Photodynamic therapy via navigational bronchoscopy for peripheral lung cancer in dogs.

OBJECTIVE: In the setting of lung cancer, photodynamic therapy (PDT) is typically used to treat centrally located endobronchial tumors. The development of navigational bronchoscopy has opened the potential for using PDT to treat peripheral lung tumors. However, there is limited information about the feasibility of this approach for treating peripheral lung cancers, and about its effects on surrounding healthy lung tissue. We studied the use of PDT delivered by electromagnetic navigational bronchoscopy to treat peripheral lung cancer in dogs. MATERIALS AND METHODS: Three dogs with peripheral lung adenocarcinomas were given intravenous porfimer sodium (Photofrin® [Pinnacle Biologics, Inc., Chicago, IL]) to photosensitize the tumors, then navigational bronchoscopy was used to deliver photoradiation. One week after PDT, the tumors and involved lung lobe were surgically excised and evaluated histologically. RESULTS: PDT was successful in all three dogs and was associated with tolerable and manageable adverse effects. Tissue sections from within PDT-treated tumors showed regions of coagulative central necrosis admixed with small numbers of inflammatory cells, and arterial thrombosis. Viable adenocarcinoma was seen in the surrounding areas. CONCLUSION: These results suggest that PDT can be successfully deployed to treat peripheral lung cancers using navigational bronchoscopy. Furthermore, damage to surrounding noncancerous tissues can be minimized with accurate placement of the optical fiber. Studies of this modality to treat peripheral lung cancers in humans may be warranted. Lasers Surg. Med. 50:483-490, 2018. © 2018 Wiley Periodicals, Inc.

Radial endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis.

Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible bronchoscopy was commonly performed for this purpose but its diagnostic yield is suboptimal. This has led to the development of new bronchoscopic modalities such as radial endobronchial ultrasound (R-EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopy (VB). We performed this meta-analysis using data from previously published R-EBUS studies, to determine its diagnostic yield and other performance characteristics. Ovid MEDLINE and PubMed databases were searched for R-EBUS studies in September 2016. Diagnostic yield was calculated by dividing the number of successful diagnoses by the total number of lesions. Meta-analysis was performed using MedCalc (Version 16.8). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. Publication bias was assessed using funnel plot and Duval and Tweedie's test. 57 studies with a total of 7872 lesions were included in the meta-analysis. These were published between October 2002 and August 2016. Overall weighted diagnostic yield for R-EBUS was 70.6% (95% CI: 68-73.1%). The diagnostic yield was significantly higher for lesions >2 cm in size, malignant in nature and those associated with a bronchus sign on computerized tomography (CT) scan. Diagnostic yield was also higher when R-EBUS probe was within the lesion as opposed to being adjacent to it. Overall complication rate was 2.8%. This is the largest meta-analysis performed to date, assessing the performance of R-EBUS for diagnosing PPLs. R-EBUS has a high diagnostic yield (70.6%) with a very low complication rate.

Airway stenting in the management of iatrogenic tracheal injuries: 10-Year experience.

BACKGROUND AND OBJECTIVE: Iatrogenic tracheal injury (ITI) is a rare yet severe complication of endotracheal tube (ETT) placement or tracheostomy. ITI is suspected in patients with clinical and/or radiographic signs or inefficient mechanical ventilation (MV) following these procedures. Bronchoscopy is used to establish a definitive diagnosis. METHODS: We conducted a retrospective, single-centre chart review of 35 patients between 2004 and 2014. Depending on the nature and location of ITI and need for MV, patients were triaged to surgical repair, endoscopic management with airway stents or conservative treatment consisting of ETT or tracheotomy cannula (TC) placement distal to the wound and bronchoscopic surveillance. RESULTS: Three of the four patients (11.43%) presenting with tracheoesophageal fistula (TEF) underwent surgery. Seven patients (20%) who did not require MV underwent endoscopic surveillance. Of the 24 ventilated patients (68.57%), 7 with ITI in the lower trachea were treated with silicone Y-stent (ETT or TC was placed inside the stent) and 17 patients with ITI in the upper trachea were managed by placing ETT or TC cuff distal to the injury. Overall management success, defined as complete healing of the ITI, was seen in 88.57% of patients. Four patients (11.43%) died of non-ITI-related comorbidities. CONCLUSION: Conservative management should be considered in non-ventilated patients with ITI and when ITI is located in the upper trachea of ventilated patients where ETT or TC bypasses the injury. Airway stenting should be considered in ventilated patients with ITI located in the lower trachea. Surgery should be reserved for TEF and conservative and endoscopic management failure.

