Clinical Outcomes of Bronchoscopic Cryotherapy for Central Airway Obstruction in Adults: An 11-Years' Experience of a Single Center.

BACKGROUND: Although bronchoscopic cryotherapy (BC) is a pragmatic modality for recanalization of central airway obstruction (CAO), the risk of complications, such as bleeding, remains a concern. This study aimed to present the clinical outcomes of BC and evaluate the factors associated with its complications. METHODS: In this retrospective study, we reviewed the medical records of patients who underwent BC for CAO at the Asan Medical Center, South Korea. Most sessions were conducted via flexible bronchoscopy under moderate sedation. A multivariate logistic regression analysis was used to identify the factors associated with the success rate and complications. RESULTS: BC was performed in 262 sessions in 208 patients between January 2009 and December 2020. The most common cause of cryotherapy was recanalization of the endobronchial tumor related CAO (233/262, 88.9%). More than partial re-establishment of airway patency was achieved in 211 of 233 (90.6%) sessions. The success rate did not differ significantly in the multivariate logistic regression analysis. The most common complication was intrabronchial bleeding (78/233, 35.5%); however, severe bleeding occurred only in one case (0.4%). Univariate and multivariate logistic regression analyses revealed that diabetes mellitus (odds ratio [OR] = 2.820, P = 0.011), respiratory failure before BC (OR = 3.546, P = 0.028), and presence of distal airway atelectasis (OR = 0.417, P = 0.021) were independently associated with moderate to severe intrabronchial bleeding, while the histologic type of tumor was not related to bleeding. BC for CAO caused by blood clot or foreign body was successful in most cases, and there were no complications. CONCLUSION: BC is an efficient and relatively safe intervention for patients with CAO. Our findings suggest that diabetes, respiratory failure before BC, and the absence of distal airway atelectasis may be risk factors of moderate to severe intrabronchial bleeding.

Lipocalin-2 promotes acute lung inflammation and oxidative stress by enhancing macrophage iron accumulation.

Lipocalin-2 (LCN2) is an acute-phase protein that regulates inflammatory responses to bacteria or lipopolysaccharide (LPS). Although the bacteriostatic role of LCN2 is well studied, the function of LCN2 in acute lung damage remains unclear. Here, LCN2 knockout (KO) mice were used to investigate the role of LCN2 in LPS-treated mice with or without recombinant LCN2 (rLCN2). In addition, we employed patients with pneumonia. RAW264.7 cells were given LCN2 inhibition or rLCN2 with or without iron chelator deferiprone. LCN2 KO mice had a higher survival rate than wild-type (WT) mice after LPS treatment. In addition to elevated LCN2 levels in serum and bronchoalveolar lavage fluid (BALF), LPS treatment also increased LCN2 protein in alveolar macrophage lysates of BALF. LCN2 deletion attenuated neutrophil and macrophage infiltration in the lungs of LPS-treated mice as well as serum and BALF interleukin-6 (IL-6). Circulating proinflammatory cytokines and LCN2-positive macrophages were prominently increased in the BALF of pneumonia patients. In addition to increase of iron-stained macrophages in pneumonia patients, increased iron-stained macrophages and oxidative stress in LPS-treated mice were inhibited by LCN2 deletion. In contrast, rLCN2 pretreatment aggravated lung inflammation and oxidative stress in LPS-treated WT mice and then resulted in higher mortality. In RAW264.7 cells, exogenous LCN2 treatment also increased inflammation and oxidative stress, whereas LCN2 knockdown markedly diminished these effects. Furthermore, deferiprone inhibited inflammation, oxidative stress, and phagocytosis in RAW264.7 cells with high LCN2 levels, as well as LPS-induced acute lung injury in WT and LCN2 KO mice. Thus, these findings suggest that LCN2 plays a key role in inflammation and oxidative stress following acute lung injury and that LCN2 is a potential therapeutic target for pneumonia or acute lung injury.

Serum Fibrinogen as a Biomarker for Disease Severity and Exacerbation in Patients with Non-Cystic Fibrosis Bronchiectasis.

