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Abstract Background and Aims Because bronchoscopy is an invasive procedure, sedatives and analgesics are commonly administered, which may suppress the patient’s spontaneous breathing and can lead to hypoventilation and hypoxemia. Few reports exist on the dynamic monitoring of oxygenation and ventilation during bronchoscopy. This study aimed to prospectively monitor and evaluate oxygenation and ventilation during bronchoscopy using transcutaneous arterial blood oxygen saturation and carbon dioxide. Methods We included patients who required pathological diagnosis using fluoroscopic bronchoscopy at our hospital between March 2021 and April 2022. Midazolam was intravenously administered to all patients as a sedative during bronchoscopy, and fentanyl was administered in addition to midazolam when necessary. A transcutaneous blood gas monitor was used to measure dynamic changes, including arterial blood partial pressure of carbon dioxide (tcPCO2), transcutaneous arterial blood oxygen saturation (SpO2), pulse rate, and perfusion index during bronchoscopy. Quantitative data of tcPCO2 and SpO2 were presented as mean ± standard deviation (SD) (min–max), while the quantitative data of midazolam plus fentanyl and midazolam alone were compared. Similarly, data on sex, smoking history, and body mass index were compared. Subgroup comparisons of the difference (Δ value) between baseline tcPCO2 at the beginning of bronchoscopy and the maximum value of tcPCO2 during the examination were performed. Results Of the 117 included cases, consecutive measurements were performed in 113 cases, with a success rate of 96.6%. Transbronchial lung biopsy was performed in 100 cases, whereas transbronchial lung cryobiopsy was performed in 17 cases. Midazolam and fentanyl were used as anesthetics during bronchoscopy in 46 cases, whereas midazolam alone was used in 67 cases. The median Δ value in the midazolam plus fentanyl and midazolam alone groups was 8.10 and 4.00 mmHg, respectively, indicating a significant difference of p

Abstract Previous studies have shown that rapid on-site evaluation (ROSE) improves the diagnostic yield of bronchoscopy using endobronchial ultrasound with a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPL). While ROSE of imprint cytology from forceps biopsy has been widely discussed, there are few reports on ROSE of brush cytology. This study investigated the utility of ROSE of brush cytology during bronchoscopy. We retrospectively analyzed data from 214 patients who underwent bronchoscopy with EBUS-GS for PPL. The patients in the ROSE group had significantly higher diagnostic sensitivity through the entire bronchoscopy process than in the non-ROSE group (96.8% vs. 83.3%, P = 0.002). The use of ROSE significantly increased the sensitivity of brush cytology with Papanicolaou staining (92.9% vs. 75.0%, P

Abstract Background In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. Methods From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. Results Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. Conclusion The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.

Objectives: Pharyngeal follicles similar to those seen in influenza have been observed in patients with coronavirus disease 2019 (COVID-19), suggesting their potential as early-stage diagnostic markers. In this study, we examined the diagnostic potential of pharyngeal follicles for COVID-19, particularly the Omicron variant and its subtypes, to obtain basic data for AI-based diagnostic imaging tools. Methods: A cross-sectional study was conducted from July 21, 2022, to March 31, 2023, at the Tokyo Shinagawa Hospital's fever clinic. Participants aged ≥15 years who underwent real-time polymerase chain reaction testing for COVID-19 and pharyngeal examinations were included. Demographic details, symptom onset, throat pain, and vaccination status were also recorded. Pharyngeal structures were categorized into four groups: follicles, buds, mixed, or absent. Results: Of the 1223 participants, 829 (67.8%) tested positive for COVID-19. Among those who tested positive, 73.6% (95% CI: 70.6%-76.6%) had follicular structures, compared to 52.8% (95% CI: 47.9%-57.7%) of those who tested negative (P = 1.0 × 10−12). Overall, 818 participants exhibited follicular structures (439 with follicles, 281 with buds, and 98 with mixed structures), while 405 lacked any follicular structures. Regression analysis identified throat pain and follicular structures as significant COVID-19 predictors (95% confidence intervals: 2.49-4.85 and 1.43-2.59, respectively). Mixed follicles were identified as a potentially characteristic feature of COVID-19. Conclusion: Pharyngeal follicular structures demonstrated high sensitivity for early COVID-19 diagnosis.

