Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Bronchoscopic Lung Volume Reduction with Endobronchial Zephyr Valves for Severe Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic lung volume reduction using Zephyr® valves has been recently adopted as a treatment option for patients with severe emphysema without collateral ventilation (CV). OBJECTIVES: To assess the efficacy and safety of Zephyr valves in such a population. METHODS: Studies were identified from MEDLINE and EMBASE databases. All searches were current until June 2018. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of Zephyr. We defined as outcome: change in forced expiratory volume in 1 s (FEV1), in the 6-min walking test (6MWT), in the St George's Respiratory Questionnaire (SGRQ), and in residual volume (RV). Safety analysis included relative risk (RR) of pneumothorax. We assessed the quality of the evidence using GRADE. RESULTS: 7 RCTs reported on Zephyr valves and 5 RCTs included only patients without CV. Zephyr improved FEV1 with a mean difference (MD) of 17.36% (CI, 9.28-25.45, I2 = 78%). Subgroup analysis showed significant FEV1 improvement following Zephyr placement in patients with heterogeneous distribution: MD = 21.78% (CI, 8.70-34.86, I2 = 89%) and 16.27% (CI, 8.78-23.76, I2 = 0%) in patients with homogeneous emphysema. Studies with a follow-up of 3 months reported FEV1 MD = 17.19% (CI, 3.16-31.22, I2 = 89%) compared to studies with a follow-up of 6-12 months, which showed a consistent improvement of FEV1 MD = 17.90% (CI, 11.47-24.33, I2 = 0%). Zephyr also showed improvement of SGRQ, 6MWT, and RV. RR of pneumothorax was 6.32 (CI, 3.74-10.67, I2 = 0%). CONCLUSION: In this population, Zephyr valves provided significant and clinically meaningful short-term improvements in either homogeneous or heterogeneous emphysema without CV but with an increase in adverse events.

Association between inflammatory bowel disease and chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: There is evidence of an association between inflammatory bowel disease (IBD) and lung conditions such as chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis explored the risk of new onset IBD in patients with COPD and new onset COPD in IBD patients. METHODS: We performed a systematic review of observational studies exploring the risk of both associations. Two independent reviewers explored the EMBASE, MEDLINE, LILACS and DOAJ databases, and the risk of bias was evaluated using the ROBBINS-I tool. Data from included studies was pooled in a random effect meta-analysis following a DerSimonian-Laird method. The quality of the evidence was ranked using GRADE criteria. RESULTS: Four studies including a pooled population of 1355 new cases were included. We found association between new onset IBD in COPD population. The risk of bias was low in most of them. Only one study reported tobacco exposure as a potential confounding factor. The pooled risk ratio (RR) for a new diagnosis of IBD in COPD patients was 2.02 (CI, 1.56 to 2.63), I2 = 72% (GRADE: low). The subgroup analyses for Crohn's disease and ulcerative colitis yielded RRs of 2.29 (CI, 1.51 to 3.48; I2 = 62%), and 1.79 (CI, 1.39 to 2.29; I2 = 19%.), respectively. DISCUSSION: According to our findings, the risk of new onset IBD was higher in populations with COPD compared to the general population without this condition. Based on our analysis, we suggest a potential association between IBD and COPD; however, further research exploring the potential effect of confounding variables, especially cigarette smoking, is still needed. REVIEW REGISTER: (PROSPERO: CRD42018096624).

Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease.

BACKGROUND: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. OBJECTIVES: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. METHODS: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. RESULTS: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. CONCLUSION: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation.

Pulmonary nodules and nodular infiltrates occur frequently during treatment of hematologic malignancies and after hematopoietic cell transplantation. In patients not receiving active immunosuppressive therapy, the most likely culprits are primary lung cancer, chronic infectious or inactive granulomata, or even the underlying hematologic disease itself (especially in patients with lymphoma). In patients receiving active therapy or who are otherwise highly immunosuppressed, there is a wider spectrum of etiologies with infection being most likely, especially by bacteria and fungi. Characterization of the pulmonary lesion by high-resolution CT imaging is a crucial first diagnostic step. Other noninvasive tests can often be useful, but invasive testing by bronchoscopic evaluation or acquisition of tissue by one of several biopsy techniques should be performed for those at risk for malignancy or invasive infection unless contraindicated. The choice of the optimal biopsy technique should be individualized, guided by location of the lesion, suspected etiology, skill and experience of the diagnostic team, procedural risk of complications, and patient status. Although presumptive therapy targeting the most likely etiology is justified in patients suspected of serious infection while evaluation proceeds, a structured evaluation to determine the specific etiology is recommended. Interdisciplinary teamwork is highly desirable to optimize diagnosis and therapy.

Prevention of acute exacerbation of chronic obstructive pulmonary disease after bronchoscopic lung volume reduction with endobronchial valves.

