Airway Vascular Permeability Index Research Articles

Exhaled breath temperature in optimally treated asthmatics: severity and underlying mechanisms

Introduction. Increased vascularity may lead to loss of heat in the airways and may modulate exhaled breath temperature (EBT). Increased EBT has been associated with uncontrolled asthma. Aim. We wanted to determine whether the measurement of EBT in optimally treated asthmatic patients is influenced by the increased vascular permeability and whether Vascular endothelial growth factor (VEGF) is implicated in the above process. Furthermore, to assess the impact of asthma severity on EBT values. The diagnostic performance of EBT for the identification of inflammatory profiles in induced sputum was also assessed. Methods. 88 stable asthmatic patients optimally treated for at least 6 months were studied (46 with Severe Refractory Asthma, SRA). EBT was measured with the X-halo device. All patients underwent spirometry, sputum induction for the measurement of % inflammatory cells and for the assessment of both VEGF and albumin in sputum supernatant. The airway vascular permeability index was calculated as the ratio of albumin concentrations in induced sputum and serum. Results. EBT (°C) was significantly higher in patients with SRA compared to those with mild to moderate asthma (median IQR 34.2 [32.4–34.6] versus 31.8 [26.3–34.1], p = 0.001). EBT was significantly associated with VEGF levels in sputum supernatant, while SRA was recognized as a significant co-variate. No other significant associations were observed. Finally, in ROC analysis, the diagnostic performance of EBT for the pure eosinophilic or/and neutrophilic profile did not reach statistical significance. Conclusion. EBT is increasing in severe asthma and is significantly modulated by VEGF levels. Despite the above results its performance for predicting cellular profiles is of limited value.

Angiopoietins 1 and 2 in sputum supernatant of optimally treated asthmatics: the effect of smoking.

Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We aimed to determine the levels of angiopoietins in sputum supernatants of patients with optimally treated asthma and to investigate whether smoking represents a significant covariate on the above possible processes. Eighty-seven patients with asthma (42 smokers) and 28 healthy subjects (14 smokers) were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of Ang-1, Ang-2, vascular endothelial growth factor, TGF-β1, MMP-2, IL-13, Eosinophilic cationic protein and IL-8 in supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-1 (ng/mL) levels were significantly higher in patients with asthma compared to normal subjects. Smoking significantly increased Ang-1 levels [median, interquartile ranges 24 (13-37) in smoking asthmatics vs 10 (7-14) in nonsmoking asthmatics vs 5·3 (3·7-6·5) and 4·6 (3·8-5·7) in healthy smokers and nonsmokers, respectively, P<0·001]. Similar results were observed for Ang-2 (pg/mL) [168 (132-203) vs 124 (82-152) vs 94 (78-113) vs 100 (96-108), respectively, P<0·001]. Regression analysis in the whole study population showed a significant negative association for Ang-1, with AVP index, and MMP-2. Smoking was a significant covariate for both Ang-1 and Ang-2 in asthmatic patients. Ang-1 and Ang-2 levels are upregulated in patients with optimally treated asthma. Our data support a possible role for smoking in the angiogenetic process in asthma.

Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma

Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor in asthma. Cysteinyl leukotrienes (Cyst-LTs) have been implicated in vascular permeability in asthma. Cyst-LTs receptor antagonists modulate vascular permeability by reducing VEGF expression. We aimed to determine the levels of VEGF and Cyst-LTs in sputum supernatants of patients with asthma and to investigate possible associations within them and with airway vascular permeability (AVP) index. Possible confounding factors were also assessed. One hundred twenty one patients with asthma (38 with severe refractory asthma, 41 smokers) and 30 healthy subjects (15 smokers) were studied. All subjects underwent lung function tests, and sputum induction for cell count identification and VEGF, Cyst-LTs, measurement in supernatants. AVP index was also assessed. Both VEGF & Cyst-LTs (pg/ml) levels were significantly elevated in patients with asthma compared to normal subjects (median, interquartile ranges 845 [487-1034] vs. 432 (327-654) and 209 [171-296] vs. 92 [75-114] respectively, p < 0.001 for both). Multivariate regression analysis in the whole group showed a significant association of Cyst-LTs levels in sputum supernatants with VEGF levels in sputum supernatants and AVP index. A similar positive association was observed between VEGF levels in sputum supernatants and AVP index. The presence of Severe asthma was a significant covariate for both associations. Our results indicate that Cyst-LTs may modulate vascular permeability by up-regulating VEGF expression. The above effect seems to be affected by asthma severity.

