Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry.

Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.

Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions.

BACKGROUND: Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited. MATERIALS AND METHODS: We conducted a prospective single-centre pharmacokinetic (PK) study in 12 healthy volunteers. Subjects received seven doses of 200 mg isavuconazole to achieve an assumed steady-state. After the first and final infusion, plasma sampling was conducted over 8 and 12 h, respectively. All subjects underwent one lumbar puncture and bronchoalveolar lavage, at either 2, 6 or 12 h post-infusion of the final dose. PBMCs were collected in six subjects from blood to determine intracellular isavuconazole concentrations at 6, 8 or 12 h. The AUC/MIC was calculated for an MIC value of 1 mg/L, which marks the EUCAST susceptibility breakpoint for Aspergillus fumigatus and Aspergillus flavus. RESULTS: C max and AUC0-24h of isavuconazole in plasma under assumed steady-state conditions were 6.57 ±â€Š1.68 mg/L (mean ±â€ŠSD) and 106 ±â€Š32.1 h·mg/L, respectively. The average concentrations measured in CSF, ELF and in PBMCs were 0.07 ±â€Š0.03, 0.94 ±â€Š0.46 and 27.1 ±â€Š17.8 mg/L, respectively. The AUC/MIC in plasma, CSF, ELF and in PBMCs under steady-state conditions were 106 ±â€Š32.1, 1.68 ±â€Š0.72, 22.6 ±â€Š11.0 and 650 ±â€Š426 mg·h/L, respectively. CONCLUSION: Isavuconazole demonstrated moderate penetration into ELF, low penetrability into CSF and high accumulation in PBMCs. Current dosing regimens resulted in sufficient plasma exposure in all subjects to treat isolates with MICs ≤ 1 mg/L.

Body Composition after Endoscopic Lung Volume Reduction with Endobronchial Valves: A Prospective Study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life but also influenced body weight. Only a few data are available on body composition changes after ELVR. METHODS: This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mass (BCM), lean body mass (ECM + BCM), and fat-free mass index. RESULTS: A total of 23 patients (mean emphysema index 37.2 ± 7.5%, BMI 23.4 ± 4.3 kg/m2) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p < 0.001). CONCLUSION: ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings.

Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.

Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [P < .001] and -1.15 ± 0.43 [P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.

Women in Interventional Pulmonology: Results from a Worldwide Survey.

BACKGROUND AND OBJECTIVES: Gender inequality in medicine remains an issue. Despite the increasing proportion of female physicians, women still appear underrepresented in interventional pulmonology (IP) careers. To date, no data are available on the gender distribution in IP. METHOD: An online survey was sent to pulmonary physicians internationally between July and December 2022. The survey included questions on gender diversity in the pulmonology departments, such as the proportion of male, female, and gender diverse physicians performing bronchoscopy, career progression, and social life. RESULTS: Responses from 92 physicians (mean age 45 ± 10 years) from 47 hospitals across 17 countries were analysed, of whom 52% were women. Overall, 79% of the respondents were pulmonologists and 83% perform bronchoscopy. Although men continue to dominate bronchoscopy (65 vs. 43%) and are more likely to be involved in research (89 vs. 77%), the observed difference is statistically not significant (p = 0.135 and p = 0.281). Leading positions are held by 60% of male respondents and 23% of female respondents (p = 0.002). Men are also more often reported to have academic awards. Discrimination based on gender was reported by 5.3% of all men and 26.8% of all women (p = 0.023). CONCLUSIONS: Men and women are almost equally involved in IP, especially in female-led bronchoscopy units. However, leading positions and academic awards are still predominantly held by men.

Impact of fibrinogen levels and modified Glasgow prognostic score on survival of stage III/N2 non-small cell lung cancer patients treated with neoadjuvant therapy and radical resection.