INTRODUCTION: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBVs) has emerged as an important treatment method for patients with severe chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD (AECOPD) are a frequent complication following BLVR with EBV. However, there is no consensus on the prevention of AECOPD. OBJECTIVES: Our study aims to compare the outcomes of different prophylactic measures on the occurrence of AECOPD after BLVR with EBV. METHODS: We conducted a multicenter, retrospective study of patients who underwent BLVR with EBV at six different institutions. Emphasis was directed towards the specific practices aimed at preventing AECOPD: antibiotics, steroids, antibiotics plus steroids, or no prophylaxis. Subgroups were compared, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. RESULTS: A total of 170 patients were reviewed. The rate of AECOPD was 21.2% for the full cohort. Patients who received prophylaxis had a significantly lower rate of AECOPD compared with those who did not (16.7% vs. 46.2%; p = 0.001). The rate was lowest in patients who received antibiotics alone (9.2%). There was no significant difference in the rate of AECOPD between patients who received steroids alone or antibiotics plus steroids, compared with the other subgroups. The OR for AECOPD was 4.3 (95% CI: 1.8-10.4; p = 0.001) for patients not receiving prophylaxis and 3.9 (95% CI: 1.5-10.1; p = 0.004) for prophylaxis other than antibiotics alone. CONCLUSIONS: Administration of antibiotics after BLVR with EBV was associated with a lower rate of AECOPD. This was not observed with the use of steroids or in combination with antibiotics.

Galactomannan testing in bronchoalveolar lavage fluid facilitates the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies and stem cell transplant recipients.

Invasive pulmonary aspergillosis (IPA) is a major cause of mortality in patients with stem cell transplants and hematologic malignancies. Timely diagnosis of IPA improves survival but is difficult to make. We evaluated the effectiveness of bronchoalveolar lavage (BAL) galactomannan (GM) in diagnosing IPA in these populations by retrospectively reviewing records of 67 consecutive patients, in whom 89 BAL GM tests were performed. For patients with IPA, only the first BAL sample linked to the IPA episode was analyzed. Eighty samples were associated with proven, 12 with probable, and 32 with possible invasive fungal infections (IFI), and 37 were associated with no IFI. Among patients with IFIs, 4 had proven, 11 probable, and 32 possible IPA. Using BAL GM ≥ 0.5 (cutoff for serum GM) and ≥ 0.85 (optimal cutoff identified by receiver-operating characteristic curve), the sensitivity in diagnosing proven or probable IPA was 73% (11/15) and 67% (10/15), respectively, and specificity was 89% (33/37) and 95% (35/37). At these cutoffs, positive and negative predictive values were 73% (11/15) and 83% (10/12), and 89% (33/37) and 87% (35/40), respectively. BAL GM was more sensitive than cytology (0%, 0/14), BAL culture (27%, 4/15), transbronchial biopsy (40%, 2/5), or serum GM (67%, 10/15) for diagnosing IPA. BAL GM was ≥ 0.85 and ≥ 0.5 in 86% (6/7) and 100% (7/7) of patients with proven or probable IPA who received a mold-active agent for ≤ 3 days. BAL GM added sensitivity to serum GM and other means of diagnosing IPA, and was not impacted by short courses of mold-active agents.

Utility of bronchoscopic intra-tumoral alcohol injection to restore airway patency.

BACKGROUND: In cases of malignant airway obstruction, achieving airway patency using conventional bronchoscopic modalities can be challenging and may not be satisfactory. We aim to present our experience of using intra-tumoral alcohol injection (ITAI) to help achieve airway patency in malignant airway obstruction. METHODS: A retrospective study of adult patients presenting with malignant airway obstruction who underwent bronchoscopy with ITAI at a university center between 2015 and 2020 was conducted. We present procedural and patients' characteristics along with any additional bronchoscopic or systemic interventions received. Patients were classified based on airway patency response (assessed qualitatively by an interventional pulmonologist) into those with good response (≥50% improvement in airway patency) vs. those with low response (<50% improvement in airway patency). RESULTS: Forty-two patients underwent ITAI, of which 34 (81%) had at least two bronchoscopies to evaluate response. The patient median age was 65.5 [interquartile range (IQR) 57.8-72]. Most patients had stage IV malignancy at the time of the bronchoscopy (57.1%) and had Eastern Cooperative Oncology Group (ECOG) performance status score of between 2-3. Eighty-two percent of the patients achieved good airway patency response at the conclusion of the procedures. The procedures were generally well-tolerated and only one patient had significant bleeding that was not directly related to ITAI and required intensive care unit monitoring for 24 hours after the procedure. CONCLUSIONS: Dehydrated alcohol is readily available, inexpensive and a safe drug that can be potentially injected directly in malignant airway obstructive lesions in a multimodality approach to achieve airway patency when traditional modalities reach their limitation. Further studies are warranted to determine whether ITAI is superior to other interventional methods, explore its utilization to treat peripheral malignant tumors, as well as to standardize the treatment protocol and determine the effects of ITAI on patient symptoms and quality of life.

