Growing evidence suggests that long non-coding RNAs (lncRNAs) play a key role in the pathogenesis of asthma. Although some differentially expressed lncRNAs have been identified in asthmatic patients, many asthma-related lncRNAs have not been annotated. In the present study, six patients and three healthy subjects were randomly selected from 34 asthmatic patients and 17 healthy subjects. Second-generation high-throughput sequencing was performed on their peripheral blood samples. There were 1,137 differentially expressed lncRNAs in the asthma patients compared to in the healthy controls, of which 485 were upregulated and 652 were downregulated. The top 30 enriched GO and KEGG terms were identified, and the cytosolic ribosome (GO:0022626) and ribosome (hsa03010) were associated with the most differentially expressed lncRNAs. The top 10 differentially expressed lncRNAs associated with asthma were verified by an lncRNA-mRNA co-expression network and RT-qPCR. Seven of the these  were down-regulated in the peripheral blood of asthmatic patients, which was consistent with the sequencing results. Three patients and three healthy subjects were randomly selected from the remaining subjects to verify these seven lncRNAs by RT-qPCR, which further confirmed the sequencing results. Public database GSE106230 was also in agreement with the FPKM (Fragments Per kilobase of exon model per Million mapped reads) trends of ENST00000564809, NONHSAT015495.2, NONHSAT181891.1, and NONHSAT190964.1. In conclusion, the present study identified seven lncRNAs that may serve as potential biological markers for asthma. Asthma is a heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling , and affLong non-coding RNAs (lncRNAs) are a type of non-coding RNA that are >200 nucleotides in length, and can interact with proteins, DNA, or RNA . LncRNAsWith the recent development and continuous improvement of second-generation high-throughput sequencing technology, current transcriptomics research depends on accurate and rapid screening for relevant lncRNAs that are related to specific diseases. An increasing number of lncRNAs have been functionally annotated. Although studies have reported some differences in lncRNAs in asthma patients during both childhood  and adulSubjects were patients with asthma who attended the Outpatient of Integrative Medicine, Huashan Hospital, Fudan University (from 1 November 2019 to 31 January 2020), and healthy volunteers who were recruited through clinical research recruitment advertisements. According to the inclusion and exclusion criteria (detailed below), a total of 34 subjects in the asthma group and 17 subjects in the healthy control group were included. Each subject signed an informed consent form.The diagnostic criteria for asthma were based on the 2016 Chinese Medical Association Respiratory Diseases Association Bronchial Asthma Prevention and Control Guidelines. 1) Clinical symptoms and signs of typical asthma: recurrent wheezing, shortness of breath, with or without chest tightness or coughing, especially at night and in the morning, and often attacks after exposure to allergens such as cold air, physical or chemical irritation, upper respiratory tract infection, or exercise. Sporadic or diffuse wheezing can be heard in both lungs during attack, with a predominant expiratory phase and prolonged expiratory phase. The above symptoms or signs are relieved spontaneously or after treatment. 2) Objective inspection of variable airflow limitation: 1) a positive bronchial diastolic test with an increase in FEV between 1% > 12% after bronchodilator inhalation, and an increase in absolute FEV between 1 > 200 ml 2) A positive bronchial provocation test. 3) Peak expiratory flow (PEF) average daily diurnal variation rate of >10% or weekly PEF variation rate of >20%. 4) The patient meets the “typical clinical symptoms and signs of asthma,” and has any of the “objective examinations of variable airflow limitation,” and wheezing, shortness of breath, chest tightness, or cough caused by other diseases are excluded.(1) Diagnosed as bronchial asthma according to 2016 Respiratory Diseases Association Bronchial Asthma Prevention and Control of Chinese Medical Association and Guidelines and 2019 Global Initiative for Asthma (GINA) guidelines (2) The selected age range was 30–55 years, regardless of gender. (3) No history of respiratory diseases, except for asthma. (4) No upper/lower respiratory tract infections and no antibiotic treatment within 4 weeks; no oral/intravenous glucocorticoid treatment or other respiratory medication except Inhaled Corticosteroids/Long-Acting Beta2 Agonist (ICS/LABA) and Short-Acting Beta2-Agonists (SABA) within 4 weeks. (5) No smoking history or had quit smoking for more than 12 months. (6) Voluntarily participated in the study and signed informed consent forms.(1) The selected age range was 30–55 years, regardless of gender. (2) The physical examination results were normal, without any abnormal symptoms or signs. (3) Laboratory/imaging examination results were normal or abnormal, but had no clinically meaningful results. (4) No smoking history or had quit smoking for more than 12 months. (5) Voluntarily participated in the study and signed informed consent forms.tuberculosis, pulmonary embolism, pleural effusion, or other lung diseases. (3) Patients with cardiovascular, cerebrovascular, digestive, endocrine, kidney, urinary, blood, and other systemic diseases or malignant tumors. (4) Patients who received antibiotic treatment within 4 weeks of the study. (5) Patients requiring treatment with glucocorticoids or immunosuppressive agents. (6) Patients who have been pregnant or breast fed within 12 months (8) Patients participating in other clinical studies during the same period. (9) Patients who refused to sign informed consent forms.(1) Patients with severe persistent and acute exacerbation of asthma requiring oral or intravenous corticosteroid treatment. (2) Patients with COPD, bronchiectasis, interstitial lung disease, active (1) Subjects who received antibiotics or glucocorticoid therapy within 4 weeks of the study. (2) Subjects who had been pregnant or had breast fed within 12 months. (3) Subjects participating in other clinical studies during the same period. (4) Subjects who refused to sign informed consent forms.This single-center, prospective, and exploratory clinical study was approved by the Ethical Review Committee of Huashan Hospital Affiliated to Fudan University. Ethical approval number (2019). Temporary Approval No (593). The study was registered with the China Clinical Trial Registration Center, clinical research registration number: ChiCTR2000031267. The study was performed according to the guidelines established by the Declaration of Helsinki.Detailed clinical consultations were conducted on asthma patients and healthy subjects, with a comprehensive physical examination performed, including body temperature, pulse, respiration, blood pressure, weight, and height. Medical histories, including allergies and other medical conditions, were obtained to confirm the asthma diagnosis. Routine blood, urine, liver and kidney function, blood sugar, peripheral blood EOS count, blood total IgE, lung function, and FeNO tests were performed for all subjects.Both lung function and FeNO tests were performed between 8:00–11:00 a.m. Subjects were required to stop vigorous activities for 2 h before the test and stay at rest for 15 min. Patients with asthma were tested before the administration of asthma control drugs. Both lung function and FeNO measurement were tested using the Pulmonary Function Room at Huashan Hospital Affiliated to Fudan University.Venous blood (4 ml) was collected from fasting subjects before 8:00 a.m., and centrifuged at 4,000 rpm for 10 min at room temperature to separate red blood cells and serum. The serum was removed and stored in 2 ml Eppendorf tubes at −80°C. An ELISA was used to detect serum inflammatory factors  and eotaxin.® 2.0 Fluorometer  was used to detect DNA concentration. A 2100 Bioanalyzer (Agilent Technologies) was used to detect the band distribution, and then cluster generation and first-direction sequencing primer hybridization were performed on the cBot for the Illumina sequencing platform, according to the manufacturer’s instructions. The Illumina sequencing reagents were prepared according to manufacturer’s instructions, and a patterned flow cell was used for improved cluster generation. Paired-end sequencing was performed using Illumina software, with real-time data analysis.Venous blood (2.5 ml) was collected from fasting subjects before 8:00 a.m. Each sample was collected in a disposable vacuum blood RNA collection tube, mixed well, and stored at −80°C. An RNEasy micro kit and RNase-Free DNAse kit were used for the extraction and purification of total RNA, according to the manufacturer’s instructions. A NanoDrop ND-2000 spectrophotometer and Agilent Biochemical Analyzer 2,100 were used to determine RNA quality by measuring RNA integrity number (RIN). The RIN values ranged from to 0 to 10, with higher scores indicating better RNA integrity. RNA samples that passed the quality assessment were used as the templates for first and second strand cDNA synthesis. A QubitSeqtk was used to filter the original data to obtain clean reads for data analysis. The spliced mapping algorithm HISAT2 (version 2.0.4) was used for genome mapping of preprocessed sequences. The human GRCh37 assembly (Ensembl) was used for genome mapping. StringTie software (version 1.3.0) was used to count the number of fragments corresponding to each gene after HISAT2 comparison, and then normalized to the trimmed mean M values (TMM)  for each gene.p-value, multiple testing correction was applied, and the p-value threshold was determined by controlling the false discovery rate (FDR), and expressed as a q-value. The fold change (FC) was calculated based on the FPKM value. Cutoffs of q-value ≤ 0.05, and FC ≥ 2 were applied to filter for differentially expressed genes. The differentially expressed genes (DEGs) were mapped to the GO database, and the number of genes corresponding to each entry was calculated. KEGG pathway enrichment analysis was performed similarly for the DEGs. Differentially expressed lncRNAs were sorted in descending |log2FC| value, and