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The "Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients" (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP "P. Giaccone" of the University of Palermo, and the results obtained were compared with those of a control group without respiratory or cardiovascular diseases. Patients with asthma showed a marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass with a significantly greater percentage of patients with overt left ventricular hypertrophy, worse left ventricular diastolic function proven by the significant difference in the E/A ratio, and worse right ventricular systolic function with global right ventricular dysfunction estimated by the Myocardial Performance Index (Tei Index). Multivariate regression analysis, after adjustment for essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, seems to indicate that the indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not left ventricular hypertrophy) correlate significantly with asthma, severe asthma, and FEV1 (and to a lesser extent with asthma duration). No correlation is apparent between inhaled therapy (ICS, SABA) and myocardial involvement. These results seem to confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease allows the identification of unrecognized cardiovascular involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment has identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserve further validation in the future. [ABSTRACT FROM AUTHOR]

Background: Poor adherence with inhaled corticosteroid (ICS) medication is common in the pediatric population and can result in poor asthma control with increased frequency of asthma-related complications. The purpose of this study was to determine whether or not the initiation of ICS administration twice per day at school/daycare in patients with poor medication adherence at home improves asthma health care outcomes. Methods: We retrospectively selected patients followed by our Pediatric Pulmonology Clinic who had poorly controlled asthma and had been assigned to receive ICS twice daily at school/daycare due to poor adherence with ICS therapy. We analyzed the number of short courses of oral corticosteroids, hospital admissions, emergency department visits, and intramuscular methylprednisolone administrations for asthma exacerbations for the year before and after the intervention. The Wilcoxon signed rank test with continuity correction was used in the primary analysis. Results: Forty-nine patients who met the inclusion criteria were identified, but only 40 actually started the intervention. The number of oral corticosteroid courses per year decreased from 1.35 ± 1.1 before the intervention to 0.68 ± 1.2 (P = 0.008) postintervention, hospital admissions per year decreased from 0.45 ± 0.7 to 0.10 ± 0.3 (P = 0.006), emergency department visits per year decreased from 0.55 ± 0.8 to 0.28 ± 0.6 (P = 0.084), and intramuscular repository methylprednisolone injections per year for asthma exacerbations decreased from 0.20 ± 0.4 to 0.10 ± 0.3 (P = 0.23). Conclusion: These results indicate that school/daycare administration of ICS may be an effective option to improve indicators of asthma exacerbations in children with poor adherence to ICS at home. [ABSTRACT FROM AUTHOR]

Background Controversial data exist on the possibility that inhaled corticosteroids ( ICs) affect growth in children with mild-to-moderate asthma. We assessed whether ICs affect growth and final height ( FH) in asthmatic children compared to controls. Methods A retrospective study was conducted on 113 asthmatic children compared with 66 control children. Asthmatic children presented with mild-to-moderate asthma and had exclusive ICs. Anthropometric data of four specific time-points were collected for both groups (pre-puberty, onset and late puberty, and FH) and converted to standard deviation scores ( SDS). Growth trajectories were assessed as follows: (i) in puberty, using peak height velocity ( PHV) and pubertal height gain SDS ( PHG- SDS); (ii) until FH achievement, using FH- SDS and FH gain SDS ( FHG- SDS). Repeated measurement analysis was performed across longitudinal study visits. A general linear model ( GLM) was performed in asthmatic group evaluating the effect of corticosteroid type, treatment duration, and cumulative dose on FH corrected for multiple variables. Results At pre-puberty, height and weight SDS were similar between the groups (p > 0.05). Height SDS progressively declined over the study period in asthmatic patients from pre-puberty to FH (p-trend < 0.05), whereas it did not change over time in controls (p-trend > 0.05), in both boys and girls. Asthmatic children had exclusive ICs [budesonide (n = 36) vs. fluticasone (n = 43) vs. mometasone (n = 34)] for a mean period of 6.25 ± 1.20 years and a mean cumulative dose of 560.07 ± 76.02 mg. They showed decreased PHG- SDS and lower PHV compared to controls (all p < 0.05). FH- SDS and FHG- SDS were significantly reduced in asthmatic group compared to controls. FH in asthmatic patients was 2.5 ± 2.89 cm lower in boys and 2.0 ± 2.03 cm lower in girls than controls. The GLM showed that FH achievement was dependent on the type of ICs, duration of the treatment, and cumulative dose (p < 0.05). Conclusions ICs affect pubertal growth determining reduced final height in asthmatic children compared to controls, in a dose- and duration-dependent manner. [ABSTRACT FROM AUTHOR]

