Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma.

Background: Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric "WA at Pi10" to assess airway disease. Methods: Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. Results: The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/µL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = -0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = -0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = -0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). Conclusion: This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated "√WA at Pi10" metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.

The prevalence of obstructive sleep apnea in Japanese asthma patients.

BACKGROUND: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population because these conditions share some comorbidities. In Japan, the prevalence of OSA in the general population is reported to be approximately 20%; however, few reports have described the prevalence of OSA in asthma patients. Furthermore, the characteristics of Japanese patients with OSA and asthma are not clear. METHODS: Adult asthma patients were recruited from the outpatient departments of our institution between August 31, 2017, and March 31, 2019. In all included patients, the presence and severity of OSA were evaluated by the Epworth Sleepiness Scale (ESS) and a home sleep test (HST) using portable polysomnography (PSG). The rate of coexisting OSA in asthma patients and the characteristics of those patients according to the severity of OSA were investigated. RESULTS: Fifty-three patients were included. OSA was detected in 36 (67.9%) patients (mild, n = 15; moderate, n = 14; and severe, n = 7). Patients with OSA had significantly higher body mass index, Brinkman index, apnea-hypopnea index (AHI), and 3% oxygen desaturation index (ODI) values in comparison to those without OSA, while the percentage of the predicted value of forced vital capacity (%FVC) and lowest SpO2 levels were significantly lower. As the severity of OSA increased, age, brain natriuretic peptide level, AHI, and 3%ODI increased, and in contrast, FVC, %FVC, forced expiratory volume in one second (FEV1), percentage of the predicted value of FEV1 (%FEV1), Epworth Sleepiness Scale (ESS), 3%ODI, and lowest SpO2 levels decreased. In particular, the fact that the ESS value was inversely correlated with the severity of OSA in our patients was different from the general characteristics of OSA. Moreover, the AHI value was negatively correlated with FVC, %FVC, FEV1, and %FEV1. BMI was the only independent factor for the presence of OSA, and for asthma severity (FEV1, % of predicted), there was a weak correlation with smoking history. CONCLUSIONS: This is the first report to investigate the prevalence of OSA in Japanese asthma patients, using an HST. This study suggests that an HST should be performed in addition to the sleep interview for asthma patients with refractory disease, a low pulmonary function, advanced age, and high BMI because the more severe the OSA, the lower the ESS value may be.

Significance of micro-EGFR T790M mutations on EGFR-tyrosine kinase inhibitor efficacy in non-small cell lung cancer.

Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

Background: Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors. Methods: This study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method. Results: A total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034). Conclusions: These results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

A case of ruptured ovarian metastasis of small cell lung cancer.

A 53-year-old woman with small-cell lung cancer (SCLC) presented at our hospital complaining of abdominal distention. Blood tests revealed rapidly progressive normocytic anemia and elevated lactate dehydrogenase levels. Pelvic magnetic resonance imaging revealed a left ovarian tumor and ascites. As her symptoms rapidly worsened, she underwent emergency surgery, which revealed a ruptured metastatic ovarian tumor of SCLC. Emergency surgery averted a life-threatening situation in this patient, and subsequent chemotherapy facilitated long-term survival. As seen from literature review, in female SCLC patients, ovarian metastasis and rupture is a rare but possible complication that should be considered because of its life-threatening nature.

Interferential Current Stimulation for Swallowing Disorders in Chronic Obstructive Pulmonary Disease: A Preliminary Study.

Objectives: Swallowing function is affected in patients with chronic obstructive pulmonary disease (COPD), putting them at risk of exacerbation of COPD. We previously reported the effectiveness of the repetitive saliva swallowing test (RSST) in screening for patients at risk of COPD exacerbation. However, evidence on how to improve swallowing function in this population is extremely limited. Interferential current transcutaneous electrical sensory stimulation (IFC-TESS) stimulates the larynx and pharynx, thereby improving their sensory function. IFC-TESS is an emerging tool to enhance airway protection and increase swallowing frequency; however, its safety and efficacy in patients with COPD is unknown. Therefore, we performed a preliminary prospective study focusing on stable COPD patients. Methods: Patients with stable COPD who were hospitalized for yearly evaluation were recruited. Patients were included if their RSST was 5 or less. Nurses carried out IFC-TESS twice daily for 10 days. Swallow screening results were compared before and after the 10-day intervention. Results: Ten patients were included in the study. The IFC-TESS intervention was performed safely. Patients and nurses reported no discomfort or concerns regarding the intervention. The EAT-10 and RSST scores improved significantly after the intervention, and tongue pressure also tended to improve. Conclusions: IFC-TESS may be a promising intervention to improve swallowing in patients with COPD who are easily fatigued and struggle to perform swallowing exercises.

