Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

Skeletal muscle is associated with exercise tolerance evaluated by cardiopulmonary exercise testing in Japanese patients with chronic obstructive pulmonary disease.

Decreasing exercise tolerance is one of the key features related to a poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cardiopulmonary exercise testing (CPET) is useful for evaluating exercise tolerance. The present study was performed to clarify the correlation between exercise tolerance and clinical parameters, focusing especially on the cross-sectional area (CSA) of skeletal muscle. The present study investigated 69 patients with COPD who underwent CPET. The correlations between oxygen uptake ([Formula: see text]) at peak exercise and clinical parameters of COPD, including skeletal muscle area measured using single-section axial computed tomography (CT), were evaluated. The COPD assessment test score (ρ = - 0.35, p = 0.02) was weakly correlated with [Formula: see text] at peak exercise. In addition, forced expiratory volume in one second (FEV1) (ρ = 0.39, p = 0.0009), FEV1/forced vital capacity (ρ = 0.33, p = 0.006), and the CSA of the pectoralis muscles (PMs) (ρ = 0.36, p = 0.007) and erector spinae muscles (ECMs) (ρ = 0.39, p = 0.003) were correlated with [Formula: see text] at peak exercise. Multivariate analysis adjusted by age and FEV1 indicated that PMCSA was weakly correlated after adjustment (ß value [95% confidence interval] 0.175 [0.03-0.319], p = 0.02). In addition, ECMCSA tended to be correlated, but not significantly after adjustment (0.192 [- 0.001-0.385] p = 0.052). The COPD assessment test, FEV1, FEV1/FVC, PMCSA, and ECMCSA were significantly correlated with [Formula: see text] at peak exercise.

First-Line Treatment with Tiotropium/Olodaterol Improves Physical Activity in Patients with Treatment-Naïve Chronic Obstructive Pulmonary Disease.

Background: Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD). We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients. Methods: A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted. Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment. Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment. Results: There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups. Changes in FEV1 (mean±standard error, 242.8±28.8 mL) and transient dyspnea index (TDI) (2.4±0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1±31.9 mL, p<0.01 and 1.5±0.3, p=0.02, respectively). Changes in the duration of physical activity with 1.0-1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (-38.7±14.7 min) tended to be reduced more than with tiotropium treatment (-4.6±10.6 min) (p=0.06), although those with ≥2.0 METs numerically increased with both treatments (+10.8±7.6 min for tiotropium/olodaterol vs +8.3±7.6 min for tiotropium, p=0.82). Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0-1.5 METs (regression coefficient, -43.6 [95% CI -84.1, -3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI. Conclusion: This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI.

Mesalazine-induced airway obstruction: Utility of pulmonary function testing in drug-induced lung diseases.

Mesalazine is a standard therapeutic agent for the treatment of inflammatory bowel diseases. A rare case of mesalazine-induced airway obstruction documented by pulmonary function testing is reported herein. The patient had Crohn's disease and was treated with mesalazine; she subsequently developed a high fever, cough, and chest pain with centrilobular nodular shadows on chest computed tomography (CT). After cessation of mesalazine, the abnormal CT findings as well as the decreased forced expiratory volume in 1 second improved. Based on these findings, pulmonary function testing appears to be a useful tool, even in the acute phase, along with chest CT in drug-induced lung diseases.

[A case of sarcoidosis with severe bronchial stenosis and right ventricular dilatation].

A 32-year-old woman visited another hospital complaining of productive cough and fever at the beginning of February 2006. Her symptoms improved after the administration of antibiotics, while infiltration shadows on chest radiographs remained unchanged. Bronchoscopic examination revealed stenosis of the left upper division bronchus, while lung biopsy was negative. She was referred to Saga University Hospital for further examination. Bronchoscopy on August 14th showed severe stenosis of the left upper division and lingular bronchi. Her illness was diagnosed as sarcoidosis on the basis of non-caseating granulomas seen in biopsy specimens from the bronchial wall and the periphery of the left upper division bronchus. Pulmonary function test revealed a marked decrease of vital capacity, while the FEV1.0/FVC ratio was 81%. Arrhythmia on electrocardiogram and marked right ventricular enlargement on cardiography were noted. We diagnosed cardiac sarcoidosis on the basis of gallium scintigraphy, thalium scintigraphy and cardiac MRI findings. We report the rare presentation of sarcoidosis with stenosis of proximal airways and marked dilatation of the right ventricle.

Relationship between the duration of trimethoprim/sulfamethoxazole treatment and the clinical outcome of pulmonary nocardiosis.