BackgroundImmune check point inhibitors (ICIs) are standard treatment for patients with non-small cell lung cancer (NSCLC). Nearly a decade has passed since nivolumab was approved by the FDA for NSCLC patients. However, long-term outcomes and clinical features remain unclear for individual cases. Pseudo-progression is a well-known paradoxical radiological response pattern under ICI treatment which occurs when tumor index lesions regress after apparent initial progression. We herein report a unique case of NSCLC with repeating pseudo-progression in late phase treated with nivolumab monotherapy for 8.5 years.Case presentationA 56-year-old male diagnosed with Non-sq NSCLC clinical stage IVA, at the left upper lobe primary lesion. The primary lesion was PD-L1 negative with no oncogenic driver mutations. He had multiple pulmonary metastases and a left adrenal gland metastasis, and subsequently, received nivolumab as third-line therapy. After initiation of nivolumab, the lung lesion and adrenal metastasis shrank rapidly; however, the patient experienced three late-phase pseudo-progressions in the mediastinal lymph node (LN). This patient is still receiving nivolumab with no symptoms and PS 0. Acquired resistance should be judged carefully in patients with LN-only oligo-progression to avoid unnecessary local therapies and the misjudgment of treatment.

Abstract Anaplastic lymphoma kinase (ALK) fusion gene‐positive lung cancer often shows brain metastasis at initial diagnosis or during the course of treatment. However, molecular‐targeted drugs are known to pass through the blood–brain barrier and present positive effects for central nervous system lesions. There are few reports suggesting how effective molecular‐targeted drug therapy alone is for brain metastasis lesions of ALK fusion‐positive lung cancer, especially after the first use of ALK‐tyrosine kinase inhibitor (TKI) or for bulky brain metastases. A patient in his mid‐fifties with stage IV pleural dissemination developed brain metastases after 10 years of crizotinib use, but showed a complete response after switching to brigatinib. Moreover, a patient in her early sixties with stage III recurrent large brain metastases 5 years after chemoradiation therapy experienced dramatic tumor shrinkage with brigatinib. In each case of ALK fusion gene‐positive lung cancer with brain metastases, brigatinib showed a high efficacy and was well‐tolerated after previous ALK‐TKI and for bulky lesions.

Abstract 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).

Abstract Airway involvement in relapsing polychondritis (RP) can be debilitating and life threatening, often requiring interventional procedures. If standard therapies including systemic corticosteroid and immunosuppressive agents are ineffective, airway stenting is often required. Recently, biologics have been reported to be effective for RP, and the early administration of biologics may avoid airway stenting. To evaluate survival rates and treatment approaches, medical records of RP patients with airway involvement were reviewed. These cases were divided into the following groups: with and without malacia, stenting and non-stenting, and with and without biologics. Kaplan–Meier was used to calculate survival rates and log rank tests were used to analyze biologics groups. A total of 77 patients were enrolled. Airway stenting was performed in 13 patients, all of which developed airway malacia. The stenting group had significantly lower survival rates than the non-stenting group (p

