Boksoon Chang

Preserved ratio impaired spirometry (PRISm) is associated with increased morbidity and mortality. However, the impact of PRISm on the postoperative outcomes of non-small cell lung cancer (NSCLC) surgery remains poorly understood. We retrospectively analyzed data of 834 patients with NSCLC from the prospective CATCH-LUNG cohort who underwent curative lung resection between March 2016 and December 2020. The patients were categorized into four groups: normal, PRISm, mild obstructive lung disease (OLD), and moderate OLD. The primary outcomes were postoperative pulmonary complications (PPCs) and cardiac complications (PCCs) that occurred within 30 days post-surgery. The incidences of PPCs and PCCs were significantly higher in the PRISm group (PPC: 11.5%; PCC: 16.4%) than in the normal lung function group (PPC: 3.3%; PCC: 4.6%). Patients with PRISm had adjusted RRs of 2.62 (95% CI: 1.10–6.23) for PPCs and 2.67 (95% CI: 1.42–4.99) for PCCs. The adjusted RRs for PPCs were 2.32 in mild OLD and 3.25 in moderate OLD, whereas those for PCCs were 1.94 in mild OLD and 2.32 in moderate OLD. Notably, among patients with PRISm, those with low FVC (<80% predicted) had markedly higher risks of PPCs (adjusted RR = 3.41; 95% CI: 1.22–9.54) and PCCs (adjusted RR = 3.31; 95% CI: 1.74–6.31) compared to those with normal FVC. PRISm, like chronic obstructive pulmonary disease, substantially increases the risk of postoperative complications of NSCLC surgery and should be recognized as an important clinical category.

Background/Objectives: Liquid biopsy using cfDNA has emerged as a promising, minimally invasive alternative to traditional tissue biopsy for detecting cancer-associated mutations. However, the extremely low proportion of mutant DNA in cfDNA poses a major challenge for accurate detection, especially when using conventional sequencing methods. To address this limitation, we sought to develop a highly sensitive diagnostic strategy to selectively enrich rare mutant sequences and improve the detection of clinically important mutations in patients with NSCLC. Methods: We established a CRISPR/Cas12a-based diagnostic system designed to selectively cleave WT DNA, thereby increasing the relative abundance of mutant DNA in cfDNA samples. Following Cas12a-mediated WT cleavage, the remaining DNA was subjected to PCR amplification for mutation identification. The system was applied to plasma cfDNA from blood samples of 48 NSCLC patients to evaluate its ability to detect two major EGFR mutations: L858R and exon 19 deletion. Results: The CRISPR/Cas12a-based diagnostic system effectively identified low-frequency EGFR mutations in cfDNA. Specifically, all 7 L858R-positive samples and 6 out of 11 samples harboring exon 19 deletions—previously validated through tissue biopsy—were successfully detected. This demonstrated a high degree of concordance between our liquid biopsy approach and conventional diagnostic methods. Conclusions: Our findings highlight the potential of the CRISPR/Cas12a-based mutation enrichment system as a powerful tool for detecting rare oncogenic mutations in liquid biopsy samples. This technique enhances diagnostic sensitivity and could be broadly applicable for the non-invasive detection of various genetic alterations in cancer and other diseases.