BACKGROUND: Despite treatment, pulmonary nocardiosis, which is a rare opportunistic disease caused by Nocardia species, has poor clinical outcomes including recurrence and death. Currently, the treatment regimen and duration for pulmonary nocardiosis are not fully understood. The present study aimed to clarify the factors related to the clinical outcome of pulmonary nocardiosis. METHODS: The medical records of 24 patients with pulmonary nocardiosis were retrospectively reviewed. The patients were divided into two groups based on the outcomes within 2 years: patients with controlled disease (n = 14) and patients who developed recurrence or died (n = 10). RESULTS: Nocardia was identified by 16S ribosomal RNA sequencing in 17 patients (70.8%) and by conventional biochemical test in five patients (20.8%). The patients' characteristics, clinical findings, radiological features, and treatment history were not different between the two groups. Compared with patients who developed recurrence or died, those with controlled disease had significantly longer total duration of treatment with antibiotics, especially trimethoprim/sulfamethoxazole (67.5 ± 111.6 days vs. 9.0 ± 6.5 days; p = 0.01). Pancytopenia was the most frequent adverse effect of trimethoprim/sulfamethoxazole. CONCLUSIONS: Longer duration of trimethoprim/sulfamethoxazole treatment was significantly associated with better outcomes of pulmonary nocardiosis. In such cases, antibiotics, especially trimethoprim/sulfamethoxazole, should be administered for more than 3 months.

Signet Ring Cell Carcinoma of Unknown Primary Complicated with Pulmonary Tumor Thrombotic Microangiopathy and Krukenberg Tumor.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare disease that shows hypoxia with severe pulmonary hypertension related to malignant tumor. Diagnosis is difficult due to rapid clinical progression and the need to demonstrate pathological findings from lung biopsy. A 64-year-old woman visited our hospital with hypoxia and pulmonary hypertension. Diffuse granular shadows in the centrilobular area and ground-glass shadows in both lungs and left ovarian tumor were found on radiological imaging. PTTM was suspected, but pulmonary artery blood aspiration by right cardiac catheter failed to detect cancer cells. We could not obtain lung or ovary biopsies because of hypoxia or pulmonary hypertension. The patient died due to respiratory failure. Signet ring cell carcinoma of unknown primary, PTTM, and Krukenberg tumor were diagnosed on autopsy. Since early diagnosis facilitates adequate treatment, physicians should not miss the opportunity for biopsy in cases of suspected PTTM.

A case of osimertinib-resistant lung adenocarcinoma responded effectively to alternating therapy.

We report a case of initial lung adenocarcinoma in which transformation to small cell lung carcinoma (SCLC) was observed after acquired resistance to the 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib and alternating treatment between chemotherapy and osimertinib was effective. A 61-year-old woman with EGFR mutation positive stage IV lung adenocarcinoma was administered 1st generation EGFR-TKI for 8 months as the first line therapy, then chemotherapy and 2nd generation EGFR-TKI after progressive disease (PD). Four years after initial diagnosis, EGFR T790M was detected in a metastatic lesion of the right thoracic wall and osimertinib was prescribed. Although partial response (PR) was achieved, a new metastatic lesion appeared in the right pleurum near the diaphragm, in which SCLC characteristics were observed with elevation of pro-gastrin-releasing peptide (pro-GRP) at the time of PD under osimertinib. Osimertinib was discontinued and carboplatin plus irinotecan chemotherapy was chosen as the next treatment, leading to PR after 2 cycles. Subsequently, the right thoracic wall tumor harboring T790M and the right pleural tumor near the diaphragm showing transformation to SCLC exhibited opposite responses to therapy alternating between osimertinib and chemotherapy. It is concluded that extended disease control can be achieved by combining appropriate treatments according to the mechanisms of resistance inferred from precise genetic and pathological examination in real time.

Primary Pulmonary Colloid Adenocarcinoma: How Can We Obtain a Precise Diagnosis?

A 76-year-old asymptomatic man was found to have a mass in the right lower lung field. Although the presence of a mucinous component in the majority of the tumor was shown by magnetic resonance imaging, the presence of cancer cells was suspected by contrast enhancement on computed tomography (CT) and based on the partial accumulation in the marginal regions of the tumor on fluorodeoxyglucose-positron emission tomography (FDG-PET). A transbronchial lung biopsy was non-diagnostic, but resection of the mass resulted in a diagnosis of colloid adenocarcinoma. The findings from combined contrast CT and FDG-PET may raise the suspicion of colloid adenocarcinoma and prompt the consideration of surgical resection.

