Biomarkers of airway and systemic inflammation in obese asthmatic paediatric patients

BackgroundIt is thought that airway inflammation is more common in obese asthmatic patients because inflammation is harder to control and does not respond well to glucocorticoid treatment.ObjectiveThis study's aim was to investigate the effect of obesity on airway and systemic inflammation in children with asthma and to identify the biomarkers that play a role in this inflammation.MethodsThe study included patients aged 6–16 years who were diagnosed with asthma in the paediatric allergy outpatient clinic of Bagcilar Training and Research Hospital in Turkey. Complete blood count parameters were compared between three groups: obese asthmatic (n = 43), obese non-asthmatic (n = 45), and non-obese non-asthmatic (control group, n = 30). Levels of high-sensitive CRP (hs-CRP), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and matrix metalloproteinase-9 (MMP-9), and 25(OH)-vitamin D were compared between the groups.ResultsNo statistically significant differences were observed in 25(OH)-vitamin D, NGAL, OPN, hs-CRP, and MMP-9 levels between groups. There was a statistically significant negative correlation between FEV1/FVC and NGAL and MMP-9.ConclusionThis is the first study to investigate levels of hs-CRP, NGAL, OPN, MMP-9, and 25(OH)-vitamin D in obese asthmatic children. Larger studies with sputum and BAL examinations are required to determine the potential of biomarkers for identifying inflammation in obese asthmatic children.     

Elevated level of serum osteopontin in school-age children with asthma

BackgroundThe role of osteopontin (OPN) has not been elucidated in childhood asthma.ObjectiveOur purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children.MethodsIn this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups.ResultsSerum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p > 0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n = 13) without allergic rhinitis (p = 0.021).ConclusionThe study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group.     

Leptin and resistin in overweight patients with and without asthma

BackgroundExcess body mass increases the risk of development of asthmatic symptoms and their severity and decreases the treatment effectiveness. One of the hypotheses explaining the link between the two diseases concerns the adipokines, hormones produced by adipose tissue with a proinflammatory character. The aim of this study was to compare the levels of the adipokines (leptin and resistin) between overweight asthmatic patients, asthmatic patients with normal weight and overweight patients without asthma.Methods80 peripheral blood samples were collected from patients and blood serum extracted. Three groups were selected: overweight asthmatic patients (BMI ≥ 25), overweight patients without asthma and asthmatic patients with normal weight (BMI < 25). Waist circumference of the patients was measured (cut-off points were 80 cm for women and over 94 cm for men) and a skin prick test performed. Comparison of adipokine concentration between the 3 groups was made and association between these concentrations and the measurements was performed.ResultsAlthough the concentrations of both adipokines were slightly higher for overweight asthmatic patients compared to overweight healthy patients, these differences were not significant. A significant association was found between leptin concentration and both BMI (p < 0.01) and waist circumference (p < 0.01). A difference for this cytokine was also found between asthmatic and non-asthmatic female patients (p < 0.05).ConclusionsAs expected overweight patients with BMI ≥ 25 and patients with increased waist circumference showed higher leptin levels. We suggest that the studied cytokines, with a stronger indication for leptin, can elicit asthmatic inflammation in obese phenotype of asthma that affects more frequently women.     

Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity,asthma control level,and asthma control test score

ObjectiveExhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children.MethodsThirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit.ResultsExhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55–146) pg/ml] was higher than in the mild persistent group [52 (21–91) pg/ml] (p = 0.05, Mann–Whitney U [MWU]). EBC 8-isoprostane in children with 1–4 asthma exacerbations/year [52 (16–80) pg/ml] was significantly lower than in children with >4 asthma exacerbations/year [114 (57–129) pg/ml] (p < 0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p = 0.015, r = −0.45).ConclusionsExhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation.     