the top 50 dysregulated lncRNAs were identified. KEGG pathways related to asthma with a large number of differentially expressed genes were selected, and the mRNAs enriched in these pathways were selected to generate an lncRNA-mRNA co-expression network and identify biologically relevant lncRNAs.The edgeR R package was used to comparatively analyze the differentially expressed genes between the sample groups. After obtaining the −ΔΔCT method was used to analyze the relative changes in gene expression, with GAPDH serving as the internal reference. Primer sequences and related information were included in PCR primers were designed using Primer Express 3.0.1 software, synthesized by Sangon Biotech Co., Ltd  and verified by Primer-BLAST. The 2t-test was used to analyze continuous variables that conformed to a normal distribution, and data are presented as the mean ± standard deviation. Data that did not conform to a normal distribution were log2 transformed, and analyzed by t-test. If the log2 transformed data did not conform to a normal distribution, a Wilcoxon test was used, and the median and interquartile intervals were used for statistical analysis. A Chi-squared test was used to compare categorical variables. Differences were considered to be statistically significant at p < 0.05.Statistical analysis was performed using SPSS 25.0 (IBM), and plots were generated using GraphPad 8.0 . A p < 0.001), with more female patients (85.29%) than male patients (14.71%) in the asthma group. There were no statistically significant differences between the two groups in terms of age and BMI (p > 0.05)  and the healthy control group (n = 17), such as age, sex, and BMI, were compared to exclude any potential sources of bias from the subsequent analysis. There was a difference in gender composition between the asthma group and the healthy control group ( > 0.05) .p < 0.05). Compared with healthy subjects, asthma patients had higher FeNO (p < 0.05), total blood IgE (p < 0.05), peripheral blood EOS counts (p < 0.05), and serum IL-8 levels (p < 0.01). The levels of inflammatory cytokines IL-17A, IL-25, IL-33, and eotaxin were higher in the asthma group than in the healthy control group, but these differences were not significant, and there were no significant differences in the levels of IL-4, IL-5, IL-9, and IL-13 between the two groups  and small airway function indexes  of the healthy subjects were significantly better than those in the asthma group  were filtered to obtain the effective sequences (clean reads) that could be used for data analysis . We compWe performed correlation co-efficient analysis and principal component analysis (PCA) using the FPKM expression data. According to the expression correlation heat map, samples 18 and 19 of the asthma group were highly similar to samples 7 and 45 of the healthy control group, and the correlation coefficients were all >0.9. Other samples in the asthma group  and the healthy control group  had good intragroup similarity . Accordi2,290 mRNAs  and 1,137 lncRNAs (485 up-regulated and 652 down-regulated) were differentially expressed between asthma group and healthy control group. The cluster analysis was used for the similarly expressed mRNAs and lncRNAs, and the heatmaps were drawn. As shown in The transcript length, number of exons, and expression levels of differentially expressed lncRNAs and mRNAs were compared and analyzed. The length of the lncRNA transcripts was similar to that of mRNA. The proportion of lncRNA transcripts with ≤3 exons was significantly greater than that of mRNA. The average FPKM expression of each lncRNA and mRNA transcript was used to generate a box plot of log10 (FPKM+1). The expression levels of lncRNA were similar to those of mRNA but were more uniform in the expression range of 0–2.5 FPKM . This suWe next performed GO analysis using the DEGs identified by sequencing. Of the DEGs, 2,290 mapped on to 57 functional GO terms. Among these, 26 were related to biological processes, with cellular process (GO:0009987) being the most frequent, 17 were related to cellular component, mainly cell (GO:0005623) and cell part (GO:0044464), and 14 were related to molecular functions, mainly binding (GO:0005488) .We next performed GO enrichment analysis on the differentially expressed genes and selected the top 30 significantly enriched GO entries. As shown in We next performed KEGG pathway enrichment analysis on the differentially expressed genes between the two groups, and identified the top 30 enriched KEGG pathways. As shown in We filtered the top 50 upregulated lncRNAs  and the p = 0.535). The expression levels of the other 7 lncRNAs in the asthma group were all lower than in the healthy control group, which was consistent with the sequencing results, and the differences were statistically significant.We performed qPCR on peripheral blood samples from four asthma patients and three healthy subjects that were previously sequenced to verify the sequencing results. The gene sequence of lncRNA NONHSAT151355.1 overlaps completely with the mRNA sequence LAPTM5, and the gene sequence of lncRNA NONHSAT220907.1 overlaps completely with the mRNA sequence of UBQLN1, so specific primers could not be designed for these lncRNAs. Therefore, we designed specific primer sets for the remaining eight asthma-associated lncRNAs. As shown in p < 0.05)  were consistent with the trends observed in the sequencing dataset, and these differences were statistically significant (both  < 0.05) . Althoughttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106230, adults; GSE117038, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117038, adults), and the other two used microarrays to detect the expression of lncRNAs in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients .Next, we compared the expression of the 7 identified lncRNAs from the present study with their expression in four public databases in the Gene Expression Omnibus (GEO). Among these four databases, two of them performed lncRNA sequencing of whole blood from asthma patients  in the GSE106230 dataset were consistent with our results, although the differences were not statistically significant in that dataset. However, the FPKM value trends of the four differentially expressed lncRNAs  in the GSE117038 database, and two lncRNAs  in the GSE143192 database disagreed with the results of the present study. It is worth noting that samples used in the GSE106230 and GSE117038 databases (whole blood samples from adults), and the PBMC samples used in the GSE143192 database (children) did not match the sample type used in the present study, perhaps limiting the utility of this comparison.in vitro studies, which could also provide much-needed functional annotation for these potentially important lncRNAs.The present study had some limitations. As shown in In conclusion, we have identified a panel of putative asthma-associated lncRNAs , which may play a role in the pathogenesis of asthma, and may be useful as diagnostic or prognostic biomarkers in the clinical setting.


Hypertension occurred in 30–80% of Takayasu arteritis (TAK) patients around the world and the occurrence of hypertension might worsen the disease prognosis. This study aimed to investigate the clinical characteristics and imaging phenotypes, as well as their associations with events free survival (EFS) in Chinese TAK patients with hypertension.This current research was based on a prospectively ongoing observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University. Totally, 204 TAK patients with hypertension were enrolled between January 2013 and December 2019. Clinical characteristics and imaging phenotypes of each case were evaluated and their associations with the EFS by the end of August 30, 2020, were analyzed.p = 0.043). Furthermore, using cases with Cluster 1 imaging phenotype and controlled blood pressure as reference, better EFS was observed in patients with Cluster 2 phenotype and controlled blood pressure , while the case with Cluster 1 phenotype plus uncontrolled blood pressure  and those with Cluster 3 phenotype and uncontrolled blood pressure  suffered worse EFS.Severe hypertension accounted for 46.1% of the entire population. Three specific imaging phenotypes were identified: Cluster 1: involvement of the abdominal aorta and/or renal artery (27.5%); Cluster 2: involvement of the ascending aorta, thoracic aorta, the aortic arch, and/or its branches (18.6%); and Cluster 3: combined involvement of Cluster 1 and 2 (53.9%). Clinical characteristics, especially hypertensive severity, differed greatly among the three imaging clusters. In all, 187 patients were followed up for a median of 46 (9–102) months; 72 events were observed in 60 patients (1–3 per person). The overall blood pressure control rate was 50.8%, and the EFS was 67.9% by the end of the follow-up. Multivariate Cox regression indicated that controlled blood pressure , Cluster 1  and Cluster 3  imaging phenotype was associated with the EFS. Kaplan–Meier curves showed that patients with controlled blood pressure showed better EFS (Blood pressure control status and imaging phenotypes showed significant effects on the EFS for TAK patients with hypertension.The online version contains supplementary material available at 10.1186/s13075-021-02579-8. Takayasu arteritis (TAK) is a chronic inflammatory large-vessel vasculitis that primarily affects the aorta and its main branches –3. HyperTo our knowledge, few studies have focused on hypertension in the TAK population up to date. In a previous research, we reported that in patients with TAK-related renal artery stenosis, the prevalence of hypertension was up to 60%, with 30% refractory hypertensive cases . Except Thus, this study was designed to investigate the clinical characteristics and specific imaging phenotypes of TAK patients with hypertension and to point out the associations of the clinical characteristics and imaging phenotypes with the events free survival (EFS).https://redcap.zs-hospital.sh.cn).The present study was based on a prospectively ongoing observational cohort-the East China Takayasu Arteritis (ECTA) cohort, centered in Zhongshan Hospital, Fudan University, Shanghai, China. All patients enrolled into the ECTA cohort had a confirmed diagnosis of TAK based on the 1990 American College