Repositioning of migrated self-expanding metallic tracheobronchial stent: predictors of a successful maneuver and its impact on survival.

BACKGROUND: Endobronchial stents that are used to treat airway obstruction may migrate over time. These stents can be repositioned. However, not much has been reported about this technique. We retrospectively reviewed our experience with self-expanding metallic stents (SEMS) and attempted to determine-(I) factors related to successful stent repositioning; (II) determine its impact on survival. METHODS: Demographic, medical history, and stent-related procedure factors were extracted from the electronic health record. Primary outcomes were bronchial stent repositioning success and survival (days until death). As validation of successful repositioning, the durations of successful and failed repositioning procedures were compared using an independent t-test. RESULTS: Seventy-six patients underwent stent repositioning, of which, 55.3% (n=42) were successfully repositioned. The probability of success in repositioning procedures was accounted for by patient sex, stent location, and stent diameter. Females were more likely to have a successful repositioning compared to males. Stent repositioning in the LMS was more likely to be successful and stents larger in diameter tended to increase the likelihood of successful repositioning. Long-term survival was higher for those who had a successful procedure. Stent location and disease subgroups predicted average length of survival. CONCLUSIONS: Repositioning of migrated stents can be successfully performed regardless of the reasons for initial placement, duration of stenting and degree of original obstruction. Larger stents are easier to reposition and so were stents in the left main stem (LMS) airway. A successful stent repositioning maneuver improved long-term survival although did not have any impact survival in the immediate post-procedural period.

Concomitant Radiation Recall Dermatitis and Organizing Pneumonia following Breast Radiotherapy: A Case Report.

PURPOSE: Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction. PATIENT: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2- invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0. RESULT: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration. CONCLUSIONS: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.

Sensitivity and Safety of Electromagnetic Navigation Bronchoscopy for Lung Cancer Diagnosis: Systematic Review and Meta-analysis.

BACKGROUND: Bronchoscopy is a useful tool for the diagnosis of lesions near central airways; however, the diagnostic accuracy of these procedures for peripheral pulmonary lesions (PPLs) is a matter of ongoing debate. In this setting, electromagnetic navigation bronchoscopy (ENB) is a technique used to navigate and obtain samples from these lesions. This systematic review and meta-analysis aims to explore the sensitivity of ENB in patients with PPLs suspected of lung cancer. RESEARCH QUESTION: In patients with peripheral pulmonary lesion suspected of lung cancer, what is the sensitivity and safety of electromagnetic navigation bronchoscopy compared to surgery or longitudinal follow up? STUDY DESIGN AND METHODS: A comprehensive search of several databases was performed. Extracted data included sensitivity of ENB for malignancy, adequacy of the tissue sample, and complications. The study quality was assessed using the QUADAS-2 tool, and the combined data were meta-analyzed using a bivariate method model. A summary receiver operatic characteristic curve (sROC) was created. Finally, the quality of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty studies with a total of 3,342 participants were included in our analysis. ENB reported a pooled sensitivity of 77% (95% CI, 72%-82%; I2 = 80.6%) and a specificity of 100% (95% CI, 99%-100%; I2 = 0%) for malignancy. The sROC showed an area under the curve of 0.955 (P = .03). ENB achieved a sufficient sample for ancillary tests in 90.9% (95% CI, 84.8%-96.9%; I2 = 80.7%). Risk of pneumothorax was 2.0% (95% CI, 1.0-3.0; I2 = 45.2%). We found subgroup differences according to the risk of bias and the number of sampling techniques. Meta-regression showed an association between sensitivity and the mean distance of the sensor tip to the center of the nodule, the number of tissue sampling techniques, and the cancer prevalence in the study. INTERPRETATION: ENB is very safe with good sensitivity for diagnosing malignancy in patients with PPLs. The applicability of our findings is limited because most studies were done with the superDimension navigation system and heterogeneity was high. TRIAL REGISTRY: PROSPERO; No.: CRD42019109449; URL: https://www.crd.york.ac.uk/prospero/.