Predictors of efficacy for endobronchial valves in bronchoscopic lung volume reduction: A meta-analysis.

Over the last several years, numerous trials have been carried out to check the efficacy of one-way valves in the management of advanced emphysema. While the design of the valves has not altered much, by selectively studying these valves in a select group of participants, such as those with and without intact fissures (FI+ and FI-), and by using different procedural techniques, our understanding of the valves has evolved. In this meta-analysis, we sought to study the effect of these factors on the efficacy of one-way valves. From PubMed and Embase, we included only those studies that provided separate data on fissure integrity or collateral ventilation. Our study outcomes included the mean change in forced expiratory volume in first second (FEV1), 6-minute walk distance (6MWD) and the St George's Respiratory Questionnaire (SGRQ). In the FI+ subgroup of participants, the pooled standardized mean difference in FEV1, 6MWD, and SGRQ were 0.50 (95% confidence interval (CI): 0.34 to 0.67), p ≤ 0.001, 0.29 (95% CI: 0.13 to 0.45), p ≤ 0.001 and -6.02 (95% CI: -12.12 to 0.06), p = 0.05, respectively. In comparison, these results were superior to the FI- subgroup of participants. A separate analysis of the FI+ subgroup based on lobar occlusion versus nonlobar occlusion favored the former for superior efficacy. The preliminary findings of our meta-analysis confirm that one-way valves perform better in a select group of patients who show intact fissures on lung imaging pretreatment and in those who achieve lobar occlusion.

COVID-19 Impact on Interventional Pulmonology Training.

Background: The impact of the coronavirus disease (COVID-19) pandemic extends beyond the realms of patient care and healthcare resource use to include medical education; however, the repercussions of COVID-19 on the quality of training and trainee perceptions have yet to be explored. Objective: The purpose of this study was to determine the degree of interventional pulmonology (IP) fellows' involvement in the care of COVID-19 and its impact on fellows' clinical education, procedure skills, and postgraduation employment search. Methods: An internet-based survey was validated and distributed among IP fellows in North American fellowship training programs. Results: Of 40 eligible fellows, 38 (95%) completed the survey. A majority of fellows (76%) reported involvement in the care of patients with COVID-19. Fellows training in the Northeast United States reported involvement in the care of a higher number of patients with COVID-19 than in other regions (median, 30 [interquartile range, 20-50] vs. 10 [5-13], respectively; P < 0.01). Fifty-two percent of fellows reported redeployment outside IP during COVID-19, mostly into intensive care units. IP procedure volume decreased by 21% during COVID-19 compared with pre-COVID-19 volume. This decrease was mainly accounted for by a reduction in bronchoscopies. A majority of fellows (82%) reported retainment of outpatient clinics during COVID-19 with the transition from face-to-face to telehealth-predominant format. Continuation of academic and research activities during COVID-19 was reported by 86% and 82% of fellows, respectively. After graduation, all fellows reported having secured employment positions. Conclusion: Although IP fellows were extensively involved in the care of patients with COVID-19, most IP programs retained educational activities through the COVID-19 outbreak. The impact of the decrease in procedure volume on trainee competency would be best addressed individually within each training program. These data may assist in focusing efforts regarding the education of medical trainees during the current and future healthcare crises.

Bronchoscopic treatment of inoperable nonsmall cell lung cancer.

Patients with unresectable lung cancer range from those with early-stage or pre-invasive disease with comorbidities that preclude surgery to those with advanced stage disease in whom surgery is contraindicated. In such cases, a multidisciplinary approach to treatment is warranted, and may involve medical specialties including medical oncology, radiation oncology and interventional pulmonology. In this article we review bronchoscopic approaches to surgically unresectable lung cancer, including photodynamic therapy, brachytherapy, endoscopic ablation techniques and airway stenting. Current and past literature is reviewed to provide an overview of the topic, including a highlight of potential emerging approaches.