The Fractional Exhaled Nitric Oxide and Serum High Sensitivity C-Reactive Protein Levels in Cough Variant Asthma and Typical Bronchial Asthma

BackgroundFractional exhaled nitric oxide (FeNO) is known to be a good marker of airway eosinophilic inflammation in bronchial asthma. Recently, serum high sensitivity C-reactive protein (hs-CRP) has been shown to be also useful to detect the airway inflammation.MethodsNewly diagnosed 90 cough variant asthma and 92 bronchial asthma patients were enrolled. FeNO, serum hs-CRP, pulmonary function tests, bronchial hyperresponsiveness, IgE and sputum eosinophils ratio were compared. Ninety healthy control subjects were set for FeNO and serum hs-CRP normal range reference. We have compared the clinical utilities of FeNO and serum hs-CRP to differentiate bronchial asthma and cough variant asthma.ResultsFeNO was significantly higher in bronchial asthma (92.6 ± 85.5 ppb) than in cough variant asthma (35.6 ± 43.3; p < 0.001) and both were significantly higher than normal range (18.0 ± 6.4, p < 0.001, respectively), and in differentiating between the two groups showed a sensitivity of 0.69 and a specificity of 0.73 at the cutoff value of 28 ppb. Serum hs-CRP did not differ significantly between bronchial asthma (723 ± 1162 ng/ml) and cough variant asthma (558 ± 758) even if both were significantly higher than normal range (345 ± 401, p < 0.01 and p < 0.05 respectively).ConclusionsFeNO is more useful than serum hs-CRP in differentiating patients with bronchial asthma from those with cough variant asthma, and healthy persons.     

Short and long-term quality of life and asthma control with omalizumab therapy in a real life setting in Portugal

BackgroundThe impact of severe asthma on patients’ quality of life (QoL) has been previously demonstrated, as well the difficulties in controlling the disease. We aimed to evaluate the effect of omalizumab on QoL and asthma control, and its safety and tolerability in real-life conditions in Portugal.MethodsProspective and open-label study in 15 adult patients with uncontrolled severe persistent allergic asthma on omalizumab treatment ≥16 weeks (w). The short (at 16 w) and long-term (at 1 and 2 years) (y) effects of omalizumab were assessed through the Asthma Life Questionnaire (ALQ) and the Asthma Control Test (ACT). Other secondary outcomes were evaluated.ResultsA significant reduction in ALQ total score (at 16 w, p = 0.002; at 1 y, p = 0.033 and at 2 y, p = 0.024), as well as in the ‘non-scheduled medical visits’ and the ‘medication use’ domains in both the short and long terms was observed. Regarding ACT, we verified a significant improvement in total score (at 16 w, p = 0.004; at 1 y, p = 0.004 and at 2 y, p = 0.008) and in almost all of the five individual questions. Asthma exacerbations and unscheduled health care visits were significantly decreased. There was a significant rise in lung function and a decrease in daily inhaled steroids dose. The most frequent adverse effects were headaches and nausea.ConclusionsOmalizumab promoted a global benefit on QoL and asthma control outcomes. It also yielded a reduction in asthma exacerbations and unscheduled health care visits, a steroid-sparing effect, and an improvement in lung function. The drug was found to be generally safe and well-tolerated.     

The relation of innate and adaptive immunity with viral-induced acute asthma attacks: Focusing on IP-10 and cathelicidin

BackgroundDespite growing evidence suggesting potential association between innate and adaptive immunity in viral-induced acute asthma, there is paucity of data in this area.ObjectiveThis study aimed to investigate the association of innate and adaptive immunity with acute asthma attacks by analysing the role of IFN-γ-inducible protein 10 (IP-10), TLR2, cathelicidin, vitamin D and cytokines.Material and methodsThis prospective study included 33 patients with viral-induced acute asthma and 30 children with controlled asthma. Nasopharyngeal swab samples were collected for virus identification and asthma attack scores assessed in acute asthma group. Blood sampling for IP-10, TLR2, cathelicidin, vitamin D levels, and spirometric indices were employed.ResultsSerum IP-10 and cathelicidin levels of acute asthma group were significantly higher and vitamin D levels were lower than controlled asthma group (IP-10; p = 0.006, cathelicidin; p = 0.002, vitamin D; p < 0.001). Serum IP-10 levels showed a significant negative correlation with age (p = 0.009), TLR2 (p = 0.05) and spirometric indices (p = 0.002) in all asthmatics and a significant positive correlation with parameters of asthma attack severity (p = 0.03) in acute asthma group. Higher cathelicidin values showed significant positive relation to IP-10 (beta coefficient: 33, p = 0.02). Serum IP-10 levels higher than 38.9 pg/ml (sensitivity: 85%, specificity: 47%, p = 0.002) were predictive of virus-induced asthma. Serum IP-10 and vitamin D levels were found to be significantly related to viral-asthma attacks (IP-10; aOR: 8.93, p = 0.03 and vitamin D; aOR: 0.82, p = 0.001).ConclusionsInnate immunity biomarkers such as serum IP-10 and cathelicidin can be used to predict viral-induced acute asthma. These biomarkers may provide potential new treatment targets for acute asthma.     

