Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study.

Various infection control measures implemented during the coronavirus disease (COVID-19) pandemic have reduced the number of respiratory infections, which are the most common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Here, we investigated whether infectious disease prevention during the COVID-19 pandemic reduced COPD exacerbations and the characteristics of patients exhibiting exacerbations before and during the COVID-19 pandemic. We included outpatients and inpatients with moderate or severe COPD exacerbations who required systemic steroids between April 1, 2018 and March 31, 2022. Their medical records were retrospectively compared and analyzed in 2-year intervals (before and during the COVID-19 pandemic). During the 4-year observation period, 70,847 outpatients and 2,772 inpatients were enrolled; 55 COPD exacerbations were recorded. The number of COPD exacerbations decreased from 36 before to 19 during the COVID-19 pandemic. Regarding the characteristics of patients with exacerbations, the % forced expiratory volume in one second (52.3% vs. 38.6%, P = 0.0224) and body mass index (BMI) (22.5 vs. 19.3, P = 0.0127) were significantly lower during the COVID-19 pandemic than before the pandemic. The number of COPD exacerbations during the pandemic decreased. Additionally, the tendency for a reduction in COPD exacerbation was greatest in patients with preserved lung function or above-standard BMI patients.

Nintedanib administration after the onset of acute exacerbation of interstitial lung disease in the real world.

Nintedanib reduces the decline in forced vital capacity and extends the time to the first acute exacerbation of interstitial lung disease (AE-ILD). However, the effect of additional nintedanib administration after AE-ILD onset is unknown. This study aimed to investigate the efficacy and safety of nintedanib administration after AE-ILD development. We retrospectively collected the data of 33 patients who developed AE-ILD between April 2014 and January 2022. Eleven patients who received nintedanib after AE-ILD development and the remaining who did not were classified into the N and No-N groups, respectively. The survival time in the N group tended to be longer than that in the No-N group. The generalized Wilcoxson test revealed that the cumulative mortality at 90 days from AE-ILD onset was significantly lower in the N group. The time to subsequent AE-ILD development was significantly longer in the N group than that in the No-N group. The incidence of adverse gastrointestinal effects and liver dysfunction in the N group was 9-18%. Treatment without nintedanib after AE-ILD development and the ratio of arterial oxygen partial pressure to fractional inspired oxygen were significant independent prognostic factors in the multivariate analysis. Thus, nintedanib administration may be a treatment option for AE-ILD.

Dramatic, significant metabolic response to a one-time pembrolizumab treatment following a relapse of pre-existing organizing pneumonia in a patient with advanced non-small cell lung cancer: A case report.

Immune checkpoint inhibitors can often trigger immune-related adverse events (irAEs), such as relapse of pre-existing interstitial pneumonia. Here, we report the case of an 88-year-Japanese man diagnosed with advanced lung adenocarcinoma with a high tumor proportion score of programmed death-ligand 1. Six years earlier, he had developed organizing pneumonia (OP), a subtype of interstitial pneumonia, that was treated with steroid pulse therapy maintained with prolonged prednisolone administration. We initiated pembrolizumab as the first-line treatment. One month after the first pembrolizumab administration, high resolution computed tomography (HRCT) of the chest demonstrated ground-glass opacities and consolidations. We suspected pembrolizumab-induced OP relapse, an irAE. His oxygenation was normal; therefore, we discontinued pembrolizumab without additional treatment for OP relapse. Four months after OP relapse, HRCT showed no new findings. After significant amelioration of OP, although the size of the tumor shadow remained the same on HRCT, positron emission tomography-computed tomography demonstrated the disappearance of the standardized uptake value of the primary tumor, mediastinal lymph nodes, and pleural nodules. In conclusion, this is the first report of a dramatic, significant metabolic response after a single pembrolizumab treatment despite the relapse of pre-existing OP in a patient with advanced lung adenocarcinoma.

High lymphocyte population-related predictive factors for a long-term response in non-small cell lung cancer patients treated with pemetrexed: a retrospective observational study.

BACKGROUND: Regimens combining pemetrexed (PEM) and immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSq-NSCLC). Recently, PEM was shown to induce immunogenic cell death (ICD) and to enhance immune-regulatory genes. Some patients demonstrate an extremely long-term response to PEM. It is possible that the continued response in these patients is dependent on not only the pharmacological induction of cytotoxic cell death but also antitumor immunity. However, factors that can predict outcomes associated with long-term PEM administration using blood test results have not yet been elucidated. We investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy. METHODS: In total, 504 patients with advanced NSq-NSCLC who received PEM combination therapy/monotherapy (n = 414) or paclitaxel (PTX) combination therapy (n = 90) between January 2010 and November 2019 were recruited; 381 patients were retained for the final analysis. Patients treated with PEM (n = 301) were divided into subgroups according to the total cycles of PEM (≥ 17 [n = 25] for the long-term administration group and ≤ 16 [n = 276] for the intermediate/short-term group) and compared with another population (n = 80) treated with PTX combination regimen. We investigated clinical features and predictive biomarkers, focusing on immune-regulatory factors, absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and PD-1 and PD-L1 expression, to predict long-term response to PEM. RESULTS: The long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group did. Both these markers displayed greater association with progression-free survival and overall survival in the PEM combination therapy group than in the PTX combination therapy group. Increased PD-1 lymphocytes were associated with the long-term PEM response group, as PD-L1 expression in tumors was associated with a high incidence of immune-related adverse effects following ICI administration. CONCLUSIONS: ALC, NLR, and PD-1 expression are PEM-mediated predictive biomarkers that are indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.

Clinical Significance of Continuable Treatment with Nintedanib Over 12 Months for Idiopathic Pulmonary Fibrosis in a Real-World Setting.

PURPOSE: The INPULSIS-ON study suggested the safety and tolerability of long-term nintedanib treatment for idiopathic pulmonary fibrosis (IPF). However, there are no real-world studies on long-term nintedanib treatment. The main aim of the study was to investigate the efficacy and the tolerability of long-term treatment with nintedanib for IPF in clinical practice. PATIENTS AND METHODS: This retrospective study enrolled 104 IPF patients who underwent treatment with nintedanib. Among these patients, 51 were able to receive nintedanib for more than 12 months (ie, treatment with nintedanib over 12 months was possible [P group]) and 53 were not able to receive nintedanib for more than 12 months (ie, treatment with nintedanib over 12 months was impossible [I group]). The tolerability and efficacy of nintedanib were compared between the two groups. RESULTS: In the I group, 29 patients were unable to continue nintedanib therapy because of adverse effects, including diarrhea and nausea/anorexia. In addition, 19 and four patients could not continue nintedanib treatment because of IPF progression and worsening of performance status (PS), respectively. One patient suddenly died during nintedanib treatment. The incidence of nausea/anorexia in the I group was significantly higher than in the P group (49.06 vs 25.49%). The survival time was significantly longer in the P group than in the I group (35 vs 12 months). The decline in forced vital capacity was significantly larger in the I group than in the P group (165 vs 10 mL/year). Poor PS at nintedanib initiation was the only significant risk factor for nintedanib treatment discontinuation over 12 months. Finally, the survival time was significantly longer in patients with good PS than in those with poor PS (27 vs 13 months). CONCLUSION: Poor PS can result in discontinuation of nintedanib after 12 months. Long-term nintedanib treatment may be effective for survival.

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.