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We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.

Background Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. Case presentation A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. Conclusions We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.

Eisuke Mochizuki,1 Yoshiihiro Kawai,2 Keisuke Morikawa,1 Yutaro Ito,1 Namio Kagoo,1 Tsutomu Kubota,1 Koshiro Ichijyo,1 Masahiro Uehara,1 Masanori Harada,1 Shun Matsuura,1 Masaru Tsukui,1 Naoki Koshimizu1 1Department of Respiratory Medicine, Fujieda Municipal Hospital, Fujieda 426-8677, Japan; 2Department of Radiology, Fujieda Municipal Hospital, Fujieda 426-8677, JapanCorrespondence: Eisuke Mochizuki Tel +81-54-646-1111Fax +81-54-646-1122Email eisukefukui@gmail.comBackground: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established.Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma.Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44– 89 years) and 11 asthma patients (five males and six females; median age 55; range: 32– 75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests.Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score < 8).Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.Keywords: COPD, asthma four-dimensional dynamic-ventilation CT

Background Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years. Case presentation An 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy. Conclusion Despite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

Rationale: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. Patient Concerns and Diagnoses: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. Intervention and Outcome: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. Lessons: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.

Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.

Immunoglobulin type G4 -related disease (IgG4-RD) is known as a chronic systemic inflammatory disease, which is sometimes associated with lung cancer. However, the detailed association between IgG4-RD and lung cancer in clinical settings is still poorly understood. An 80-year-old man was diagnosed with progressive lung adenocarcinoma carrying an EGFR point mutation at L858R, and osimertinib treatment was administered. Two months later, although osimertinib treatment showed good response to the primary tumor, fever and anorexia appeared, and multiple lymph nodes, in particular in the left axillary, became swollen. Ultrasonography-guided biopsy of the axillary lymph node revealed infiltration of lymphocytes with IgG4-positive plasma cells and fibrosis. Serum IgG4 levels were also increased. These results suggested that the multiple swollen lymph nodes were not metastasis, but IgG4-related disease. Based on these results, therapy using prednisolone was initiated. Multiple lymphadenopathy gradually decreased, and his symptoms improved. Currently, his good responses to osimertinib treatment have been maintained. Like in our case, multiple lymphadenopathy with IgG4-positive plasma cell infiltration during successful anti-cancer treatment is quite rare. In this case, it was hypothesized that anti-cancer treatment with osimertinib induced IgG4-positive plasma cell infiltration in multiple lymph nodes. When lymphadenopathy occurs during lung cancer treatment, IgG4-RD has to be considered other than lung cancer metastasis.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) 1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD 1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD 20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

Sarcoidosis affects multiple organs and rarely has unusual manifestations. A 78-year-old woman was referred to our hospital for coughing symptoms. A chest computed tomography (CT) scan revealed bilateral diffuse miliary patterns and right pleural effusion. Bronchoscopy showed multiple nodules in the carina and the bronchus intermedius. A CT scan of her abdomen revealed hypovascular lesions involving the pancreatic head and body. A transbronchial lung biopsy, bronchial mucosal biopsy, and endoscopic ultrasound-guided fine-needle aspiration of the pancreatic mass demonstrated non-caseating granulomas. We diagnosed the patient with sarcoidosis. She received no treatment for sarcoidosis and has been followed up for one year, during which no pulmonary disease progression had been observed and the pancreatic masses partially regressed.

Background There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. Methods Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis. Results Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p

Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL-positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD.

Chronic obstructive pulmonary disease (COPD) is an underdiagnosed lung disease in Japan and worldwide. A nationwide survey in Japan estimated the prevalence to be at least 8.6% (5 million patients) [1]. However, it has been reported that only 220,000 patients are receiving treatment [2]. We hypothesized that some patients hospitalized with pneumonia would have undiagnosed COPD. In this prospective observational single-center study, we clarified the prevalence and clinical features of undiagnosed COPD in hospitalized patients diagnosed with pneumonia.