Objective: While the majority of individuals with asthma retain normal lung function over time, some exhibit accelerated lung function decline. Preservation of lung function is an important aspect of asthma management. Whether the asthma guidelines can prevent lung function decline remains controversial. This study was performed to determine the distribution of asthmatic subjects with greater lung function decline and to identify characteristic clinical features of such subjects treated in accordance with clinical guidelines by using hierarchical cluster analysis. Methods: Eighty-six asthmatic subjects without a history of smoking were assessed with respect to eight variables selected from clinical phenotypes by using step-wise multiple regression analysis. Hierarchical cluster analysis using Ward's method generated a dendrogram for estimation of the number of clusters within the population and the differences between them. Results: Three distinct clusters were identified. Cluster 1 ( n = 40) comprised women with late-onset asthma. Cluster 2 ( n = 17) comprised subjects with early-onset asthma, atopy and long disease duration. Cluster 3 ( n = 29) predominantly comprised older men who had late-onset asthma, a lower prevalence of exacerbation and a lower predicted % forced expiratory volume in 1 s (FEV1) at baseline. Subjects in cluster 3 showed a mean decline in FEV1 of 69 mL/year, which was the greatest lung function decline among the three clusters. Conclusion: We identified a subgroup of patients with accelerated lung function decline despite appropriate asthma treatment based on guidelines constructed by using subjective symptoms. [ABSTRACT FROM AUTHOR]

The effect of long-term use of inhaled corticosteroid (ICS) on growth in asthmatic children and adolescents remain a controversial issue. Objective: To determine whether inhaled steroid therapy causes delayed linear growth and other anthropometric parameters change (height, weight, body mass index--BMI) in children with asthma in a 2 years survey. Methods: 76 children (5-18 years old) with mild to severe persistent asthma treated with inhaled coricosteroids alone or in association with long acting beta agonist therapy and other anti-inflammatory therapy (montelukast) in conformity with GINA 2006 guideline was assessed in Department of Clinical Allergology and Immunology "St. Marie" Children Hospital--Iassy. The dynamic relationship between ICS--dose and linear growth was followed. Height/age, weight/age and BMI/age Z scores were calculated every twelve months and the data obtained was compared with those recorded from 75 children--control group. Results: after 2 years of ICS use in children with asthma we found a decrease in height gain velocity especially in the second year of survey (p=0,012), without any statistical significant impact on weight and BMI. There was no correlation between the level of ICS dose (small, medium or height) and the growth curve in height, weight and BMI. Conclusions: long-term ICS therapy might affect the linear growth in children with asthma regardless of dose, without a significant impact on weight or BMI. [ABSTRACT FROM AUTHOR]

Background Active cigarette smoking has detrimental effects on asthma morbidity and severity. Angiopoietin-1 has been shown to protect the microvessels against plasma leakage, whereas angiopoietin-2 enhances vascular permeability and subsequently induces airway mucosal oedema. Therefore, it is recently thought that angiopoietin-2 may contribute to the pathophysiology of asthma. Objective To determine whether angiopoietin-2 levels in the airways are associated with clinical profiles in smoking asthmatics. Methods We measured angiopoietin-1 and -2 levels in induced sputum in 35 normal controls (18 non-smokers and 17 smokers) and 49 asthmatics (24 non-smokers and 25 smokers) before and after inhaled beclomethasone dipropionate (BDP: 800 μg/day) therapy for 12 weeks. Results Angiopoietin-1 and -2 levels in induced sputum were significantly higher in asthmatics than in normal controls. Moreover, angiopoietin-2 levels were significantly higher in smoking asthmatics than in non-smoking asthmatics ( P=0.0001). The airway vascular permeability index was also higher in smoking asthmatics than in non-smoking asthmatics. Moreover, the angiopoietin-2 level was positively correlated with the airway vascular permeability index (non-smoking asthmatics: r=0.87, P<0.001, smoking asthmatics: r=0.64, P=0.002). After BDP therapy, angiopoietin-1 levels were significantly decreased in non-smoking asthmatics, smoking-cessation asthmatics, and active-smoking asthmatics. In contrast, angiopoietin-2 levels did not differ from before to after BDP therapy in non-smoking asthmatics and active-smoking asthmatics. However, its levels were significantly decreased from before to after BDP therapy in smoking-cessation asthmatics ( P=0.002). Although forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) before BDP therapy was comparable in all subgroups, this parameter after BDP therapy was significantly lower in active-smoking asthmatics than in non-smoking and smoking-cessation asthmatics. Moreover, the reduction in angiopoietin-2 levels after BDP therapy in smoking-cessation asthmatics was significantly correlated with an mprovement in FEV1/FVC. Conclusion Angiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses. [ABSTRACT FROM AUTHOR]