Background and Objective: Although rigid bronchoscopy is generally performed in the operating room (OR), the intervention is sometimes emergently required at the intensive care unit (ICU) bedside. The aim of this study is to evaluate the safety of rigid bronchoscopy at the ICU bedside. Materials and Methods: We retrospectively analyzed medical records of patients who underwent rigid bronchoscopy while in the ICU from January 2014 to December 2020. According to the location of rigid bronchoscopic intervention, patients were classified into the ICU group (n = 171, cases emergently performed at the ICU bedside without anesthesiologists) and the OR group (n = 165, cases electively performed in the OR with anesthesiologists). The risk of intra- and post-procedural complications in the ICU group was analyzed using multivariable logistic regression, with the OR group as the reference category. Results: Of 336 patients, 175 (52.1%) were moribund and survival was not expected without intervention, and 170 (50.6%) received invasive respiratory support before the intervention. The most common reasons for intervention were post-intubation tracheal stenosis (39.3%) and malignant airway obstruction (34.5%). Although the overall rate of intra-procedural complications did not differ between the two groups (86.0% vs. 80.6%, p = 0.188), post-procedural complications were more frequent in the ICU group than in the OR group (24.0% vs. 12.1%, p = 0.005). Severe complications requiring unexpected invasive management occurred only post-procedurally and were more common in the ICU group (10.5% vs. 4.8%, p = 0.052). In the fully adjusted model, the ICU group had increased odds for severe post-procedural complications, but statistical significance was not observed (odds ratio, 2.54; 95% confidence interval, 0.73–8.88; p = 0.144). Conclusions: Although general anesthesia is generally considered the gold standard for rigid bronchoscopy, our findings indicate that rigid bronchoscopy may be safely performed at the ICU bedside in selective cases of emergency. Moreover, adequate patient selection and close post-procedural monitoring are required to prevent severe complications.

Purpose: Reactive oxygen species modulator 1 (Romo1) is a key regulator of intracellular reactive oxygen species production. Previous studies have shown that Romo1 overexpression in tumor tissue is associated with poor clinical outcomes in various clinical settings for lung cancer treatment. The aim of the present study was to assess the predictive value of serum Romo1 in patients received curative resection for lung cancer. Methods: Serum samples were collected from patients with lung adenocarcinoma who underwent surgical resection. Baseline serum Romo1 and carcinoembryonic antigen (CEA) levels before surgery were measured. Univariate and multivariate analyses were performed to identify whether serum Romo1 was associated with disease-free survival (DFS). Results: A total of 77 samples were analyzed. Using the cut-off value of 866 pg/mL, the population was classified into low (n = 42, 54.4%) and high (n = 35, 45.4%) Romo1 groups. The median DFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (25.5 months vs not reached [NR], p = 0.0105). In addition, the median DFS of patients in the high CEA (> 2.9 ng/mL) group was significantly shorter than those in the low CEA group (26.8 months vs NR, p = 0.0092). Multivariate analyses showed that both high Romo1 and CEA levels were independently associated with poor DFS (hazard ratio [HR] = 2.19; 95% confidence interval [CI]: 1.14– 8.37, and HR = 2.95; 95% CI: 1.23– 9.21, respectively). Moreover, combination of these two biomarkers resulted in higher HR of 4.11 (95% CI, 1.53– 14.05) for DFS than those of Romo1 and CEA. Conclusion: Elevated serum Romo1 levels were significantly associated with early recurrence in patients with lung adenocarcinoma treated with surgical resection. Serum Romo1 may be a promising predictive biomarker for this patient population.

In patients, with cerebral infarction resulting from intracranial arterial stenosis, the combined administration of clopidogrel and aspirin may be needed for to prevent subsequent ischemic attacks. Clopidogrel has an inevitable adverse effect profile, and the most common complications are related to hemorrhagic propensity. A 79-year-old female patient had used aspirin (100 mg/day) for cerebral infarction and then a dual antiplatelet regimen of aspirin and clopidogrel (75 mg/day) because of severe stenosis in both anterior cerebral arteries. Two weeks later, the patient presented with dyspnea started 3 days ago, which had worsened in the last 24 hours. Chest computed tomography on admission showed symmetric peribronchial ground-glass opacity with reticulation in both lungs. Microorganism tests, including serology and bronchoalveolar lavage for infection, were all negative. Clopidogrel was withdrawn because of suspected clopidogrel-induced interstitial lung disease, and steroid treatment was initiated. Clinical signs and chest radiographs improved after steroid treatment, and she was discharged on day 21 of admission. This case report shows that clopidogrel can induce interstitial lung disease as a rare complication and underscores the importance of recognizing this adverse effect in clinical practice.

Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated.Methods: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay.Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR.Conclusions: PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

The clinical diagnosis of asbestosis is primarily based on chest radiographic evidence of pleural thickening and interstitial fibrosis combined with a history of exposure to asbestos. We report herein the case of a 65-year-old man with asbestosis pathologically diagnosed after surgical lung biopsy. He had a work history including farming, cementing, and casting and was admitted with dyspnea. Chest computed tomography revealed multiple well-defined nodules in both lungs and a 4.1 cm peribronchial consolidation with fibrotic changes in the right lower lobe. We suspected metastatic lung cancer and video-assisted thoracoscopic biopsy was performed in the lung lesion of the right lower lobe. Asbestosis was confirmed following histological examination. The patient is currently completing outpatient visits without significant changes.

Background In patients with cerebral infarction resulting from intracranial arterial stenosis, combined administration of clopidogrel and aspirin may be needed for the thereafter ischemic attack. Clopidogrel has an inevitable adverse effect profile, and the most common complications are related to hemorrhagic propensity. Case presentation A 79-year-old female patient had taken aspirin (100mg/d) for old cerebral infarction, and started taking the dual antiplatelet drug consisted of aspirin and clopidogrel (75mg/d) due to severe stenosis on both anterior cerebral arteries. Two weeks later, the patient presented dyspnea started 3 days ago, which had been worsened the last 24 h. Chest computed tomography on admission showed symmetric peribronchial ground glass opacity with reticulation in both lungs. Microorganism tests, including serology and bronchoalveolar lavage for infection, were all negative. Suspecting clopidogrel-induced acute interstitial pneumonitis, we withdrew clopidogrel and initiated steroid treatment. The patient’s clinical signs and chest radiographs improved after steroid treatment, and she was discharged on the 21st day of hospitalization. Conclusions Clopidogrel can induce acute interstitial pneumonitis as a rare complication. The present report shows the importance of recognizing this rare adverse effect of clopidogrel in clinical practice.

Particulate matter (PM) of 10‐μm‐sized fine dust in the air penetrates the respiratory tract and contributes to the increasing incidence of various lung diseases, but its definite mechanism is not known. Recently, polydeoxyribonucleotide (PDRN) has been shown to have anti‐inflammatory and regenerative effects in various tissues. However, the bronchial‐related mechanism is not well‐understood. Hence, this experiment is intended to demonstrate the beneficial effect of PDRN administration on PM10‐induced injury in human bronchial‐derived NCI‐H358 cells. To confirm the protective effect of PDRN, PM10 was applied after PDRN pretreatment to confirm changes in NCI‐H358 cells. Experiments were conducted to measure cell survival, cytotoxicity, inflammation, and apoptotic factor changes. WST‐8 assay was used to confirm cell viability, and lactate dehydrogenase assay was used to obtain cytotoxicity. In addition, changes in inflammatory cytokines and apoptotic factors were confirmed by enzyme‐linked immunosorbent assay and Western blot. Decreased cell viability and increased cytotoxicity, inflammatory cytokines, and apoptotic factors were observed after exposure to PM10. However, pretreatment with PDRN enhanced cell viability and reduced cytotoxicity. In addition, the expression of inflammatory cytokines such as tumor necrosis factor‐α, interleukin‐6 (IL‐6), and IL‐1β, and cell death factors such as Apaf‐1, cyt c, caspase‐3, caspase‐9, Bid, and Bax/Bcl‐2 ratio were decreased by PDRN administration in PM10‐exposed NCI‐H358 cells. PDRN, an A2AR agonist, affects cAMP activation and regulation of phosphorylation of PKA and CREB. In addition, treatment with A2AR antagonist 3,7‐dimethyl‐1‐propargylxanthine significantly blocked PDRN's effect. These anti‐cytotoxicity, anti‐inflammation, and anti‐apoptosis effects of PDRN can be attributed to the adenosine A2AR enhancing effect on PM10‐exposed bronchial cells.

Purpose: Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). Methods: We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group. Results: Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1– 49%, and < 1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (43.5% vs 72.1% vs 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004) and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (13.3% vs 40.0% vs 53.3%, all p = 0.001). PD-L1 TPS ≥ 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043). Conclusion: High PD-L1 expression was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.