Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

Budesonide/glycopyrronium/formoterol fumarate triple therapy prevents pulmonary hypertension in a COPD mouse model via NFκB inactivation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression. METHODS: We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endothelial cells (MLEC) were treated with TNFα with/without BGF treatment to analyze NFκB signaling and cytokine expression changes. RESULTS: We observed significant reductions in the proinflammatory phenotype observed in the lungs and bronchoalveolar lavage fluid (BALF) 1 day after elastase administration in mice treated with BGF compared with that in mice administered elastase alone (BALF neutrophil percentage, p = 0.0011 for PBS/Vehicle vs. PBS/Elastase, p = 0.0161 for PBS/Elastase vs. BGF). In contrast, only BGF treatment significantly ameliorated the elastase-induced emphysematous lung structure and desaturation after three weeks of elastase instillation (mean linear intercept, p = 0.0156 for PBS/Vehicle vs. PBS/Elastase, p = 0.0274 for PBS/Elastase vs. BGF). Furthermore, BGF treatment prevented COPD-PH development, as shown by improvements in the hemodynamic and histological phenotypes four weeks after elastase treatment (right ventricular systolic pressure, p = 0.0062 for PBS/Vehicle vs. PBS/Elastase, p = 0.027 for PBS/Elastase vs. BGF). Molecularly, BGF acts by inhibiting NFκB-p65 phosphorylation and subsequently decreasing the mRNA expression of proinflammatory cytokines in both alveolar epithelial and pulmonary endothelial cells. CONCLUSION: Our results collectively showed that BGF treatment could prevent PH in addition to ameliorating COPD progression via the inhibition of inflammatory NFκB signaling.

Randomized single-blind comparative study of the midazolam/pethidine combination and midazolam alone during bronchoscopy.

BACKGROUND: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy. METHODS: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant. RESULTS: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036). CONCLUSIONS: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients. TRIAL REGISTRATION: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018).

Characteristics of the nocturnal desaturation waveform pattern of SpO2 in COPD patients: an observational study.

BACKGROUND: Nocturnal desaturation is common in patients with chronic obstructive pulmonary disease (COPD) and impacts disease exacerbation and prognosis. In our previous study, we developed a diagnostic algorithm to classify nocturnal desaturation from SpO2 waveform patterns based on data from patients receiving home oxygen therapy. In this study, we aimed to investigate nocturnal desaturation in patients with COPD based on SpO2 waveform patterns and the associations between the waveforms and clinical data. METHODS: We investigated patients diagnosed with COPD and measured SpO2 and nasal airflow with a type 4 portable long-term recordable pulse oximeter. Then, we classified the SpO2 waveforms with the algorithm and compared the clinical data. RESULTS: One hundred fifty-three patients (136 male and 17 female) were analysed. One hundred twenty-eight of the 153 (83.7%) patients had nocturnal desaturation, with an intermittent pattern (70.6%), sustained pattern (13.1%) and periodic pattern (68.0%). Intriguingly, desaturation with an intermittent pattern was associated with the apnoea-hypopnea index obtained with the portable monitor, and desaturation with a sustained pattern was associated with the cumulative percentage of time at a SpO2 below 90%. CONCLUSIONS: We found that nocturnal desaturation was frequently observed in patients with COPD and could be classified into 3 types of waveform patterns.

[A Case of Multiple Brain Tumors Successfully Diagnosed with Liquid Biopsy and Treated with Osimertinib].

A seventy‒year‒old man complaining of left arm weakness and gait disturbance was diagnosed with multiple tumors and severe edema in the brain as well as right lung mass lesion, suggesting brain metastases. He started whole brain radiation therapy but had to discontinue it since his neurological symptoms were worsened including paralysis, aphasia, and coma. These symptoms made it difficult to perform tumor biopsy for cancer diagnosis as well as oncogene mutations. Liquid biopsy, which examines EGFR gene mutations in plasma sample, revealed EGFR L858R point mutation. Treatment with osimertinib improved his symptoms, resulting in discharge to home. Even a patient severely ill with metastatic brain tumors can benefit from the molecular‒targeted therapy using liquid biopsy to diagnose EGFR‒mutated lung cancer, suggesting an important differential diagnosis in such patients.

Occupational respiratory allergy to lettuce in lettuce farmers.