The Japanese Respiratory Society guidelines may reduce unnecessary chest computed tomography in patients with pneumonia requiring hospitalization: A retrospective study.

BACKGROUND: With the abundance of CT scanners in Japan, doctors can easily order CT scans to diagnose pneumonia. The Japanese Respiratory Society (JRS) guidelines uniquely recommend conditions for which additional CT scans should be considered at the time of diagnosis of pneumonia, a feature not found in other guidelines. In this study, we aimed to evaluate the usefulness of the recommendations in a bid to reduce the number of unnecessary CT examinations. METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with pneumonia hospitalized between April 2016 and March 2017 to extract patients' backgrounds and clinical courses. Conformity with the JRS guideline recommendations was also examined. In the patients who did not meet the recommendations, we investigated the proportion of them for whom an additional CT scan influenced the clinical decisions. Finally, we evaluated whether there was a difference in hospital stay depending on the additional chest CT at the time of admission. RESULTS: We included 363 hospitalized patients with pneumonia. Chest CT scan was performed in 306 patients (84.3%), of whom 186 (60.8%) did not meet the JRS guideline recommendations. Chest CT revealed findings requiring a change in treatment strategy in only 14 (7.5%) of the 186 patients. Among the 240 patients (66.1%) who did not meet the recommendations, no statistically significant difference was observed in the hospital stay or mortality between patients with and without CT scans. CONCLUSIONS: Adherence to the JRS guideline recommendations may reduce the excessive use of CT scans in the diagnosis of pneumonia.

Cryptococcosis in the Vocal Cords, Trachea, and Bronchi.

Laryngeal and endobronchial cryptococcosis are rare conditions, and to our knowledge, there have been only 23 cases of laryngeal cryptococcosis, and 18 cases of endobronchial cryptococcosis previously reported in the English literature. We herein report an extremely rare case of cryptococcosis with simultaneous laryngeal and endobronchial involvement. This case highlights the importance of paying close attention to possible occurrence of cryptococcosis of the airway tract in patients with asthma treated with high-dose inhaled corticosteroids.

A Need for a Diagnostic Management Protocol in Barium Aspiration.

We experienced a patient who presented with lung abscess one month after aspirating barium during a gastric cancer screening examination. The patient had no subjective symptoms suggesting a swallowing disorder. Rigorous history taking under suspicion of aspiration and a further assessment of the cause of aspiration revealed hypopharyngeal cancer. Lung abscess and hypopharyngeal cancer, both treatable but potentially fatal conditions, were not diagnosed until one month after the aspiration. This highlights the need for guidance for patients and physicians to follow in the event of barium aspiration, as it is the most common complication of a barium examination. A health checkup for one condition (gastric cancer) may also be an opportunity to diagnose another underlying condition.

Hemorrhaging from an Intramedullary Cavernous Malformation Diagnosed Due to Recurrent Pneumonia and Diffuse Aspiration Bronchiolitis.

While aspiration pneumonia constitutes the majority of pneumonia cases in the elderly, it remains highly underdiagnosed. We experienced a case of recurrent pneumonia and chronic cough that was later diagnosed as aspiration pneumonia and diffuse aspiration bronchiolitis (DAB) due to recurrent hemorrhaging from an intramedullary cavernous malformation. The patient was finally diagnosed when life-threatening respiratory depression caused emergency attention. This is the first report of hemorrhaging from an intramedullary cavernous malformation diagnosed due to aspiration pneumonia and DAB. These findings highlight the importance of considering aspiration in cases with recurrent pneumonia or chronic cough. The underlying cause may be a life-threatening condition.