Levels of angiopoietins 1 and 2 in induced sputum supernatant in patients with COPD

Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process.Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed.Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147–367) vs. 112 (67–171) and 98 (95–107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF.Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease.

Increased levels of angiopoietins 1 and 2 in sputum supernatant in severe refractory asthma

Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes. Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA. Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.

Airway vascular damage in elite swimmers

We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18 ± 3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years). Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum. Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils. In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability.

Increased levels of angiopoietin‐2 in induced sputum from smoking asthmatic patients

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. To determine whether angiopoietin-2 levels in the airways are associated with clinical profiles in smoking asthmatics. 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 microg/day) therapy for 12 weeks. 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 (FEV(1))/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 improvement in FEV(1)/FVC. Angiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses.

Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients

Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma. Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks. VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level. Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.

Potential Mechanisms of Improvement of Airway Hyperresponsiveness by Inhaled Corticosteroid Therapy in Asthmatic Patients

Objective. Recent clinical trials with administration of IL-5 antibodies to asthmatic patients have revealed reduction of eosinophilia but unaltered airway hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy eliminates both eosinophilia and AHR. This study was designed to examine the mechanisms by which ICS improves airway hyperresponsiveness in asthmatic patients.Methods. Clinical variables of asthma involving vascular permeability and IL-5 levels were examined in 23 asthmatic patients and 11 normal control subjects. After the first sputum induction, inhaled beclomethasone dipropionate (BDP 800 μg/day) was administered to asthmatic patients for 8 weeks, and sputum induction was repeated.Results. IL-5 levels in induced sputum and airway vascular permeability index were significantly higher in asthmatic patients. IL-5 was positively correlated with percentage of eosinophils in induced sputum, and negatively correlated with FEV1, but not correlated with PC20 methacholine. After BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to the same levels as in normal subjects. Conversely, PC20 methacholine and airway vascular permeability did not improve to the same levels as in normal subjects. Increase in PC20 methacholine from before to after BDP therapy was significantly correlated with decrease in airway permeability index, but not with decrease in IL-5 level.Conclusion. Our results suggest a clear dissociation between IL-5 and AHR. ICS therapy improves AHR at least in part through decrease in airway vascular permeability.

A case–control study of bronchial asthma associated with ulcerative colitis: role of airway microvascular permeability

Recent attention has been devoted to the respiratory manifestations that may be associated with diseases of distant organs. The most prevalent and distinctive pattern of respiratory involvement in ulcerative colitis (UC) is airway inflammation. This study was designed to examine the contribution of airway microvascular permeability to the pathophysiological association of asthma with UC. Sputum induction and methacholine provocation test were performed in 27 asthmatic patients (15 without UC and 12 with UC), nine patients with UC and 15 normal controls. Inflammatory indexes, vascular endothelial growth factor (VEGF) levels in induced sputum, airway vascular permeability index and exhaled nitric oxide (NO) levels were examined in all subjects. The percentage of eosinophils and concentration of eosinophil cationic protein in induced sputum were similar in all four groups. Though exhaled NO levels were significantly higher in asthmatics with or without UC than in normal controls or UC patients, these levels were comparable in asthmatics with and without UC. VEGF levels in induced sputum and airway vascular permeability index were significantly higher in asthmatics without UC (VEGF: 1920 (990) pg/mL; airway vascular permeability index: 0.018 (0.008)) and asthmatics with UC (6570 (1000) pg/mL; 0.040 (0.006)) than in normal controls (950 (700) pg/mL; 0.009 (0.003)), whose levels were comparable to those of UC patients (900 (600) pg/mL; 0.011 (0.003)). In particular, these parameters were markedly increased in asthmatics with UC than in asthmatics without UC. VEGF level was significantly correlated with airway vascular permeability index in asthmatics with UC. Moreover, VEGF level and airway vascular permeability index was inversely correlated with degree of airway obstruction and airway hyper-reactivity to methacholine in these asthmatics. Airway microvascular hyper-permeability induced by VEGF may have a profound effect on airway function and can explain the heightened airway hyper-responsiveness characteristic of asthma associated with UC.