BACKGROUND: Lettuce-associated respiratory allergy has never been reported before. The aim of this study was to clarify the clinical condition of lettuce-associated respiratory allergy and to identify the lettuce antigen which induces allergic symptoms. METHODS: We distributed questionnaires to 1168 lettuce farmers and performed medical examinations in those who exhibited respiratory symptoms related to occupational exposure to lettuce. We analysed specific IgE-binding proteins in the sera of patients through immunoblotting analysis and determined molecular characterization of the IgE-binding bands using liquid chromatography-mass spectrometry. RESULTS: A total of 932 farmers (80%) responded to the questionnaire. Of those, 7% exhibited lettuce-associated respiratory symptoms, during harvesting and packaging. Thirteen patients were diagnosed with allergy to lettuce and agreed to undergo further examinations. The percentage of activated basophils in these patients was significantly higher compared with that reported in negative controls (P < .05). Lettuce-specific IgE (ImmunoCAP® ) and skin prick testing was positive in 46% and 62% of patients, respectively. Notably, occupational lettuce-allergic asthma was detected in one patient through specific bronchial provocation testing. The IgE-binding bands recognized in the sera of >50% of patients were identified as epidermis-specific secreted glycoprotein EP1-like (51 kDa). CONCLUSION: The present analysis identified a novel lettuce allergen. This allergen may have clinically useful applications, such as specific IgE testing and allergen-specific immunotherapy.

Overexpression of CD 133 and BCL-2 in non-small cell lung cancer with neuroendocrine differentiation after transformation in ALK rearrangement-positive adenocarcinoma.

Transformation to small cell lung cancer is one phenomenon of acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in ALK rearrangement-positive non-small cell lung cancer (NSCLC). Few case reports have focused on other types of histological transformation. We report a case of transformation of ALK rearrangement-positive adenocarcinoma to NSCLC with neuroendocrine differentiation during alectinib therapy. A 36-year-old woman presented with a tumor in the left lower lobe and bone metastases. She was diagnosed with ALK rearrangement-positive adenocarcinoma by histopathology of the primary tumor. Alectinib had been effective for 8 months before new lesions appeared. Histopathological re-examination of a recurrent tumor revealed poorly differentiated carcinoma with insulinoma-associated protein 1 (INSM1) expression, which remained ALK-positive. Expression of CD133, BCL-2, and SOX2 was positive in comparison to the initial tumor. Expression of SOX2 became more strongly positive than it was before treatment. The immunohistochemical findings of these markers associated with cancer stem-like cells and/or neuroendocrine differentiation suggest that cancer stem cells play a role in the mechanisms of histological transformation and acquired resistance of ALK rearrangement-positive cancer. To our knowledge, this is the first report to suggest an association between cancer stem-like cells and histological transformation in ALK rearrangement-positive lung cancer.

The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study.

BACKGROUND: Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. METHODS: This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. RESULTS: A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54-7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but not with chronic respiratory disease. These effects were not affected by age group. CONCLUSIONS: The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults.

HIP1-ALK-Rearranged Lung Cancer in a Young Adult With BRAF V600E Mutation Detected After ALK Tyrosine Kinase Inhibitor Therapy: A Case Report.

HIP1-ALK is a relatively rare fusion pattern in ALK-rearranged NSCLC. Existing studies on the efficacy of ALK tyrosine kinase inhibitor (TKI) resistance mechanisms and treatment strategies in HIP1-ALK-rearranged lung cancer are limited. Here, we report the case of an 18-year-old man with HIP1-ALK-rearranged adenocarcinoma who developed BRAF V600E and V1180L mutations after ALK TKI therapy, in whom the administration of BRAF and MEK inhibitors was ineffective. Brigatinib was effective after chemotherapy with cytotoxic drugs. Development of effective treatments is desirable for rare variants of ALK-rearranged lung cancer after acquiring resistance to ALK TKIs.

Impact of concurrent medications on the outcome of immunotherapy in non-small cell lung carcinoma.

BACKGROUND: There have been reports on the impact of concurrent drugs on the outcome of immunotherapy for non-small cell lung carcinoma (NSCLC). However, the effect of some drugs, such as antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), has not been clarified in patients with NSCLC. In the present study, we aimed to assess the association between concurrent drugs and the outcomes of immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy for patients with advanced NSCLC. METHODS: We retrospectively assessed patients with advanced NSCLC who underwent ICI treatment between September 2017 and December 2021 at Kobe University Hospital. We evaluated the data regarding the use of antibiotics within 30 days before ICI initiation, as well as the use of proton pump inhibitors (PPIs) and NSAIDs during ICI initiation. RESULTS: A total of 127 patients were assessed, among whom 28 (22.0%) patients received antibiotics, 39 (30.7%) PPIs, and 36 (28.3%) NSAIDs. No significant differences were observed between the patients with and without antibiotic use. However, patients using NSAIDs had significantly worse objective response rates (ORR) and progression-free survival (PFS) with ICI alone or in combination with chemotherapy compared to those who did not (ORR, 47.2% vs. 67.0%; p = 0.045. PFS, 6.3 months vs. 10.8 months; p = 0.02). Patients using PPIs demonstrated a worse ORR of ICI in combination with chemotherapy compared to those who did not (ORR, 45.2% vs. 72.6%; p = 0.013). CONCLUSIONS: The unnecessary use of NSAIDs along with immunotherapy should be discouraged.