Osimertinib for Lung Squamous Cell Carcinoma: A Case Report and Literature Review.

The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung squamous cell carcinoma is said to be low. Thus far, only four cases of osimertinib in lung squamous cell carcinoma have been published. We experienced a case of EGFR mutant lung squamous cell carcinoma in which fifth-line treatment with osimertinib was effective after T790M EGFR mutation turned positive. Osimertinib was resumed after sixth-line chemotherapy was ineffective, showing efficacy again. Osimertinib may be a promising treatment option for EGFR mutant lung squamous cell carcinoma. This is the first report to show its effect in a case of rechallenge after intervening chemotherapy. It may therefore be important to evaluate EGFR in never-smoker lung squamous cell carcinoma patients.

A case of large-cell lung carcinoma successfully treated with pembrolizumab but complicated with cholangitis.

Large-cell carcinoma (LCC) of the lung is defined as an undifferentiated non-small cell lung cancer (NSCLC) and accounts for approximately 7.5% of lung cancers. Immune checkpoint inhibitors (ICIs) may be effective for LCC, but there has been no firm evidence due to its low frequency. We herein report an 80-year-old woman with LCC of the lung who was successfully treated with pembrolizumab but developed sclerosing cholangitis as an immune-related adverse event. This case highlights the efficacy of ICIs for LCC as well as the importance of the immediate and detailed management of ICI-related sclerosing cholangitis.

Intractable pleural effusion associated with superior vena cava and upper extremity deep vein thrombosis in a patient with advanced lung cancer.

We herein report a case with intractable pleural effusion attributed to superior vena cava (SVC) and upper extremity deep vein thrombosis in a patient with lung cancer. A 62-year-old woman presented to our hospital with shortness of breath and bilateral upper extremity edema. One year ago, she was diagnosed with stage IVB lung adenocarcinoma with bilateral malignant pleural effusions. A genetic analysis of the cells from pleural effusion revealed an epidermal growth factor receptor (EGFR) point mutation at exon 21 (L858R); since then, she was treated with gefitinib. Although her lung cancer and metastatic lesions had markedly reduced and the tumor cells in the pleural effusion had disappeared, pleural effusion remained. Contrast-enhanced whole-body computed tomography (CT) revealed intravenous thrombosis extending from the SVC to the left brachiocephalic and subclavian veins, and her pleural effusion was attributed to this thrombosis. Anticoagulant therapy with intravenous heparin and oral warfarin was started, nevertheless, the thrombus remained and pleural effusion did not decrease. After the placement of a pleuroperitoneal shunt, her pleural effusion resolved and her symptoms improved. This case highlights the importance of awareness of SVC or upper extremity deep vein thrombosis as a differential diagnosis of intractable pleural effusion in lung cancer patients.

An autopsy case of ruptured liver metastases from small cell lung cancer: A case report and literature review.

A 50-year-old male presented to our hospital complaining of dry cough and slight fever. A chest CT scan showed a mass in the right upper lung lobe, pleural effusion on both sides, and multiple liver tumors. He was diagnosed with small cell lung cancer (SCLC), and then antitumor chemotherapy was started. Thereafter, his condition deteriorated rapidly, and died 2 days later. An autopsy revealed that the cause of death was ruptured liver metastases. SCLC is a highly invasive disease and often metastasizes to the liver, but the rupture of liver metastases is rare. Clinical features and imaging findings were of a great help in diagnosing ruptured hepatic metastasis. Physicians need to pay attention to this condition, especially after chemotherapy has initiated.

Pneumocystis jirovecii Pneumonia in an Immunocompetent Japanese Man: A Case Report and Literature Review.

We herein report the case of a 37-year-old immunocompetent man who died from Pneumocystis jirovecii pneumonia (PCP). He was initially treated for an acute exacerbation of interstitial pneumonia; however, the elevation of the patient's serum (1-3) ß-D glucan (BG) level suggested the possibility of PCP and sulfamethoxazole trimethoprim was added. A postmortem pathological examination and retrospective Grocott's methenamine silver (GMS) staining of the bronchoalveolar lavage fluid (BALF), which was obtained on the day of admission, revealed PCP. The present case suggests that it is essential to perform a BG assay and GMS staining of BALF specimens when patients show diffuse ground-glass opacity on chest computed tomography, regardless of their immune status.