PURPOSE: The prognostic value of pretreatment and preoperative fibrinogen plasma levels and the modified Glasgow prognostic score (mGPS) in stage III/N2 non-small cell lung cancer (NSCLC) patients who receive neoadjuvant treatment followed by radical surgery is yet unclear. METHODS: Fibrinogen levels and mGPS of 84 patients with initial stage III/N2 NSCLC, who received neoadjuvant therapy followed by complete surgical resection from 2002 to 2014 were retrospectively analyzed and correlated with clinical parameters and overall survival (OS). Data were analyzed using log-rank and Cox regression analysis adjusted for clinical and pathological factors. RESULTS: Median serum fibrinogen level after neoadjuvant treatment was 439 mg/dL (IQR 158 mg/dL). Elevated fibrinogen levels (> 400 mg/dL) after neoadjuvant treatment were significantly associated with poorer OS (28.2 months vs. 60.9 months, HR 0.562, p = 0.048). Importantly, a decrease in fibrinogen levels after neoadjuvant treatment (n = 34) was found to be an independent predictor for favorable OS in multivariate analysis (HR 0.994, p = 0.025). Out of 80 patients, 55, 19 and 6 patients had a mGPS of 0, 1 and 2, respectively. Moreover, elevated mGPS after neoadjuvant treatment (mGPS 1-2) showed a non-significant trend for poorer OS compared to mGPS 0 (28.2 vs. 46.5 months, HR 0.587, p = 0.066). CONCLUSION: Elevated fibrinogen levels after neoadjuvant therapy prior to surgery in stage III/N2 NSCLC patients are associated with significant disadvantage for OS. A decrease in fibrinogen levels after neoadjuvant therapy was found to be a predictor for superior OS in this retrospective patient cohort.

Endoscopic Valve Therapy in COPD Patients with Hypercapnia.

BACKGROUND: Endoscopic valve therapy has been established as a therapeutic option for patients with severe emphysema. Several randomized controlled trials confirmed the efficacy of this therapeutic approach in COPD patients without significant collateral ventilation. However, patients with clinical relevant hypercapnia were excluded from these trials. AIMS AND OBJECTIVES: Patients with hypercapnia who underwent endoscopic valve treatment were enrolled in this retrospective analysis. The efficacy of valve treatment and its impact on blood gases were analysed. METHODS: COPD patients with mild to severe hypercapnia (pCO2 ≥45 mm Hg) who were treated by endoscopic valve placement at the Thoraxklinik, University of Heidelberg, were enrolled in this retrospective trial. Lung function test (vital capacity [VC], forced expiratory volume in 1 s [FEV1], residual volume [RV]), blood gases (pO2, pCO2), and 6-minute-walk test (6-MWT) were assessed prior to intervention and at 3 and 6 months following valve implantation. RESULTS: 129 patients (mean age 64 ± 7 years) with severe COPD (mean FEV1 26 ± 12% of predicted, mean RV 285 ± 22% of predicted) with hypercapnia (pCO2 ≥45 mm Hg, mean pCO2 50 ± 5 mm Hg) underwent endoscopic valve treatment. 3 and 6 months following intervention, statistical significant improvement was observed in VC, FEV1, RV, and 6-MWT (all p < 0.001). Blood gas analysis revealed a significant improvement of mean pCO2 at 3- and 6-month follow-up (both p < 0.001). 40% of the patients had normal pCO2 values 3 and 6 months following intervention. CONCLUSION: COPD patients with hypercapnia should not be excluded from valve treatment, as the hyperinflation reduction improves the respiratory mechanics and thus leading to improvement of hypercapnia.

Comparison of pulmonary function test, diffusion capacity, blood gas analysis and CT scan in patients with and without persistent respiratory symptoms following COVID-19.

BACKGROUND: Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations. METHODS: In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients. RESULTS: In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042). CONCLUSION: Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.

Technical Innovations in Pneumology: E-Health, Screening, Diagnostics, and Therapy.

At the 2020 "Luftschlösser" (castles in the air) conference, experts from a wide range of pneumological fields discussed technical innovations in pneumology, which can be seen in many different areas of the field, including e-health, screening, diagnostics, and therapy. They contribute to substantial advancements ranging from the innovative use of diagnostic tools to novel treatments for chronic lung diseases. Artificial intelligence enables broader screening, which can be expected to have beneficial effects on disease progression and overall prognosis. There is still a high demand for clinical trials to investigate the usefulness and risk-benefit ratio. Open questions remain especially about the quality and utility of medical apps in an inadequately regulated market. This article weighs the pros and cons of technical innovations in specific subspecialties of pneumology based on the lively exchange of ideas among various pneumological experts.

Expert Statement: Pneumothorax Associated with One-Way Valve Therapy for Emphysema: 2020 Update.

For selected patients with advanced emphysema, bronchoscopic lung volume reduction with one-way valves can lead to clinically relevant improvements of airflow obstruction, hyperinflation, exercise capacity, and quality of life. The most common complication of this procedure is pneumothorax with a prevalence of up to ±34% of the treated patients. Patients who develop a pneumothorax also experience meaningful clinical benefits once the pneumothorax is resolved. Timely resolution of a post-valve treatment pneumothorax requires skilled and adequate pneumothorax management. This expert panel statement is an updated recommendation of the 2014 statement developed to help guide pneumothorax management after valve placement. Additionally, mechanisms for pneumothorax development, risk assessment, prevention of pneumothorax, and outcomes after pneumothorax are addressed. This recommendation is based on a combination of the current scientific literature and expert opinion, which was obtained through a modified Delphi method.

