The objective of the present study was to investigate the kinetics of high doses of inhaled steroid fluticasone in comparison with oral steroid prednisone on plasma protein leakage and bronchial eosinophilia in adults with moderate asthma exacerbations. The study design was a randomised, double-blind, placebo-controlled prospective trial. In total, 45 patients treated at the emergency department for moderate asthma exacerbations were recruited and 39 were assigned to receive fluticasone and placebo of prednisone (19 patients), or prednisone and placebo of fluticasone (20 patients). Medication was administered to all patients via a metered-dose inhaler and spacer (16 puffs; 4,000 microg.day(-1) or placebo) plus one pill (prednisone 30 mg.day(-1) or placebo). Spirometry and induced sputum for differential cell counts, albumin and alpha(2)-macroglobulin levels and blood eosinophils, interleukin-5 and granulocyte-macrophage colony-stimulating factor levels were obtained before treatment and at 2, 6 and 24 h after treatment. Symptoms clearly improved after 24 h in both groups. No differences were seen between groups in peak expiratory flow or forced expiratory flow in one second, which improved progressively but then decayed slightly after 24 h. Eosinophil counts in sputum also improved over time in both groups. The effect was faster with fluticasone than with prednisone, but was partially lost at 24 h. However, plasma proteins in sputum and eosinophil count in blood both decreased until 24 h, with no significant differences between groups. There was no correlation between eosinophil counts and plasmatic protein levels. In conclusion, both treatments improved symptoms, airway obstruction and inflammation, and plasma protein leakage at 24 h. Prednisone reduced blood eosinophil counts, while fluticasone reduced airway eosinophil counts, suggesting that the anti-inflammatory performance of fluticasone is exerted locally.

OBJECTIVE: Although altered vascular permeability and edema of the bronchial mucosa are associated with asthma attack, their influence on its severity remains unknown. We address this issue by comparing relative indices for the concentration of albumin (RIAlb) and alpha(2)-macroglobulin (RI alpha M-2) in induced sputum and peripheral blood from patients with exacerbated asthma, patients with stable asthma, and control subjects.PATIENTS AND METHODS: Forty-six volunteers participated in the study: 14 with exacerbated asthma (forced expiratory volume in the first second [FEVt] 74.3% [SD, 20.8%] of reference), 23 with stable asthma (FFV, 93.6% [7.5%]), and 9 controls (FEVt 101.1 % [9.9%]). The concentrations of albumin and alpha(2)-macroglobulin were quantified by immunoturbidimetry and immunonephelometry, respectively. The relative index was then calculated by dividing the concentration in sputum supernatant by the concentration in peripheral blood.RESULTS: The mean RIAlb was 1.2 (1.1) in the control group, 2.9 (3.1) in the stable asthma group, and 6.0 (6.7) in the exacerbated asthma group. The RI alpha M-2 values were 11.7 (10.9), 11.9 (14.7), and 3.2 (3.8) for the control group and stable and exacerbated asthma groups, respectively. The increases in the RIAlb values between all groups, and the decrease in the RI alpha M-2 value between the exacerbated asthma and control groups were statistically significant (P <.05). The percentage of neutrophils, but not of eosinophils. in sputum was correlated with the RIAlb (r=0.39; P=.008) but not the RI alpha M-2 (r=0.035, P=.82). FEV displayed an inverse relaionship with the RIAlb (r=-0.43; P=.009) but not with the RI alpha M-2 (r=-0.206, P=.24). No correlation was found between oxyhemoglobin saturation and either the RIAIb (r=-0.33; P=.19) or the RI alpha M-2 (r=0.12; P=.84).CONCLUSIONS: Vascular permeability is altered during asthma exacerbations and appears to be correlated with the presence of neutrophils and the degree of bronchial obstruction.