Repetitive saliva swallowing test and water swallowing test may identify a COPD phenotype at high risk of exacerbation.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) are known to present with dysphagia from an early stage. Dysphagia leads to swallowing-related complications, in turn leading to COPD exacerbation. Dysphagia screening is recommended; however little is known of its utility in detecting a COPD phenotype at risk for exacerbation. The simple swallowing provocation test (SSPT), considered to be a standard screening test, requires specific equipment, physician skill and patient discomfort. OBJECTIVES: The aim of this study was to find an easier and less invasive measure to screen for dysphagia in patients with COPD. METHODS: We retrospectively reviewed patients with COPD who were screened for dysphagia [Repetitive saliva swallowing test (RSST), water swallowing test (WST), SSPT and a questionnaire] from June to November 2016. The patients were classified into two groups according to the presence of COPD exacerbation in the past 3 years (ie, exacerbation and non-exacerbation group), and the dysphagia screening results were compared between the groups. RESULTS: Of the 80 cases included, 42 had 1 or more exacerbations in the past 3 years (exacerbation group), and 38 had none (non-exacerbation group). Statistically significant differences between the groups were observed in the RSST, and vocal change in the WST (P < 0.05). There were no significant differences between the groups in the results of SSPT, COPD stage and other clinical status. CONCLUSIONS: Compared to the SSPT, RSST and WST may be more appropriate screening methods in patients with COPD. A prospective study is necessary for further assessment.

"Pulmonary Actinomycosis attributable to Actinomyces meyeri presenting as cardiac tamponade: a case report".

BACKGROUND: Recently, it is reported that Actinomyces meyeri is the most common species causing actinomycosis. However, to our knowledge, there was no report about pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. CASE PRESENTATION: Hereby we describe a case of pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. At first, the patient was diagnosed with bacterial pericarditis with lung abscess in the left lower lung lobe and underwent pericardial drainage. Three days after the removal of the drainage tube, atrial fibrillation followed by cardiac arrest with asystole occurred and immediate cardiopulmonary resuscitation restored his circulation. Thereafter, he underwent pneumocentesis of the lung abscess and the culture grew A. meyeri. He was successfully treated with penicillin G. CONCLUSION: This is the first case of pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. We believe that an increased awareness of the disease is necessary to expedite diagnosis therefore minimizing morbidity and mortality.

Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) presenting as an endobronchial lesion: Case report and literature review.

Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) is a rare entity of lymphoma. We herein report an even rarer case of a 68-year-old male with PTCL-NOS presenting as an endobronchial lesion, and review previously published cases in the literature. Initially, he was referred to our hospital for further investigation of the right upper lobe consolidation on chest radiograph. Computed tomography and 18F-fludeoxyglucose positron emission tomography revealed a right hilar mass with obstruction of the main bronchus and submandibular, right axillary and mediastinal lymphadenopathy. Pathological examination of the biopsy specimens from of the endobronchial lesion and subcutaneous nodule revealed PTCL-NOS. Chemotherapy was started but he finally died due to septic shock after the second-line chemotherapy.

Miliary Tuberculosis in a Young Woman with Hemophagocytic Syndrome: A Case Report and Literature Review.

We herein report a rare case of miliary tuberculosis-associated hemophagocytic syndrome (HPS) complicated with respiratory failure. A 19-year-old Japanese woman with a fever, general malaise, and chest radiograph abnormalities was referred to our hospital. After admission, she developed respiratory failure with pancytopenia. A histological examination of lung and bone marrow biopsy samples revealed noncaseating granulomas without evidence of acid-fast bacilli or lymphoma. In addition, a bone marrow biopsy showed marked histiocyte hyperplasia with hemophagocytosis, and a bronchoalveolar lavage fluid culture grew Mycobacterium tuberculosis. Therefore, a diagnosis of miliary tuberculosis-associated HPS was made. The patient was successfully treated with antituberculous therapy.