of Rheumatology (ACR) criteria . The demIn all, 204 TAK patients with hypertension, were enrolled in to the current research from the ECTA cohort between January 2013 and December 2019. Clinical characteristics and imaging features of each case were evaluated by professional rheumatologists. The main outcome of the investigation was the EFS by the end of August 30, 2020  was performed in 92/204 (45.1%) patients at clinic by using a noninvasive blood pressure monitor . For those without subclavian artery involvement, the reading from the arm with the higher value was used as the reference measurement. For patients with unilateral subclavian artery involvement, the reading from the unaffected side was analyzed, while for those with bilateral subclavian artery involvement, higher values of blood pressure of the lower limbs were used for analysis.The severity of hypertension was classified at baseline as previously reported : (i) milBlood pressure control status was classified as: (i) controlled: systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg; (ii) improved: SBP≥ 140 mmHg, but decreased by ≥ 20 mmHg and/or DBP ≥ 90 mmHg, but decreased by ≥ 10 mmHg; and (iii) failed: failed meeting the above-defined criteria . The bloImaging assessments, mainly the whole-body enhanced magnetic resonance angiography (MRA) or computed tomography angiography (CTA), were performed at the time of enrollment. Angiography findings were classified according to the classification by Numano et al. in 1996 .Diagnosis of AR was confirmed by echocardiography according to the guideline of the American Society of Echocardiography . The sevPatients, who completed at least 6 months of follow-up, were included in the outcome analysis. The occurrence of any events during the follow-up included (i) renal insufficiency including new occurrence, persistent insufficiency (≥ 6 months) or deterioration of renal function (≥ 20% increase in creatinine concentration or ≥ 20% decrease in glomerular filtration rate (GFR)); (ii) persistent refractory hypertension (≥ 6 months) or malignant hypertension; (iii) congestive heart failure including new occurrence or deterioration of heart function; (iv) new occurrence of cerebrovascular events; (v) arterial dissection or rupture of aneurysms; or (vi) TAK-related death .t tests, Wilcoxon tests, or one-way ANOVA. For variables with significant differences among three or more groups, pair-wise comparisons were further performed using Student’s t tests, Wilcoxon tests, or chi-square tests.Categorical variables were summarized as counts and percentages and were compared using chi-square or Kruskal–Wallis tests. Continuous variables are presented as means ± standard deviations (SD) or as medians with interquartile range (IQR), depending on the normality of distribution, and were compared using Student’s To identify specific imaging phenotypes for hypertensive TAK patients, 14 arteries including bilateral carotid arteries, brachiocephalic trunk, bilateral subclavian arteries, aortic arch, ascending aorta, thoracic aorta, pulmonary artery, abdominal aorta, bilateral renal artery, superior mesenteric artery, and celiac axis were included in the cluster analysis by a two-step progress as described previously . Tree dep < 0.05 was considered to indicate statistical significance.Cox proportional hazards regression model was used to evaluate associations of imaging phenotypes and clinical characteristics with EFS during the follow-up by adjusting for age, sex, disease duration, disease activity, and received treatment including medications and revascularization procedures. Hazard ratios (HR) and 95% confidence intervals (CIs) were reported. The Kaplan–Meier method was used to plot the proportion distribution of EFS in the above subgroups over time with log-rank test. Statistical analyses were performed using SPSS 22.0 . Two-sided In total, 204 (33%) patients  suffered from hypertension in our cohort, with dizziness/headache , chest distress , and weakness  as the most common manifestations. According to the 1996 classification, type V  was the most common imaging type, followed by type IV . The demographic and clinical characteristics were presented in Supplementary Table p = 0.001) and heart failure  was observed in patients with hypertension. Imaging types and arterial involvement significantly differed (p < 0.001), showing a higher prevalence of renal artery involvement  and abdominal aorta involvement  in patients with hypertension , renal artery involvement (p = 0.043), as well as blood pressure control status (p < 0.001) significantly differed among the three hypertension categories. Patients with severe hypertension were more likely to experience failure control of blood pressure than those with mild  and moderate hypertension , respectively.Mild, moderate, and severe hypertension was observed in 48 (23.5%), 62 (30.4%), and 94 46.1%) cases, respectively. Clinical characteristics of the three categories were summarized in Table % cases, p = 0.008) ; Cluster 2: involvement of ascending aorta, thoracic aorta, and/or the aortic arch and its branches ; and Cluster 3: combined involvement of Cluster 1 and Cluster 2 . The clinical characteristics of patients with different imaging phenotypes were shown in Table As significant differences of artery involvement were demonstrated in patients with hypertension, cluster analysis was further performed to explore new imaging phenotypes for TAK patients with hypertension  and age (p < 0.001), the prevalence of baseline features, including renal insufficiency (p = 0.046), heart failure (p = 0.013), cerebral infarction (p = 0.007), severe hypertension (p = 0.014), and severe AR (p = 0.047) differed significantly among the three imaging phenotype clusters. Furthermore, Cluster 1 had a higher prevalence of severe (> 75%) renal artery stenosis than Cluster 3 , though Cluster 3 involves some same lesions with Cluster 1. The blood pressure control status also differed among the three clusters of imaging phenotypes. Patients with Cluster 1 imaging phenotype experienced a lower prevalence of controlled hypertension  and higher prevalence of failure control  than those with Cluster 2 phenotype . Lower prevalence of Cluster 1 imaging phenotype was observed in the controlled group compared with improved  and failure group . Meanwhile, higher prevalence of Cluster 2 imaging phenotype was also observed in the controlled group compared with improved  and failure group   and β-blocker  compared with the failure group   patients were followed up for a median of 46 (9–102) months, among whom, 127 cases did not experience any events, with a medium follow-up duration of 36 (8–100) months. Seventy-two events (1–3 per person) were observed in 60 (32.1%) patients, with a median follow-up duration of 48 (6–92) months. The events included persistent refractory or malignant hypertension , persistent or deteriorated renal insufficiency , heart dysfunction , cerebrovascular events , aortic dissection , abdominal aortic dissection , rupture of abdominal aortic aneurysm , and death .The EFS by the end of the follow-up was 67.9% in the entire population, while it was 81.4%, 70.8%, and 59.8% in patients with mild, moderate, and severe hypertension, respectively; 59.6%, 80.0%, and 67.6% in patients with Cluster 1, Cluster 2, and Cluster 3 imaging phenotype, respectively; and 75.8%, 61.8%, and 50.0% in patients with controlled, improved, and control failure hypertension, respectively (Tables p = 0.043), controlled blood pressure , Cluster 1 , and Cluster 3 imaging phenotype  were significantly associated with the EFS (Table p = 0.027), while those had Cluster 1 imaging phenotype with uncontrolled blood pressure  and Cluster 3 imaging phenotype with uncontrolled blood pressure  suffered worse EFS  about 33% of TAK patients in our cohort suffered from hypertension, among whom, almost half were severe hypertension; (ii) three specific imaging phenotypes were identified for TAK patients with hypertension, which could be distinguished from those without hypertension; (iii) only 50.8% patients got controlled blood pressure in the present study and the overall EFS was 67.9% by the end of a median 48 months follow-up; and (iv) patients with controlled hypertension showed better EFS, while imaging phenotype also showed effects on the EFS, though not statistically significant.Previous studies have reported that hypertension occurred in 33–83% of TAK patients, with younger disease onset age (mostly < 40 years) –10, 21. Previous studies have revealed that renal artery stenosis-associated hypertension was observed in about 50% of TAK cases , 27, 28.Except for renal artery, hypertension in TAK could be caused by multifactorial conditions. In Cluster 2, hypertension might be caused by the involvement of the ascending aorta, thoracic aorta, aortic arch, and its branches instead of the renal and abdominal aorta. Hamida et al. reported that lesions of supraaortic trunks, carotid lesions, and immunosuppressive drugs might contribute to the genesis of hypertension in TAK . Former In the current investigation, only 50.8% of cases had blood pressure controlled during the follow-up, which was relatively low. More importantly, patients with blood pressure control showed significantly better EFS. Thus, the main treatment goal for TAK patients with hypertension should be not only to achieve and maintain disease remission, but also to achieve blood pressure control. For anti-hypertensive treatment, we found that patients with controlled blood pressure showed more usage of ACEI/ARB and β-blocker, which might indicate that ACEI/ARB and β-blocker could be a better choice for TAK patients with hypertension. However, in patients with bilateral renal artery involvement, ACEI/ARB was forbidden; in patients with unilateral renal artery involvement, close monitoring of serum creatinine and potassium should be done during the treatment with ACEI/ARB. Combined with the above data, we also made a decision tree diagram using three variables: imaging phenotype, blood pressure control status, and co-existence of severe AR , which could be distinguished from non-hypertensive cases (B).Additional file 2:. Supplementary Table 1. General characteristics in Takayasu arteritis patients with and without hypertension.


