Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma–COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of − 860 HU to − 950 HU (RVC_{− 860 to-950}) and the expiration-to-inspiration ratio of the mean lung density (MLD_E/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC_{− 860 to − 950} levels decreased in the following order: ACO, COPD, and asthma. RVC_{− 860 to − 950} independently predicted FEV1% in asthmatic patients; LAA% and MLD_E/I in COPD patients; and LAA%, WA% and RVC_{− 860 to − 950} in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.

Background: Epidermal growth factor receptor exon 20 insertion (EGFR ex20ins), an uncommon mutation in non-small cell lung cancer (NSCLC), can induce poor patient response to EGFR tyrosine kinase inhibitors (EGFR-TKI). However, the clinical features and prognosis of patients with EGFR ex20ins are not clearly understood. This study investigated the clinical characteristics and prognosis of advanced NSCLC patients with EGFR ex20ins. Methods: Advanced NSCLC patients treated at Fujian Cancer Hospital were consecutively recruited from June 1, 2014 to December 20, 2021 and retrospectively examined. EGFR ex20ins was identified by polymerase chain reaction (PCR) or next-generation sequencing (NGS). The clinical characteristics, treatment methods, and patient outcomes were retrieved from the hospital database. The progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. Results: Fourteen mutation subtypes of EGFR ex20ins were identified in the 24 enrolled patients, with EGFR ex20ins mutation more prevalent in non-smoking women. A763_Y764insFQEA and A767_V769dup (12.5% for both) were the most common mutation subtypes. Notably, no significant differences in PFS and OS were found between the first-line targeted therapy group [PFS: 257 days, 95% confidence interval (CI): 116-397 days; OS: not reached] and chemotherapy-based combination therapy group (PFS: 182 days, 95% CI: 156-207 days; OS: 998 days, 95% CI: 674-1321 days). TP53 mutation was the commonest concomitant mutation (62%), followed by EGFR amplification (25%). Chemotherapy combined with immunotherapy improved the prognosis of patients with high PD-L1 expression. Conclusion: For NSCLC patients with EGFR ex20ins, limited therapeutic benefits can be gleaned from either EGFR-TKIs or chemotherapy-based combination therapy.

Human epidermal growth factor receptor 2 (HER2) mutations occur in approximately 4% of non-small cell lung cancer (NSCLC) patients and represent targetable gene alteration. Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody-drug conjugate, was approved in China, the USA and EU based on the results of DESTINY-Lung02 and DESTINY-Lung05 for the treatment of pretreated unresectable or metastatic HER2-mutated NSCLC patients. Herein, we present five cases of HER2-mutated advanced NSCLC who received T-DXd in second or later line settings. The median age of patients was 67 years (range 48-76 years). Four patients were males, and one was female. All five patients had HER2 exon 20 insertional mutations. They received T-DXd in the 2nd or later line settings. One patient had complete response, two had partial response and two had stable disease. T-DXd led to a progression-free survival of up to 41 months from the start of T-DXd therapy. The median overall survival of the five patients was 15 months post T-DXd treatment (range 9-41 months). Adverse events during T-DXd treatment were expected and manageable. Challenge with T-DXd was successful in a patient with a history of interstitial lung disease. In this small case series, T-DXd demonstrated encouraging antitumor activity and manageable safety in heavily pretreated patients with HER2 mutated, metastatic NSCLC. Although selected patients had durable benefits, the findings are anecdotal and should be interpreted with caution. Larger real‑world cohorts and prospective studies are needed to validate the consistency, durability, and safety of T‑DXd in routine clinical practice.