Phenotype properties and status of corticosteroid resistance among patients with uncontrolled asthma

BackgroundControl cannot be achieved in some asthmatics although optimal monitoring and treatment is administered. Glucocorticoid (GC) resistance is one of the reasons of poor asthma control. We aimed to investigate GC resistance by lymphocyte proliferation suppression test (LPST) in uncontrolled asthmatics.MethodsAfter assessing asthma control level of 77 asthmatics their treatment was adjusted upon GINA guidelines. They were followed-up for three to six months and the patients who remained uncontrolled were accepted as uncontrolled patients. Steroid resistance test (SRT) was applied to them (7–14 days oral prednisolone) and the patients who were still uncontrolled and/or had a FEV1 increase <15% after SRT were assessed as the “case group” while the remaining composed the “control group”. Optimal treatment was adjusted and at the end of a follow-up period LPST was performed to both groups.ResultsFourteen of the case (n = 22) and four (n = 8) of the control groups could be evaluated by LPST. Proliferated lymphocytes were observed to be significantly suppressed in all dexamethasone concentrations in the control group (p = 0.001). However, in the case group LPST was positive only at 10^?6 and 10^?4 concentrations although statistically not significant (p = 0.147). There was no significant relationship between clinically GC resistance and LPST positivity (p = 0.405).ConclusionWe determined that in vitro responses to the GCs were significantly declined in the uncontrolled asthma cases. An SRT alone does not seem to be very sensitive for evaluating GC sensitivity, LPST may be performed for demonstrating GC responsiveness in asthmatic patients in addition to SRT.     

Diagnostic and prognostic value of some biochemical markers in early knee osteoarthritis

BackgroundOsteoarthritis (OA); the most common joint disease, is not only characterized by cartilage destruction; but also by alteration of bone and synovial tissue metabolism, though their relative importance in the initiation and progression of OA is still debated. To identify patients with a high risk for destructive OA, more sensitive techniques than plain X-rays are needed.Aim of the workTo study the diagnostic and prognostic value of some biochemical markers serum hyaluronic acid (HA) and serum cartilage oligomeric matrix protein (COMP), high sensitive C-reactive protein (hs-CRP) in the included patients had early OA knees and their relation to disease progression.Patients and methodsSixty patients had early knee OA and 20 control subjects were included. WOMAC index, laboratory investigations (COMP, HA, hs-CRP) and radiological evaluation (Kellgren and Lawrence grading scale and Thomas compartmental score) were performed for each patient at baseline and after one year.ResultsHA was significantly higher in patients than controls (p > 0.001) with the highest specificity and positive predictive value. It was significantly correlated with COMP at baseline and after one year (p = 0.01). The levels of HA at baseline correlated with its levels after one year (p > 0.001). It also correlated with K–L grading score (p = 0.02). COMP was significantly higher in patients than controls (p > 0.001). It was significantly correlated with Thomas score after one year (p = 0.007). Baseline levels of COMP correlated significantly with its levels after one year (p = 0.005). The differences of the serum levels of hs-CRP at the baseline evaluation and after one year between patients and controls were not statistically significant (p = 0.4, 0.5, respectively).ConclusionsThe measurements of HA and COMP may be of diagnostic and prognostic value in differentiating patients with early joint destruction and in determining disease progression. A single biochemical marker has definitive diagnostic value and the combination with other biochemical markers as well as with clinical and radiographic data would most likely help to improve the clinical assessment of patients. Serum hs-CRP is not a good predictor of individual patient progression and has a poor sensitivity and specificity.     