The clinical and biochemical improvement observed in kidney transplant (RT) recipients is remarkable. The correct functioning of the allograft depends on various factors such as the donor's age, the alloimmune response, the ischemia-reperfusion injury, arterial hypertension, and the interstitial fibrosis of the allograft, among others. Antihypertensive drugs are necessary for arterial hypertension patients to avoid or reduce the probability of affecting graft function in RT recipients. Oxidative stress (OS) is another complex pathophysiological process with the ability to alter posttransplant kidney function. The study's objective was to determine the effect of the administration of Enalapril, Losartan, or not antihypertensive medication on the oxidative state in RT recipients at the beginning of the study and one year of follow-up. All patients included in the study found significant overexpression of the oxidative damage marker to DNA and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In contrast, it was found that the determination of the total antioxidant capacity decreased significantly in the final determination at one year of follow-up in all the patients who ingested Enalapril and Losartan. We found dysregulation of the oxidative state characterized mainly by oxidative damage to DNA and a significant increase in antioxidant enzymes, which could suggest a compensatory effect against the imbalance of the oxidative state. Chronic allograft dysfunction (CAD) is a progressive and irreversible entity and is a cause of long-term kidney transplant failure –3. The min vitro and in vivo and selectively blocks AT1 recipients ameliorated nonhemodynamic effects (reduction of OS) in renal nephrotoxicity due to CNI [Various therapeutic interventions are used to minimize kidney graft damage associated with CNI including the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) –14. ACE e to CNI , 19. Like to CNI .The study's objective was to determine the effect of the administration of Enalapril, Losartan, or not antihypertensive on the oxidative state in RT recipients at the beginning of the study and one year of follow-up.An open, randomized clinical trial was conducted with a control group. It was carried out in the Transplant Division of the High Specialty Medical Unit of the Hospital de Especialidades, Centro Médico Nacional de Occidente of the Mexican Institute of Social Security in Guadalajara, Jalisco, Mexico. The sample size was based on the formula to evaluate mean differences for clinical trials . Three sPatients who received an RT from a deceased donor, from a donor >55 years, with renal comorbidities at the time of the study , with blood dyscrasias, second transplantation, treatment with nonsteroidal anti-inflammatory drugs, statins, spironolactone, and pentoxifylline and patients with neurodegenerative processes or who withdrew the letter of consent under information were excluded.Baseline determinations were made the day before RT and at one year of posttransplant follow-up. Type of donor and cold and hot ischemia time were recorded.α basiliximab 20 mg at day 0 and 4 posttransplant). The immunization maintenance scheme was carried out by administering TAC at 0.1-0.2 mg/kg (the dose was modified according to serum levels). The target levels of TAC on days 1-30 posttransplantation were 9-15 ng/mL and from day 31 to 365 posttransplantation 8-10 ng/mL. The dose of mycophenolate mofetil was administered 1 g twice a day. Prednisone was administered at 1 mg/kg/day from the start of RT and was reduced to 0.1 mg/kg/day in the second month after transplantation [TAC carried out the induction of immunosuppression at doses of 0.12 mg/kg/day divided into two doses, mycophenolate mofetil 2 g/day, and methylprednisolone 500 mg (day 0), polyclonal antibodies , 25 to 29.9 kg/m2 (overweight), and ≥30 kg/m2 (obesity) [2).Patients were classified according to body mass index (BMI) 18.5-24.9 kg/mobesity) , and theobesity) . The bio2) = 186 × CrS − 1.154 × (age) − 0.203 × (0.742 in case of being a woman)[The clearance of sCr was calculated with the formula: MDRD = GFR (mL/min × 1.73 m a woman).The serum LPO was measured using an FR12 assay kit . Plasma samples treated with N-methyl-2-phenylindole were centrifuged at 12,791 rpm for 10 min, and the supernatant was obtained. The supernatant was added to a microplate, and the absorbance was measured at 586 nm. The duplicate standard intra-assay CV was 6.4%.μL of the sample) and vortexed for one min, and the samples were centrifuged at 10,000 × g for 10 min at 4°C. For measuring NO, the kit NB98, Oxford Biochemical, Oxford, MI, USA, was used. The colorimetric signal was read at 540 nm. The duplicate standard intra-assay CV was 7.9%.Before the assay, plasma samples were deproteinized by adding zinc sulfate  was used. The serum samples were diluted at 1 : 2 in sample buffer before the colorimetric assay. Color development was read at a wavelength of 440 nm. The dilution factor was used to calculate the results. The duplicate standard intra-assay CV was 5.4%.μL) were added to a microplate of 96 wells with 70 μL of buffer, 50 μL of glutathione and glutathione reductase mixture, and 50 μL of NADPH. The activity was obtained by measuring the absorbance decrease at 340 nm every min for 20 min. The activity is expressed as nmol/min/mL. The duplicate of positive control intra-assay CV was 1.5%.The assay kit GPx 703,102 was used . Plasma samples . The duplicate standard intra-assay CV was 5.7%.The total antioxidant capacity (TAC) quantification was done following the Total Antioxidant Power Kit . The serum samples and standards were diluted at 1 : 40, and 200 p ≤ 0.05 values were considered statistically significant.The results are presented in measures of central tendency and dispersion. The qualitative variables were determined in frequencies and percentages; the chi-square test was used when required. The results are expressed as mean ± standard deviation. The normality of data was determined, and the Shapiro-Wilk test was performed. For intragroup differences, the Wilcoxon rank test was used. The Kruskal-Wallis test was used for intergroup differences. The different letter denotes statistically significant difference using the Dunn-Bonferroni paired test. All NCT05232370.The study adhered to the ethical principles for medical research in human beings stipulated in the Declaration of Helsinki 64th General Assembly, Fortaleza, Brazil, October 2013 and in the Belmont Report. The Standards of Good Clinical Practice and the International Conference on Harmonization were followed. The study was category III (risk more significant than the minimum). The following provision of the General Health Law in Mexico on health research, Title Two, of the Ethical Aspects of research in human beings, Chapter I, Article 17 Letter of Consent Under Information, was required with the signature of witnesses. The study was approved by the Local Ethics and Research Committee with registration 2018-1001-214, before Cofepris 17CI11 020 146 and before Bioethics with number 11 CEI 003 20188080. The clinical trial registration number is p < 0.01). Kidney donors were <50 years. The male gender predominated in the three study groups. Age showed a difference in the group that did not require antihypertensive medication 29 ± 3.83 years vs. those treated with Enalapril 24.38 ± 1.61 years (p ≤ 0.01). The stature of the patients treated with Enalapril was greater than that of the other groups (p ≤ 0.01). The number of transfusions and the time of hot and cold ischemia were similar in the three study groups (The recipients of the three RT groups were young patients (y groups .p < 0.01). Patients with RT who did not require antihypertensive medication kept their blood pressure normal throughout the study. Thirteen patients who had elevated baseline systolic and diastolic blood pressure (134.62 ± 7.54 mmHg and 87.31 ± 4.34 mmHg) (p < 0.01) were administered with Enalapril. After one year of follow-up of the patients who ingested Enalapril, their blood pressure was significantly modified . The thirteen patients with baseline systolic blood pressure values of 140 ± 4.83 mmHg and diastolic 89.92 ± 5.48 mmHg (p < 0.01) were administered with Losartan. In the determination at one year of follow-up, the systolic blood pressure was modified to 131.31 ± 7 mmHg and diastolic to 80.77 ± 5.3 mmHg (p < 0.01). Glucose decreased its concentration in the group without antihypertensive medication in the final determination with 137.38 ± 80.42 mg/dL baseline vs. 90.46 ± 17.46 mg/dL final (p = 0.03). The sCr levels were similar in the three groups in the baseline determination. At the end of the study, an apparent decrease in sCr levels was shown in the three study groups. The patients who did not require antihypertensive medication obtained sCr levels in the baseline determination, 12.84 ± 3.77 mg/dL vs. 1.18 ± 0.15 mg/dL at one year of follow-up (p < 0.01). Those who ingested Enalapril had baseline sCr levels of 12.16 ± 4.63 mg/dL and final levels of 1.17 ± 0.21 mg/dL (p < 0.01). The baseline sCr levels in those who ingested Losartan were 13.38 ± 1.79 mg/dL and at one year of follow-up 2.6 ± 3.27 mg/dL (p < 0.01). Area concentration in the three groups was different (p = 0.02), the group without antihypertensive was 122.92 ± 37.74 mg/dL at baseline levels vs. 31.39 ± 6.68 mg/dL in the final determination (p < 0.01). In those who ingested Enalapril, the baseline urea determination was 155.59 ± 28.3 mg/dL vs. 30.82 ± 5.05 mg/dL at the end of follow-up (p < 0.01). For the group treated with Losartan, the baseline urea levels were 127.40 ± 32.11 mg/dL vs. 70.04 ± 72.94 mg/dL at the end of follow-up (p < 0.04). TAC levels were homogeneous in the three study groups between the baseline results and one year of follow-up  in patients who did not require antihypertensive medication can be seen. The LPO levels in the patients taking Enalapril and Losartan were similar between baseline and final results. NO metabolites did not show significant differences between the baseline and final results in the three study groups.p < 0.01). At one year of follow-up, the levels of those who ingested Enalapril increased significantly to 74.29 ± 0.63 ng/mL (p = 0.02) vs. baseline levels 52.94 ± 21.45 ng/mL. The same behavior was observed in the patients who ingested Losartan; in the baseline determination, 62.71 ± 19.6 ng/mL was obtained with a significant increase at one year of follow-up of 73.78 ± 1.88 ng/mL (p < 0.01). Significant intragroup differences were obtained . The activity of the SOD enzyme in the basal Enalapril group was 0.39 ± 0.17 U/L vs. at one year of follow-up 1.31 ± 0.67 U/L (p < 0.01). The activity of the SOD enzyme at the end of the follow-up of those who ingested Losartan was 1.19 ± 0.46 vs. the basal activity of the enzyme 0.25 ± 0.21 U/L (p < 0.01) (A significant increase in the enzyme superoxide dismutase (SOD) activity was observed in the three study groups. In patients who did not require antihypertensive medication, baseline levels were 0.3 ± 0.2 U/L and at the end of follow-up 1.17 ± 0.63 U/L ( < 0.01) .p = 0.03). GPx activity in those who ingested Enalapril and Losartan was similar.The GPx enzyme only showed a significant increase in its activity for the group that did not require antihypertensive treatment with 343.76 ± 214.82 nmol/min/mL (baseline) vs. 518.15 ± 163 nmol/min/mL  . Patients who ingested Enalapril also decreased CAT levels between baseline 65.45 ± 18.99 μM vs. the levels obtained at the end of the follow-up 14.2 ± 3.2 μM (p < 0.01). A similar situation was observed in the patients who ingested Losartan where the baseline levels were 61.10 ± 24.07 μM, and a significant decrease was observed at the end of the study 20.7 ± 5.3 μM (p < 0.01)  showed a significant decrease in its baseline concentration of 59.78 ± 1.89  < 0.01) .Significant overexpression of the oxidative DNA damage marker in the determination at one year of follow-up in the RT recipients who did not require antihypertensive medication is striking; the same phenomenon occurred in those who ingested Enalapril and Losartan. Changes in the epigenome and DNA methylation also could be implicated in each of the processes mentioned above to affect the kidney or other organ systems . The incβ-carotene, and coenzyme Q. The enzyme SOD is considered the first line of antioxidants capable of antagonizing the imbalance of the redox state. Following the present study, a significant increase in the activity of the SOD enzyme has recently been reported in patients undergoing hemodialysis [The antioxidant activity of the SOD enzyme was found to be significantly increased in the final determination in the three groups of patients, those treated with Enalapril and Losartan and those that did not require antihypertensive medication, possibly trying to compensate for the oxidative imbalance that occurs in the posttransplant period. Two antioxidants antagonize free radicals, including the antioxidant enzymes SOD, GPx, and catalase, and non-enzymatic antioxidants such as vitamin E, C, dialysis . The actdialysis . It was dialysis .In addition to traditional cardiovascular risk factors, the attention of RT recipients has focused on other complex pathophysiological processes related to posttransplant renal function, including the effect of OS. It is widely known that OS is increased in CKD and is further aggravated by renal replacement therapies. OS is associated with the appearance of atherosclerosis, left ventricular hypertrophy, and cardiorenal syndrome . VariousIndeed, the quality of life is low in patients with CKD; however, RT can improve the quality of life similar to healthy individuals . The cliLosartan is a potent, orally active, and selective nonpeptide blocker of the angiotensin II receptor type 1. Losartan reduces blood pressure, proteinuria, serum uric acid level, and posttransplant erythrocytosis. Losartan has positive effects on renal excretory function in adult CKD patients and RT recipients , 42. LosVarious factors have been associated with increased cardiovascular risk in RT recipients during the postoperative period, such as the development of diabetes mellitus, arterial hypertension, dyslipidemia, and obesity . ApproxiThe determination of sCr and urea and the estimation of GFR through different equations are considered biomarkers of kidney graft function used routinely in clinical transplantation. The sensitivity and specificity of these biomarkers are low, but they are inexpensive and readily accessible , 50. In Another benefit of RT is the improvement in hemoglobin levels found in the three study groups in the determination at one year of follow-up under the previously reported. The authors found improvement in hemoglobin and hematocrit in patients with RT treated with TAC .We consider that it is essential to monitor the expression of the oxidative damage marker to DNA, oxidants, and the activity of antioxidant enzymes as well as the function of the transplanted organ in addition to traditional kidney function tests to detect early alterations that can be corrected early to avoid the loss of the transplanted organ.In conclusion, all the patients included in the study, regardless of the management with or without antihypertensive, presented overexpression of the marker of oxidative DNA damage, a significant increase in the activity of the SOD enzyme, and a significant decrease in the total antioxidant capacity as a systemic buffer of the redox state, which could suggest oxidative state imbalance. The increase in the activity of the SOD enzyme in all patients, including the increase in the GPx enzyme in patients who did not require antihypertensive medication, could suggest a compensatory effect in light of the significant increase in LPO in this group of patients. The present study results suggest that the determination of other markers in addition to those traditionally requested is required: sCr, urea, potassium, and glomerular filtration rate.The limitations of the study are based on the small number of patients included and the short length of follow-up.The study's strengths are based on the fact that it is a prospective cohort study before and after in patients with de novo RT with follow-up at one year. Soon, another study will be carried out with a longer follow-up time and a larger sample size.