Abstract Background Relapsing polychondritis (RP) is a chronic and recurrent inflammatory disease of the cartilage tissues in the body. The cause of RP is unknown, and since it is a rare disease with symptoms that affect multiple organs, diagnosis is often delayed. Case presentation A 62-year-old woman with no smoking history visited our institution complaining of fever, cough, and dyspnoea. Chest CT showed a stenosis from the left main bronchus to the left lower lobe branch. Bronchoscopy visualised intense erythema and oedema at the left main bronchus, with airway narrowing. Biopsy of the ear revealed degenerative vitreous cartilage and fibrous connective tissue with a mild inflammatory cell infiltrate. She was subsequently diagnosed with RP and administered systemic corticosteroid therapy. Her symptoms improved rapidly, and post-treatment bronchoscopy revealed that although mild erythema of the airway epithelium remained, oedema markedly improved, and the airway stenosis was resolved. Conclusions We report a case where pre-treatment bronchoscopy was able to visually confirm RP at the acute stage. Since RP is difficult to diagnose, severe airway narrowing can occur prior to diagnosis. Therefore, to determine the stage of the disease, it is helpful to perform bronchoscopic observation before treatment. However, bronchoscopic observation before treatment should be performed by experienced bronchoscopists due to the risk of airway obstruction.

Abstract There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P

Recently, several biologics have been approved for the treatment of severe asthma. Dupilumab, a biologic used to treat severe asthma, is a monoclonal antibody targeting interleukin-4 and interleukin-13. In the present case, inhaled corticosteroid-induced glucocorticoid hypersensitivity was suspected, and the administration of omalizumab and mepolizumab had no beneficial effects. Subsequently, we switched to dupilumab therapy, which produced better effectiveness. Therefore, when a biologic agent proves ineffective, changing to another suitable biologic agent should be considered.

Bronchial schwannoma is extremely rare, accounting for a small percentage of benign bronchial tumors, with no determined standardized treatment. An 89-year-old woman with a persistent cough underwent CT scan which revealed a tracheal tumor. A diagnosis of endobronchial schwannoma was confirmed based on tissue obtained by high-frequency snare polypectomy. A hybrid stent was implanted in the trachea due to tumor regrowth; however, stent migration occurred, and it was removed after 1 month. Subsequently, radiation therapy was performed, and airway patency was well maintained for over 3 years. In general, surgical resection is recommended for endobronchial schwannoma; however, due to the age of this patient, resection was deemed invasive. Therefore, radiation therapy was administered as an alternative treatment.

Abstract Background In this study we aimed to clarify the PD‐L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. Methods A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD‐L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. Results When PD‐L1 expression‐positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD‐L1 expression, SPA was the only subtype which was statistically significant when both PD‐L1 expression‐positive was defined by TPS ≥ 1% (p

Immune checkpoint inhibitor (ICI)-induced myocarditis is rare but fatal. Because of the rapid course of ICI-induced myocarditis, understanding of clinical course is only possible through information from case reports. We report a case of pembrolizumab-induced myocarditis in which we were able to document the course of electrocardiographic changes from onset to death. A 58-year-old woman with stage IV lung adenocarcinoma, who had completed her first cycle of pembrolizumab, carboplatin, and pemetrexed, was admitted with pericardial effusion. She underwent pericardiocentesis after admission. A second cycle of chemotherapy was administered 3 weeks after the first cycle. Twenty-two days after admission, she developed a mild sore throat and tested positive for SARS-CoV-2 antigen. She was diagnosed with mild coronavirus disease 2019 (COVID-19), isolated, and treated with sotrovimab. Thirty-two days after admission, an electrocardiogram showed monomorphic ventricular tachycardia (VT). Suspecting myocarditis caused by pembrolizumab, the patient was started on daily methylprednisolone after coronary angiography and endocardial biopsy. Eight days after the start of methylprednisolone administration, she was considered to have passed the acute stage. However, four days later, R-on-T phenomenon triggered polymorphic VT and she died. The impact of viral infections such as COVID-19 on patients be treated with immune checkpoint inhibitors is still unknown and we need to be careful with systemic management after viral infections.

Abstract Background The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand‐1 (PD‐L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. Methods From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD‐L1 status and age, sex, stage, histological type, and prognosis were investigated. Results PD‐L1‐positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD‐L1‐positive PSC cases, two showed high PD‐L1 expression in the vimentin‐positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD‐L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD‐L1 staining in the sarcomatoid survived, whereas the other with negative PD‐L1 staining did not. Conclusion The present study showed that sarcomatoid carcinoma had a higher PD‐L1 expression compared to non‐small‐cell lung cancer and that both PSC and MPM tended to exhibit PD‐L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.