La IgE total en esputo inducido (EI) y su relación con la IgE total en el suero (S) no están bien definidas. El objetivo de este trabajo fue estudiar la relación entre la concentración de IgE total en EI con la concentración de IgE total en S y la inflamación de las vías aéreas. Se estudiaron 21 pacientes con asma estable y 13 controles sanos. De cada paciente se recogieron los datos clínicos y espirométricos, y a todos se les hicieron pruebas cutáneas (prick test) con 13 aeroalergenos comunes en nuestra área. Se determinó la concentración de IgE total en EI y en S por inmunoensayo con el sistema UNICAP (Pharmacia-Uppsala, Suecia) y la concentración de albúmina por el método de turbidimetría Cobas Integra® (Roche Diagnostics, Basel, Suiza). El porcentaje de eosinófilos (%) en EI de asmáticos fue de 8,7 (11,8) y 0,5 (1) en sanos. La concentración de IgE (KU/L) en EI fue 43,2 (23) en asmáticos vs 25,6 (3) en sanos, y en S fue 329 (413) en asmáticos vs 57 (78) en sanos. La correlación entre IgE total en EI e IgE total en S fue de r = 0,71 (p = 0,048) pero no se relacionó con el índice relativo de albúmina. No hubo relación entre IgE en EI y número de eosinófilos en EI. La IgE total puede medirse en esputo inducido y su concentración se relaciona con la IgE determinada en sangre. La ausencia de relación con la albúmina sugiere que la IgE en esputo no proviene exclusivamente de la extravasación, sino que podría intervenir una cierta producción local. The correlation between total IgE in induced sputum (IS) and serum is not well defined. The aim of this study was to investigate the relationship between total IgE in IS and total IgE in serum and airway inflammation. Twenty-one patients with stable asthma and thirteen healthy controls were studied. Clinical and spirometric data were collected and a skin prick test to the 13 most common aeroallergens in our area was performed in all subjects. Total IgE in IS and serum was determined by the UNICAP immunoanalysis system (Pharmacia Uppsala, Sweden) while albumin concentration in IS and serum was determined using the Cobas Integra® turbidimetric method (Roche Diagnostics, Basel, Switzerland). The percentage of eosinophils in EI was 8.7 (11.8) in asthmatic subjects and was 0.5 (1) in healthy controls. Total IgE (KU/L) was 43.2 (23) in asthmatics vs 25.6 (3) in healthy controls in IS, and was 329 (413) in asthmatics vs 57 (78) in controls in serum. Total IgE in IS was significantly correlated with total IgE in serum; r = 0.71 (p = 0.048), but not with the albumin relative index. No correlation was found between IgE and the number of eosinophils in IS. Total IgE can be measured in IS. Total IgE in IS is mildly correlated with total IgE measured in serum. The lack of correlation between total IgE and albumin in IS suggests that IgE in IS could be locally produced, at least in part.

La alteración de la permeabilidad vascular y el edema de la mucosa bronquial se asocian con las crisis de asma. Hay pocos datos publicados y además no se conoce su relación con la gravedad de éstas. Así se propuso comparer los índices relativos de albúmina (IRAlb) y de macroglobulina α2 (IRMα2), entre esputo inducido y sangre periférica, de asmáticos agudizados (AA), asmáticos estables (AE) y controles. Se estudió a 46 voluntarios: 14 del grupo AA (volumen espiratorio forzado en el primer Segundo [FEV1]: 74,3 ± 20,8), 23 del AE (FEV1: 93,6 ± 7,5) y 9 controles (FEV1: 101,1 ± 9,9). Se cuantificó la concentración de albúmina (turbidimetría inmunoquímica) y de macroglobulina α2 (nefelometría inmunoquímica) en el sobrenadante del esputo y en sangre venosa periférica y se calcularon los índices relativos. La media ± desviación estándar del IRAlb fue de 1,2 ± 1,1 en el grupo control, de 2,9 ± 3,1 en AE y de 6,0 ± 6,7 en AA. El IRMα2 fue 11,7 ± 10,9, 11,9 ± 14,7 y 3,2 ± 3,8, respectivamente. El incremento del IRAlb entre los grupos AA, AE y control, y el descenso del IRMα2 entre AA y control fueron estadísticamente significativos (p < 0,05). Se relacionó el porcentaje de neutrófilos, y no el de eosinófilos,con el IRAlb (r = 0,39; p = 0,008), pero no con el IRMα2 (r =–0,035; p = 0,82). El FEV1 se relacionó inversamente con el IRAlb (r = –0,43; p = 0,009) y no con el IRMα2 (r = –0,206; p = 0,24), y tampoco se relacionó la saturación de oxihemoglobina con el IRAlb (r = –0,33; p = 0,19) o el IRMα2 (r =–0,12; p = 0,84). La permeabilidad vascular está alterada en las agudizaciones de asma y parece relacionarse con la presencia de neutrófilos y el grado de obstrucción bronquial. Although altered vascular permeability and edema of the bronchial mucosa are associated with asthma attack, their influence on its severity remains unknown. We address this issue by comparing relative indices for the concentration of albumin (RIAlb) and α2-macroglobulin (RIα2M) in induced sputum and peripheral blood from patients with exacerbated asthma, patients with stable asthma, and control subjects. Forty-six volunteers participated in the study: 14 with exacerbated asthma (forced expiratory volume in the first second [FEV1] 74.3% [SD, 20.8%] of reference), 23 with stable asthma (FEV1 93.6% [7.5%]), and 9 controls (FEV1 101.1% [9.9%]). The concentrations of albumin and α2-macroglobulin were quantified by immunoturbidimetry and immunonephelometry, respectively. The relative index was then calculated by dividing the concentration in sputum supernatant by the concentration in peripheral blood. The mean RIAlb was 1.2 (1.1) in the control group, 2.9 (3.1) in the stable asthma group, and 6.0 (6.7) in the exacerbated asthma group. The RIα2M values were 11.7 (10.9), 11.9 (14.7), and 3.2 (3.8) for the control group and stable and exacerbated asthma groups, respectively. The increases in the RIAlb values between all groups, and the decrease in the RIα2M value between the exacerbated asthma and control groups were statistically significant (P<.05). The percentage of neutrophils, but not of eosinophils, in sputum was correlated with the RIAlb (r=0.39; P=.008) but not the RIα2M (r=–0.035; P=.82). FEV1 displayed an inverse relationship with the RIAlb (r=–0.43; P=.009) but not with the RIα2M (r=–0.206; P=.24). No correlation was found between oxyhemoglobin saturation and either the RIAlb (r=–0.33; P=.19) or the RIα2M (r=–0.12; P=.84). Vascular permeability is altered during asthma exacerbations and appears to be correlated with the presence of neutrophils and the degree of bronchial obstruction.

