Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy

<p>Abstract</p> <p>Objective</p> <p>Anti IgE treatment with omalizumab is efficacious in the treatment of patients suffering from allergic asthma, improving asthma control and improving quality of life. Furthermore, this approach could be beneficial for patients with concomitant atopic dermatitis. We assessed quality of life and asthma control in atopic patients with allergic asthma and concomitant atopic dermatitis versus those with asthma and without atopic dermatitis treated with omalizumab.</p> <p>Methods</p> <p>A total of 22 patients with severe allergic asthma were treated with omalizumab for 12 months. 13 patients with allergic asthma without concomitant atopic dermatitis (IgE 212 ± 224 IU/ml) and 9 patients with concomitant allergic asthma and atopic dermatitis (IgE 3,528 ± 2,723 IU/ml) were included. Asthma-related quality of life (AQLQ), atopic dermatitis related quality of life (DLQI), and asthma-related treatment were compared between both groups at baseline and after initiating omalizumab treatment.</p> <p>Results</p> <p>DLQI was significantly in favor of omalizumab after 2 months in the atopic dermatitis/asthma group (P = 0.01); AQLQ was improved after 6 months in the asthma group (P = 0.01), while no change was seen in AQLQ in the atopic dermatitis/asthma group (P = 0.12). Omalizumab controlled oral corticosteroid use more effective (P < 0.01) in patients with asthma and atopic dermatitis (in 9/9 cases) compared to patients with asthma alone (9/13). Baseline IgE as well as other factors do not predict response to omalizumab.</p> <p>Conclusions</p> <p>Omalizumab is effective in improving atopic dermatitis-related quality of life scores and modulates oral corticosteroid use in patients with concomitant asthma and atopic dermatitis in a positive fashion.</p

Risk and fate of residual interatrial shunting after transcatheter closure of patent foramen ovale: a long term follow up study

<p>Abstract</p> <p>Background</p> <p>Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke is an alternative to medical therapy. There is still debate on different outcome for each currently available device. The impact of residual shunting after PFO-clo- sure on recurrent arterial embolism is unknown.</p> <p>Aims</p> <p>(i) To evaluate the prevalence of residual interatrial shunting after device- closure of PFO, (ii) to identify risk factors predicting residual interatrial shunting after device implantation, and (iii) to investigate the outcome of patients after PFO-closure during long- term follow- up (FU).</p> <p>Methods and results</p> <p>Between 2000- 2005 PFO-closure was performed in 124 patients using four different devices: Amplatzer PFO-(n = 52), CardioSeal (n = 33), Helex (n = 23) and Premere (n = 16) occluder. All patients underwent serial contrast-enhanced transesophageal echocardiography (TEE) for 24 months after PFO- closure; clinical FU was at minimum 5 years up to 9.75 years (mean 6.67 ± 1.31 years). Overall-closure rate was 87% at 2 years, device-specific closure time curves differed significantly (p-logrank = 0.003). Independent risk factors for residual-shunting were implantation of a Helex occluder (hazard ratio [HR] 12.6, 95% confidence interval [CI] 2.6- 57.4, p = 0.002), PFO- canal- lengths (HR 1.2, 95%CI 1.1- 1.3, p = 0.004) and extend of atrial-septal-aneurysm (HR 1.1, 95%CI 0.9- 1.3; p = 0.05). 4 (3.2%) arterial embolic events occurred during a FU-period of 817.2 patient-years, actuarial annual thromboembolic-risk was 0.49%. All ischemic events were not related to residual PFO-shunting or device-related thrombus- formation.</p> <p>Conclusion</p> <p>Success rates of PFO- closure are mainly dependent on occluder-type, extend of concomitant atrial-septum-aneurysm and PFO-canal- length. Importantly, residual shunting after PFO-closure was not associated with recurrence of arterial embolism during long-term follow-up.</p

An International Multi-Center Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multi-center collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (JLNS2, N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc > 460ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 JLNS2 patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9 ± 38.6ms) compared to genotype positive family members (441.8 ± 30.9ms, p<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR]: 11.6, 95% confidence interval [CI]: 2.6-52.2; p=0.001). Event incidence did not differ significantly for JLNS2 patients relative to the overall heterozygous cohort (10.5% [2/19]; HR: 1.7, 95% CI: 0.3-10.8, p=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database (gnomAD), which is a human database of exome and genome sequencing data from now over 140,000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs. 0.001%). Conclusions: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT-prolongation, however the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for JLNS2 patients

Efficacy and safety of sacubitril/valsartan in an outpatient setting: A single-center real-world retrospective study in HFrEF patients with focus on possible predictors of clinical outcome

