In the 1980s, randomized-controlled trials showed that high-dose corticosteroid treatment did not improve the mortality of acute respiratory distress syndrome (ARDS). However, while the diagnostic criteria for ARDS have since changed, and supportive therapies have been improved, no randomized-controlled trials have revisited this issue since 1987; thus, the effect of high-dose corticosteroid treatment may be different in this era. We evaluated the effect of high-dose corticosteroid treatment in patients with ARDS using a nationwide administrative database in Japan in a retrospective and observational study. This study was performed with a large population using the 2012 Japanese nationwide administrative database (diagnostic procedure combination). We evaluated the mortality of ARDS patients receiving or not receiving high-dose corticosteroid treatment within 7 days of hospital admission. We employed propensity score weighting with a Cox proportional hazards model in order to minimize the bias associated with the retrospective collection of data on baseline characteristics and compared the mortality between the high-dose and non-high-dose corticosteroid groups. Data from 2707 patients were used; 927 patients were treated with high-dose corticosteroid and 1780 patients were treated without high-dose corticosteroid, within 7 days of admission. After adjusting for confounds, mortality rates within 3 months were significantly higher in the high-dose corticosteroid group compared to the non-high-dose corticosteroid group (weighted hazard ratio: 1.59; 95% CI: 1.37-1.84; P < 0.001). Our results suggest that high-dose corticosteroid treatment does not improve the prognosis of patients with ARDS, even in this era. However, this study has limitations owing to its retrospective and observational design.

Rationale: Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. Objectives: To determine the role of NOSs in BM cells in PH. Methods: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)^−/−, iNOS (inducible NOS)^−/−, eNOS (endothelial NOS)^−/−, and n/i/eNOSs^−/− mice. Measurements and Main Results: In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSs^−/− genotype and, to a lesser extent, in the eNOS^−/− genotype as compared with the WT genotype. In the n/i/eNOSs^−/− genotype exposed to hypoxia, the number of circulating BM-derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein–transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs^−/−-BM transplantation significantly aggravated hypoxia-induced PH in the WT genotype, and WT-BM transplantation significantly ameliorated hypoxia-induced PH in the n/i/eNOSs^−/− genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs^−/−-BM compared with those with WT-BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia-induced PH caused by n/i/eNOSs^−/−-BM transplantation. Conclusions: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.

We herein present a case of Good syndrome complicated by diffuse pulmonary lesions similar to diffuse panbronchiolitis (DPB). A 45-year-old Japanese man was referred to our department due to recurrent lower respiratory tract infections that had started and ameliorated nine months after thymectomy for pure red cell aplasia and myasthenia gravis. Diffuse centrilobular opacities on chest computed tomography and positivity for HLA-B54 were consistent with DPB. Additionally, hypogammaglobulinemia and a marked decrease of B-lymphocytes were observed, and therefore Good syndrome was considered. Combination therapy with azithromycin and clarithromycin alleviated the patient's respiratory symptoms and reduced the exacerbation of chronic bronchitis.

The system of nitric oxide synthases (NOSs) is comprised of three isoforms: nNOS, iNOS, and eNOS. The roles of NOSs in respiratory diseases in vivo have been studied by using inhibitors of NOSs and NOS-knockout mice. Their exact roles remain uncertain, however, because of the non-specificity of inhibitors of NOSs and compensatory up-regulation of other NOSs in NOS-KO mice. We addressed this point in our triple-n/i/eNOSs-KO mice. Triple-n/i/eNOSs-KO mice spontaneously developed pulmonary emphysema and displayed exacerbation of bleomycin-induced pulmonary fibrosis as compared with wild-type (WT) mice. Triple-n/i/eNOSs-KO mice exhibited worsening of hypoxic pulmonary hypertension (PH), which was reversed by treatment with sodium nitrate, and WT mice that underwent triple-n/i/eNOSs-KO bone marrow transplantation (BMT) also showed aggravation of hypoxic PH compared with those that underwent WT BMT. Conversely, ovalbumin-evoked asthma was milder in triple-n/i/eNOSs-KO than WT mice. These results suggest that the roles of NOSs are different in different pathologic states, even in the same respiratory diseases, indicating the diversity of the roles of NOSs. In this review, we describe these previous studies and discuss the roles of NOSs in respiratory health and disease. We also explain the current state of development of inorganic nitrate as a new drug for respiratory diseases.

Diffuse alveolar hemorrhaging (DAH) due to oral anticoagulation (OAC) is a life-threatening condition that leads to severe respiratory failure. There is a clinical dilemma in that OAC-induced DAH often forces the discontinuation of OAC therapy and the administration of high-dose corticosteroids, which increases the risk of stroke and cardiovascular events. We herein report the first case of OAC-induced DAH and atrial fibrillation (AF) in a patient who completely discontinued OAC therapy and high-dose corticosteroids after experiencing percutaneous left atrial appendage (LAA) occlusion. This case suggests that percutaneous LAA closure may aid in the management of OAC-induced DAH and AF.