Immune checkpoint inhibitors in patients with lung cancer having chronic interstitial pneumonia.

Background: In interstitial pneumonia (IP)-associated lung cancer, immune checkpoint inhibitor pneumonitis (ICIP) is common with immune checkpoint inhibitor (ICI) treatment. The purpose of the present study was to clarify the safety and efficacy of ICI treatment for patients with lung cancer with IP. Methods: This multicentre retrospective observational study was conducted from June 2016 to December 2020 in patients with primary lung cancer with IP who received ICI treatment. Results: A total of 200 patients (median age 70 years; male/female, 176/24) were enrolled from 27 institutions. ICIP occurred in 61 patients (30.5%), pneumonitis grades 3-5 in 32 patients (15.5%) and death in nine patients (4.5%). The common computed tomography pattern of ICIP was organising pneumonia in 29 patients (47.5%). Subsequently, diffuse alveolar damage (DAD) pattern was observed in 19 patients (31.1%) who had a significantly worse prognosis than those with a non-DAD pattern (median progression-free survival (PFS) 115 days versus 226 days, p=0.042; median overall survival (OS) 334 days versus 1316 days, p<0.001). Immune-related adverse events (irAEs) occurred in approximately 50% of patients. Patients with irAEs (n=100) had a better prognosis than those without irAEs (n=100) (median PFS 200 days versus 77 days, p<0.001; median OS 597 days versus 390 days p=0.0074). The objective response rate and disease control rate were 41.3% and 68.5%, respectively. Conclusions: Although ICI treatment was effective for patients with lung cancer with IP, ICIP developed in approximately 30% of patients. Patients with irAEs had a significantly better PFS and OS than those without irAEs.

A Phase I Trial of Weekly Nab-paclitaxel Plus Carboplatin With Thoracic Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: This study aimed to evaluate the safety and recommended dose of nab-paclitaxel in combination with carboplatin and thoracic radiotherapy for locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Nab-paclitaxel was administered weekly with escalating doses, combined with carboplatin area under the curve (AUC) 2 and concurrent standard thoracic radiotherapy. Escalating doses of nab-paclitaxel were as follows: level 0, 30 mg/m2; level 1, 35 mg/m2; level 2, 40 mg/m2; level 3, 45 mg/m2 Results: Twelve patients were enrolled and received the treatment according to the protocol; seven patients (58%) had squamous cell carcinoma and all cases had stage III disease. At level 1, none of the three patients experienced dose limiting toxicity (DLT). At level 2, one of the first three patients experienced a fatal DLT of bronchopulmonary hemorrhage. None of the three more additional patients experienced DLT. At level 3, two of the three patients experienced a DLT of grade 3 febrile neutropenia and grade 4 neutropenia, respectively. Consolidation chemotherapy was provided to 10 of 12 patients. Radiation pneumonitis developed in five of 12 patients (42%). Eight patients (66.7%) showed partial response, and four (33.3%) showed stable disease. For the above reasons, level 2 (40 mg/m2) was considered the recommended dose in this study. CONCLUSION: Concurrent chemoradiotherapy with weekly nab-paclitaxel (40 mg/m2) and carboplatin (AUC 2) is a feasible and well-tolerated regimen in patients with previously untreated locally advanced NSCLC. A phase II trial with this regimen is warranted.

Prospective Real-World Analysis of Asthma Patients With Preserved and Reduced Physical Activity.

BACKGROUND: Asthma is a highly heterogeneous airway disease, and the clinical characteristics of patients with asthma with preserved and reduced physical activity are poorly understood. OBJECTIVE: We aimed to investigate the risk factors and clinical phenotypes associated with reduced physical activity in a wide range of patients with asthma. METHODS: We conducted a prospective observational study of 138 patients with asthma, including patients with asthma without chronic obstructive pulmonary disease (COPD) (n = 104) and asthma-COPD overlap (n = 34), and 42 healthy controls. Physical activity levels were measured for 2 weeks using a triaxial accelerometer at baseline and 1 year later. RESULTS: Higher eosinophils and body mass index (BMI) were associated with reduced physical activity in patients with asthma without COPD. Cluster analysis of asthma without COPD revealed 4 asthma phenotypes. We identified a cluster with preserved physical activity (n = 43) that was characterized by good symptom control and lung function and included a high proportion of biologics users (34.9%). Multivariate regression analysis revealed that patients with late-onset eosinophilic (n = 21), high-BMI noneosinophilic (n = 14), and symptom-predominant asthma phenotypes (n = 26) had lower levels of physical activity than controls. Patients with asthma-COPD overlap also had significantly lower physical activity levels than controls. Similar trends in physical activity levels were observed in each asthma group at 1-year follow-up. CONCLUSION: This study showed the clinical features of patients with asthma with preserved and reduced physical activity. Reduced physical activity was observed in various asthma phenotypes and in asthma-COPD overlap.

An Investigation into the Factors Associated with Incorrect Use of a Pressurized Metered-Dose Inhaler in Japanese Patients.