Background: Currently, data on sacubitril/valsartan therapy from the real-world settings are scarce and the predictors of a good clinical responsiveness to this drug are unknown. Objectives: To assess efficacy and safety profile of sacubitril/valsartan and to identify predictors for a better clinical outcome. Materials and methods: Clinical, laboratory and echocardiographic data of 95 chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) were retrospectively analyzed. A good efficacy of sacubitril/valsartan was defined as the fulfilment of at least 2 of the following criteria: improvement of left ventricular ejection fraction (LVEF) or functional status, and reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels or hospitalization rates. Results: Under sacubitril/valsartan, major improvements were observed in LVEF, the New York Heart Association (NYHA) class, NT-proBNP levels, and hospitalization rates. Patients with a good efficacy of sacubitril/valsartan were characterized by initially worse LVEF (median (interquartile range (IQR)): 29.0% (23.0–33.0%) compared to 32.0% (28.5–38.0%) with more frequent nonischemic etiology (65.4% compared to 41.9%) and hospitalizations for CHF/month (0.016 (0.004–0.057) compared to 0.000 (0.000–0.012)), lower cholesterol (42.3% compared to 65.1%), higher C-reactive protein (CRP) levels at baseline (0.5 mg/L (0.5–1.0 mg/L) compared to 0.5 mg/L (0.5–0.5 mg/L)), and a shorter timespan between CHF diagnosis and the start of sacubitril/valsartan treatment (66.0 (11.0–127.0) compared to 111 (73.0–211.0) months) (p < 0.05 each). In a multivariate Cox analysis, only the last 2 parameters were shown to be independent predictors of good clinical responsiveness to sacubitril/valsartan (hazard ratio (HR) = 1.263, 95% confidence interval (95% CI) = [1.048; 1.521]; HR = 0.992, 95% CI = [0.987; 0.997], p < 0.05, respectively). Conclusions: Sacubitril/valsartan improved LVEF, NYHA class, NT-proBNP levels, and hospitalization rates, mostly without relevant side effects. The independent predictors of a good clinical efficacy were higher CRP levels at baseline and a shorter delay between CHF diagnosis and the initialization of sacubitril/valsartan therapy

Diaphragm involvement in heart failure: Mere consequence of hypoperfusion or mediated by hf-related pro-inflammatory cytokine storms?

status: publishe

Validity of transit time–based blood pressure measurements in patients with and without heart failure or pulmonary arterial hypertension across different breathing maneuvers

Purpose: Pulse transit time (PTT) derived by ECG and plethysmographic signal can be a promising alternative to invasive or oscillometry-based blood pressure (BP) monitoring in sleep laboratories because it does not cause arousals from sleep. Therefore, this study assessed the validity of PTT for BP monitoring under sleep laboratory-like conditions. Methods: Ten volunteers (55.8 ± 19.6&nbsp;years), 12 patients with heart failure with reduced ejection fraction (HFrEF; 67.3 ± 8.6&nbsp;years), and 14 patients with Nizza class I pulmonary arterial hypertension (PAH; 59.5 ± 13.4&nbsp;years) performed different breathing patterns to simulate nocturnal sleep-disordered breathing (SDB). BP was measured at least every 15&nbsp;min over 1&nbsp;h using oscillometry (Task Force Monitor™) and PTT (SOMNOscreen™) devices in free breathing conditions and during SDB simulation (alternating phases of hyperventilation and apneas). Results: One hundred forty-two points of measurements were collected. No difference was found in both mean systolic BP (SBP) and diastolic BP (DBP) between oscillometric PTT-based BP measurements in the whole population and throughout the whole recording (SBP 111.3 ± 15.1&nbsp;mmHg versus 110.0 ± 14.7&nbsp;mmHg, p = 0.051; DBP 69.9 ± 12.2 versus 69.9 ± 14.2&nbsp;mmHg, p = 0.701). Likewise, no significant difference in SBP and DBP was found between the two methods in the subgroups of healthy subjects, HFrEF patients and PAH patients, both in free breathing conditions (p &gt; 0.05) and during SDB simulation (p &gt; 0.05). Conclusions: When monitoring BP in healthy subjects, and in patients with HFrEF or PAH, PTT provides a BP estimation comparable with oscillometric measurement, though slightly inaccurate, both in the condition of regular and unstable breathing

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis

BackgroundSarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis.ObjectivesThe aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis.Methods54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay.ResultsBetween 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (pConclusionsAmong patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF

High prevalence of COPD in atherosclerosis patients

Izabela Tuleta, Tarik Farrag, Laura Busse, Carmen Pizarro, Christian Schaefer, Simon Pingel, Georg Nickenig, Dirk Skowasch, Nadjib Schahab Department of Internal Medicine II &ndash; Cardiology, Pulmonology and Angiology, University of Bonn, Bonn, Germany Abstract: Atherosclerosis and COPD are both systemic inflammatory diseases that may influence each other. The aim of the present study was to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD. Following the diagnosis of cerebral and/or peripheral artery disease by means of duplex sonography, 166 consecutive patients underwent body plethysmography with capillary blood gas analysis. Thereafter, blood tests with determination of different parameters such as lipid profile, inflammatory and coagulation markers were conducted in remaining 136 patients who fulfilled inclusion criteria of the study. Thirty-six out of 136 patients suffered from COPD, mostly in early stages of the disease. Residual volume indicating emphysema was increased (162.9%&plusmn;55.9% vs 124.5%&plusmn;37.0%, p&lt;0.05) and diffusion capacity was decreased (55.1%&plusmn;19.5% vs 75.3%&plusmn;18.6%, p&lt;0.05) in COPD patients vs non-COPD group. In capillary blood gas analysis, COPD patients had lower partial pressure of oxygen (70.9&plusmn;11.5 vs 75.2&plusmn;11.0 mmHg, p&lt;0.05) and higher partial pressure of carbon dioxide (36.8&plusmn;7.5 vs 34.4&plusmn;4.4 mmHg, p&lt;0.05) compared with non-COPD individuals. Presence of COPD was associated with predominance of diabetes mellitus, interleukin-8-related systemic neutrophilic inflammation and anemia. In conclusion, COPD is highly prevalent in patients with atherosclerotic artery disease. Keywords: cerebral artery disease, peripheral artery disease, lung function, capillary blood gas, diabetes mellitus, inflammation, interleukin-8, anemi