Background: Serum biomarkers associated with severe non-cystic fibrosis (CF) bronchiectasis are currently lacking. We assessed the association of serum fibrinogen, adiponectin, and angiopoietin-2 levels with the severity and exacerbation of bronchiectasis. Methods: Serum levels of fibrinogen, adiponectin, and angiopoietin-2 were measured and compared in patients with stable non-CF bronchiectasis (n = 61) and healthy controls (n = 16). The correlations between the three biomarkers and the bronchiectasis severity index (BSI) or FACED scores were assessed. Univariate and multivariate linear regression analyses were performed to identify variables independently associated with BSI and FACED scores in patients with bronchiectasis. Additionally, the exacerbation-free survival was compared between groups of patients with high and low fibrinogen levels, while the predictors of exacerbation were analyzed using Cox proportional hazards regression. Results: Patients with non-CF bronchiectasis carried higher fibrinogen (3.00 ± 2.31 vs. 1.52 ± 0.74 µg/mL; p = 0.016) and adiponectin (12.3 ± 5.07 vs. 9.17 ± 5.30 µg/mL; p = 0.031) levels compared with healthy controls. The serum level of angiopoietin-2 was comparable between the two groups (1.49 ± 0.96 vs. 1.21 ± 0.79 ng/mL, p = 0.277). Correlations of adiponectin and angiopoietin-2 with BSI and FACED scores were not significant. However, there were significant correlations between fibrinogen and both BSI (r = 0.428) and FACED scores (r = 0.484). Multivariate linear regression analysis revealed that fibrinogen level was an independent variable associated with both BSI and FACED scores. A total of 31 (50.8%) out of 61 patients experienced exacerbation during the follow-up period of 25.4 months. Exacerbation-free survival was significantly longer in patients with low fibrinogen levels than in those with high fibrinogen (log-rank test, p = 0.034). High fibrinogen levels and Pseudomonas colonization were independent risk factors for future exacerbation (HR 2.308; p = 0.03 and HR 2.555; p = 0.02, respectively). Conclusions: Serum fibrinogen, but not adiponectin or angiopoietin-2, is a potential biomarker closely associated with the severity and exacerbation of non-CF bronchiectasis.

Preoperative electromagnetic navigation bronchoscopy-guided one-stage multiple-dye localization for resection of subsolid nodules: A single-center pilot study.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB)-guided transbronchial dye marking and video-assisted thoracoscopic surgery (VATS) is an emerging technique that enables successful resection of multiple small subsolid pulmonary nodules. The aim of this study was to evaluate the accuracy and safety of preoperative ENB-guided transbronchial multiple dye localization for VATS resection of subsolid pulmonary nodules. METHODS: As a single-center pilot study, we recruited patients with at least two small or subsolid pulmonary nodules. Multiple-dye localization was performed by intraoperative ENB-guided transbronchial injection of an indigo carmine dye. The patients underwent VATS for sublobar resection immediately after localization. The accuracy of ENB-guided dye marking was checked. RESULTS: ENB-guided one-stage multiple dye localization was conducted for 18 pulmonary nodules in seven patients between September 2018 and December 2019. The mean diameter of the pulmonary nodules was 9.3 mm (range, 4-18) and the mean distance from the pleura to pulmonary nodule was 6 mm (range, 1-17 mm). ENB-guided transbronchial multiple dye localization was successfully performed in 94.4% (17/18), and the accuracy of ENB-guided dye marking was 88.2% (15/17). When two nodules were not seen in intraoperative fields, anatomical sublobar resection was performed. There was no conversion to thoracotomy and operative mortalities. Among the seven patients, only one patient showed mild intrabronchial bleeding but stopped spontaneously. The changes in lung function after multiple wedge resections (-1.6% to 24.8%) were tolerable level. CONCLUSIONS: ENB-guided one-stage transbronchial dye localization showed accurate and safe intraoperative identification of multiple subsolid pulmonary nodules. A large scale prospective clinical study is warranted.

Impact of coexistent preserved ratio impaired spirometry on the survival of patients with lung cancer: Analysis of data from the Korean Association for Lung Cancer Registry.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor. METHODS: We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1 ] < 80% predicted and FEV1 /forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis. RESULTS: Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel-Cox log-rank test, p < 0.05). In the risk-adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC. CONCLUSIONS: PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre-existing PRISm should be considered a predictive factor of poor prognosis.