Effects of Tongue Strength Training on Patients with Mild to Moderate Sleep-disordered Breathing: A Randomized Controlled Trial.

Objectives: : Several studies have reported that oropharyngeal myofunctional therapy (OMT) reduces the severity of obstructive sleep apnea (OSA). However, because OMT protocols are often complicated, they take time and effort to implement. The aim of this study was to determine the therapeutic effect of 8 weeks of simple tongue strength training with a training device. Methods: : Twenty patients with mild to moderate sleep-disordered breathing were randomized to the control group (n=10) or intervention group (n=10). The patients in the intervention group completed 8 weeks of daily tongue strength training using a training device. After 8 weeks, we evaluated each patient for sleep-disordered breathing by portable monitoring. We also evaluated each patient's body mass index (BMI), neck circumference, Epworth Sleepiness Scale (ESS) score, and tongue pressure. Results: No significant difference was found in the change in apnea hypopnea index (AHI) from baseline to 8 weeks between the control and intervention groups (P=0.44). However, the changes in neck circumference (P=0.02) and maximum tongue pressure (P=0.03) from baseline to 8 weeks were significantly different between the two groups. No significant difference was found for changes in BMI and ESS scores from baseline to 8 weeks between the two groups. Conclusions: : Tongue strength training in patients with sleep-disordered breathing did not significantly improve AHI as measured by portable monitoring, although significant changes were observed for increased tongue pressure and reduced neck circumference.

Postmortem Diagnosis of Gallbladder Cancer Presenting as Pulmonary Lymphangitic Carcinomatosis With Concurrent Gallbladder Adenomyomatosis.

In pulmonary lymphangitic carcinomatosis, it can be difficult to identify the primary site of the cancer on computed tomography (CT) imaging. Here, we report a rare case of pulmonary lymphangitic carcinomatosis, which was difficult to diagnose as gallbladder cancer. An 81-year-old woman, previously followed up for gallbladder adenomyomatosis, presented with persistent cough. CT revealed multiple small nodular opacities, irregular interlobular septal thickening, and bilateral pleural effusions. Based on the CT findings and the presence of malignant cells in the pleural fluid, a presumptive diagnosis of pulmonary lymphangitic carcinomatosis was made, but the primary site was not identified. The patient died of respiratory failure in two months. Autopsy confirmed gallbladder cancer with pulmonary lymphangitic carcinomatosis and multiorgan metastasis. Clinicians should be aware that in patients with gallbladder adenomyomatosis, gallbladder cancer can present with rapidly progressive respiratory symptoms even in the absence of an evident mass or increased gallbladder wall thickening.

Diagnostic yield and the number of tumor cells of ultrathin bronchoscopy for peripheral lung lesions: A comparison with thin bronchoscopy.

Ultrathin bronchoscopy has been reported to have a higher diagnostic yield than thin bronchoscopy for small peripheral lung lesions in transbronchial biopsy under radial endobronchial ultrasonography (EBUS). However, data comparing the number of tumor cells in non-small cell lung cancer (NSCLC) are limited. We retrospectively compared the number of NSCLC tumor cells in peripheral lung lesions obtained using an ultrathin bronchoscope and a thin bronchoscope with radial EBUS between April 2020 and October 2021. In all patients, we used virtual bronchoscopic navigation (VBN) software, and guide sheaths were used in thin bronchoscopy cases. A total of 175 patients were enrolled in this study. Ultrathin bronchoscopy cases (n = 69) had lesions with a smaller diameter that are more peripherally located compared to thin bronchoscopy cases (n = 106) (median, 25.0 vs. 26.5 mm, mean bronchial generations accessed by bronchoscopy; 4.4±1.2 vs. 3.8±1.0, respectively; p<0.010). There were no significant differences in the overall diagnostic yield (ultrathin vs. thin bronchoscopy cases, 68.1% vs. 72.6%, p = 0.610) or diagnostic yield in only lung cancer cases (78.6% vs. 78.5%, p = 1.000). In histologically NSCLC cases (n = 102), the maximum number of tumor cells per slide as the primary endpoint was similar (average, 307.6±246.7 vs. 328.7±314.9, p = 0.710). The success rate of the Oncomine™ analysis did not differ significantly (80.0% vs. 55.6%, p = 0.247). The yield of NSCLC tumor cells was not different between the samples obtained by the ultrathin bronchoscope and those obtained by the thin bronchoscope.

