Renáta Böcskei

Reference values of aortic pulse wave velocity in a large healthy population aged between 3 and 18 years.

Objective: The measurement of aortic pulse wave velocity (PWVao) is an accepted marker in stratifying individual cardiovascular risk in adults. There is an increasing volume of evidence concerning impaired vascular function in different diseases in paediatric populations, but, unfortunately, only a few studies are available on the measurement of normal PWVao values in children. The aim of our study was to determine the reference values of PWVao in a large healthy population using a newly developed technique. Methods: Three thousand, three hundred and seventy-four healthy individuals (1802 boys) aged 3–18 years were examined by an invasively validated, occlusive, oscillometric device. Results: The mean PWVao values increased from 5.5 ± 0.3 to 6.5 ± 0.3 m/s (P < 0.05) in boys and from 5.6 ± 0.3 to 6.4 ± 0.3 m/s (P < 0.05) in girls. The increase, however, was not constant, and the values exhibited a flat period between the ages of 3 and 8 years in both sexes. The first pronounced increase occurred at the age of 12.1 years in boys and 10.4 years in girls. Moreover, between the ages of 3 and 8 years, the brachial SBP and mean blood pressures increased continuously and gradually, whereas the PWVao remained unchanged. By contrast, beyond the age of 9 years, blood pressure and aortic stiffness trends basically moved together. Conclusion: Our study provides the largest database to date concerning arterial stiffness in healthy children and adolescents between the ages of 3 and 18 years, and the technology adopted proved easy to use in large paediatric populations, even at a very young age.

Extrafine inhaled corticosteroid therapy in the control of asthma

Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits.

The Influence of Gastroesophageal Reflux Disease and its Treatment on Asthmatic Cough

Gastroesophageal reflux is known to cause chronic cough and is also implicated in worsening of asthma. We conducted a prospective study to examine the clinical significance of gastroesophageal reflux disease (GERD) in asthmatic patients with chronic cough to analyze the temporal relationship between reflux events and coughing and to assess the effect of esomeprazole treatment on respiratory symptoms and lung function in these patients. Asthmatic patients (126) with chronic dry cough were studied. Diagnosis of GERD was based on typical symptoms and the effectiveness of therapeutic test or on pH monitoring. Patients without GERD (negative pH results) consisted of the control group. The results of pH monitoring showed that 64% of cough episodes were related to acid reflux and in 91% of reflux events preceded coughing. Esomeprazole treatment (40 mg/day for 3 months) not only diminished GERD symptoms but also improved asthma outcome Baseline FEV1 and PEF values increased significantly together with a decrease in symptom scores and the use of rescue medication. In most patients included in the extended part of the study for another 3 months, the dose of inhaled steroids could be reduced with sustained GERD therapy. Our data showing that reflux events preceded coughing in most cases and that treatment of GERD resulted in an improvement in different outcome measures of asthma suggest that GERD worsens asthma, and its treatment is of clinical importance to effectively manage these patients.

Relationship of Circulating C5a and Complement Factor H Levels With Disease Control in Pregnant Women With Asthma

BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576–2.563), 1.783 (IQR 0.6064–2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively (P = .02 in all cases). C5a correlated negatively with FEV1 (r = −0.44, P = .039) and FVC values (r = −0.64, P = .001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the non-pregnant asthma group (n = 12, r = 0.78, P = .004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] μg/mL vs 559.7 [IQR 388.7–783.1] μg/mL, P = .002 and P = .004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] μg/mL, P = .10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma).

Circulating survivin levels in healthy and asthmatic pregnancy

BackgroundAsthma is one of the most common conditions which complicate pregnancy. Pro- and anti-apoptotic mechanisms can be modulated by asthma accompanying pregnancy. Survivin, an anti-apoptotic protein has been implicated in the pathomechanism of asthma and also in the development of pathological pregnancies; however survivin has not been studied in pregnant asthmatics.MethodsTwenty-eight asthmatic pregnant (AP), 25 asthmatic non-pregnant (ANP), 21 healthy pregnant (HP) and 29 healthy non-pregnant (HNP) women were enrolled in this cross-sectional study. Plasma survivin concentration was determined by ELISA.ResultsPlasma survivin was significantly lower in HP (1.64 /0-74.9/ pg/ml) than in HNP (24.6 /0-333.3/ pg/ml, p = 0.01). However, this difference was not observed between the asthmatic groups (p = 0.64). Similarly, there was no difference either between HNP and ANP (10.5 /0-215.4/ pg/ml, p = 0.23) or between HP and AP (13.9 /0-364.1/ pg/ml, p = 0.30) groups.ConclusionsDecreased plasma survivin levels in physiological but not in asthmatic pregnancy may suggest that the normal apoptotic mechanisms are compromised in asthmatic gestation.

DIURNAL RHYTHM OF CENTRAL HEMODYNAMICS DURING TWENTY-FOUR-HOUR AMBULATORY MONITORING

Objective: 24-hour ABPM is a better method for diagnosing hypertension and predicting BP-related complications than office-based measurements. In addition increasing amount of evidences supports that central (aortic) BP is stronger predictor of cardiovascular risk than the conventional brachial BP. Dipping status of subjects can be easily assessed according to night-to-day brachial BP ratio provided by ABPM. However there is no data in the literature whether the diurnal rhythm of central aortic systolic blood pressure (CASP) follows the same pattern as the brachial one (BrSP). The aim of our study was to compare the 24-hour pattern of peripherial and central blood pressure in the same individuals. Design and method: 24-hour monitoring of aortic and brachial blood pressure was performed with Arteriograph24, a newly developed upper-arm cuff oscillometric device in 55 hypertensive and normotensive subjects, 36 males and 19 females. The 24-hour systolic pressure amplification, the difference of brachial and aortic cystic pressures measured simultaneously was calculated. Augmentation index (AIx) which is one of the main determinants of central blood pressure was also assessed. Results: The nocturnal fall of CSP was significantly lower than the peripheral pressure fall in 47 subjects of 55. 24-hour systolic pressure amplification was significantly lower during the night than during the day. In contrast to the nighttime decrease of central-to-peripherial systolic pressure Augmentation index was increased during the night. Conclusions: Central hemodynamic parameters (AIx, cSBP) also have diurnal rhythm but in contrast to peripherial BP the circadian variation of central BP is not necessarily parallel with the corresponding peripherial values. Theoretically elevated peripherial vascular resistance (which is represented by the augmentation index) during nighttime helps to maintain the appropriate central systolic pressure which is mandatory for the perfusion of the brain, heart and kidneys.

From genomes to diaries: a 3-year prospective, real-life study of ragweed-specific sublingual immunotherapy

During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and maximize its benefits for the society. To provide a comprehensive phenome-wide overview in sublingual immunotherapy, using ragweed allergy as a target, we planned and carried out a longitudinal, prospective, observational, open-label study (DesensIT). In this paper we present challenges of using deep and comprehensive phenotypes embracing biological, clinical and patient-reported outcomes in allergen-specific immunotherapy and show how we designed the DesensIT project to optimize data collection, processing and evaluation.