Analysis of vascular endothelial growth factor levels in induced sputum samples from patients with cough variant asthma

We previously found that vascular endothelial growth factor (VEGF) levels in induced sputum samples are increased in patients with classic asthma and are associated with the degree of airflow obstruction and airway microvascular permeability. To examine VEGF levels and the degree of airway microvascular permeability in patients with cough variant asthma (CVA). Levels of VEGF in induced sputum samples and airway microvascular permeability were examined in 12 controls, 16 patients with CVA, and 16 patients with classic asthma. We also evaluated the relationship between VEGF level and the clinical features of these 2 disorders. Mean (SD) VEGF levels and airway vascular permeability index values were significantly higher in patients with CVA (VEGF: 2,520 [1,050] pg/mL; P < .001; vascular permeability index: 0.017 [0.006]; P = .003) and classic asthma (4,750 [1,260] pg/mL; P < .001; 0.028 [0.009]; P < .001) than in controls (1,420 [1,230] pg/mL; 0.009 [0.003]). Furthermore, these values were significantly higher in patients with classic asthma vs CVA. We also found significant correlations between VEGF level and airway vascular permeability index in patients with CVA (r = 0.60; P = .02) vs classic asthma (r = 0.83; P = .001). Furthermore, VEGF levels were inversely correlated with the degree of airflow obstruction and airway hyperresponsiveness to methacholine in patients with CVA and classic asthma. Airway microvascular hyperpermeability induced by elevated VEGF levels contributes to abnormal airway function in CVA and classic asthma, and differences in the clinical features of these 2 disorders may depend on airway VEGF levels.

Relationship Between Vascular Endothelial Growth Factor and Angiopoietin-2 in Asthmatics Before and After Inhaled Beclomethasone Therapy

Vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) play complementary roles in the process of vascular remodeling. Therefore, this study was designed to examine an interaction between VEGF and Ang-2 in asthmatic airways. VEGF, Ang-2, and hepatocyte growth factor (HGF) levels in induced sputum obtained from 17 asthmatic patients and 10 normal control subjects were examined. Eight weeks of inhaled beclomethasone dipropionate (BDP) therapy (800 µg/day) was administered to all asthmatic patients, and sputum induction was repeated. VEGF, Ang-2, and HGF levels in induced sputum were significantly higher in asthmatic patients than in control subjects. Ang-2 levels were significantly correlated with VEGF levels but not with HGF levels. We also found that there was a significant correlation between airway vascular permeability index and VEGF levels but not HGF levels. In addition, VEGF/Ang-2 ratio in asthmatic patients was significantly higher than that in control subjects, and it was significantly correlated with airway vascular permeability index. After inhaled BDP therapy, VEGF levels were significantly decreased, but Ang-2 levels did not change. Therefore, VEGF/Ang-2 ratio after BDP therapy was markedly decreased to the same level as in the control subjects. Our findings suggest that interaction between VEGF and Ang-2 in asthmatic airways may exist and that high VEGF/Ang-2 ratio may be responsible for increased airway microvascular permeability. In addition, inhaled glucocorticoids therapy may reduce airway vascular permeability and remodeling via VEGF/Ang-2-dependent mechanism.