In-hospital Mortality among Patients with High-flow Nasal Cannulas in the General Ward.

High-flow nasal cannulas (HFNCs) have become common devices for patients with respiratory failure who are treated in general wards. Few reports have been published on in-hospital mortality associated with the ratio of oxygen saturation (ROX) index, measured by pulse oximetry/fraction of inspired oxygen to respiratory rate, in patients treated with HFNCs. We aimed to examine in-hospital mortality and associated factors in patients who initiated HFNC use in a general ward. Sixty patients who initiated HFNC use in general wards at Kobe University Hospital between December 2016 and October 2020 were retrospectively enrolled. We assessed in-hospital mortality, comorbidities, and ROX index. The in-hospital mortality was 48.3%, and ROX index values were significantly lower in patients who died than in those who did not (at HFNC oxygen therapy initiation; 6.93 [2.73-18.5] vs. 9.01 [4.62-18.1], p = 0.00861). Although the difference was not statistically significant, the change in ROX index values between HFNC initiation and 12 hours after initiation tended to be greater in the patients who died in the hospital (0.732 [-2.84-3.5] vs. -0.35[-4.3-2.6], p = 0.0536). Lower ROX index values may be associated with the in-hospital death of patients who are treated with HFNCs in general wards.

Identification of a 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy in farmers.

BACKGROUND: We have identified and reported a novel antigen, nonprotein-specific secreted EP1-like glycoprotein (51 kDa), for lettuce-related respiratory allergy. OBJECTIVE: We aimed to identify a novel antigen for lettuce-related respiratory allergy that is different from epidermis-specific secreted EP1-like glycoprotein. METHODS: Immunoblotting was performed using an immunoglobulin E-specific antibody. The antigen-antibody reaction was confirmed by means of enzyme-linked immunosorbent assaying. LC-MS/MS analysis was carried out to detect a novel protein found in sera from 3 of 13 patients with lettuce-related respiratory allergy. Finally, we purified a novel protein from Escherichia coli. RESULTS: Immunoblotting assays showed common bands of 17 kDa in the sera of 3 of 13 patients. An enzyme-linked immunosorbent assay confirmed that the patient sera reacted with lettuce latex juice. A 17 kDa protein band that showed antigenic reactivity in 3 of 13 patient sera was identified as a kirola-like protein by LC-MS/MS. In addition, although we purified this protein, we failed to show the inhibitory effect. CONCLUSION: A 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy was identified. In further studies, we will focus on purifying this novel protein to diagnose lettuce allergy.

Drug-induced interstitial lung disease after chemoimmunotherapy for extensive-stage small cell lung cancer.

Objectives: The combination of chemotherapy and immune checkpoint inhibitors (chemo-ICI) has become the new standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). Recently, slight changes in interstitial shadows, defined as interstitial lung abnormalities (ILA), have been identified. In patients with ES-SCLC who received chemo-ICI, there are limited data on the incidence of drug-induced interstitial lung disease (D-ILD) in daily practice and the association between the development of D-ILD and ILA in the baseline computed tomography (CT). Materials and methods: A multicenter, retrospective study was conducted to investigate the incidence of D-ILD, the risk factors for developing D-ILD, progression-free survival (PFS), and overall survival (OS) in patients with ES-SCLC who received chemo-ICI between August 2019 and November 2021. Results: This study enrolled 70 patients (median age, 71 years; including 58 men) from nine institutions in Japan. There were 62 patients (89%) treated with carboplatin/etoposide/atezolizumab and 8 patients treated with carboplatin or cisplatin/etoposide/durvalumab. Twenty-nine patients (41.4%) were found to have ILA at baseline CT. Eleven patients (15.7%) developed D-ILD. The proportion of patients with ILA was significantly higher in the group who developed D-ILD than in the group who did not (9/11 (81.8%) vs. 20/59 (33.9%), respectively, P = 0.0057). In addition, the frequency of ground glass attenuation (GGA) and reticulation was higher in patients who developed D-ILD. There was no significant difference in PFS and OS between patients who developed D-ILD and those who did not (median PFS, 8.0 (95% confidence interval (CI), 5.5-9.5) months vs. 5.0 (95% CI, 4.5-5.6) months, respectively, P = 0.11 and median OS, not reached (NR) (95% CI, 8.7-NR) vs. 18.2 (95% CI, 13.2-NR) months, respectively, P = 0.20). Conclusion: The incidence of D-ILD in patients with ES-SCLC who received chemo-ICI in clinical practice was higher than that in clinical trials. Patients with pre-existing ILA were more likely to develop D-ILD.