Comparison of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration With Stylet Retracted Partially Versus Completely for Molecular Testing.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered to be the initial diagnostic modality for most patients with lung cancer. However, the optimal technique for maximizing yield continues to vary in the real-world setting. OBJECTIVES: To evaluate the diagnostic yield of EBUS-TBNA with capillary sampling compared with complete stylet removal for molecular testing. METHODS: Retrospective study, data from patients between January to May 2017 with indication of EBUS-TBNA whom ancillary testing, that is, next-generation sequencing, anaplastic lymphoma kinase (ALK), and programed death ligand-1 (PD-L1) expression was reviewed. The yield of 2 techniques, stylet retracted halfway (group 1) versus complete retraction (group 2), was compared. RESULTS: A total of 24/27 (88.88%) samples were adequate for next-generation sequencing analysis in group 1 and 21/23 (91.30%) in group 2. For other molecular analyses, 24/27 (88.88%) samples in group 1 and 20/23 (86.95%) samples in group 2 were adequate for ALK analysis. 23/27 (85.18%) samples for group 1 and 20/23 (86.95%) samples for group 2 were adequate for PD-L1 analysis. Positive expression of PD-L1>50% was achieved in 9/23 (39.13%) of group 1 and 5/20 (25%) of group 2. There was no statistical difference in the yield between the 2 groups. CONCLUSION: EBUS-TBNA using either capillary sampling or complete stylet removal are effective and has a high proportion of satisfactory results for ancillary testing.

Photodynamic Therapy for Bronchial Microscopic Residual Disease After Resection in Lung Cancer.

BACKGROUND: The goal of lung cancer surgery is a complete tumor resection (R0 resection) with clear margins. 4% to 5% of resections have microscopic residual disease associated with worse prognosis. Definitive management is resection of residual tumor, which may not be tolerated by many patients, and definitive management is not well studied in these patients. We treated patients with stage I cancer and bronchial mucosal residual disease (MRD) with bronchoscopic photodynamic therapy (PDT). METHODS: All patients who underwent definitive surgery for early-stage lung cancer were reviewed. Patients with R1 resection, stage I disease with MRD and or carcinoma in situ along the stump site were treated with bronchoscopic PDT. Patient characteristics, histology, type and site of surgery, pattern of recurrence, recurrence status, adverse events, and survival data were evaluated. RESULTS: Eleven patients with bronchial mucosal R1 resection were treated with PDT along the stump site. The median age was 67. Three patients had carcinoma in situ and 8 had MRD. One patient (9%) had local recurrence 1 year after PDT treatment and was treated with radiation. Four patients (36%) had no evidence of recurrence to date after a median follow-up of 4 years and the other 6 patients had evidence of regional (16%) or distant (39%) recurrence. The local control rate was 91%. One patient developed pneumonia and other had photosensitivity reaction. CONCLUSION: Bronchoscopic PDT is safe and effective in selected group of patients with non-small cell lung cancer who have MRD along the stump site.

Diagnostic Accuracy of Endobronchial Ultrasound Transbronchial Needle Aspiration in Lymphoma. A Systematic Review and Meta-Analysis.

Rationale: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method used to diagnose suspected mediastinal lymph nodes or masses. However, the accuracy of the diagnosis in patients with suspected lymphoma is unclear.Objectives: To evaluate the diagnostic yield of EBUS-TBNA in patients with suspected lymphoma.Methods: A literature search including EMBASE, MEDLINE, Cochrane Library, and Google Scholar was performed by two reviewers. Included articles were evaluated using the QUADAS-2 tool and meta-analysis with a binary method model to compare the sensitivity, specificity, and summary receiver operating characteristic curve in patients with suspected lymphoma.Results: Fourteen studies (425 participants) were pooled in the analysis. EBUS-TBNA reported an overall sensitivity of 66.2% (confidence interval [CI], 55-75.8%; I2 = 76.2%) and specificity of 99.3% (CI, 98.2-99.7%; I2 = 40%). For a new diagnosis of lymphoma, 13 studies including 243 participants reported sensitivity of 67.1% (CI, 54.2-77.9%; I2 = 66.8%) and specificity of 99.6% (CI, 99.1-99.8%; I2 = 0%). For recurrence of lymphoma, 11 studies including 166 participants reported sensitivity of 77.8% (CI, 68.1-85.2%; I2 = 20.2%) and specificity of 99.5% (CI, 98.9-99.8%; I2 = 0%). In the recurrence group, we found the use of rapid onsite examination, sample size, and flow cytometry increased the sensitivity of EBUS-TBNA, albeit a potential source of heterogeneity.Conclusions: EBUS-TBNA has fair sensitivity for identifying a new diagnosis of lymphoma and fair to good sensitivity for identifying recurrence.Trial Registry: PROSPERO CRD42018102773 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=102773.

Pathophysiology of the pleura.

The pleural mesothelial cell is an essential cell in maintaining the normal homeostasis of the pleural space and it is also a central component of the pathophysiologic processes affecting the pleural space. In this review, we will review the defense mechanisms of the pleural mesothelium and changes in pleural physiology as a result of inflammatory, infectious, and malignant conditions with a focus on cytokine and chemokine networks. We will also review the processes involved in the pathogenesis of pleural fibrosis.