Effects of Pranlukast Administration on Vascular Endothelial Growth Factor Levels in Asthmatic Patients

We have previously found that vascular endothelial growth factor (VEGF) levels in induced sputum were increased in asthmatic patients, and that its levels were closely associated with the degree of airway obstruction and microvascular permeability. Therefore, this study was designed to examine the effects of pranlukast, a selective leukotriene receptor antagonist, on VEGF levels in induced sputum from steroid-untreated or steroid-treated asthmatic patients. Double-blind, randomized, placebo-controlled, crossover study. University hospital. Twenty-three asthmatic patients (steroid-untreated, 13 patients; steroid-treated, 10 patients) and 10 healthy control subjects. All asthmatic patients received 4-weeks of therapy with pranlukast (225 mg bid), and sputum induction was performed before and after the 4-week treatment course. In steroid-untreated asthmatic patients, the mean percentage of eosinophils (%EOS) and mean eosinophil cationic protein (ECP) levels in induced sputum were significantly decreased after 4 weeks of pranlukast administration (%EOS: before, 16.7% [SD, 7.1%]; after, 12.3% [SD, 4.0%]; p = 0.03; ECP levels: before, 774 ng/mL [SD, 258 ng/mL]; after, 564 ng/mL [SD, 204 ng/mL]; p = 0.034). Moreover, VEGF levels in the induced sputum and the airway vascular permeability index also were decreased after pranlukast administration (VEGF levels: before, 5,670 pg/mL [SD, 1,780 pg/mL]; after, 4,380 pg/mL [SD, 1,540 pg/mL]; p = 0.026; airway vascular permeability index: before, 0.032 [SD, 0.012]; after, 0.017 [SD, 0.006]; p = 0.01). In addition, the change in airway vascular permeability index from before to after pranlukast administration was significantly correlated with the change in VEGF levels (r = 0.782; p = 0.007). However, in steroid-treated asthmatic patients there was no significant difference in mean VEGF levels in induced sputum between placebo administration (before, 3,640 pg/mL [SD, 1,020 pg/mL]; after, 3,640 pg/mL [SD, 960 pg/mL] and pranlukast administration (before, 3,660 pg/mL [SD, 940 pg/mL]; after, 2,950 pg/mL [SD, 890 pg/mL]). Pranlukast administration decreased airway microvascular permeability through, at least in part, a decrease in airway VEGF levels in steroid-untreated asthmatic patients. However, it is likely that pranlukast administration added little efficacy to inhaled corticosteroid therapy for reduction in airway VEGF levels.

Role of Microvascular Permeability on Physiologic Differences in Asthma and Eosinophilic Bronchitis

Asthma and eosinophilic bronchitis are characterized by a similar type of eosinophilic inflammation. However, eosinophilic bronchitis differs from asthma in that there is no variable airflow obstruction or airway hyperresponsiveness. We evaluated the roles of vascular endothelial growth factor (VEGF) and microvascular permeability in causing these differences between the two diseases. Inflammatory indexes in induced sputum, exhaled nitric oxide levels, and vascular permeability index were examined in 11 normal control subjects, 19 beclomethasone dipropionate (BDP)-treated subjects with asthma, 20 non-BDP-treated subjects with asthma, and 17 patients with eosinophilic bronchitis. The percentage of eosinophils in sputum and exhaled nitric oxide levels were significantly higher in non-BDP-treated subjects with asthma and patients with eosinophilic bronchitis than in other two groups; however, VEGF levels and vascular permeability index were significantly higher in non-BDP-treated (VEGF: mean; 4,710 [SD; 1,150] pg/ml, p < 0.0001; vascular permeability index: 0.028 [0.009], p < 0.0001) and BDP-treated (2,560 [1,070] pg/ml, p = 0.0002; 0.016 [0.006], p = 0.004) subjects with asthma than in patients with eosinophilic bronchitis (1,120 [800] pg/ml; 0.01 [0.005]) and normal control subjects (1,390 [1,280] pg/ml; 0.008 [0.003]). We found significant correlations between the VEGF level and the airway vascular permeability index in all patient groups. Thus, interaction between airway microcirculation and VEGF may be a key element in differences in airway function between asthma and eosinophilic bronchitis.