A successful diagnostic case of Pneumocystis pneumonia by the loop-mediated isothermal amplification method in a patient with dermatomyositis.

Pneumocystis pneumonia (PCP) can occur in patients with many causes of the immunocompromised state other than human immunodeficiency virus (HIV). It is quite difficult to diagnose PCP without HIV because there is no method for detecting Pneumocystis jirovecii. Thus, non-HIV PCP continues to have high mortality. Recently, loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We report a non-HIV PCP case successfully diagnosed by the LAMP method. It was previously reported that PCR in BALF specimens had been the most sensitive method in the diagnosis of PCP without HIV. The LAMP method would be more sensitive than conventional PCR and an effective tool in the early diagnosis of PCP.

Cross-sectional study of cholinergic urticaria subtypes and bronchial hyperresponsiveness.

Cholinergic urticaria (CholU) is classified into several subtypes: (1) conventional sweat allergy-type CholU (conventional SAT-CholU), (2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd); 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the subtypes. We analyzed bronchial responsiveness using the methacholine dose indicator Dmin, respiratory symptoms, and exhaled nitric oxide (FeNO). Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU (n = 11), CholU-PA (n = 11), and CholU-Anhd (n = 11) was 0.381 (- 0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p = 0.516). Respiratory symptoms were less frequently observed in CholU-Anhd than in conventional SAT-CholU or CholU-PA. FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p = 0.237). Nine% of conventional SAT-CholU patients and more than half of CholU-PA patients required treatment for asthma. Log Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. CholU-PA might be associated with asthma.

The utility of bispectral index monitoring in flexible bronchoscopy: A single-center, retrospective observational study.

BACKGROUND: The desired depth of sedation during flexible bronchoscopy is one in which verbal contact is possible whenever necessary. Although it is common that the depth of sedation is assessed by validated instruments such as the modified observer's assessment of alertness and sedation (MOAA/S) score, the repeated stimulation associated with the assessment can affect the sedation. The bispectral index (BIS) has been widely used for general anesthesia due to its objective and noninvasive nature. However, the utility of BIS monitoring and a target BIS value for use during bronchoscopy have not been fully elucidated. METHODS: We performed a retrospective observational study to assess the utility of the BIS value for monitoring conscious sedation during bronchoscopy at Kobe University Hospital from August 2020 to April 2021. RESULTS: Eighteen patients underwent bronchoscopy with BIS monitoring. The BIS value significantly correlated with the MOAA/S score (r = 0.2, p < 0.01), and the correlation was stronger in sufficiently sedated patients (r = 0.486, p < 0.01). The lowest MOAA/S score during the procedure was highly correlated with the BIS value (r = 0.625, p < 0.01). The BIS monitoring seemed to be more sensitive to changes in the sedation level than the MOAA/S score, heart rate and mean arterial pressure. The median BIS value at an MOAA/S score of 3-4, the desired depth of sedation, was 82.0. CONCLUSIONS: BIS value is useful for monitoring sedation during bronchoscopy. This study suggests that a BIS value of 82 reflects an adequate level of sedation.

[A case of 2009 influenza A (H1N1) virus-associated pneumonia diagnosed from bronchoalveolar lavage specimen].

A 41-year-old man admitted for fever and respiratory failure had visited a local clinic 8 days earlier for fever and cough. Several days earlier, his 3 children had been diagnosed with influenza A by rapid influenza diagnostic test (RIDT) by nasopharyngeal swabs. At the clinic, RIDT done by nasopharyngeal swab two times on two consecutive days had negative results. On admission, chest computed tomography (CT) showed bilateral subpleural and peribronchovascular opacity, although RIDT by nasopharyngeal swab was negative. His respiratory distress worsened rapidly over the next several hours, necessitating intubation. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) with nasopharyngeal secretion was also negative. Despite test results, 2009 influenza A (H1N1) was strongly suspected due to chest CT and history. Oseltamivir was administered and respiratory distress gradually disappeared. He was extubated on hospital day 7. Bronchoalveolar-lavage collected on admission and sent to the laboratory for RT-PCR on hospital day 8, from which the result was positive for influenza A. He was discharged on hospital day 22.