BackgroundObesity affects 93.3 million adults in the United States and is a predisposing factor for the development and progression of chronic kidney disease (CKD). The objective of this study is to examine the association between weight loss and renal function in participants undergoing bariatric surgery following a 12-week multidisciplinary, community-based weight loss program.MethodologyThis is a retrospective chart review of participants who voluntarily enrolled in a 12-week multidisciplinary weight loss program prior to bariatric surgery from 2009 to 2018. The primary outcome was to assess the association between weight loss and renal function in participants undergoing bariatric surgery. Secondary outcomes included changes in hemoglobin A1c, lipids, fasting glucose, and blood pressure.Results2, 80% were female, and the average baseline weight was 131 kg. At one-year post-intervention, 69% of patients improved in the CKD stage, with 45% of the participants improving from stage 3A to stage 2. GFR improved to 15 mL/min/1.73m2 (p = 0.025), and there was a negative correlation (rs = -0.3556) between weight and GFR (p = 0.013). Participants with hyperlipidemia had a 12 mL/min/1.73m2 rise in GFR, while participants without the diagnosis at one year had a 24 mL/min/1.73m2 rise in GFR (p = 0.007).Among the 55 participants, baseline glomerular filtration rate (GFR) was 49 mL/min/mConclusionsThis study demonstrated improved renal function and reduced progression of CKD following a combined lifestyle and surgical intervention, indicating the importance of a comprehensive approach for the management of the chronic disease. Obesity affects 93.3 million adults in the United States and current projections indicate that nearly half of the population aged 18 and older will be obese within the next 10 years . The mecIn patients with obesity, the renal system causes increased glomerular hyperfiltration to compensate for metabolic demands placed on the body, resulting in glomerulomegaly and focal glomerulosclerosis . Renal h2 or for patients with a BMI greater than or equal to 35 kg/m2 who also have at least one obesity-related comorbid condition, including type II diabetes, hypertension, or cardiovascular disease [Bariatric surgery is currently indicated for patients with a body mass index (BMI) greater than 40 kg/m disease . Bariatr disease . Additio disease . In pati disease .Bariatric surgery has been associated with a 58% reduction in the risk of proteinuria and albuminuria and a 54% reduction in the risk of hyperfiltration in patients with obesity and impaired renal function . AdditioThis study aimed to take a real-world approach to chronic care management by focusing on patient-controlled factors such as lifestyle modifications. Studies have shown improved post-surgical outcomes if lifestyle and behavioral changes are incorporated prior to surgery. This study sought to examine the association between weight loss following bariatric surgery and renal function among patients who participated in a 12-week intensive lifestyle modification weight loss program prior to surgery.Research participants2 were excluded from the study  and five servings of fruits and vegetables daily with a minimum intake of 800 kilocalories per day. Participants were additionally encouraged to complete 300 kilocalories per day of physical activity.Participants met weekly with the staff to report compliance with established intake goals. They attended group classes that provided a sense of community and assisted with accountability and support throughout the 12-week program. Comorbid conditions were optimized by a physician through medical and lifestyle management.Outcome measurement and data collectionα × max-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]) ) . The CKDSecondary outcomes included fasting plasma glucose, HbA1c, total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and systolic and diastolic blood pressure. Patients with hypertension were defined as systolic blood pressure greater than 130 mmHg, diastolic blood pressure greater than 80 mmHg, or those taking antihypertensive medications. Patients with diabetes were defined as those having a fasting plasma glucose greater than or equal to 125 mg/dL, HbA1c greater than 6.5%, or taking medications for diabetes. Patients with hyperlipidemia were defined as those having an HDL less than or equal to 40 mg/dL, triglycerides greater than or equal to 150 mg/dL, LDL greater than or equal to 140 mg/dL, or those taking cholesterol-lowering medications.Study data were managed using a secure Research Electronic Data Capture (REDCap) tool . This stStatistical analysisData were analyzed using SAS version 9.4 . Frequencies, proportions, means, and standard deviations were generated from the initial dataset. Likelihood ratio chi-square and Fisher’s exact tests were used to test for associations between two nominal or categorical variables. Prior to the main analyses, the Shapiro-Wilk test was conducted to test for the normal distribution of the outcomes. The relationship between weight loss and GFR was evaluated using the Spearman Rho correlation coefficient. The main analyses were conducted through a random coefficient model under the framework of a generalized linear mixed model. This approach accounted for the individual fluctuations during the measurement time points, addressed questions of scientific interest about trajectories for individual units either in the study or future units, and accounted for within-individual and among-individual variation. The model parameter estimates were obtained, including maximum likelihood, with adaptive quadrature. Hannan-Quinn information criterion was considered in the model to select the correct set of variance and covariance patterns that better fit the outcome variable. The Wilcoxon signed-rank test was conducted to test the difference between baseline and final measurements of GFR based on hypertension, hyperlipidemia, and diabetes diagnosis. All statistical tests at p ≤ 0.05 were noted as significant.A total of 55 participants were enrolled in the study, with the majority being female  and Caucasian  with a mean age of 59 ± 10 years (range: 38 to 77 years) Table .2 and continued to increase at three months (62 ± 14 mL/min/m2), six months (63 ± 13 mL/min/m2), and one year (64 ± 15 ml/min/m2)  between weight loss and GFR.The average weight at baseline was 131 ± 26 kg and decreased to 98 ± 30 kg at one year, representing an average of 25% total body weight loss at one-year post-surgical intervention. The average GFR at baseline was 49 ± 8 mL/min/mSecondary outcome measures, including triglycerides, hbA1C, and fasting glucose, showed a significant improvement from baseline to one-year post-surgical intervention Table . Triglyc2  = 6.52; p = 0.007)). There was no statistically significant difference in GFR change from baseline to one-year post-intervention in patients with diabetes or hypertension compared to patients without the diagnoses.Patients with hyperlipidemia had a smaller increase in GFR from baseline to one year when compared to patients without hyperlipidemia  with limited ethnicity distribution. This limits the generalizability of this study to larger, more diverse populations. Additionally, long-term follow-up was limited to only one-year post-intervention. Future studies exploring the long-term effects of lifestyle modifications prior to bariatric surgery and assessments of renal perfusion and glomerular sclerosis in this population will provide additional information about the potential mechanisms associated with improved renal function after lifestyle and surgical interventions.This study demonstrated that weight loss after bariatric surgery combined with lifestyle interventions is associated with significant improvements in renal function. These noted improvements indicate that a real-world, multimodal, lifestyle-modification weight loss program prior to bariatric surgery may play an important role in GFR improvement. Additionally, this study found that patients without hyperlipidemia had greater GFR improvement after bariatric surgery, indicating that patients with or without certain comorbidities may further benefit from lifestyle interventions prior to bariatric surgery. The findings of this study further support bariatric surgery as a potential treatment option for CKD patients with obesity to prevent disease progression and reduce cardiovascular risk factors.