Determinants of the Severity of Exercise‐Induced Bronchoconstriction in Patients with Asthma

Aim. In examining the mechanisms of exercise‐induced bronchoconstriction (EIB), it is important to determine which factors most strongly affect the severity of EIB. We determined such factors in patients with asthma by stepwise multiple‐regression analysis. Methods. Twenty‐three patients with asthma underwent pulmonary function tests, methacholine provocation test, and sputum induction. Eosinophilic inflammatory indices and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in sputum samples, and then an exercise test was performed by all asthmatics. Results. There was a significant correlation between the severity of EIB and degree of eosinophilic inflammation in induced sputum. Moreover, there was a significant correlation between the severity of EIB and airway vascular permeability index. Although we could not find a significant correlation between the severity of EIB and 1‐sec forced expired volume, 20% provocation concentration of (PC20) methacholine tended to be correlated with the severity of EIB. By stepwise multiple‐regression analysis, we also found that airway vascular permeability index, eosinophil cationic protein levels in sputum, and PC20 methacholine are independent predictors of the severity of EIB. Conclusion. We found that airway vascular hyperpermeability, eosinophilic inflammation, and bronchial hyperreactivity are independent factors predicting the severity of EIB.

Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients.

Vascular endothelial growth factor (VEGF) is highly expressed in the airway of asthmatic patients. As VEGF increases airway vascular permeability, consequent thickening of the airway wall mucosa may lead to narrowing of the airway lumen. We evaluated the relationship between VEGF levels in induced sputum and eosinophilic inflammatory profiles, and the degree of airway vascular permeability in asthmatic patients and we evaluated the effect of inhaled corticosteroids on VEGF levels in induced sputum. Induced sputum specimens were obtained from 28 glucocorticosteroids free asthmatics and 11 healthy control subjects. We examined VEGF levels and airway vascular permeability index in induced sputum. After the initial sputum induction, 21 asthmatics received 8-week inhaled beclomethasone dipropionate (BDP, 800 micro g/day) therapy, then sputum induction was repeated. The VEGF levels in asthmatics were significantly higher than in healthy control subjects (P < 0.0001). The VEGF levels were negatively correlated with forced expiratory volume of 1 s (FEV1, % predicted, r = - 0.68, P < 0.001), the percentage of eosinophils (r = 0.51, P < 0.01) and ECP levels (r = 0.39, P < 0.05). Moreover, the VEGF levels were significantly correlated with airway vascular permeability index (r = 0.61, P < 0.001). After 8-week inhaled BDP therapy, the VEGF levels were significantly decreased compared to pretreatment levels (P < 0.0001) and the VEGF levels were significantly correlated with airway vascular permeability index even in post-treatment asthmatics (r = 0.62, P < 0.01). The VEGF levels in induced sputum were increased in asthmatics and its levels were associated with degree of airway narrowing and airway vascular permeability. These findings provide strong evidence that VEGF may play an important role in the pathogenesis of bronchial asthma.

Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients

Background: There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF),...

Vascular Involvement in Exercise-Induced Airway Narrowing in Patients With Bronchial Asthma

The bronchial microcirculation has the potential to contribute to the pathophysiologic mechanisms of exercise-induced bronchoconstriction (EIB) in asthmatic patients. This study was designed to determine whether increase in airway vascular permeability is associated with the severity of EIB in asthmatic patients. Cross-sectional analysis. University hospital. Twenty-five asthmatic patients and 12 normal control subjects. All asthmatics performed an exercise test, and the percentage of maximal fall in FEV(1) and the area under the curve of the percentage fall in FEV(1) plotted against time for 30 min (AUC(0-30)) were determined. The inflammatory indexes, NO levels, and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in all subjects. The airway vascular permeability index was significantly higher in EIB-positive asthmatics (0.031 +/- 0.009) than in EIB-negative asthmatics (0.020 +/- 0.005, p = 0.0011) and normal control subjects (0.008 +/- 0.003, p < 0.0001). We also found that there was a significant correlation between NO levels in induced sputum and the airway vascular permeability index (r = 0.525, p = 0.0101). Moreover, the airway vascular permeability index was significantly correlated with the severity of EIB (percentage of maximal fall in FEV(1) [r = 0.761, p = 0.0002], AUC(0-30) [r = 0.716, p = 0.0005]). However, this index was not significantly correlated with magnitude of eosinophilic inflammation. Our findings suggest that increased airway vascular permeability due to excessive production of NO correlates with the severity of EIB in asthmatics, and that assessment of albumin flux in airway lining fluid stimulated by hypertonic saline solution is a sensitive predictor of the severity of EIB.