Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital's coordinated care system.

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.

Pulmonary function and chest CT abnormalities 3 months after discharge from COVID-19, 2020-2021: A nation-wide multicenter prospective cohort study from the Japanese respiratory society.

BACKGROUND: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. METHODS: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. RESULTS: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. CONCLUSION: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.

Surveillance of seasonal influenza viruses during the COVID-19 pandemic in Tokyo, Japan, 2018-2023, a single-center study.

Introduction: COVID-19 pandemic led to significant reductions in influenza detection worldwide, fueling debates on whether influenza truly ceased circulating in communities. The number of influenza cases decreased significantly in Japan, raising concerns about the potential risk of decreased immunity to influenza in the population. Our single-center study aimed to investigate influenza trends before and during the COVID-19 pandemic in Tokyo, Japan. Materials and Methods: This cross-sectional study included patients of all ages who visited Tokyo Shinagawa Hospital between April 1, 2018, and March 31, 2023. Influenza and COVID-19 tests were conducted using Quick Navi-Flu2 and polymerase chain reaction (PCR). We analyzed data from before and during the COVID-19 epidemic, based on patient background, hospitalization, and deaths, collected from medical records. Results: A total of 12 577 influenza tests were conducted, with approximately 100 tests consistently performed each month even in the influenza off-season. Throughout the observation period, 962 positive cases were identified. However, no cases were observed for 27 months between March 2020 and November 2022. Influenza A cases were reobserved in December 2022, followed by influenza B cases in March 2023, similar to the influenza incidence reports from Tokyo. The positivity rate during the 2022-2023 winter season was lower than before the COVID-19 epidemic and decreased in elderly patients, with no hospitalizations or deaths observed. Conclusion: This single-center study provided actual trend data for influenza patients before and during COVID-19 outbreaks in Tokyo, which could offer insights into the potential impact and likelihood of influenza virus infection in Japan.

A Quantitative Computed Tomography Analysis of Fissure Integrity and Emphysema Destruction in Japanese Patients with Severe Chronic Obstructive Pulmonary Disease.

Objective Bronchoscopic lung volume reduction (BLVR) using a one-way endobronchial valve (EBV) can provide clinically meaningful benefits to chronic obstructive pulmonary disease (COPD) patients. Although the Japanese Pharmaceuticals and Medical Devices Agency approved EBVs in November 2022, information regarding the number of Japanese patients with severe COPD eligible for BLVR treatment is still lacking. We therefore screened computed tomography (CT) images of patients with severe COPD using a quantitative CT (QCT) analysis to estimate the proportion of candidates eligible for BLVR treatment with an EBV. Methods CT scans of COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4 were retrospectively analyzed using QCT to evaluate fissure integrity and tissue destruction. The difference in volume-weighted percentage was measured using the density scores of the target lobe and ipsilateral non-target lobe at -910 Hounsfield units. The target lobe was defined as the most affected lobe, with an emphysema destruction score of >50% for each patient. Results High-resolution CT scans of 32 patients (GOLD 3=19, GOLD 4=13) were analyzed. The target lobe could not be identified in 1 patient, whereas the target lobes for 8 patients were not surrounded by fissures with ≥80% completeness. Conversely, in 13 patients, the target lobes were surrounded by fissures with >95% completeness. The remaining 10 patients had fissure completeness between 80% and 95% at the target lobes and were considered candidates for collateral ventilation assessment. Conclusion A QCT analysis showed that 23 of 32 patients with severe COPD could be considered for a thorough examination of BLVR treatment with EBV.

A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19.

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).

Bilateral Pneumothorax after a Transbronchial Lung Cryobiopsy for Interstitial Lung Disease.

We herein report a case of bilateral pneumothorax after a unilateral transbronchial lung cryobiopsy (TBLC). A 73-year-old man with no history of cardiothoracic surgery underwent a TBLC for the reevaluation of interstitial lung disease. Five hours later, he developed bilateral pneumothorax, pneumomediastinum, and subcutaneous emphysema. He underwent bilateral chest drainage and was discharged 18 days later. The lung biopsy specimens obtained from the TBLC contained visceral pleura and bronchial cartilage, suggesting bronchial injury as the cause of the bilateral pneumothorax.

High efficacy of brigatinib for brain metastases in ALK fusion gene-positive non-small cell lung cancer: A case series.

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.

Dupilumab in a patient with severe asthma and glucocorticoid hypersensitivity: a case report.

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.

EML4-ALK Gene Mutation Detected with New NGS Lung Cancer Panel CDx Using Sputum Cytology in a Case of Advanced NSCLC.

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.

Evaluation of airway involvement and treatment in patients with relapsing polychondritis.

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 < 0.001). Stent-related complications were granulation tissue (85%) and mucostasis (69%). In the non-stenting group, a lower mortality rate was observed. A significantly higher survival rate was seen in patients administered biologics than without (p = 0.014). The early administration of biologics shows promise in preventing severe airway disorders that require airway stenting.

Pre-treatment bronchoscopic evaluation in a case of relapsing polychondrits.

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.

Case report: Electrocardiographic changes in pembrolizumab-induced fatal myocarditis.

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.

Efficacy of combined transbronchial lung cryobiopsy and conventional forceps biopsy for lung malignancies: a prospective cohort study.

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 < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.

RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report.

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.

Predicting the aggravation of coronavirus disease-19 pneumonia using chest computed tomography scans.

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.

Temporary stenting in a case of bronchomalacia due to relapsing polychondritis.

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.

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification: clinical features with a progressive phenotype.

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 <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) 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 <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. CONCLUSIONS: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens.

Background: Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Methods: Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. Results: In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2-99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. Conclusion: The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Changes in Pulmonary Function Test Results and Respiratory Symptoms before and after Airway Stent Removal.

BACKGROUND: Airway stenting is a useful form of palliation for patients with airway stenosis/fistulas; the stent can be removed after addressing the cause of the airway disorder. Patients with airway stents often complain of coughing and difficulty with expectoration, so the use of such stents can negatively affect pulmonary function and worsen symptoms. OBJECTIVES: The aim of this study was to compare pulmonary function and respiratory symptoms before and after stent removal. METHODS: Patients who would later undergo simple airway stent removal were prospectively recruited in two institutions. All stents were removed using both rigid and flexible bronchoscopes with patients under general anesthesia. Pulmonary function tests were performed before stent removal and at 1 and 4 weeks after stent removal. All patients self-reported their respiratory symptoms using a 100-mm visual analog scale (VAS). RESULTS: Of the 31 patients enrolled, 28 (23 with malignant stenoses, 3 with benign stenoses, and 2 with fistulas [21 silicone and 7 metallic stents]) were included in analyses. Pulmonary function measurements before stent removal and at 1 and 4 weeks after stent removal were as follows: vital capacity, 3.00, 3.04, and 3.08 L (p = 0.387); forced expiratory volume in 1 s, 1.96, 1.96, and 2.12 L (p = 0.034); and peak expiratory flow, 3.60, 4.28, and 5.06 L/s, respectively (p < 0.001). Symptoms (cough, sputum production, difficulty with expectoration, and dyspnea) evaluated using the VAS improved significantly after stent removal. No complications were encountered during removal. CONCLUSION: Removal of unnecessary airway stents improves pulmonary function and respiratory symptoms. Any stent that is no longer functioning should be removed.