Interventional Bronchoscopy.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10-15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

[Morphological and functional sequelae after COVID-19 pneumonia]. / Morphologische und funktionelle Folgen nach COVID-19-Pneumonie.

BACKGROUND: Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment. OBJECTIVES: To discuss the role of long-term assessment of COVID-19 patients to determine which patients may benefit from follow-up. MATERIALS AND METHODS: This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia. RESULTS: Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time. CONCLUSIONS: Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a multidisciplinary manner.

Quantitative CT detects progression in COPD patients with severe emphysema in a 3-month interval.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by variable contributions of emphysema and airway disease on computed tomography (CT), and still little is known on their temporal evolution. We hypothesized that quantitative CT (QCT) is able to detect short-time changes in a cohort of patients with very severe COPD. METHODS: Two paired in- and expiratory CT each from 70 patients with avg. GOLD stage of 3.6 (mean age = 66 ± 7.5, mean FEV1/FVC = 35.28 ± 7.75) were taken 3 months apart and analyzed by fully automatic software computing emphysema (emphysema index (EI), mean lung density (MLD)), air-trapping (ratio expiration to inspiration of mean lung attenuation (E/I MLA), relative volume change between - 856 HU and - 950 HU (RVC856-950)), and parametric response mapping (PRM) parameters for each lobe separately and the whole lung. Airway metrics measured were wall thickness (WT) and lumen area (LA) for each airway generation and the whole lung. RESULTS: The average of the emphysema parameters (EI, MLD) increased significantly by 1.5% (p < 0.001) for the whole lung, whereas air-trapping parameters (E/I MLA, RVC856-950) were stable. PRMEmph increased from 34.3 to 35.7% (p < 0.001), whereas PRMNormal decrased from 23.6% to 22.8% (p = 0.012). WT decreased significantly from 1.17 ± 0.18 to 1.14 ± 0.19 mm (p = 0.036) and LA increased significantly from 25.08 ± 4.49 to 25.84 ± 4.87 mm2 (p = 0.041) for the whole lung. The generation-based analysis showed heterogeneous results. CONCLUSION: QCT detects short-time progression of emphysema in severe COPD. The changes were partly different among lung lobes and airway generations, indicating that QCT is useful to address the heterogeneity of COPD progression. KEY POINTS: • QCT detects short-time progression of emphysema in severe COPD in a 3-month period. • QCT is able to quantify even slight parenchymal changes, which were not detected by spirometry. • QCT is able to address the heterogeneity of COPD, revealing inconsistent changes individual lung lobes and airway generations.

Endobronchial Ultrasound Elastography for Differentiating Benign and Malignant Lymph Nodes.

BACKGROUND: Endobronchial ultrasound elastography that provides information on tissue stiffness may help distinguish malignant from benign mediastinal and hilar lymph nodes. OBJECTIVES: In this prospective trial, we assessed the diagnostic value of elastographic images and the interobserver agreement in its evaluation. METHOD: Elastographic images from 77 lymph nodes in 65 patients were reviewed by 3 pneumologists. The elastographic image was classified based on the predominant colour: predominantly green, intermediary, and predominantly blue. With 2 or 3 interobserver matches, the corresponding elastographic image was correlated with the pathological result obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and/or other invasive procedures. RESULTS: All 3 reviewers had agreement in classifying elastographic images in 45% (35/77). Overall, the interobserver agreement among the 3 readers for classifying elastographic pattern was found to be moderate (Fleiss Kappa index = 0.519; 95% CI = [0.427; 0.611]). On cytological/histological evaluation, 55 lymph nodes were malignant and 22 were benign. In classifying "green" as benign and "blue" as malignant, the sensitivity and specificity were 71% (95% CI = [54%; 85%]) and 67% (95%-CI = [35%; 90%]), respectively. CONCLUSIONS: Elastography will not replace invasive EBUS-TBNA due to a moderate interobserver agreement and insufficient sensitivity and specificity. However, elastography will, maybe, present an additional feature to identify malignant lymph nodes in the context of clinical, radiological, and cytological results.

Efficacy and Safety of the 9-mm Intrabronchial Valve in Patients with Advanced Emphysema.