[A case of pulmonary artery pseudoaneurysm secondary to lung abscess].

A 53-year-old man visited his family doctor complaining of chest pain and cough in January 2006. He had a 5-year history of uncontrolled diabetes mellitus. His illness was diagnosed as pneumonia of the left lingular division. Antibiotics were started but his pneumonia worsened repeatedly after insufficient antibiotics due to his poor compliance with medication. In addition to pneumonia, he began to have hemoptysis at the end of May and was admitted to our hospital. Contrast-enhanced CT scan on admission showed a lung abscess on the left lingular division and formation of a pulmonary pseudoaneurysm inside the abscess. Treatment with SBT/ABPC rapidly improved his condition but massive hemoptysis recurred 9 days after admission. Embolization of the bronchial artery and pulmonary pseudoaneurysm successfully controlled airway bleeding. When hemoptysis occurs due to sustained inflammation such as a lung abscess, bleeding from the pulmonary artery should be considered and a precise evaluation including contrast-enhanced CT and pulmonary angiography made.

Characteristics and prognosis of microscopic polyangiitis with bronchiectasis.

BACKGROUND: Major pulmonary manifestations associated with microscopic polyangiitis (MPA) include diffuse alveolar hemorrhage (DAH) and interstitial pneumonia (IP).We previously showed bronchiectasis (BE) was one of the pulmonary complications of MPA. However, clinical features of BE patients with MPA are not fully understood. We investigated the characteristics and prognosis of BE patients with MPA. METHODS: Forty-five MPA patients were retrospectively studied. The patients were divided into two groups: patients with BE and those without BE. RESULTS: Thirty-one of 45 patients (69%) had pulmonary involvement including IP (23/45, 51%), BE (7/45, 16%), and DAH (5/45, 11%). There were no differences between the patients with BE versus those without with regard to clinical characteristics and initial treatments. However, the prognosis for patients with BE was better than those without BE during the first year after diagnosis, but it was worse between 1 and 5 years, which was statistically significant. Two BE patients died between 1 and 5 years as a result of pneumonia. CONCLUSIONS: BE as a complication of MPA might be related to lower mortality in the acute phase and higher mortality in the chronic phase compared to other pulmonary manifestations. More attention to pulmonary infection is needed for patients with BE during the chronic phase.

Disseminated infection by Bipolaris spicifera in an immunocompetent subject.

We report a case of disseminated infection due to Bipolaris spicifera in an immunocompetent male. Histopathological studies of lymph node, lung, and liver biopsy specimens showed a dark pigmented, granular fungal structure inside the granuloma. The disease was accompanied by the unusual feature of positive lupus anticoagulant in serum and low-density areas expanding along the portal vein in the liver. The disease responded to combination therapy with intravenous amphotericin B and voriconazole, but recurred during oral itraconazole. The fungal isolate from the lymph node was identified as Bipolaris spicifera on the basis of morphology and molecular biological data.

High-resolution computed tomography characterization of interstitial lung diseases in polymyositis/dermatomyositis.

OBJECTIVE: Interstitial lung disease (ILD) associated with polymyositis (PM) and dermatomyositis (DM) sometimes progresses rapidly and is resistant to therapy. Clinical features that forecast the prognosis of the disease remain to be elucidated. Our aim was to assess if selected clinical features and high-resolution computed tomography (HRCT) findings can assist in predicting the clinical course of ILD in PM/DM. METHODS: We examined HRCT findings retrospectively for ILD identified in 17 patients with PM and 16 with DM. Radiological patterns and clinical features are analyzed in comparison with clinical course. RESULTS: Mortality rates were 12% and 44% for ILD associated with PM and DM, respectively. Most patients with DM died of rapidly progressive lung deterioration. No patient in the PM group died of respiratory failure. In the DM group, all patients with fatal ILD had ground-glass attenuation and reticular opacity as the principal radiological findings. Consolidation was recognized frequently as the principal pattern in nonfatal cases. Radiological patterns were categorized into 3 groups; A: consolidation dominant, B: ground-glass attenuation/reticular opacity dominant without chronic fibrosing process, and C: ground-glass attenuation/reticular opacity dominant with chronic fibrosing process. Occurrences of fatal disease were 0%, 83%, and 20%, in groups A, B, and C. CONCLUSION: The prognosis of ILD associated with DM differs from that with PM. The former can be classified into 3 subgroups on the basis of radiological findings, which are closely associated with clinical course.