Effect of Adding Inhaled Corticosteroid to Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist Therapy Among Patients With Chronic Obstructive Pulmonary Disease.

Background The role of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) is unclear. Hence, this study aimed to evaluate the efficacy of ICS as an add-on to long-acting muscarinic antagonist (LAMA)/long-acting beta 2 agonist (LABA), which was assessed using the impulse oscillation system (IOS), in patients with COPD. Methodology We included patients with COPD whose treatment was changed from LAMA/LABA (≥four weeks) to ICS/LAMA/LABA between April 2019 and March 2021. To gain insight into the effect and safety of ICS-containing triple therapy for COPD, pulmonary function; Short-Form 36, St. George's Respiratory Questionnaire, COPD Assessment Test, and modified Medical Research Council scores; and airway resistance assessed using the IOS from one week before LAMA/LABA was switched to ICS/LAMA/LABA therapy until more than eight but less than twelve weeks after switching were evaluated. Results In total, 46 patients with COPD (mean age: 72.28 ± 7.81 years) were included in the study. None of the pulmonary function test parameters significantly changed from baseline values (mean difference in forced expiratory volume in one second [FEV1.0]: +0.032, P = 0.12; percentage FEV1.0 [FEV1.0%]/forced vital capacity [FVC]: -0.58, P = 0.42; and FVC: +0.087, P = 0.058). Meanwhile, the IOS showed that resonant frequency (mean difference from baseline: -2.12, P < 0.0001) and bodily pain scores in the St. George's Respiratory Questionnaire (mean difference: -7.03, P = 0.031) significantly decreased. Conclusions Switching from LAMA/LABA to ICS/LAMA/LABA therapy reduces airway elasticity-to-inertial resistance ratios, which may lead to structural airway improvements in patients with COPD.

Severe Pneumonitis with Alveolar Hemorrhage Associated with Herbal Medicines: A Case Report.

We report a case of pneumonitis with alveolar hemorrhage induced by herbal medicines in a 73-year-old woman who was admitted to our hospital because of dyspnea and an abnormal shadow on a chest radiograph. She had received treatment with numerous drugs, including the herbal medicines Seisin-renshi-in, Chotosan, Rikkunshi-to, and Shakuyakukannzo-to. Chest radiography revealed diffuse ground-glass shadows in both lungs, and bronchoalveolar lavage fluid was progressively hemorrhagic. A culture of the fluid showed no evidence of microorganisms. Moreover, there were no findings suggestive of rheumatic disease or vasculitides. On the basis of this evidence, we suspected drug-induced diffuse alveolar hemorrhage. She discontinued all medicines and started treatment with corticosteroids. Her respiratory condition and chest radiographic findings improved. The timing of administration and rechallenge with other drugs suggested that the herbal medicines were the causative drugs. The primary concern was Seisin-renshi-in, because it contains Ougon (skullcap; a known cause of pneumonitis) and because a drug lymphocyte stimulation test was positive for Seisin-renshi-in. This is the first report indicating that Seisin-renshi-in may cause diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage due to herbal medicines is a rare but emergent disorder. Therefore, treating physicians should be aware that it may be caused by herbal medicines, including Seisin-renshi-in.

Anti-MDA5 antibody-positive rapidly progressive interstitial pneumonia without cutaneous manifestations.

A 47-year-old man was referred to our hospital with a 1-month history of fever and dyspnea after inhalation of insecticide in a confined space. We diagnosed rapidly progressive interstitial pneumonia. High-dose methylprednisolone, tacrolimus, and intermittent infusion of cyclophosphamide were administered. His condition rapidly deteriorated; therefore, extracorporeal membrane oxygenation therapy was performed. Unfortunately, he died 69 days after admission. Although typical skin findings suggestive of dermatomyositis were absent, anti-melanoma differentiation-associate gene (anti-MDA5) antibody was positive. Our findings suggest that in patients with hyperferritinemia and rapidly progressive interstitial lung disease (RP-ILD) demonstrating random ground glass shadows and peripheral consolidations by high-resolution computed tomography (HRCT) even if skin manifestations related to dermatomyositis are not complicated, we should assume anti-MDA5 antibody-positive interstitial pneumonia.

ß-Catenin-dependent transcription is central to Bmp-mediated formation of venous vessels.

ß-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that ß-catenin is required for vascular development. However, the precise function of ß-catenin-mediated gene regulation in vascular development is not well understood, since ß-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of ß-catenin transcriptional activity specifically in ECs and discovered that ß-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels. During caudal vein (CV) formation, Bmp induces the expression of aggf1, a putative causative gene for Klippel-Trenaunay syndrome, which is characterized by venous malformation and hypertrophy of bones and soft tissues. Subsequently, Aggf1 potentiates ß-catenin transcriptional activity by acting as a transcriptional co-factor, suggesting that Bmp evokes ß-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated activation of ß-catenin induces the expression of Nr2f2 (also known as Coup-TFII), a member of the nuclear receptor superfamily, to promote the differentiation of venous ECs, thereby contributing to CV formation. Furthermore, ß-catenin stimulated by Bmp promotes the survival of venous ECs, but not that of arterial ECs. Collectively, these results indicate that Bmp-induced activation of ß-catenin through Aggf1 regulates CV development by promoting the Nr2f2-dependent differentiation of venous ECs and their survival. This study demonstrates, for the first time, a crucial role of ß-catenin-mediated gene expression in the development of venous vessels.