Rationale: Inhalation of the correct dose of a short-acting beta 2 agonist (SABA) from a pressurized metered-dose inhaler (pMDI) is essential for the relief of symptoms in patients with asthma and/or chronic obstructive pulmonary disease. The aim of this study was to evaluate the prevalence and factors associated with the incorrect use of a pMDI. Methods: This study retrospectively assessed the electronic medical records of 161 patients with various respiratory diseases. The patients had never used a pMDI and underwent training by pharmacists educated in the use of a pMDI followed by bronchodilator reversibility testing at our hospital. The patients' characteristics and various lung capacity parameters were evaluated for association with the incorrect use of a pMDI. Results: Thirty-nine of the 161 (24.2%) patients, including 46% of 28 patients older than 80 years, used the pMDI incorrectly, mainly because of incoordination between activation of the device and inhalation (n = 11), inadequate strength to manipulate the device (n = 9), too short duration of inhalation (n = 6), and difficulty in breath holding (n = 3). Advanced age; lower height; and decreased lung volumes, including vital capacity (VC), inspiratory capacity, inspiratory reserve volume (IRV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate, were associated with the incorrect use of a pMDI. Neither the body weight, tidal volume, expiratory reserve volume, %FVC predicted, %FEV1 predicted, nor FEV1% was associated with the incorrect use of a pMDI. Multivariate binomial logistic regression analysis identified decreased IRV as the only independent predictor associated with the incorrect use of a pMDI. Conclusions: Physicians should be aware that elderly patients or patients with decreased IRV might be unable to obtain the correct SABA dose from a pMDI. A large-scale prospective study is required to confirm these findings from our retrospective study with a small group of patients.

Anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis caused by bacterial organizing pneumonia in a patient with Sjogren's syndrome.

A 58-year-old woman with a history of Sjogren's syndrome was admitted to our hospital with cough, decreased right lung breath sounds and arthralgia in both thumbs. Chest computed tomography showed consolidation with air bronchogram in the right lung. Levels of anti-cyclic citrullinated peptide antibody and rheumatoid factor levels were significantly elevated. She was diagnosed with rheumatoid arthritis induced by bacterial organizing pneumonia. Treatment with salazosulfapyridine was added for rheumatoid arthritis and arthralgia gradually improved. This case highlights that respiratory infections could lead to anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis in patients with Sjogren's syndrome.

Sex-specific differences in the association between birth weight and lung volume in Japanese young adults.

BACKGROUND: Fetal growth disturbances may influence adult lung function and can lead to pulmonary diseases in adulthood. Although the results of previous studies are controversial, low birth weight seems to be associated with poor adult lung function. This study aimed to assess previously unknown information about the sex-specific association between birth weight and adult lung volume in the Japanese population. METHODS: We evaluated pulmonary parameters in 200 consenting young medical students (age, 20-29 years) with a never smoking history at Kochi University. Subjects whose lung function was not sufficiently examined or those with evidence of current or previous respiratory diseases were excluded (n=7). All students underwent spirometry, and their weight records at birth or 3 years of age were obtained from their maternal and child handbooks. Associations between the spirometric parameters and birth/3-year weights were statistically analyzed. RESULTS: We evaluated 91 male and 102 female students. Their mean age was 23.3 years. Assessment revealed that birth weight significantly correlated with the percent predicted value of forced vital capacity (%FVC; rs=0.17, p=0.018) but not with the forced expiratory volume in 1 s/FVC ratio. Sex-specific analysis revealed significant correlations between birth weight and %FVC in males (rs=0.22, p=0.041) but not in females. Body weight at the age of 3 years also significantly correlated with %FVC only in males (rs=0.32, p=0.021). CONCLUSIONS: Birth weight is significantly associated with pulmonary function in Japanese young adults. The associations are especially significant in males.

Carboplatin plus Weekly Paclitaxel with Bevacizumab for First-line Treatment of Non-small Cell Lung Cancer.

AIM: The present study aimed to evaluate the effectiveness and safety of weekly paclitaxel (PTX) combined with carboplatin (CBDCA) plus bevacizumab (BEV), followed by maintenance BEV in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with unresectable stage IIIB and IV NSCLC (n=43) were treated with CBDCA (AUC 6, day 1), BEV (15 mg/kg, day 1), and PTX (70 mg/m(2), days 1, 8, 15) intravenously every 4 weeks, for 3 to 6 cycles, followed by maintenance BEV (15 mg/kg) every 3 weeks. RESULTS: The objective response rate and disease control rate were 67.4% and 90.7%, respectively. The median progression-free survival was 7.6 months. The median overall survival was 17.7 months. Common adverse events were tolerable bone marrow suppression, fatigue, hypertension, and nasal bleeding. CONCLUSION: Weekly administration of PTX combined with CBDCA plus BEV therapy was effective, and well-tolerated by advanced NSCLC patients.

Effect of recombinant human soluble thrombomodulin on clinical outcomes of patients with coagulopathy after hematopoietic stem cell transplantation.

From 2001 to 2012, 71 individuals with hematological diseases received HSCT in our institution. Of these, 41 developed disseminated intravascular coagulation (DIC) in association with various underlying conditions. The patients who developed DIC after 2008 (n = 23) were treated by recombinant human soluble thrombomodulin (rTM), and the others (n = 11) were treated by either heparin and/or antithrombin III concentrate. Seven patients did not receive any anticoagulant therapy. Of note, treatment for coagulopathy by rTM significantly improved clinical outcomes of patients at day 100 and dramatically prolonged their overall survival (P = 0.044). Taken together, rTM is useful to improve clinical outcomes of transplant recipients with coagulopathy.

Recombinant human soluble thrombomodulin safely and effectively rescues acute promyelocytic leukemia patients from disseminated intravascular coagulation.

We treated individuals for disseminated intravascular coagulation (DIC) caused by acute promyelocytic leukemia (APL) (n=9) using human soluble thrombomodulin (rTM) in combination with all-trans retinoic acid (ATRA) and chemotherapy, and compared the clinical outcomes with historical control patients (n=8) treated with ATRA and/or chemotherapy. Two control patients developed intracranial vascular incidents. On the other hand, no bleeding related mortality was noted in rTM-treated patients. Notably, treatment with rTM rescued patients from DIC earlier than historical controls (log rank test, p=0.019). These results suggest that administration of rTM should be considered for the treatment of individuals with DIC associated with APL.