Abstract Airway involvement in relapsing polychondritis (RP) can often be debilitating and life threatening. Interventional procedures such as stenting can be useful to improve airway stenosis. This case was diagnosed with RP with a circumferential obstruction at the left main bronchus. We determined that a silicone airway stent would be placed. The silicone stent was removed after 22 months due to granulation tissue. After stent removal, bronchoscopic findings revealed a collapsing left main bronchus during exhalation, but airway patency was maintained during inhalation without any respiratory symptoms. In this case, bronchomalacia remained after stent removal. However, since there were no severe respiratory symptoms, we decided that stent replacement was unnecessary. In general, it is difficult to remove airway stents in severe tracheobronchomalacia; however, temporary stenting might be a useful procedure in cases with unilateral main bronchial stenosis.

Personalized medicine using molecular-targeted drugs to achieve better therapeutic response and long-term prognosis is common practice for lung cancer treatment. However, in cases before gene batch tests were available, medical treatment continued without the detection of rare mutations. We report a sixty-seven-old year man diagnosed with adenocarcinoma T1cN3M1a, stage IVA. Initial screening performed 7 years earlier using EGFR mutation and ALK immunohistochemical tests were negative. Although first-line cytotoxic combination chemotherapy was remarkably effective, a gradual regression of the primary lesion was noted. After a recent bronchoscopic re-biopsy, RET fusion was detected by gene panel test. In addition, we were able to confirm RET from FFPE specimens obtained from 7-year-old pleural effusion cell blocks. Subsequent administration of the molecular-targeted drug selpercatinib, was highly effective for the primary lesion and all metastatic lesions including brain metastases. We describe a case of RET fusion-positive lung cancer where molecular targeted therapy and cytotoxic drug showed a drastic response and long-term therapy was well maintained. Next generation sequencing was able to correctly diagnose RET fusion mutation using re-biopsy specimen after going undiagnosed for 7 years.

Background Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.Methods We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.Results Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted 20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx.

Abstract Background Consolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown. Methods We retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum‐based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology. Results A total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients. Conclusion Cisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma.

Abstract Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p

Abstract Autofluorescence imaging (AFI) is a technique for detecting early‐stage lung cancer by amplifying the difference in autofluorescence of the bronchial mucosa. However, there are few reports detailing its other applications. Here, we report the case of a 54‐year‐old woman with stage IVa esophageal cancer who completed chemoradiation therapy, but developed a bronchoesophageal fistula at the left main bronchus and underwent fasting treatment. Computed tomography confirmed that the fistula had closed; however, she subsequently developed aspiration pneumonia and underwent bronchoscopy for confirmation. Although it was difficult to identify the site of the pinhole bronchoesophageal fistula under white light, AFI could easily identify the fistula and digestive mucus in light magenta. AFI may therefore be worth considering for the detection of pinhole bronchoesophageal fistulas.

Immune checkpoint inhibitors (ICIs) are the key drugs used in patients with non‐small cell lung cancer (NSCLC). However, anti‐PD‐1 therapy might worsen chronic infection by reactivating the immune response to infectious diseases. Here, we describe a case of successful treatment with nivolumab in a patient with NSCLC complicated by pulmonary aspergilloma, which was safely treated by surgical resection before administration of nivolumab. In conclusion, to safely treat patients with locally limited chronic pulmonary aspergillosis (CPA), surgical resection should be considered before ICI therapy.