Bronchoscopic Lung Volume Reduction with Valves and Coils. A Network Meta-analysis.

Background: Coils and endobronchial valves are the most widely used bronchoscopic lung volume reduction devices in patients with advanced emphysema. However, the choice of each specific device depends on emphysema characteristics (homogeneous vs. heterogeneous) and presence of lobar collateral ventilation (CV). These devices have not been compared in a head-to-head study design.Objectives: To conduct a network comparative meta-analysis studying the effect of valves in patients with heterogeneous emphysema without CV, and to also study the effects of valves and coils in patients with mixed homogeneous and heterogeneous emphysema.Data Sources and Data Extraction: PubMed and Web of Science were searched for potentially includable randomized active comparator trials from inception to January 20, 2020, and data were extracted in the working sheets of Comprehensive Meta-analysis.Synthesis: Network meta-analysis was conducted in R program using package "netmeta."Results: In patients with heterogeneous emphysema without CV, both Spiration and Zephyr valves showed significant increases in forced expiratory volume in 1 second (FEV1) (0.11 L [95% confidence interval (CI), 0.05 to 0.16] and 0.14 L [0.08 to 0.19], respectively) and in reducing St. Georges Respiratory Questionnaire (SGRQ) scores (-9.32 [-14.18 to -4.45] and -8.14 [-11.94 to -4.35], respectively) as compared with control, with no significant interintervention differences. Only Zephyr valves showed significant improvement (52.3 m [95% CI, 26.53 to 77.93]) in six-minute walk distance (6MWD). Both were ranked as equally efficacious in these patients. In the mixed homogeneous and heterogeneous emphysema group of patients, both Zephyr valves and coils showed significant increases in FEV1 and 6MWD and reduction in SGRQ, as compared with control. Although there were no significant interintervention differences, the magnitude of improvement in these parameters was highest with Zephyr valves (e.g., 6MWD increased by 56.74 m [23.66 to 89.81] vs. 30.31 m [4.00 to 56.63]) in coils), ranking them first. In both populations, these interventions showed a statistically significant association with procedure-related pneumothorax but not with chronic obstructive pulmonary disease exacerbation.Conclusions: In patients with heterogeneous emphysema without CV, both Zephyr and Spiration valves were equally efficacious in FEV1 and SGRQ improvement. However, in the mixed patients with homogeneous and heterogeneous emphysema, Zephyr valves show relative superiority over coils especially with respect to improvement in 6MWD.

Treatment options for malignant pleural effusion.

PURPOSE OF REVIEW: Thirty percent of lung cancers eventually result in malignant pleural effusion (MPE). Devastating consequences of MPE, such as dyspnea and cough, severely deteriorate the quality of life of these patients. Malignant pleural effusion portends a dismal prognosis of less than 6-month longevity, with the exception of breast and ovarian cancer. Given the poor prognosis of the majority of these patients, palliation, rather than cure, should be the goal of therapy. RECENT FINDINGS: Chest tube insertion and sclerotherapy remain the standard of care. Emerging therapeutic options such as medical pleuroscopy and indwelling pleural catheters offer cost-effective and outpatient treatments for MPE. SUMMARY: In the following review, the medical, economic, and social aspects of different current options for the management of MPE are discussed.

Interventional Pulmonology: A Focused Review for Primary Care Physicians.

Interventional pulmonology (IP) has evolved in recent decades, and recent advances have greatly expanded the services offered by IP physicians. IP is best defined as the use of advanced techniques for the evaluation and treatment of benign and malignant pulmonary disorders. The field has further advanced with the recent establishment of a board certification via the American Association of Bronchology and Interventional Pulmonology and the release in 2017 of accreditation standards for specialized fellowship training. This article provides a broad overview of the field to serve as a resource for primary care physicians.

Community-acquired Pneumonia and Hospital-acquired Pneumonia.