Increased level of resistin predicts development of atrial fibrillation

BackgroundResistin is a peptide hormone that is secreted from lipid cells and is linked to type-2 diabetes, obesity, and inflammation. Being an important adipocytokine, resistin was proven to play an important role in cardiovascular disease. We compared resistin levels in patients with and without atrial fibrillation (AF) to demonstrate the relationship between plasma resistin levels and AF.MethodOne hundred patients with AF and 58 control patients who were matched in terms of age, gender, and risk factors were included in the trial. Their clinical risk factors, biometric measurements, echocardiographic work up, biochemical parameters including resistin and high-sensitivity C-reactive protein (hs-CRP) levels were compared.ResultsIn patients with AF, plasma resistin levels (7.34 ± 1.63 ng/mL vs 6.67 ± 1.14 ng/mL; p = 0.003) and hs-CRP levels (3.01 ± 1.54 mg/L vs 2.16 ± 1.28 mg/L; p = 0.001) were higher than control group. In subgroup analysis, resistin levels were significantly higher in patients with paroxysmal (7.59 ± 1.57 ng/mL; p = 0.032) and persistent AF (7.73 ± 1.60 ng/mL; p = 0.006), but not in patients with permanent AF subgroups (6.86 ± 1.61 ng/mL; p = 0.92) compared to controls. However, hs-CRP levels were significantly higher only in permanent AF patients compared to control group (3.26 ± 1.46 mg/L vs 2.16 ± 1.28 mg/L; p = 0.02). In multivariate regression analysis using model adjusted for age, gender, body mas index, hypertension, diabetes mellitus, and creatinine levels, plasma resistin levels [odds ratio (OR): 1.30; 95% confidence interval (CI): 1.01–1.70; p = 0.04] and hs-CRP levels (OR: 1.44; 95% CI: 1.12–1.86; p = 0.004) were the only independent predictors of AF.ConclusionThe elevated levels of plasma resistin were related to paroxysmal AF group and persistent AF group, but not to permanent AF group.     

Serum levels of adiponectin and leptin in asthmatic patients and its relation with asthma severity,lung function and BMI

IntroductionAsthma is one of the diseases which has a high prevalence in developed and developing countries. The relationship between asthma and obesity has always been focused by researchers. In this field, adipokines, especially adiponectin and leptin have highly attended by the scientist. The aim of this study was to determine the serum level of adiponectin, leptin and the leptin/adiponectin ratio in asthmatic patients and its relationship with disease severity, lung function and BMI (body mass index).MethodsIn this cross-sectional study, 90 asthmatic women admitted to the tertiary referral hospital in Kurdistan province – Iran, were examined. First, BMI was measured and then pulmonary function tests were performed in all asthmatics patient. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC, were measured. At the end, blood samples were collected and serum level of adiponectin and leptin were measured by ELISA method.ResultSerum leptin and leptin/adiponectin levels correlated positively with asthma severity and BMI (p = 0.0001), but there was no correlation between adiponectin level with asthma severity and BMI (p > 0.05), also serum leptin and leptin/adiponectin levels inversely correlated with FEV1 and FVC in patient (p = 0.0001).ConclusionAsthma is linked with obesity, and there is an association between asthma severity and BMI with serum leptin and leptin/adiponectin levels, but our results do not support a significant role of adiponectin in obesity or asthma.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.     

Relación entre la expresión de IL-2 e IL-4 y sus polimorfismos y los riesgos de padecer infección por Mycoplasma pneumoniae y asma en niños

IntroductionAsthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children.Methods392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA.ResultsWe found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376).ConclusionsIL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children.     