BACKGROUND: Endoscopic valve therapy aims at lung volume reduction that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. The size of intrabronchial valves of the Spiration® Valve System (SVS) selected to achieve lobar occlusion may have an influence on treatment outcomes. METHODS: 49 severe emphysema patients (M/F: 24/25, age: 64 ± 7 years), with complete interlobar fissures on the side intended to be treated, underwent treatment with at least one 9-mm intrabronchial valve implantation at 3 centers and were followed up at 30, 90 and 180 days after intervention. Changes in pulmonary function tests (PFT), 6-min walk test (6MWT), modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive pulmonary disease assessment test scores as well as possible complications were recorded. RESULTS: Forced expiratory volume in 1 s (FEV1) improved significantly over the 6-month period of the study, and the proportion of patients achieving a minimal clinically important difference (MCID) for FEV1 was 46.4% at 6 months. Regarding the remaining PFT values, the changes were not statistically significant at 6 months, but when looking at the MCIDs, 44.4% of the patients achieved the MCID decrease for residual volume. The 6MWT distance also improved statistically significantly, and an MCID increase of ≥26 m was reached by 41.7% of the patients. Furthermore, there was a statistically significant improvement in the mMRC score. The incidence of pneumothoraxes requiring drainage was 26.5% while a valve dislocation rate of 24% was observed but only in the lower lobes. CONCLUSIONS: Endoscopic lung volume reduction with the 9-mm SVS valves was associated with statistically significant but modest improvement of FEV1, mMRC and 6MWT up to 6 months after intervention. These results were accompanied by an anticipated and acceptable risk profile. The relative increased incidence of device dislocation observed needs to be further elucidated.

Survival after Endoscopic Valve Therapy in Patients with Severe Emphysema.

BACKGROUND: Endoscopic valve therapy leads to an improvement of lung function, exercise tolerance, and quality of life in a selected cohort of patients with advanced emphysema. So far, only few data exist on the long-term outcome. OBJECTIVES: This analysis evaluated the impact of valve therapy on the survival of emphysema patients. METHODS: Survival rates of emphysema patients who underwent valve therapy were assessed according to their radiological outcome following valve placement. RESULTS: From 2005 to 2013, 449 emphysema patients (mean age 64 ± 7 years) underwent valve therapy and were followed for a mean time of 37.3 ± 21.3 months. A total of 128 patients (29%) developed complete lobar atelectasis, 34 out of these also experienced a pneumothorax; 50 patients (11%) developed pneumothorax without lobar atelectasis, and 261 patients (58%) target lobe volume reduction or no volume change. Patients with atelectasis showed significantly better baseline forced expiratory volume in 1 second (%), residual volume (L), total lung capacity (L), and transfer factor for carbon monoxide (%; all p < 0.05), but there was no significant difference in the BODE score (p = 0.195). Patients with valve-induced lobar atelectasis had a significant survival benefit compared to patients without atelectasis (p = 0.009; 5-year survival rate 65.3 vs. 43.9%). The advent of pneumothorax in 84 patients did not influence survival (p = 0.52). CONCLUSIONS: Lobar atelectasis following endoscopic valve therapy is associated with a survival benefit.

Bronchoscopic Thermal Vapor Ablation: Best Practice Recommendations from an Expert Panel on Endoscopic Lung Volume Reduction.

Bronchoscopic thermal vapor ablation (BTVA) represents one of the endoscopic lung volume reduction (ELVR) techniques that aims at hyperinflation reduction in patients with advanced emphysema to improve respiratory mechanics. By targeted segmental vapor ablation, an inflammatory response leads to tissue and volume reduction of the most diseased emphysematous segments. So far, BTVA has been demonstrated in several single-arm trials and 1 multinational randomized controlled trial to improve lung function, exercise capacity, and quality of life in patients with upper lobe-predominant emphysema irrespective of the collateral ventilation. In this review, we emphasize the practical aspects of this ELVR method. Patients with upper lobe-predominant emphysema, forced expiratory volume in 1 second (FEV1) between 20 and 45% of predicted, residual volume (RV) > 175% of predicted, and carbon monoxide diffusing capacity (DLCO) ≥20% of predicted can be considered for BTVA treatment. Prior to the procedure, a special software assists in identifying the target segments with the highest emphysema index, volume and the highest heterogeneity index to the untreated ipsilateral lung lobes. The procedure may be performed under deep sedation or preferably under general anesthesia. After positioning of the BTVA catheter and occlusion of the target segment by the occlusion balloon, heated water vapor is delivered in a predetermined specified time according to the vapor dose. After the procedure, patients should be strictly monitored to proactively detect symptoms of localized inflammatory reaction that may temporarily worsen the clinical status of the patient and to detect complications. As the data are still very limited, BTVA should be performed within clinical trials or comprehensive registries where the product is commercially available.