Abstract Background Ramucirumab plus docetaxel (RAM+DOC) is expected to prolong survival in patients with advanced non‐small cell lung cancer (NSCLC); however, the efficacy and safety for older patients remains unknown. The objective of this study was to evaluate the efficacy and safety of RAM+DOC in patients 75 years and older. Methods We retrospectively reviewed consecutive patients with advanced NSCLC who had received RAM+DOC treatment at three institutions. We compared the efficacy and safety in patients 75 years and older to those under 75 years of age. Results A total of 114 patients were identified. The median progression‐free survival, time to treatment failure and overall survival was 3.6 (95% CI: 0.4–6.7), 3.1 (95% CI: 2.4–3.9) and 11.2 months (95% CI: 5.6–16.8) in the older group (N = 23), and 4.2 (95% CI: 3.3–5.0), 3.4 (95% CI: 3.3–5.0) and 12.2 months (95% CI: 9.1–15.4) in the younger group (N = 91), respectively. Survival curves were similar for each group, while the objective response rate was 30.4% (95% CI: 13.2–52.9%) in older patients and 35.2% (95% CI, 25.4–45.9%) for the younger group. A total of 22 older patients (95.7%) and 73 (80.2%) younger patients received primary prophylactic pegylated‐granulocyte‐colony stimulating factor (PEG‐G‐CSF). Four older patients (17.3%) and 14 younger patients (15.3%) discontinued RAM+DOC due to adverse events. Conclusions RAM+DOC is expected to be efficacious and tolerable in older patients when supported with prophylactic PEG‐G‐CSF therapy. Key points Significant findings of the study ・PFS, OS, and ORR in older patients were similar to those under 75 years of age. ・Safety of RAM+DOC was well tolerated in older patients with prophylactic PEG‐G‐CSF. ・Prophylactic PEG‐G‐CSF with RAM+DOC may contribute to better efficacy. What this study adds ・This study suggests that RAM+DOC with prophylactic PEG‐G‐CSF is expected to be a useful option in older patients with advanced NSCLC.

Programmed cell death‐1 immune checkpoint inhibitor (ICI) antibody has proven to be effective in advanced non‐small cell lung cancer (NSCLC) patients positive for programmed cell death‐1 ligand‐1. However, there are currently no reports which evaluate drug efficacy by continuous bronchoscopic observation. A 75‐year‐old man with complete right atelectasis was diagnosed with squamous cell carcinoma (SCC) of the right lower lobe (tumor proportion score: TPS 90%, cT4N3M0, stage 3C). For first‐line chemotherapy, carboplatin and nab‐paclitaxel were effective for the primary lesion and the right lung atelectasis improved. However, due to repeated febrile neutropenia with pneumonia, treatment was modified to pembrolizumab monotherapy. Bronchoscopic rebiopsy prior to second‐line treatment revealed high TPS, with a severe stenosis in the right main bronchus. After three courses of pembrolizumab, the right main bronchus opened completely, and no signs of malignancy were observed. Bronchoscopic narrow‐band and autofluorescence imaging also confirmed a complete endobronchial response. Subsequent bronchoscopic observation two years after the initial diagnosis showed a complete and continued response to treatment. ICIs can result in a drastic bronchoscopic response. In this case, the healing process was notable with minimal scarring, and resulted in continued locally bronchoscopic and complete pathological response to treatment compared to previous cytotoxic chemotherapy.