Pneumonia is among the leading causes of morbidity and mortality worldwide. Although Streptococcus pneumoniae is the most likely cause in most cases, the variety of potential pathogens can make choosing a management strategy a complex endeavor. The setting in which pneumonia is acquired heavily influences diagnostic and therapeutic choices. Because the causative organism is typically unknown early on, timely administration of empiric antibiotics is a cornerstone of pneumonia management. Disease severity and rates of antibiotic resistance should be carefully considered when choosing an empiric regimen. When complications arise, further work-up and consultation with a pulmonary specialist may be necessary.

Orphan Lung Diseases.

There are hundreds of rare orphan lung diseases. We have highlighted five of them, one from each of the five major categories of pulmonary disorders: pleuroparenchymal fibroelastosis (a rare diffuse parenchymal lung disease), pulmonary alveolar proteinosis (a rare autoimmune and diffuse parenchymal lung disease), lymphangioleiomyomatosis (a rare cystic lung disease), yellow nail syndrome (a rare pleural disease), and Mounier-Kuhn syndrome (a rare airway disorder). The pathogenesis, clinical presentation, diagnostic criteria, treatment options, and prognosis of each disorder is discussed. This review is by no means exhaustive and further research is needed to improve our understanding of these disorders.

Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study.

BACKGROUND: Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear. METHODS: We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture. RESULTS: Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture. CONCLUSION: Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.

Photodynamic therapy for treatment of solid tumors--potential and technical challenges.

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.

Emerging paradigms in the management of malignant pleural effusions.

Malignant pleural effusions (MPE) are a common clinical problem in patients with neoplastic disease. The development of MPEs in advanced malignancies can cause significant morbidity and mortality. Predominant symptoms of dyspnea, cough, and chest discomfort are usually debilitating. Given the poor prognosis of majority of these patients, palliation is more desirable than cure of an individual complication. Despite multiple new therapies placement of chest tube with sclerotherapy remains the standard of care. The purpose of this article is to review the emerging therapeutic options for MPE management.

Bronchoscopic Therapies for Peripheral Lung Malignancies.

Current advances in guided bronchoscopy methods permit minimally invasive access to essentially any area of the lungs. This provides a potential means to treat patients with localized lung malignancies who might not otherwise tolerate conventional treatment, which commonly relies on surgical resection. Ablation methods have long been used for bronchoscopic treatment of central airway malignancies and percutaneous treatment of peripheral lung cancer. This article reviews ablation technologies being adapted for use with guided bronchoscopy and the current state of investigation for the treatment of peripheral lung malignancies.

Tracheobronchomalacia and Excessive Dynamic Airway Collapse.

Tracheobronchomalacia (TBM) and excessive dynamic airway collapse (EDAC) are more frequently being recognized as the etiology of multiple types of respiratory complaints from chronic cough to exertional syncope to recurrent infections. Identification of these conditions requires a high suspicion, as well as a thorough history and physical examination. Dynamic computed tomography imaging and bronchoscopic evaluation are integral in achieving an accurate diagnosis. Once recognized, treatment ranges from addressing underlying contributing conditions to surgical stabilization of the airway. Referral to an institution familiar with the evaluation and treatment of TBM/EDAC is essential for the appropriate management of these conditions.

Advances in Interventional Pulmonology.

Much has changed since the last review of interventional pulmonology (IP) published in this Clinics series. The rate of development of new techniques and their complexities require IP physicians to be constantly maintaining and updating their skill set. International agreed training pathways help ensure that the interventionalists of the present and future have the required knowledge of anatomy, manual dexterity, and clinical judgment to keep up with the continuing advances that are constantly expanding IP's diagnostic and therapeutic boundaries. IP remains one of the most desirable subspecialities in pulmonology, and the technologic advances make the future an exciting one.

Pediatric Interventional Pulmonology.

Although controversy over the role of flexible versus rigid bronchoscopy for airway foreign body management persists, the effort should focus on prevention of aspiration of foreign bodies instead. This article discusses several recent advances in the bronchoscopic management of congenital tracheal stenosis, pediatric airway stenting, and the use of different types of lasers in children. The lack of randomized clinical trials leaves pediatric interventional bronchoscopic procedures without much national or international standards or guidelines. The number of published data in the form of cases reports and case series remains modest. More bronchoscopists should be trained in this growing field to overcome these limitations.