Decreased soluble RAGE in neutrophilic asthma is correlated with disease severity and RAGE G82S variants.

The advanced glycosylation end product-specific receptor (RAGE) has been demonstrated to be an important mediator of asthma pathogenesis. The soluble isoform of RAGE (sRAGE) acts as a 'decoy' to sequester RAGE ligands, and thus prevents their binding to the receptor. A number of reports have linked deficiency of sRAGE to the severity and outcomes of various human diseases, and association with RAGE G82S variants. However, whether sRAGE levels are increased or decreased in asthmatic patients is unclear. The aim of the present study was to determine plasma sRAGE levels in different asthma phenotypes and associations of plasma sRAGE levels with RAGE G82S variants. A total of 85 neutrophilic and 109 non­neutrophilic newly diagnosed asthmatic patients, and 118 healthy controls, were recruited. Plasma sRAGE levels were measured by ELISA analysis. RAGE G82S genotypes were detected using the Sanger sequencing method. Plasma sRAGE levels were decreased in neutrophilic asthmatics (443.67±208.9 pg/ml) and increased in non­neutrophilic asthmatics (677.63±300.75 pg/ml) compared with healthy controls (550.02±300.83 pg/ml) (P<0.001). Plasma sRAGE levels were positively correlated with FEV1% predicted (FEV1% Pre) (rp=0.258; P=0.023) in neutrophilic asthmatics. The frequency of G82S genotypes was significantly different between neutrophilic and non­neutrophilic asthmatics (P=0.009). Neutrophilic asthmatics with genotypes A/G or A/A (389.83±150.37 and 264.59±161.74 pg/ml, respectively) had significantly decreased sRAGE levels compared with the G/G genotype (498.64±235.37 pg/ml) (P=0.022). Those with the A/G and A/A genotype (60.14±22.36%) displayed a trend toward lower FEV1% Pre compared with those with the G/G genotype (64.51±27.37%). No significant difference in sRAGE levels or an association with FEV1% Pre was observed between the different genotypes in non­neutrophilic asthmatics. In conclusion, the results of the present study indicated that plasma sRAGE levels are altered in different asthma inflammatory phenotypes. Plasma sRAGE may be a biomarker of asthma severity and may be associated with G82S gene variants in neutrophilic asthmatics.

A case report of PVOD patient combined with pulmonary embolism: Anticoagulation or not?

RATIONALE: Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH). Oral anticoagulation is confined to patients with idiopathic PAH (IPAH), but no oral anticoagulation has been recommended for PVOD, because occult pulmonary hemorrhage was a common finding in PVOD. PATIENT CONCERNS: We report a case of PVOD, who was misdiagnosed as IPAH for 5 years with worsening dyspnea and two episodes of pulmonary embolism (PE). DIAGNOSES: He was confirmed as PVOD combined with PE by biopsy of the explanted lung specimen. INTERVENTIONS: He took oral anticoagulation, warfarin, to treat his first-time PE in July 2010, and his disease was kept stable for about 4 years, until he discontinued the anticoagulation therapy by himself sometime in 2014. Later on, a life-threatening PE recurred in January 2015, so he resumed the anticoagulation therapy. OUTCOMES: Fortunately, the bilateral sequential lung transplantation that was performed in July 2015 in time saved his life. He has been living well without dyspnea and the echocardiography showed the normalizations of the once increased pulmonary arterial pressure and the once enlarged right ventricle of his heart. In addition, to the best of my knowledge, he was the first PVOD patient receiving lung transplantation in China. LESSONS: We recommend that PVOD patients combined with PE should be treated with anticoagulation therapy indefinitely to prevent the recurrence of life-threatening PE until they get a chance for lung transplantation.