Presently, coronavirus disease-19 (COVID-19) is spreading worldwide without an effective treatment method. For COVID-19, which is often asymptomatic, it is essential to adopt a method that does not cause aggravation, as well as a method to prevent infection. Whether aggravation can be predicted by analyzing the extent of lung damage on chest computed tomography (CT) scans was examined. The extent of lung damage on pre-intubation chest CT scans of 277 patients with COVID-19 was assessed. It was observed that aggravation occurred when the CT scan showed extensive damage associated with ground-glass opacification and/or consolidation (p < 0.0001). The extent of lung damage was similar across the upper, middle, and lower fields. Furthermore, upon comparing the extent of lung damage based on the number of days after onset, a significant difference was found between the severe pneumonia group (SPG) with intubation or those who died and non-severe pneumonia group (NSPG) ≥3 days after onset, with aggravation observed when ≥14.5% of the lungs exhibited damage at 3-5 days (sensitivity: 88.2%, specificity: 72.4%) and when ≥20.1% of the lungs exhibited damage at 6-8 days (sensitivity: 88.2%, specificity: 69.4%). Patients with aggravation suddenly developed hypoxemia after 7 days from the onset; however, chest CT scans obtained in the paucisymptomatic phase without hypoxemia indicated that subsequent aggravation could be predicted based on the degree of lung damage. Furthermore, in subjects aged ≥65 years, a significant difference between the SPG and NSPG was observed in the extent of lung damage early beginning from 3 days after onset, and it was found that the degree of lung damage could serve as a predictor of aggravation. Therefore, to predict and improve prognosis through rapid and appropriate management, evaluating patients with factors indicating poor prognosis using chest CT is essential.

Driver mutations in lung cancer have been generally considered mutually exclusive; however, multiple gene screenings have recently become mainstream. Therefore, it is not uncommon to identify two or more mutations at first diagnosis, making it difficult to determine which tyrosine kinase inhibitor to administer. A 69-year-old woman complaining of back pain was diagnosed with adenocarcinoma T4N3M1c, stage IVB. Although PCR mutation test detected exon21 L858R point mutation by bronchoscopic sample, the therapeutic effect of afatinib was poor. Subsequently, next-generation sequencing (NGS) panel test of a metastasized bone specimen confirmed BRAF V600E. Furthermore, high sensitivity NGS panel system found the gene mutation allele frequency was higher for BRAF V600E than EGFR exon21 L858R for both primary lung tissue and the metastasized specimen. Subsequent BRAF/MEK inhibitor administration showed a remarkable treatment effect. When two or more driver mutations are detected in lung cancer, confirming the allelic frequency of the mutant gene might be useful in selecting more effective agents for front-line treatment.

Background This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non–small-cell lung cancer (NSCLC). Methods We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUV max ) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. Results PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUV max (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUV max were significantly negative prognostic factors in univariate analysis for overall survival (OS) ( P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) ( P = 0.0012 and P < 0.0001). Kaplan–Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUV max < 3, intermediate in patients with positive PD-L1 expression and SUV max < 3 and those with negative PD-L1 expression and SUV max ≥ 3, and poor in patients with positive PD-L1 expression and SUV max ≥ 3. Conclusion Combining PD-L1 expression and preoperative FDG-PET/CT SUV max in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

Abstract Background Programmed cell death-1 (PD-1) immune checkpoint inhibitor antibody has proven to be effective in advanced non-small cell lung cancer (NSCLC) patients positive for programmed cell death-1 ligand-1 (PD-L1). However, there are currently no prospective studies evaluating PD-L1 expression for small biopsy samples. Methods To prospectively investigate the reliability of small samples for NSCLC, we included patients who underwent diagnostic biopsy by flexible bronchoscopy, computed tomography (CT) and ultra-sonography (US) guided core-needle to determine the PD-L1 expression status. In pathologically confirmed NSCLC, PD-L1 expression was evaluated using companion diagnostic PD-L1 immunohistochemistry. We evaluated: 1) tumor cell count and sample size, 2) tumor proportion score (TPS):

