Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of “TH2-high” asthma. ...The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma.
Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry.
The serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics 70.0 (54.0–93.5) ng/ml than in healthy subjects 57.0 (39.0–63.0) ng/ml, though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize “high-periostin” phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03–0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02–0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the “high-periostin” phenotype.
Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 ...in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Limb ischemia caused by tumor embolus is rare. In this study, we report the case of a 77-year-old woman who suffered from acute ischemic limb. Computed tomography showed a tumor in the right bronchus ...invading the left atrium. The tumor fragments scattered resulting in the occlusion of the right iliac artery. The excluded embolus was revealed as a squamous cell carcinoma. Regarding the popliteal venous thrombus, Trousseau’s syndrome was complicated. The patient was discharged without any complications. We believe that advanced lung cancer is a differential diagnosis of acute ischemic limbs and that successful limb rescue contributed to a patient’s quality of life.
We evaluated the real-world efficacy and safety of nivolumab in 142 patients with advanced non–small-cell lung cancer in Japan and identified the clinical characteristics that influence the efficacy. ...Negative EGFR/ALK mutation status and previous radiotherapy were significantly associated statistically with the treatment response. These findings might aid in the efficient immunotherapeutic management of lung cancer.
Nivolumab, an immune checkpoint inhibitor, is now a standard treatment for previously treated advanced non–small-cell lung cancer based on the results from phase III clinical trials. We evaluated the real-world efficacy and safety of nivolumab in a nonselected population and identified the clinical characteristics that influence efficacy.
A total of 142 patients with advanced non–small-cell lung cancer who were administered nivolumab at Keio University and affiliated hospitals in Japan from January to July 2016 were enrolled. The treatment efficacy and adverse events were retrospectively reviewed, and the clinical characteristics associated with the nivolumab response were evaluated using univariate and stratified analyses and the Cochran-Mantel-Haenszel test.
The objective response rate was 17.0% (95% confidence interval CI, 12.0%-24.0%), the median progression-free survival (PFS) was 58 days (95% CI, 50-67 days), and the proportion of patients with adverse events of any grade was 45.0%. EGFR/ALK mutation status was inversely associated with the treatment response (P < .05), and the difference in PFS for the mutation-positive versus mutation-negative patients was statistically significant (49 vs. 63 days; hazard ratio, 1.9; 95% CI, 1.1-5.2; P = .029). Previous radiotherapy also had a positive association with the treatment response (P = .012).
The objective response rate, PFS, and adverse event profiles were comparable to those observed in previous clinical trials. EGFR/ALK mutation-negative status and previous radiotherapy might be key clinical characteristics associated with a positive treatment response. Our findings could aid in the efficient immunotherapeutic management of lung cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•The PS 0 - 2 patients showed a longer median OS than the PS 3 -4 patients.•Biomarker-matched therapy is effective even in the very elderly.•Biomarker-matched therapy is related to better prognoses, ...even in the very elderly.•Chemotherapy for biomarker-negative/unknown PS 0 - 2 patients is questionable.
The optimal treatment for advanced non-small cell lung cancer (NSCLC) in very elderly patients is unclear. We aimed to evaluate their treatment in real-world clinical practice and identify suitable therapy that can improve their prognosis.
The medical records of 132 Japanese patients aged 80 years and older with advanced NSCLCs who were enrolled at a university hospital and its 9 affiliates were retrospectively analyzed. Clinical characteristics and overall survival (OS) were compared based on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and biomarker statuses. Patients were defined as biomarker-positive if programmed death-ligand 1 tumor proportion score (PD-L1 TPS) was ≥ 50% or activating mutations were present in epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1. Finally, the factors contributing to better prognosis were explored in both PS 0 - 2 and PS 3 - 4 patient groups.
The PS 0 - 2 patients showed a longer median OS than the PS 3 - 4 patients (5.5 vs. 1.6 months). PS 0 - 2 patients with positive biomarkers who received chemotherapy showed a significantly longer median OS than those without (18.1 vs. 3.7 months). Among the biomarker-negative/unknown PS 0 - 2 patients, the median OS showed no significant difference between those who received chemotherapy and those who did not (4.5 vs. 3.1 months). The multivariate analysis showed that treatment with tyrosine kinase inhibitors or immune checkpoint inhibitors was related to better prognoses in the PS 0 - 2 group.
Biomarker-matched therapy is effective even in very elderly patients. Meanwhile, the effectiveness of chemotherapy for biomarker-negative/unknown PS 0 - 2 patients is questionable.