Endoscopic Valve Removal >180 Days since Implantation in Patients with Severe Emphysema.

BACKGROUND: Valve implantation provides a reversible effective therapy in a selected group of emphysema patients. Knowing predictors for successful therapy, the rate of treatment failure has decreased. Some patients, however, do not benefit, so that the valves may have to be removed. OBJECTIVES: To assess implant-related events, complications during valve removal, and clinical outcome after endoscopic procedure. METHODS: The data of 76 consecutive emphysema patients who underwent valve removal > 6 months since implantation were collected. RESULTS: Seventy-six patients (mean age 62 years, 54% male) underwent removal of all valves after a mean time of 624 days (193-3,043 days) since implantation. Granulation tissue was observed in 39.5% (30/76) and significant secretion in 34.2% (26/76). In 5.3% (4/76), valve removal was complicated requiring another bronchoscopy in 2 of them. In 5.3% (4/76) of the patients, one valve could not be removed and remained in situ. Bleeding requiring intervention occurred in 3.9% (3/76) during valve removal. Following bronchoscopy, there was a need for antibiotics in 34.2% (26/76), glucocorticosteroids in 1.3% (1/76), and both in 6.6% (5/76) due to productive cough or chronic obstructive pulmonary disease (COPD) exacerbation. Due to respiratory failure, invasive ventilation or noninvasive ventilation was necessary in 2.6% (2/76) and 6.6% (5/76), respectively, following procedure. No statistical significant change in lung function was observed following valve removal. CONCLUSIONS: Valve removal after > 6 months since implantation is feasible and associated with an acceptable safety profile. However, close monitoring of these patients with limited pulmonary reserve is recommended with particular attention to COPD exacerbations and respiratory failure.

Motion monitoring during a course of lung radiotherapy with anchored electromagnetic transponders : Quantification of inter- and intrafraction motion and variability of relative transponder positions.

PURPOSE: Anchored electromagnetic transponders for tumor motion monitoring during lung radiotherapy were clinically evaluated. First, intrafractional motion patterns were analyzed as well as their interfractional variations. Second, intra- and interfractional changes of the geometric transponder positions were investigated. MATERIALS AND METHODS: Intrafractional motion data from 7 patients with an upper or middle lobe tumor and three implanted transponders each was used to calculate breathing amplitudes, overall motion amount and motion midlines in three mutual perpendicular directions and three-dimensionally (3D) for 162 fractions. For 6 patients intra- and interfractional variations in transponder distances and in the size of the triangle defined by the transponder locations over the treatment course were determined. RESULTS: Mean 3D values of all fractions were up to 4.0, 4.6 and 3.4 mm per patient for amplitude, overall motion amount and midline deviation, respectively. Intrafractional transponder distances varied with standard deviations up to 3.2 mm, while a maximal triangle shrinkage of 36.5% over 39 days was observed. CONCLUSIONS: Electromagnetic real-time motion monitoring was feasible for all patients. Detected respiratory motion was on average modest in this small cohort without lower lobe tumors, but changes in motion midline were of the same size as the amplitudes and greater midline motion can be observed in some fractions. Intra- and interfractional variations of the geometric transponder positions can be large, so for reliable motion management correlation between transponder and tumor motion needs to be evaluated per patient.

Interventional pulmonology in chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and emphysema are widespread diseases associated with progressive dyspnea because of airflow limitation and hyperinflation. Fundamental therapeutic strategies consist of pulmonary rehabilitation, pharmacotherapy, long-term oxygen therapy, noninvasive ventilation, and surgical therapeutic approaches. RECENT FINDINGS: In the last 14 years, endoscopic therapeutic modalities emerged as a substantial part of severe COPD and emphysema treatment. Techniques of the endoscopic lung volume reduction (ELVR) aim at reduction of hyperinflation. Thereby, the reversible valve implantation of which the efficacy was confirmed in various randomized controlled trials (RCT) results in lobar volume reduction and clinical benefit in emphysema patients with absent interlobar collateral ventilation. Nonblocking ELVR methods that are independent of collateral ventilation include the partially irreversible coil implantation leading to parenchymal compression, the irreversible bronchoscopic thermal vapor ablation and polymeric lung volume reduction both inducing inflammatory reaction. The nonblocking methods have been examined in only a few RCTs. The targeted lung denervation as a novel bronchoscopic therapy for COPD patients aims at sustainable bronchodilation by ablation of parasympathetic pulmonary nerves. SUMMARY: The review summarizes the various endoscopic treatment approaches for managment of COPD and emphysema, their mechanism of action, their complications and the current available results of the most important RCTs.