Background Probe‐based confocal laser endomicroscopy (pCLE) is a novel, noninvasive technology that provides real‐time lung imaging during bronchoscopy. pCLE shows the elastic fiber network without the use of a fluorescent dye. Elastic fibers produce argon laser‐induced autofluorescence at a wavelength of 488 nm, but tumor cells do not produce autofluorescence at this wavelength. As a result, the tumor cells cannot be observed directly. Therefore, we stained transbronchial biopsy (TBB) specimens with acriflavine to evaluate the benign and malignant structures using pCLE of ex vivo samples and to determine whether rapid histopathological diagnosis of TBB specimens could be made via pCLE. Methods After bronchoscopy, 36 TBB specimens were stained with acriflavine and observed using pCLE. Benign and malignant lesions were classified by cell density and nuclear magnitude disparity. Results We defined the confocal laser endomicroscopic atypia classification from the findings of the cells. The sensitivity for malignancy was 91.3%, and the specificity was 76.9%. Both inter‐observer (κ = 0.48) and intra‐observer (κ = 0.57) agreement confirmed moderate agreement. Conclusion pCLE with acriflavine staining was useful to differentiate malignant from benign TBB specimens, and might be useful as a substitute for rapid on‐site evaluation of histopathological diagnosis.

Key message Relapsing polychondritis (RP) often develops into severe tracheobronchial stenosis with malacia. Although tracheal tears rarely occur by intubation, treatment decisions for tears can be difficult due to airway inflammation in RP patients. In this case, due to advanced age and immunosuppressive treatment, we decided against invasive surgery.

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein’s receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.

Obstructive pulmonary diseases, such as diffuse panbronchiolitis (DPB), asthma, chronic obstructive pulmonary disease (COPD), and asthma COPD overlap syndrome (ACOS) trigger a severe reaction at some situations. Detecting early airflow limitation caused by diseases above is critical to stop the progression. Thus, there is a need for tools to enable self-screening of early airflow limitation at home. Here, we developed a novel non-contact early airflow limitation screening system (EAFL-SS) that does not require calibration to the individual by a spirometer. The system is based on an infrared time-of-flight (ToF) depth image sensor, which is integrated into several smartphones for photography focusing or augmented reality. The EAFL-SS comprised an 850 nm infrared ToF depth image sensor (224 × 171 pixels) and custom-built data processing algorithms to visualize anterior-thorax three-dimensional motions in real-time. Multiple linear regression analysis was used to determine the amount of air compulsorily exhaled after maximal inspiration (referred to as the forced vital capacity, FVCEAFL–SS) from the ToF-derived anterior-thorax forced vital capacity (FVC), height, and body mass index as explanatory variables and spirometer-derived FVC as the objective variable. The non-contact measurement is automatically started when an examinee is sitting 35 cm away from the EAFL-SS. A clinical test was conducted with 32 COPD patients (27/5 M/F, 67–93 years) as typical airflow limitation cases recruited at St. Marianna University Hospital and 21 healthy volunteers (10/11 M/F, 23–79 years). The EAFL-SS was used to monitor the respiration of examinees during forced exhalation while sitting still, and a spirometer was used simultaneously as a reference. The forced expiratory volume in 1 s (FEV1%EAFL–SS) was evaluated as a percentage of the FVCEAFL–SS, where values less than 70% indicated suspected airflow limitation. Leave-one-out cross-validation analysis revealed that this system provided 81% sensitivity and 90% specificity. Further, the FEV1EAFL–SS values were closely correlated with that measured using a spirometer (r = 0.85, p < 0.0001). Hence, EAFL-SS appears promising for early airflow limitation screening at home.

ObjectivesTo investigate the potential of computed tomography (CT)-based texture analysis and elastographic data provided by endobronchial ultrasonography (EBUS) for differentiating the mediastinal lymphadenopathy by sarcoidosis and small cell lung cancer (SCLC) metastasis.MethodsSixteen patients with sarcoidosis and 14 with SCLC were enrolled. On CT images showing the largest mediastinal lymph node, a fixed region of interest was drawn on the node, and texture features were automatically measured. Among the 30 patients, 19 (12 sarcoidosis and 7 SCLC) underwent endobronchial ultrasound transbronchial needle aspiration, and the fat-to-lesion strain ratio (FLR) was recorded. Texture features and FLRs were compared between the 2 patient groups. Logistic regression analysis was performed to evaluate the diagnostic accuracy of these measurements.ResultsOf the 31 texture features, the differences between 11 texture features of CT ROIs in the patients with sarcoidosis versus patients with SCLC were significant. Among them, the grey-level run length matrix with high gray-level run emphasis (GLRLM-HGRE) showed the greatest difference (PConclusionTexture analysis, particularly combined with the FLR, is useful for discriminating between mediastinal lymphadenopathy caused by sarcoidosis from that caused by metastasis from SCLC.