The present study aimed to investigate how advanced NSCLCs in the patients aged 80 and over were treated and what types of therapy can improve their prognosis. We found that biomarker-matched therapy (tyrosine kinase inhibitors or immune checkpoint inhibitors) was effective, while the effectiveness of chemotherapy, especially cytotoxic chemotherapy alone, for biomarker-negative/unknown patients was questionable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Febrile neutropenia (FN) during cancer chemotherapy can lead to morbidity and mortality. The Multinational Association of Supportive Care in Cancer (MASCC) and clinical index of stable ...febrile neutropenia (CISNE) scores have been widely used to predict the risk of severe medical complications in patients with FN; however, there are few tools for predicting chemotherapy delays or discontinuation after FN.
Methods
Patients admitted to two university hospitals between 2014 and 2018 with a FN diagnosis during the first cycle of chemotherapy for lung cancer were reviewed retrospectively.
Results
Among 539 patients who received 813 courses of chemotherapy for lung cancer, 49 (9%) developed FN during the first treatment cycle. Although all the patients recovered from their primary infection, 19 patients (38.8%) developed serious medical complications, 11 (22.4%) were unable to resume chemotherapy and one (2.0%) declined to resume chemotherapy, and nine (18.4%) died within 90 days. Patients who failed to resume chemotherapy had a lower MASCC score (median 8.5 vs. 17, p < 0.01) and a higher CISNE score (median 3 vs. 1, p < 0.01) at the onset of FN. The specificity to predict the patient who failed to resume chemotherapy was 90% or more with MASCC score ≤9 or CISNE score ≥3, with the sensitivity of 61%. MASCC score ≤ 16 can also be a sensitive indicator with the sensitivity and specificity of 89 and 52%, respectively.
Conclusion
The MASCC and CISNE scores are useful in identifying lung cancer patients who are unable to resume chemotherapy as scheduled after the onset of FN.
Forty‐nine patients developed febrile neutropenia (FN) during 813 courses of lung cancer chemotherapy; 12 patients were unable or declined to resume chemotherapy even after recovery of infection and nine of them died within 90 days. The MASCC and CISNE scores, widely used to predict the risk of severe medical complications during FN, were also useful to identify lung cancer patients who are unable to resume chemotherapy as scheduled and exhibit poor prognosis after the onset of FN.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background:
Both advanced cancer patients and their family caregivers experience distress and have a range of concerns after cancer diagnosis. However, longitudinal studies on this topic have been ...lacking.
Aim:
To investigate concerns in both patients with advanced lung cancer and their family caregivers longitudinally from diagnosis.
Design:
A multi-center prospective questionnaire-based study.
Setting/participants:
We recruited patients with newly diagnosed advanced lung cancer and their family caregivers at 16 hospitals in Japan. We prospectively assessed the prevalence of their concerns using the Concerns Checklist and investigated the associations between their concerns and mental status as well as quality of life until 24 months after diagnosis.
Results:
A total of 248 patients and their 232 family caregivers were enrolled. The prevalence of serious concerns was highest at diagnosis (patients: 68.3%, family caregivers: 65.3%). The most common serious concern was concern about the future in both groups at diagnosis (38.2% and 40.5%, respectively) and this remained high in prevalence over time, while the high prevalence of concern about lack of information improved 3 months after diagnosis in both groups. Approximately one-third of patient-family caregiver dyads had discrepant reports of serious concerns. The presence of serious concerns was significantly associated with anxiety and depression continuously in both groups.
Conclusions:
The majority of advanced lung cancer patients and their family caregivers have serious concerns from diagnosis, which is associated with their psychological distress. The spectrum of concerns alters over the disease trajectory, warranting efficient tailored care and support for both groups immediately after diagnosis.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Although the development of new antifibrotic agents (pirfenidone, nintedanib) has modified the disease progression of idiopathic pulmonary fibrosis (IPF), there is still no effective treatment for ...acute exacerbation of interstitial lung diseases (ILD) including IPF. We herein report a case of acute exacerbation of ILD (AE-ILD) treated only with nintedanib without any environmental changes and any other medications such as corticosteroid therapy, diuretic and anti-biotics, which resulted in the gradual improvement of the patient's clinical symptoms, high-resolution computed tomography findings, and forced vital capacity. This case might suggest the possibility that nintedanib not only modifies the disease progression of Idiopathic Pulmonary Fibrosis (IPF), but also facilitate the recovery from the acute exacerbation of ILD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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