Serum level of zinc in asthmatic patients: A case–control study

BackgroundHypozincemia could lead to a variety of defects in growth and the immune system, while it seems to be associated with increased rate of asthmatic attacks in children.MethodsThis study was performed to assess the serum zinc level in 100 paediatric asthmatic patients in comparison with a control group.ResultsMean serum level of zinc in the asthmatic patients was 70.5 ± 22.6 μg/dL, which was significantly lower than 80.9 ± 16.9 μg/dL in the control group (p < 0.001). Forty-two asthmatic patients (42%) had hypozincemia, while this rate was 12% in healthy children (p < 0.001). There was a significant association between the zinc level and severity of asthma (p < 0.001). However, no significant association was detected between the serum level of zinc and other factors, including control and treatment of the disease.ConclusionsAs for high rate of hypozincemia in the asthmatic children, evaluation of serum zinc level in asthmatic children could be suggested, while zinc substitution in the diet of those with hypozincemia could be recommended.     

Asthma,allergic sensitization and lung function in sickle cell disease

BackgroundPulmonary disease is a frequent acute and chronic manifestation in sickle cell disease (SCD), presenting high morbidity and mortality.ObjectivesTo identify the prevalence and association of asthma, allergic sensitization and altered pulmonary function in patients with SCD (SS and Sβ^o).MethodsA single-center, cross-sectional study was conducted, in which 70 patients with SCD and 44 controls, aged six to 18 years, responded to the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), complemented with an anamnesis regarding the associated clinical outcomes. All patients underwent immediate hypersensitivity skin tests with aeroallergens and a pulmonary function evaluation (spirometry). Regarding the statistical analysis, parametric and non-parametric methods were used, depending on the variables studied. Tests were considered significant when p < 0.05.ResultsThere was no significant difference between the patients and controls regarding the prevalence of asthma and allergic sensitization (p > 0.05). The number of occurrences of acute chest syndrome per patient per year was significantly higher for asthmatic patients than for non-asthmatic patients (p = 0.04). Obstructive pulmonary function occurred in 30.9% of the patients and in 5.4% of the controls, and restrictive pulmonary function occurred in 5.5% of the patients and 5.4% of the controls. Asthma and wheezing in the last 12 months had significant associations with obstructive pulmonary function (p = 0.014 and p = 0.027, respectively).ConclusionsThe occurrence of asthma, allergic sensitization and alteration in lung function in patients with SCD reinforces the importance of routine monitoring of these diagnoses, which allows for early treatment and prevention of the evolution of pulmonary disease in adulthood.     

Effects of l-arginine supplementation associated with continuous or interval aerobic training on chronic heart failure rats

ObjectiveChronic heart failure (CHF) is related with exercise intolerance and impaired nitric oxide (NO) production, which can lead to several functional capacity alterations. Considering the possible superiority of aerobic interval training compared to continuous training and the capacity of l-arginine to restore the NO pathway, the aim of the present study was to investigate whether these treatments are beneficial to exercise capacity, muscle mass preservation and hemodynamic, inflammatory and oxidative stress parameters in CHF rats.MethodsThirty-eight male Wistar rats post 6 weeks of myocardial infarction (MI) surgery were randomly assigned into 6 CHF groups: sedentary (SED, n = 6); SED + Arg (n = 7); ACT (n = 8); ACT + Arg (n = 5); AIT (n = 7); AIT + Arg (n = 5). Exercise test capacity (ETC) was performed pre and post 8 weeks of intervention. Supplemented rats received Arg (1 g/kg) by oral gavage (7 ×/week). Exercise training was performed on a rat treadmill (5 ×/week). Hemodynamic variables, tissue collection, congestion, inflammatory cytokines, and oxidative parameters were evaluated at the end of protocols.ResultsAll trained groups showed a superior exercise capacity compared to SED groups on the post-intervention test (p < 0.0001). Pulmonary congestion was attenuated in AIT and AIT + Arg compared with the SED group (p < 0.05). Left ventricular end-diastolic pressure (LVEDP) was lower in ACT + Arg, AIT, and AIT + Arg groups than SED group (p < 0.05). Association of AIT with Arg supplementation was able to improve hemodynamic responses (left ventricular systolic pressure (LVSP), systolic blood pressure (SBP), + dP/dt_max, and − dP/dt_max (p < 0.05), likewise, decrease muscular and renal lipid peroxidation and tumor necrosis factor (TNF)-α, and increase interleukin (IL)-10/TNF-α plasmatic levels (p < 0.01). Groups that associated aerobic exercise with Arg supplementation (ACT + Arg and AIT + Arg) revealed higher gastrocnemius mass compared to the SED group (p < 0.01).ConclusionsBoth aerobic training protocols were capable to improve aerobic capacity, and the association with Arg supplementation was important to attenuate muscle loss. Moreover, interval training associated with Arg supplementation elicits greater improvements in hemodynamic parameters, contributing to reduction in pulmonary congestion, and demonstrated particular responses in the inflammatory profile and in the antioxidant status.     