BACKGROUND:The correlation between total IgE in induced sputum (IS) and serum is not well defined. The aim of this study was to investigate the relationship between total IgE in IS and total IgE in serum and airway inflammation.METHODS:Twenty-one patients with stable asthma and thirteen healthy controls were studied. Clinical and spirometric data were collected and a skin prick test to the 13 most common aeroallergens in our area was performed in all subjects. Total IgE in IS and serum was determined by the UNICAP immunoanalysis system (Pharmacia Uppsala, Sweden) while albumin concentration in IS and serum was determined using the Cobas Integra turbidimetric method (Roche Diagnostics, Basel, Switzerland).RESULTS:The percentage of eosinophils in EI was 8.7 (11.8) in asthmatic subjects and was 0.5 (1) in healthy controls. Total IgE (KU/L) was 43.2 (23) in asthmatics vs 25.6 (3) in healthy controls in IS, and was 329 (413) in asthmatics vs 57 (78) in controls in serum. Total IgE in IS was significantly correlated with total IgE in serum; r = 0.71 (p = 0.048), but not with the albumin relative index. No correlation was found between IgE and the number of eosinophils in IS.CONCLUSIONS:Total IgE can be measured in IS. Total IgE in IS is mildly correlated with total IgE measured in serum. The lack of correlation between total IgE and albumin in IS suggests that IgE in IS could be locally produced, at least in part.

Nonspecific hyperresponsiveness to adenosine monophosphate is better related to airway inflammation than methacholine. Adenosine induces mast cells and other cells to release inflammatory mediators that produce bronchoconstriction and perhaps other inflammatory effects, such as plasma exudation, which have not been well studied. We compared the plasma exudation effect, as measured in induced sputum, between adenosine and methacholine challenge in healthy and asthmatic subjects. In a cross-over design, 42 subjects were randomly challenged with adenosine or methacholine. After recovery, induced sputum was collected on 2 separate days, 48 to 72 hours apart. In the control group, an additional challenge with saline was performed. Differential cell counts and albumin and alpha2-macroglobulin levels were determined. The sputum volume obtained was sufficient to measure proteins in only 34 subjects: 10 healthy individuals and 24 mild asthmatics. There was a significant difference between adenosine and methacholine in sputum albumin (mean differences: 68[73.4] μg/L in controls, p = 0.039 and 48.0[162.9] μg/L in asthmatics) and cell counts, but only a tendency in alpha2-macroglobulin. PC20 adenosine was better related to eosinophil counts than methacholine (r = −0.44, p = 0.014). Albumin or alpha2-macroglubulin levels were not significantly correlated with baseline FEV1, PC20, or eosinophil counts. Adenosine, but not methacholine challenge, produces a mild airway plasma exudation that does not seem to be relevant to bronchoconstriction. However, this could be relevant, to some supernatant measurements after adenosine challenge.