Research on the biology of airway epithelium in the last decades has progressively uncovered the many roles of this cell type during the immune response. Far from the early view of the epithelial layer simply as a passive barrier, the airway epithelium is now considered a central player in mucosal immunity, providing innate mechanisms of first-line host defense as well as facilitating adaptive immune responses. Alterations of the epithelial phenotype are primarily involved in the pathogenesis of allergic airways disease, particularly in severe asthma. Appreciation of the epithelium as target of glucocorticoid therapy has also grown, because of studies defining the pathways and mediators affected by glucocorticoids, and studies illustrating the relevance of the control of the response from epithelium in the overall efficacy of topical and systemic therapy with glucocorticoids. Studies of the mechanism of action of glucocorticoids within the biology of the immune response of the epithelium have uncovered mechanisms of gene regulation involving both transcriptional and posttranscriptional events. The view of epithelium as therapeutic target therefore has plenty of room to evolve, as new knowledge on the role of epithelium in immunity is established and novel pathways mediating glucocorticoid regulation are elucidated. [Copyright &y& Elsevier]

In the study reported here, investigators explored the following: (1) the effects of inhaled corticosteroid (ICS) therapy on insulin sensitivity (IS) (the Homeostatic Model Assessment-Insulin Resistance [HOMA-IR] Index, which has never been used before in nondiabetic patients with asthma and chronic obstructive pulmonary disease [COPD], was used in this investigation); and (2) differences and similarities between asthma and COPD groups. A total of 12 patients with asthma and 6 with COPD who were not previously treated with oral corticosteroids or ICSs were treated with budesonide, 400 μg twice daily for 8 wk, via dry powder inhaler through the Aerolizer. Pretreatment and posttreatment values were recorded for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, C-reactive protein (CRP), blood glucose, serum insulin levels, area under the curve (AUC) for glucose and insulin in an oral glucose tolerance test (OGTT), and HOMA-IR Index. The trapezoid technique, the formula for HOMA-IR, and Wilkinson, Mann-Whitney U, and t tests were used. In the group of patients with asthma, posttreatment values for the HOMA-IR Index, glucose, and insulin at all time points during OGTT and AUC for glucose and AUC for insulin were not statistically different compared with pretreatment values. In patients with COPD who had been given ICS therapy, however, the second hour glucose level during OGTT increased significantly compared with pretreatment values ( P=.46). Pretreatment and posttreatment second hour insulin values and posttreatment AUC for glucose were significantly higher in the COPD group than in the asthma group ( P=.047, P=.044, and P=.031, respectively). A moderate positive correlation was noted between the percentage of difference in FEV1 and the change in HOMA-IR (pretreatment mean value of HOMA-IR±standard deviation [SD], 2.7±2.6) in asthmatic patients as the result of therapy (r=0.50, P=.138). Investigators concluded the following: (1) Differences in pathogenesis between asthma and COPD seem to offer the most plausible explanation for differences in carbohydrate metabolism achieved through ICS therapy; (2) the effect of an ICS on IS is associated not only with dose, treatment period, age, and body mass index (BMI) but also with the severity of initial mucosal inflammation; and (3) as a result of improvements in respiratory function noted after treatment had been given, IS was increased in asthmatic patients. [ABSTRACT FROM AUTHOR]

Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects., Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM)., Results: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group ( p : 0.012). Reduced level of FEV 1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension ( p : 0.0002), higher day SBP levels ( p : 0.003), higher day DBP levels ( p : 0.03), higher 24 h-SBP levels ( p : 0.005) and higher 24h-DBP levels ( p : 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29-11.1)., Conclusions: hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.

Background: There is a growing belief that patients with bronchial asthma (BA) should be provided an individualized and optimized treatment plan. We aimed to clarify the predictors of long-term prognoses in patients with mild BA., Methods: We conducted a retrospective study of consecutive patients who were newly diagnosed with mild BA at Iwate Medical University from 2011 to 2013, focusing on achievement of full asthma control based on the Asthma Control Test as an indicator of prognosis. Predictors were identified on the basis of a chart review., Results: Among 71 patients with mild BA, 37 patients completed regular clinic visits for 1 year. Nineteen (51.4%) of these patients achieved full asthma control. Current smoking and the fractional exhaled nitric oxide (FeNO) level at the first patient visit were identified by multivariate logistic regression as possible predictors of the discontinuation of clinic visits and achievement of full asthma control, respectively. Low FeNO levels at the first clinic visit yielded a receiver operating characteristic-area under the curve of 0.860 (95% confidence interval [CI]=0.774-0.975) for the achievement of full asthma control. Using an FeNO cut-off level of 34 parts per billion yielded a sensitivity of 76.5% (95% CI=59.5-88.2%) and specificity of 73.7% (95% CI=58.5-84.2%)., Conclusion: Our preliminary results suggested that patients with newly diagnosed mild BA who display higher FeNO levels at their first clinic visits should be appropriately educated during early visits to receive optimal treatment and complete regular clinic visits., (Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)