Correlation between nasal eosinophils and nasal airflows in children with asthma and/or rhinitis monosensitised to house dust mites

BackgroundAllergic rhinitis and asthma due to mite sensitisation are diseases which are frequently associated and characterised by persistent inflammation. In the present study, we aimed to investigate the relationship between nasal airflows and nasal eosinophils in patients with asthma and/or rhinitis due to house dust mite sensitisation.MethodsTwenty-four children with both rhinitis and asthma (R + A), 13 children with rhinitis and no asthma (R) and 10 non-allergic healthy children were evaluated prospectively. The patients belonging to the first two groups had moderate–severe grade of nasal obstruction. Total nasal symptom scores, peak nasal inspiratory flows (PNIFs) obtained by anterior rhinomanometry, skin prick tests, nasal eosinophils and FEV1 values were all assessed.ResultsPercentages of nasal eosinophils and PNIFs in patients with R + A and R (r = −0.415, p = 0.04) were found to be statistically significant and to have an inverse correlation. Skin prick tests were also significantly correlated with nasal eosinophils and PNIFs (r = 0.372, p = 0.01 and r = −0.306, p = 0.04, respectively). Both PNIFs and nasal eosinophils of patients with R + A were significantly correlated with FEV1 values (r = −0.641, p = 0.001 and r = 0.548, p = 0.007, respectively).ConclusionIn this study, a close relationship was demonstrated between eosinophil infiltration and nasal airflows in children having asthma and/or rhinitis monosensitised to mites. Additionally, the significant association found between FEV1 values and nasal eosinophils or PNIFs supported the close link of upper and lower airways.     

Effect of maternal asthma,inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis

BackgroundFetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear.ObjectiveWe examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis.Study subjects and designFetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n = 145). At delivery, umbilical vein plasma was collected from male (n = 61, controls n = 16 and asthmatic n = 45) or female (n = 84, controls n = 22 and asthmatic n = 62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA.ResultsCord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3.ConclusionThe data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.     

IFN-γ stimulation of dental follicle mesenchymal stem cells modulates immune response of CD4+ T lymphocytes in Der p1+ asthmatic patients in vitro

BackgroundHouse dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4⁺ T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells.ObjectiveWe aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-γ stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid.Material and methodsPBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-γ or Der p1 or Dexamethasone for 72 h. CD4⁺ T proliferation, cell viability, CD4⁺CD25⁺FoxP3⁺ Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry.ResultsDF-MSCs suppressed proliferation of CD4⁺ T lymphocytes (p_CDmix < 0.01, p_Derp1 < 0.01, p_IFN < 0.005) by increasing the number of FoxP3 expressing CD4⁺CD25⁺ T regulatory cells (p_CDmix < 0.005, p_Derp1 < 0.01, p_IFN < 0.001) and suppressed lymphocyte apoptosis (p_CDmix < 0.05, p_Derp1 < 0.05, p_IFN < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-γ stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4⁺CD25⁺ T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (p_CDmix < 0.01, p_Derp1 < 0.05, p_IFN < 0.05) and upregulating IFN-γ levels (p_CDmix < 0.01, p_Derp1 < 0.05, p_IFN < 0.005) in asthmatic patients.ConclusionIFN-γ stimulated DF-MSCs were found to have a high modulatory effect on CD4⁺ T cell responses, while Dexamethasone had an apoptotic effect on CD4⁺ T cells in asthmatic patients. DF-MSCs may be a new cell-based therapy option for allergic diseases including asthma.