A 51-year-old male patient was receiving treatment for Mycobacterium abscessus infection for approximately 10 years. However, as his condition gradually progressed to type II respiratory insufficiency, he was referred to our hospital, which was near his home. Computed tomography on his first visit revealed an abscess in the right lower lobe. Because respiratory insufficiency was evident, he was admitted the same day. We began treatment with meropenem, amikacin, and clarithromycin, but his symptoms did not improve. In accordance with the 2007 American Thoracic Society/Infectious Diseases Society of America statement, we administered linezolid, which resulted in gradual improvement in his physical status and imaging findings. Keywords: Nontuberculous mycobacterium, Mycobacterium abscessus, Linezolid

BACKGROUND: In patients with bronchial obstruction, pulmonary function tests may not change significantly after intervention. The airflow asynchrony in both lungs due to unilateral bronchial obstruction may be applicable as a physiological indicator. The airflow asynchrony is reflected by the difference in the left and right lung sound development at tidal breathing. OBJECTIVES: To investigate the usefulness of left and right lung asynchrony due to unilateral bronchial obstruction as a physiological indicator for interventional bronchoscopy. METHODS: Fifty cases with central airway obstruction were classified into three groups: tracheal, bronchial and extensive obstruction. The gap index was defined as the absolute value of the average of gaps between the left and right lung sound intensity peaks for a 12-second duration. RESULTS: Before interventional bronchoscopy, the gap index was significantly higher in the bronchial (p

BACKGROUND: Regional lung sound intensity in chronic obstructive pulmonary disease (COPD) patients is influenced by the severity and distribution of emphysema, obstructed peripheral airways, and altered ribcage and diaphragm configurations and movements due to hyperinflation. Changes in the lung sound distribution accompanied by pulmonary function improvements in COPD patients were observed after bronchodilator inhalation. We investigated the association of lung sound distribution with pulmonary functions, and the effects of emphysematous lesions on this association. These studies were designed to acquire the basic knowledge necessary for the application of lung sound analysis in the physiological evaluation of COPD patients. METHODS: Pulmonary function tests and the percentage of upper- and lower-lung sound intensity (quantitative lung data [QLD]) were evaluated in 47 stable male COPD patients (54 - 82 years of age). In 39 patients, computed tomography taken within 6 months of the study was available and analyzed. RESULTS: The ratio of lower QLD to upper QLD showed significant positive correlations with FEV1 %predicted (%FEV1; ρ=0.45, p40%, n=20) and were stronger in less emphysematous patients (n=19, %FEV1; ρ=0.64, p

Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique.The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation.A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p

Embora os quistos de ar paratraqueais sejam raros, os autores consideram que a sua incidência está subvalorizada. Neste estudo os autores foram investigar a sua prevalência e os aspectos clínicos em 535 homens japoneses de meia-idade saudáveis. Foram feitas tomografias axiais computorizadas que diagnosticaram 4 casos (0,75%) a nível da traqueia torácica. Todos os quistos tinham localização póstero-lateral direita da traqueia. Foram encontradas pequenas fístulas com bolhas, arejadas do lado direito da região membranosa da traqueia, diagnosticadas por broncofibroscopia. Duas fístulas comunicavam com os quistos paratraqueais. Todos os casos de quistos paratraqueais não tinham história de doença pulmonar ou sintomas pulmonares. Todos os casos tinham o estudo da função pulmonar normal e não havia limitação dos débitos. Com estes resultados é difícil afirmar que os quistos paratraqueias sejam um sinal de doença pulmonar obstrutiva crónica.