Hypertension is prevalent in Singapore and is a major risk factor for cardiovascular morbidity and mortality and increased health care costs. Strategies to lower blood pressure include lifestyle modifications and home blood pressure monitoring. Nonetheless, adherence to home blood pressure monitoring remains low. This protocol details an algorithm for remote management of primary care patients with hypertension.The objective of this study was to determine whether wireless home blood pressure monitoring with or without financial incentives is more effective at reducing systolic blood pressure than nonwireless home blood pressure monitoring .This study was designed as a randomized controlled open-label superiority study. A sample size of 224 was required to detect differences of 10 mmHg in average systolic blood pressure. Participants were to be randomized, in the ratio of 2:3:3, into 1 of 3 parallel study arms :(1) usual care, (2) wireless home blood pressure monitoring, and (3) wireless home blood pressure monitoring with financial incentives. The primary outcome was the mean change in systolic blood pressure at month 6. The secondary outcomes were the mean reduction in diastolic blood pressure, cost of financial incentives, time taken for the intervention, adherence to home blood pressure monitoring, effectiveness of the framing of financial incentives in decreasing nonadherence to blood pressure self-monitoring and the adherence to antihypertensive medication at month 6.This study was approved by SingHealth Centralised Institutional Review Board and registered. Between January 24, 2018 and July 10, 2018, 42 participants (18.75% of the required sample size) were enrolled, and 33 participants completed the month 6 assessment by January 31, 2019.Due to unforeseen events, the study was stopped prematurely; therefore, no results are available. Depending on the blood pressure information received from the patients, the algorithm can trigger immediate blood pressure advice , weekly feedback on blood pressure monitoring, medication titration, or skipping of routine follow-ups. The inclusion of financial incentives framed as health capital provides a novel idea on how to promote adherence to remote monitoring, and ultimately, improve chronic disease management.ClinicalTrials.gov NCT 03368417; https://clinicaltrials.gov/ct2/show/NCT03368417DERR1-10.2196/27496 Hypertension is prevalent in Singapore, affecting 23.5% of adults between 18 to 69 years of age ,5. The gFor patients whose blood pressure remains high, doctors routinely recommend home blood pressure monitoring for better blood pressure control. Home blood pressure monitoring allows the doctor to monitor response to treatment, detect white-coat hypertension, and predict cardiovascular risk ,8. NonetBehavioral economic theory suggests that the high rates of nonadherence to lifestyle modifications result, at least in part, from patients not perceiving a clear cause and effect relationship between greater adherence and reduced likelihood of adverse health consequences  ,30. The Therefore, this study aimed to leverage the potential of wireless and mobile technology and introduce financial incentives to improve the effectiveness of home blood pressure monitoring. The primary objective of this study was to determine whether wireless home blood pressure monitoring, with or without financial incentives, is more effective at reducing systolic blood pressure than nonwireless home blood pressure monitoring that relies on patient self-report . The secondary objectives were to improve adherence to blood pressure monitoring and antihypertensive medication(s).The study was designed as a randomized controlled open-label superiority study with 3 parallel arms. Patients with hypertension who were on antihypertensive medication were randomized to (1) usual care, (2) wireless home blood pressure monitoring only, and (3) wireless home blood pressure monitoring with financial incentives arms, in a ratio of 2:3:3. Participants were randomly stratified based on whether they had diabetes mellitus (diabetes) and by clinic. The study intervention was to last 6 months. This protocol conforms to CONSORT  guideliPatients were recruited from Bedok and Marine Parade Polyclinics  in Singapore. Bedok and Marine Parade Polyclinics provide primary health care services to the eastern and southern region of Singapore. Hypertension management is one of the key services provided. Participant eligibility was based on the inclusion and exclusion criteria .Inclusion criteriaParticipants had to fulfil all of the following:Diagnosed hypertension and on at least 1 antihypertensive medicationSystolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg for patients without diabetes (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥85 mmHg for patients with diabetes), which was verified by the average of the last 2 of 3 blood pressure readings taken on the day of the screening visit at 3-minute intervals   with data plan or regular Wi-Fi accessAbility to perform self-monitoring of blood pressure as assessed by the clinical research coordinatorExpecting to be a patient of Bedok or Marine Parade Polyclinics for the duration of the trialExclusion criteriaPatients with any of the following were not enrolled:Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg which was verified by the average of the last 2 of 3 blood pressure readings taken on the day of the screening visit at 3-minute intervals Started on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers within the last 3 monthsClinically unstable heart failureAdvanced kidney disease Known liver disease Atrial fibrillationOn warfarin or anticoagulants Underwent double mastectomyPregnantKnown allergy to epoxy resinNewly referred to specialist outpatient clinics or upon follow-up for complications related to hypertensionDischarged from hospital within the last 3 months for complications related to hypertensionAny other major debilitating disease or mental illness that precludes validity of informed consent or would result in the patient being unable to take their blood pressure independentlyLiving in a household where another member has been recruited into the trialParticipants were recruited via posters and referrals at Bedok and Marine Parade Polyclinics. A screening visit was arranged during which the study’s purpose was explained and the screener administered. For eligible patients, the clinical research coordinator went through the participant information sheet, and if the patient agreed to participate, obtained informed consent .Blood pressure was assessed at baseline and at month 6. Participants wore an ambulatory blood pressure monitor  for 12 hours while awake . A period of 12 hours instead of 24 hours was chosen to reduce participant burden . A diarySingHealth Polyclinics have a structured framework for hypertension management. Patients who are newly diagnosed with hypertension would be prescribed antihypertensive medication if deemed necessary by the doctor. All patients are subsequently referred to a nurse who would provide further information on hypertension and come up with a lifestyle modification plan with the patient. Patients are then followed up by the doctors and nurses at 3- to 4-month intervals (or more), based on their blood pressure trend. Further education is given at these visits as needed. Patients with good blood pressure control can teleconsult with a trained nurse, alternating with in-person doctor's consultation at up to 6-month intervals if they monitor their blood pressure at home. There are in-house pharmacists who assist patients in understanding their medication doses and regimens. Regular blood tests  are also carried out annually to monitor the patient’s response to treatment and to detect any disease progression and complications. Patients with evidence of disease progression and complications would be closely monitored and referred to the appropriate specialists if required.Participants in the usual care arm were advised to use their existing blood pressure monitor. Participants who did not have a home blood pressure monitor were given a blood pressure monitor . In order to properly identify the effect of contingent financial incentives, all participants received a participant leaflet .The clinical research coordinator also provided advice on self-management and education on how to interpret blood pressure readings according to a standard self-monitoring guideline . The selParticipants in Arm 1 recorded their blood pressure readings on the SingHealth Polyclinics home blood pressure charting form (in paper format) as part of usual care. For monitoring adherence to hypertensive medicines, an eCAP (Information Mediary Corp) was used. The eCAP device passively recorded the dates and times the bottle was opened; these data are stored in the memory via an radiofrequency identification tag. Data were extracted by scanning the eCAP device on a reader (CertiScan desktop). Participants were assessed for adherence within specified time windows .Aim to achieve blood pressure readings in the normal rangeMeasure your blood pressure on at least 3 days each weekRecommendations:It is best to measure your blood pressure in the morning, before you take your medication, coffee, tea, smoke or exercise. Please sit for at least 5 minutes before measuring your blood pressure.It is also recommended that you measure your blood pressure before you sleep at night.Get activeEat better. Reduce your salt intakeTake your medication as prescribed by your doctor.Participants in Arm 2 used an asynchronous telehealth system that consisted of a wireless home blood pressure monitor and app . The stuThe participants monitored their blood pressure using a wireless upper arm blood pressure monitor . The blTo be clinically more responsive to uncontrolled blood pressure, remote titration is integrated in this intervention as per the Joint National Committee 8  recommenOn each working day, the clinical research coordinator logged-in to the study website, monitored the dashboard for flags and intervened accordingly. The clinical research coordinator unflagged the flag once the intervention had been carried out.Study participants had doctor consultations at month 3 and at month 6 during the intervention period. For Arm 1 participants, the clinical research coordinator met with them prior to their doctor consultation and made a copy of their blood pressure readings for record. For Arm 2 and 3 participants, the clinical research coordinator passed them the blood pressure readings captured by the wireless monitoring system on the day of the doctor consultation for review by the doctor; except in cases where the visit was skipped due to good blood pressure control (green protocol).Participants in this arm received an intervention identical to those in Arm 2, with the addition of financial incentives for blood pressure monitoring. This arm was subdivided into 2 arms; participants were eligible to receive the same incentive amounts but framed differently. In the instant reward subarm, participants received SGD $3 (an exchange rate of approximately SGD $1 to US $0.75 was applicable at the time of publication) for each day they measured their blood pressure, up to 3 times per week . In the health capital subarm, participants received an initial health capital of SGD $72. Participants’ health capital