. The authors reported complete remission in eight patients (of whom 2 had undergone 1 injection, 2 had 2 injections, and 4 had an average of 4.2 injections). Seventeen patients had mild disease at the end of the therapeutic trial. The authors did not note any significant adverse events.
There are limited data at present describing the long-term efficacy of cidofovir injections for the management of RRP. Milczuk followed four children with RRP who had each undergone six treatments, 6–8 weeks apart, consisting of surgical papilloma excision and intralesional injections of cidofovir. One year after completing treatment, one patient continued to experience remission of his disease, whereas two patients had recurrence of symptoms (which began to recur during the initial treatment protocol). The fourth patient did not respond to cidofovir injections. Tanna et al. followed 13 adults who had previously experienced disease remission after an average of six cidofovir injections, reporting that 6 did not require subsequent interventions, whereas 7 required further treatment of their RRP after an average of 1 year. Additional research must be done in order to determine the long-term efficacy of intralesional cidofovir injections.
Lung Transplant–Associated Bronchial Stenosis
Despite improvements in surgical techniques over the past several decades, airway complications remain a relatively common complication of lung transplantation, with approximately 15% of lung transplant recipients affected. Airway complications may have tremendous implications on a patient’s quality of life, oftentimes provoking cough, progressive dyspnea, and/or recurrent infections. These complications frequently require multiple posttransplantation interventions depending on the underlying etiology of the complication. There are a wide variety of airway complications, including anastomotic necrosis and dehiscence, anastomotic infections, fistulas (bronchopleural, bronchovascular, or bronchomediastinal), and, most commonly, bronchial stenosis. Bronchial stenoses may occur at or distal to the anastomotic site and can develop months to years following transplant. According to a review by Yousem et al., histopathologic studies of bronchial cartilage in posttransplant recipients demonstrate ossification, calcification, and fibrovascular ingrowth, presumably due (at least in part) to inflammation and decreased bronchial perfusion following transplantation.
The bronchoscopic management of posttransplant bronchial stenosis encompasses a variety of interventions aimed at dilating the airway. Historically, rigid bronchoscopy with bougie dilation was the standard treatment modality, though flexible bronchoscopy with balloon dilation has become increasingly prevalent in recent years. Other interventions include airway stenting, cryotherapy, electrocautery, laser therapy, and endobronchial brachytherapy. There are also data to support the bronchoscopic application of topical agents, most notably mitomycin C, to regions affected by bronchial stenosis. Erard et al. published the first case report describing the local application of mitomycin C in recurring bronchial stenosis in 2001 ( Fig. 11.5 ). They describe a patient with a history of cystic fibrosis and multidrug-resistant Burkholderia cepacia who underwent bilateral lung transplantation complicated by recurrent bronchial stenosis despite treatment with argon laser electrocoagulation and multiple attempts at dilatation and stenting. At postoperative week 42, the authors applied a cotton swab soaked in a solution of 2 mg/mL of mitomycin C to granulation tissue in the patient’s stenosed right upper lobe bronchus and bronchus intermedius for 2 min. They reported improvement in the patient’s FEV 1 (forced expiratory volume in the first second) that persisted for several months, though they did note that the patient developed a recurring stricture in the bronchus intermedius, which was treated again with topical mitomycin C with good efficacy.