RATIONALE: Since high-grade neuroendocrine tumors are rapidly progressive, most cases are inoperable when diagnosed. There are few reports about the prognosis of patients or the course of the disease after surgery. OBJECTIVES: To clarify the clinical course of the disease after surgery and factors influencing the prognosis. METHODS: We retrospectively assessed 27 patients receiving surgery for small cell carcinoma (22 cases) and large neuroendocrine carcinoma (5 cases) from January 2005 through January 2015 at our hospital. RESULTS: Patients were all male, with an average age of 70.9 years. Of the 27 patients, 22 had received postoperative adjuvant chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 1.1 and 5.5 years, respectively. Ten patients were recurrence-free. Ten patients who underwent surgery within 60 days after the diagnosis demonstrated a better prognosis regarding OS (p CONCLUSIONS: Early surgical resection for high-grade neuroendocrine carcinoma stage I may lead to a better prgonosis.

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting β2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5Hz (R5), as well as a difference between R5 and R20 (R5-R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment.

By utilizing a specific solvent and highly active 2-azaadamantane-N-oxyl (AZADO) as an organocatalyst, we have improved the recycling protocol of the adamatane reagent 1 to be faster and more operationally simple for the hypervalent iodine/nitroxyl radical mediated alcohol oxidation. This very mild system can efficiently mediate the oxidation of a range of alcohols to carbonyl compounds with a broad substrate scope, and after the reactions, the reduced adamantane tetraiodide 1', which automatically precipitated from the reaction mixtures as the reactions progresses, could be directly recovered by filtration.

We report a successful treatment with voriconazole (VRCZ) for chronic progressive pulmonary aspergillosis (CPPA) in a patient with dermatomyositis-associated interstitial lung disease (DM-ILD) treated with tacrolimus. A 73-year-old man with DM-ILD, treated with tacrolimus and prednisolone, complained of productive cough and his chest X-ray showed infiltration in the left upper lung field. We diagnosed CPPA and added VRCZ. Although we reduced the dose of tacrolimus for drug interaction, serum VRCZ level increased after the treatment. The patient was found to have cytochrome P450 (CYP) 2C19 *2/*2, a genetic polymorphism in poor metabolizers of VRCZ. We adjusted the doses of both drugs and treated him successfully. We recommend performing individual therapeutic drug monitoring (TDM) in CYP-mediated drug interactions and considering the effect of CYP polymorphisms.

The subject was a 52-year-old man with Japanese cedar pollinosis, which developed between February and May. He had no history of asthma and was an ex-smoker. He underwent fractional exhaled nitric oxide (FeNO) measurements twice a week from 2010 to 2012. The pollen counts in 2010 were the lowest during the last decade, and the FeNO level was less than 30 ppb for the whole year. In contrast, the mean pollen count in 2011 was very high and the patient’s FeNO level rose to more than 100 ppb. The mean pollen count in 2012 was comparable with that of 2010; however, high counts were detected in April and May, and the FeNO level rose to 70 ppb during the latter stages of the pollen season. These results indicate that pollen counts should be taken into consideration during the interpretation of FeNO data in asthma or allergic rhinitis.

Asthma exacerbation is associated with respiratory infections, including those by viruses and atypical bacteria. We herein report a case of severe acute asthma in an adult caused by Chlamydophila pneumoniae (C. pneumoniae) infection. A 39-year-old woman without a history of asthma reported to the emergency department with progressive worsening of cough, shortness of breath, and wheezing with low oxygen saturation. A computed tomography (CT) scan revealed patchy ground-glass opacity and bronchial wall thickening. She was treated with systemic corticosteroids, inhaled short-acting β2 agonists, aminophylline, doripenem, and levofloxacin. Through successful treatment in the intensive care unit (ICU), her condition and the chest X-ray and CT findings improved. Chlamydophila pneumoniae infection was confirmed by elevated paired serum C. pneumoniae-specific IgA antibodies. Chlamydophila pneumoniae infection is an important cause of severe acute asthma. On CT, findings typical of C. pneumoniae pneumonia were noted.

By utilizing a specific solvent and highly active 2-azaadamantane-N-oxyl (AZADO) as an organocatalyst, we have improved the recycling protocol of the adamatane reagent 1 to be faster and more operationally simple for the hypervalent iodine/nitroxyl radical mediated alcohol oxidation. This very mild system can efficiently mediate the oxidation of a range of alcohols to carbonyl compounds with a broad substrate scope, and after the reactions, the reduced adamantane tetraiodide 1', which automatically precipitated from the reaction mixtures as the reactions progresses, could be directly recovered by filtration.