increased by SGD $6 on each week they measured their blood pressure on at least 3 different days. Participants’ health capital decreased weekly by 10% per missing blood pressure reading. Health capital decreased by 10% if the participant measured their blood pressure on 2 different days, by 20% if the participant measures their blood pressure only on 1 day, and by 30% if the participant did not measure their blood pressure. Therefore, at the end of the 24-week intervention, Arm 3 participants could receive incentives up to SGD $216 for blood pressure monitoring.Noncontingent study payments  to Arm 1During the study intervention, the clinical research coordinator reviewed the participants’ medical records and contacted the participants via phone to determine if there were any serious adverse events, changes in medical condition, hospitalizations, or referrals to specialist outpatient clinics that may require a withdrawal from the study. The study doctor reviewed the participant’s medical records and determined when there was a need to do so. Participants who were newly diagnosed with a hypertension related condition or complication or met the following exclusion criteria: clinically unstable heart failure, acute kidney injury, glomerulonephritis, liver disease, atrial fibrillation, prescribed warfarin or anti-coagulants, double mastectomy, pregnant, epoxy-resin allergy, referred to specialist outpatient clinic, or hospitalized for complications were withdrawn. Those who had a progression of an existing condition  could remain in the study. For study participants who were withdrawn by the study team, a payment of SGD $80 in compensation for forgoing potential payments that the participant might have received had they remained in the study was given. Participants were free to withdraw their consent and discontinue their participation at any time during the intervention, without prejudice or effect on their medical care; however, all data collected until the time of the participants’ withdrawal were kept to allow for a comprehensive evaluation.The outcome measures and schedule of collection can be found in The primary outcome was the mean reduction in systolic blood pressure in 6 months. This was to be obtained from the participants’ month 6 ambulatory blood pressure monitor results. systolic blood pressure is associated with increased risk of cardiovascular disease -47.Secondary outcomes were mean reduction in diastolic blood pressure in 6 months, obtained from the participants’ month 6 ambulatory blood pressure monitor results; mean cost of financial incentives at month 6, calculated as the total financial incentives earned by Arm 3 participants at the end of the intervention and to be used as part of the cost-effectiveness analysis; mean time taken for the intervention at month 6, calculated as the total number of minutes spent by the clinical research coordinator intervening for the colored flags, adherence calculation, and payment of financial incentives for all study arm participants during the month 6 assessment and to be used as part of the cost-effectiveness analysis; mean adherence to home blood pressure monitoring at month 6; effectiveness of the framing of financial incentives in decreasing nonadherence to blood pressure self-monitoring; and mean adherence to antihypertensive medication (prescribed to be taken most frequently) at month 6.Diastolic blood pressure may have some associations with future systolic hypertension and with increased risk of cardiovascular disease -51.Exploratory outcomes were the proportion of participants who have target blood pressure (defined as less than 130 mmHg/80 mmHg) at month 6; mean change from baseline in European Quality of Life-5 Dimensions-5 Levels  score atA key parameter is the systolic blood pressure. To assess this, we computed the sample size to be able to detect differences of 10 mmHg in average systolic blood pressure between study arms at the 5% level with 80% power. To compute the overall sample size, we computed the size of the intervention groups that is required for testing for difference between intervention groups (study arms 2 and 3). After applying a Bonferroni correction , we found that 68 patients per intervention group is necessary to detect mean differences in systolic blood pressure of 10 mmHg (with 2.5% significance level and 80% power). Given the resulting cumulated sample size for the 2 intervention arms of 136, we then computed the size required for the control group to test the overall effect of the wireless home blood pressure monitoring  with the same effect size, significance level, and power. This computation yielded a size of 45 for the control group. After accounting for 25% attrition in each arm, the resulting sample sizes were 56 for the control group and 84 for each intervention group, resulting in a total of 224 patients. We assumed throughout that the standard deviation of systolic blood pressure is 19  to create an assignment schedule for block-randomization to allocate eligible participants into 1 of the 3 study arms in a ratio of 2:3:3. Randomized stratification was based on whether the patient had diabetes and study site. The block size was not communicated to SingHealth Polyclinics to minimize the predictability of the random sequence. Furthermore, in order to test a secondary hypothesis (H5), the patients in the home blood pressure monitoring with financial incentives arm were further randomly divided into 2 equal-size groups, 1 per incentive type. The project coordinator and principal investigator then stored the assignment schedule on a secure server at Duke–NUS Medical School. For allocation concealment, the project coordinator and a Duke–NUS Medical School staff external to the study team enclosed the assignments in sequentially numbered, opaque, sealed randomization envelopes. These were handed over to the clinical research coordinator for participant enrollment and assignment.The clinical research coordinators were not blinded to the group allocation during the study intervention as there was a need for the clinical research coordinators to know the participants’ arms to assign study devices to the participants and carry out the intervention accordingly and disburse payouts for the incentive arm participants (Arm 3). The site investigators were also not blinded as they had to explain the remote titration action plan and advise on intervention for the colored protocols (Arm 2 and 3).To maintain confidentiality, all enrolled participants were issued a unique ID based on their randomization number and were referred to via their unique ID thereon. Identifiable data were kept at locked cabinets at Bedok and Marine Parade Polyclinics and only accessible by the SingHealth Polyclinics team. Only deidentified research data were passed to Duke–NUS Medical School, and all data transfers were documented. All keyed in deidentified research data were encrypted, password-protected and stored on a secure server. Blood pressure readings and home blood pressure monitoring adherence data from the mobile app were transmitted automatically to the app via the application programming interface daily. The app did not contain any identifying information, was password protected, and only authorized members of the Duke–NUS Medical School team had access to the website via 2-factor authentication. Investigators have access to the research data collected. All hardcopy research data collected are archived for the next 10 years in compliance with NUS's research data management policies. No Data and Safety Monitoring Board was used for this trial as the study was deemed to be low risk by the investigators as this intervention was modelled after an existing standard of care by the Polyclinics and not involving more than minimal risk to the participants. Compensation was to be considered on a case-by-case basis for unexpected injuries due to nonnegligent causes. This trial was subjected to study review visits and audits to ensure that all investigator-initiated research is conducted effectively and efficiently.This study was approved by the SingHealth Centralised Institutional Review Board E (2016/2026). Amendments to the protocol or other study-related documents were approved by the institutional review board.All main analyses were to be based on intent to treat. The mean difference in the systolic blood pressure at 6 months was to be assessed in the context of a linear mixed-effects model with a random effect for subject and fixed effects for baseline mean (the same in both arms) and change in mean at 6 months for each treatment arm (one for each arm). The mixed-effects model allows nonmissing data to be used in analysis without imputation. For estimates of the treatment arm effects to be unbiased, data must be missing-at-random. However, it is possible that the analysis of the pattern of attrition would indicate that additional covariates needed to be included in the mixed-effects models. If data are not normally distributed, appropriate transformations will be attempted before resorting to using nonparametric statistical analysis methods.Recruitment at Bedok Polyclinic began on January 24, 2018 and at Marine Parade Polyclinic on June 26, 2018. From January 24, 2018 to July 10, 2018, 42 participants  were enrolled, and 33 participants completed the 6-month assessment by January 31, 2019. A decision was made to terminate the study prematurely due to unforeseen delays and resulting funding issues. No analysis was carried out due to the lack of sample size and therefore no results are available.This paper reports a protocol for a randomized trial to determine whether a wireless home blood pressure monitoring system, with or without financial incentives, is more effective at reducing blood pressure than a nonwireless home blood pressure monitoring that relies on patient self-report or best practices. While the 6-month study intervention is sufficient to detect potential blood pressure improvement that is clinically significant, a longer period would be needed to test for the long-term effectiveness of the intervention. There is currently no prior intervention that has the same components as those in our wireless home blood pressure monitoring system.Unfortunately, due to unforeseen events the study was stopped prematurely. Regardless, as this study raises an interesting set of research questions, this protocol may be of value to other researchers considering similar efforts for blood pressure control or other behavioral targets. Results of such a study would provide evidence on whether a telemonitoring system with or without financial incentives can improve hypertension management, thereby reducing long-term complications and health care cost. By interacting socioeconomic characteristics with the intervention effect, this study may also have provided evidence on the benefit incidence of interventions involving financial incentives. The framing of financial incentives as reward versus health capital, would also have informed the design of future incentive strategies in hypertension management and other chronic diseases. The study would also have added to telemonitoring knowledge on hypertension self-management in patients and remote clinical management of hypertension, which is increasingly relevant in light of COVID-19 and an increase in the use of telehealth in managing chronic diseases.