Serum hepatocyte growth factor as a predictor of disease severity and future exacerbations in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Serum biomarkers associated with the severity of non-cystic fibrosis (CF) bronchiectasis are insufficient. This study determined the association of serum hepatocyte growth factor (HGF), osteopontin, and pentraxin-3 levels with disease severity and exacerbation in patients with non-CF bronchiectasis. METHODS: Serum levels of HGF, osteopontin, and pentraxin-3 were measured in patients with clinically stable non-CF bronchiectasis (n = 61). The correlation between the biomarkers and bronchiectasis severity index (BSI) and FACED score was assessed using univariate and multivariate linear regression analyses. Predictive variables associated with exacerbation were analyzed using a Cox proportional hazards model and the time to first exacerbation in high and low HGF groups during the observation period was compared using Kaplan-Meier survival curves. RESULTS: The BSI showed significant correlation with HGF (r = 0.423; p = 0.001) and pentraxin-3 (r = 0.316; p = 0.013). The FACED score was significantly correlated with HGF (r = 0.406; p = 0.001). Univariate and multivariate linear regression analysis revealed that serum level of HGF was independently associated with both scoring systems. The high HGF group showed a significantly shorter time to first exacerbation (Log-rank test, p = 0.014). Multivariate Cox proportional hazards regression analysis revealed that high serum HGF level and colonization with non-pseudomonas organisms were independent predictors of future exacerbations (HR 2.364; p = 0.024 and HR 2.438; p = 0.020, respectively). CONCLUSION: Serum level of HGF is a potential biomarker that is closely associated with disease severity and future risk of exacerbations in patients with non-CF bronchiectasis.

Serum albumin is a predictor of respiratory hospitalization in patients with bronchiectasis.

We evaluated serum albumin as an index for predicting respiratory hospitalization in patients with bronchiectasis. We retrospectively reviewed the medical records of 177 patients with bronchiectasis, categorized them into low and normal albumin groups, and compared their clinical characteristics. The prediction of respiratory hospitalization by factors such as serum albumin level, bronchiectasis severity index (BSI), and FACED score (an acronym derived from five variables of forced expiratory volume in 1 s; FEV1, age, chronic colonization of Pseudomonas aeruginosa, extent of bronchiectasis, and dyspnea) was assessed. There were 15 and 162 patients categorized in the low and normal albumin groups, respectively. The low albumin group had lower body mass index and forced expiratory volume in 1 s, and higher age, frequency of previous respiratory hospitalization, percentage of Pseudomonas colonization, number of affected lobes, BSI and FACED scores, and C-reactive protein (CRP) level, than the normal albumin group. The areas under the receiver operating characteristic curve of serum albumin level and BSI and FACED scores for predicting respiratory hospitalization were 0.732 (95% confidence interval (CI), 0.647-0.816), 0.873 (95% CI, 0.817-0.928), and 0.708 (95% CI, 0.618-0.799), respectively. Albumin level, CRP, modified Medical Research Council score, and chronic Pseudomonas aeruginosa (and other organisms) colonization were independent risk factors for respiratory hospitalization. Low serum albumin level was associated with worse clinical condition, higher severity scores, and respiratory hospitalization in patients with bronchiectasis.

Isolated left bronchial isomerism that was incidentally detected as a severe obstructive ventilatory disturbance in an asymptomatic adult patient: A case report.

RATIONALE: Left bronchial isomerism is generally associated with abnormal arrangement of the atrium and abdominal viscera; therefore, its diagnosis is confirmed in early childhood. PATIENT CONCERNS: Here we report a rare case involving a 36-year-old man with isolated left bronchial isomerism that presented as an asymptomatic severe obstructive ventilatory disturbance during pulmonary function tests performed as part of routine assessments for an orbital wall fracture. The patient was a current smoker and did not show any respiratory symptoms. DIAGNOSIS: Chest computed tomography revealed left bronchial isomerism, and further tests showed that there was no involvement of other organs. INTERVENTIONS: We recommended smoking cessation and the long-term use of an inhaled long-acting bronchodilator. OUTCOMES: The findings from this case highlight the causative role of left bronchial isomerism in asymptomatic adults with chronic obstructive pulmonary disease. LESSONS: Physicians should consider this condition as a cause of obstructive ventilatory disturbances in asymptomatic adult patients.