Thrombotic microangiopathy (TMA) is a rare disease that presents with haemolysis and organ damage. The kidney is one of the main affected organs, and TMA is associated with serious complications and increased mortality. In transplanted patients, TMA is even less common and has a variety of possible causes, including thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS), infections, drugs, autoimmune disease, tumours, and malignant hypertension. Transplant-related causes, such as antibody-mediated rejection, calcineurin inhibitors, and viral infections, need to be considered as well. The authors report a rare case of TMA in a kidney transplant recipient, whose investigation revealed malignant hypertension secondary to primary hyperaldosteronism. Thrombotic microangiopathy (TMA) is a rare disease that presents with arteriolar and capillary thrombosis –3. TMA iAlthough rare in kidney transplant recipients, with an incidence of 5.6 cases per 1000 renal transplant recipients per year, TMA is a serious complication in these patients. It associates with poor outcomes, both on kidney allograft and patient , 9–11.Thrombotic thrombocytopenic purpura (TTP) and haemolytic-uremic syndrome (HUS) are the two most frequent causes of TMA. Other less common causes are infections , drugs (such as chemotherapy agents and ticlopidine), autoimmune diseases (such as systemic lupus erythematosus and scleroderma), disseminated intravascular coagulation, malignant tumours, HELLP syndrome, malignant hypertension, and bone marrow transplant , 12, 13.TMA secondary to malignant hypertension is a very rare entity , 16. TheA 47-year-old female was evaluated in her routine posttransplant appointment on May 2020. She had a history of end-stage chronic kidney disease due to autosomal dominant polycystic kidney disease. Haemodialysis was initiated in 2005 and she received a deceased donor kidney transplant in 2008. She remained stable for 10 years posttransplant when she developed antibody-mediated acute rejection, for which she was given rituximab and intravenous immunoglobulin, with stabilization but reduced kidney function. Eight months later, she developed a severe CMV colitis with prolonged hospital stay and her baseline creatinine remained at 2.6 mg/dL. Although chronic hypertension had been present for several years, resistant hypertension ensued for about eight months, and she was diagnosed with hypertensive retinopathy two months earlier. She also had hypertensive cardiomyopathy with left ventricular hypertrophy, hypokalaemia with need for potassium supplementation, and previous asthma. Four antihypertensive drugs  were insufficient to control adequately blood pressure, and her maintenance immunosuppression included tacrolimus, everolimus, and prednisone.Her routine lab results revealed a normochromic normocytic anaemia (Hb 8.5 g/dL) with high reticulocyte count (2.9%), no iron or vitamin deficiency and no abnormalities in other blood cell lines. Graft function was stable, and urinalysis revealed mild albuminuria that was already previously present. There were no history of blood loss or associated symptoms. No changes in physical examination were present besides obesity and grade 3 hypertension. She was started on epoetin and reevaluated three weeks later.de novo thrombocytopenia (109.000/uL), high lactate dehydrogenase (LDH) levels (469 U/L), undetectable haptoglobin, and presence of schistocytes on peripheral blood smear. She was then admitted to the Nephrology Department with the diagnosis of TMA.On reevaluation, she had worsened anaemia (Hb 6.6 g/dL) and higher reticulocyte count (5.5%). There was also ADAMTS13 and Shiga toxin were negative, and complement activity  was normal; therefore, plasmapheresis was not initiated. Over the first ten days after admission, she presented severe anaemia requiring multiple red blood cell transfusions, platelet downward trend, and high LDH levels . Neverth2), was grade 3 hypertension   and no aOn follow-up appointments, she was asymptomatic and with controlled hypertension. Her blood analysis significantly improved. Four months after discharge, she had normal hemoglobin (12.6 g/dL) and LDH levels (208 U/L), normal serum potassium (4.8 meq/L) without need for supplementation, and stable renal function (creatinine 2.4 mg/dL). Chronic vascular changes (left ventricular hypertrophy and hypertensive retinopathy) remained present. Histopathology examination confirmed adrenocortical adenoma.We report a very unusual case of a kidney transplant patient with TMA secondary to malignant hypertension. After extensive investigation, we concluded that it was caused by primary hyperaldosteronism. TMA is one of the most devastating complications in kidney transplant patients . RegardlThe kidney is one of the most frequent affected organs, along with the nervous system, but any system can be afflicted . TMA's uApart from the common TMA causes, such as TTP, HUS, drugs, malignant tumours, and auto-immune diseases, in renal transplant patients, other specific causes need to be considered: antibody-mediated acute rejection, calcineurin inhibitors, and viral infections , 13, 18.Malignant hypertension is a rare cause of TMA. Its incidence is around 1% of all hypertensive patients , 16. RetAfter ruling out most of TMA common causes, we hypothesized that our patient's uncontrolled hypertension could explain this clinical condition. In the setting of a 47-year-old woman with new onset resistant hypertension with end organ damage (recently diagnosed severe hypertensive retinopathy and cardiomyopathy), we studied potential secondary causes. Her unexplained long-term hypokalaemia with high transtubular potassium gradient led us to suspect of hyperaldosteronism, which was then confirmed by the extended study. Pheochromocytoma was excluded by catecholamine analysis and MIBG scintigraphy. She was then diagnosed with a primary hyperaldosteronism due to a functional adrenal adenoma. Although not confirmed by iodo-methyl norcholesterol scintigraphy, impossible to perform due to life-threatening risks of the interruption of spironolactone, all other studies were suggestive, along with the hypertension and hypokalaemia improvement with spironolactone. The fact that she developed acute hypertensive pulmonary oedema after suspending this drug was also very suggestive. The diagnosis was then confirmed by histology of the adrenal mass. Also, gradual improvement of acute laboratory and clinical features in the following weeks and months corroborated our suspicion. Chronic vascular changes remained as it would be expected due to previous long-standing hypertension.Antibody-mediated acute rejection was the only cause of TMA that was not completely excluded throughout our investigation. To exclude this hypothesis, we would need to perform a graft biopsy, difficult to justify both because of the major risk of bleeding associated with thrombocytopenia, anaemia, and severe hypertension, and because her renal function and proteinuria remained stable during these events, making rejections a less likely explanation. Lastly, even if she had an antibody-mediated rejection, we would be reluctant to give additional immunosuppression due to her previous significant infectious complications.There are several TMA cases due to malignant hypertension reported in the literature but few in kidney transplant patients or secondary to hyperaldosteronism. Basturk and Pamukcu reported a case of TMA caused by malignant hypertension due to hyperaldosteronism that was successfully treated with spironolactone . In thisde novo or recurrent TMA in the graft must be investigated. We report a very rare case of malignant hypertension TMA due to primary hyperaldosteronism in a kidney transplant patient.In kidney transplanted patients, the differential diagnosis of TMA is wide, and all causes of


Similarly, the asthma control test at 4 weeks improved by 3.91 points (p = .024), also statistically and clinically significant. Improvements in forced expiratory volume in 1 s at 2 weeks were neither statistically, nor clinically significant. Improvements at 4 weeks , and 3 months , were statistically significant and clinically borderline significant. No severe adverse events or hypereosinophilia were observed. No adverse events led to treatment discontinuation. Most patients (85%) had previously received monoclonal antibody treatment for severe asthma. Previous monoclonal antibody treatment had been discontinued in these patients due to a lack of clinical response. Dupilumab is effective and safe in Austrian real‐life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti‐immunoglobulin E or anti‐IL5/IL5R monoclonal antibody treatments or do not adequately respond to these.Dupilumab is a monoclonal antibody against the IL‐4 receptor alpha which has shown efficacy in T2 high severe asthmatics in phase 3 randomized controlled trials. The purpose of this real‐life study is to demonstrate the real‐life effectiveness of dupilumab in Austrian severe asthma patients. We retrospectively analyzed all patients receiving dupilumab at our severe asthma clinic. Thirteen patients have so far received dupilumab at our center. The primary outcome, asthma control questionnaire 6‐item scale at 2 weeks, improved by 0.57 points ( This is a real‐life study that shows that dupilumab is effective and safe in Austrian real‐life severe asthmatics. It rapidly improved asthma control. These improvements are comparable to previous randomized controlled trials. Randomized controlled trials (RCTs) have shown the efficacy of dupilumab in severe, type 2 high, asthma.The purpose of this retrospective, real‐life study is to add evidence on the real‐life effectiveness of dupilumab in severe asthma. This is, to our knowledge, the second worldwide, and first Austrian real‐life study on dupilumab in severe asthma.All patients who received at least one application of dupilumab at our tertiary care severe asthma clinic were included for analysis (see methods in the Online Supporting Information). Approval from the local ethics committee was granted. Due to the retrospective study design, written informed consent was not needed.n = 10; 2.50 ± 1.41 at baseline and 1.53 ± 1.22 at week 2, p = .014, see Figure n = 11; 14.82 ± 5.69 at baseline and 18.73 ± 4.96 at week 4, p = .024, see Figure n = 7; −0.82; 2.20 ± 1.38 at baseline and 1.38 ± 1.29 at 3 months, p = .045) and ACT . ACT was still significantly and clinically significantly improved at 6 months , due to missing data points formal analysis for ACQ6 was not performed for this timepoint.Thirteen patients have so far received dupilumab at our center. The baseline characteristics are summarized in Table n = 13; 2613 ± 649 ml at baseline and 2710 ± 651 ml at week 2, p = .176, see Figure n = 11; + 220 ml; 2517 ± 661 ml at baseline and 2737 ± 598 ml at week 4, p = .041), 3 months  were statistically significant and clinically borderline significant. At 6 months FEV1 improvement was only minimal .FEV1 improved by 97 ml at 2 weeks (p = .01) compared to the pretreatment annual exacerbation rate (2 [2–4]). No severe adverse events were observed. No adverse events were linked to the injection and/or hypereosinophilia. No adverse events led to treatment discontinuation. See results on biomarkers in the Online Supporting Information.All three patients who received maintenance OCS at baseline were able to reduce their OCS dose by at least 50% at 3 months while improving asthma control. Eight patients had chronic rhinosinusitis with nasal polyps (CRSwNP) at baseline. Of those patients, six (75%) showed clinically relevant CRSwNP improvements after 1 month. These improvements continued until the end of follow‐up in five of those patients. In one patient, symptoms returned to baseline levels at 3 months. Two patients had no relevant change in CRSwNP symptoms under dupilumab treatment. During dupilumab treatment, the annualized exacerbation rate was significantly reduced . For that reason, the evidence on exacerbation rate improvement is weak and needs to be confirmed in real‐life studies with a longer follow‐up period.Dupilumab rapidly improved asthma control in real‐life severe asthmatics. This improvement was both statistically and clinically significant. The clinical improvements seen here are comparable to both RCTsDupilumab is effective and safe in Austrian real‐life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti‐immunoglobulin E or anti‐IL5/IL5R mABs or do not adequately respond to these.Prof. Pohl reports personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, GSK, GILEAD, MedImmune, Menarini, Novartis, Sciotec, and Teva, outside the submitted work.Conception and design of the study, data analysis, interpretation of the data, wrote the first draft of the manuscript: Andreas Renner. Critically reviewed and edited the manuscript, data acquisition: Katharina Marth and Karin Patocka. Critically reviewed and edited the manuscript: Marco Idzko. Conception and design of the study, data acquisition, interpretation of the data, critically reviewed and edited the manuscript: Wolfgang Pohl.Supporting information.Click here for additional data file.