[A clinical study on the significance of airway hyperresponsiveness monitoring in the adjustment of combined therapy for asthmatic patients].

OBJECTIVE: To monitor the changes of symptom scores, airway hyperresponsiveness (AHR, represented by PC(35) sGaw), FEV(1)% and PEF% in patients with mild and moderate persistent asthma who received combined therapy of inhaled corticosteroids (ICS) and long-acting beta(2) agonists (LABA) and to evaluate the clinical significance of PC(35) sGaw and other parameters in guiding the adjustment of asthma stepwise therapy. METHODS: Patients with asthma were allocated randomly to group A (22 subjects), B (22 subjects), and C (21 subjects). The initial regimens for all patients in the first three months included ICS (fluticasone) plus LABA (salmeterol). For patients in group A, a fixed dosage was maintained for 18 months, while those in group B received tailored dosage or withdrawal of therapy according to the clinical control level (well or total control). The regimens for patients in group C included step-down or withdrawal according to PC(35) sGaw besides the clinical control. All subjects were followed-up for 18 months and the symptom scores, PC(35) sGaw, FEV(1)% and PEF% were measured and analyzed. The asthma clinical control levels of the three groups at end point were compared. RESULTS: A total of 65 subjects were enrolled and 46 completed the study. From the first to the third month after treatment, the symptom scores, FEV(1)% and PEF% improved significantly (t = 9.54, 13.17, 14.27, 12.4, 6.72, 6.59, 8.31, 5.22, and 5.96, respectively, all P < 0.01), and then maintained at relatively normal levels in a narrow range without significant progressive improvement during the later phases of the study. Meanwhile AHR declined abruptly in the first three months (t = 9.71, 12.04, and 14.31 in group A, B, C, respectively, all P < 0.01), followed by a slow but continuous improvement from the third to ninth month, and then maintained at a very low level. AHR disappeared in 4 cases but relapsed in 1 case after therapy withdrawal. The asthma clinical control level at the end point of group A, group B and group C were 93.3%, 53.3% and 93.8%, respectively (group A and group C versus group B, P < 0.01, respectively; group A versus group C, P > 0.05). There were fewer patients who underwent step-down therapy or withdrawal in group C compared to group B. However, patients in group C gained better asthma control and experienced less exacerbations compared to those in group B. CONCLUSIONS: (1) Combined therapy with ICS plus LABA significantly improves symptoms, lung function and AHR of asthmatic patients. (2) Adjustment of therapy based only on clinical parameters may lead to early step-down or withdrawal and therefore asthma exacerbations. (3) PC(35) sGaw, an index of AHR, may be valuable in assessing asthma severity, evaluating the efficacy of treatment and guiding medication adjustment.

[A study on the relevance of airway inflammatory indices in induced sputum and airway hyperresponsiveness in asthmatics].

OBJECTIVE: To analyze the correlations between NO(3)(-)/NO(2)(-), eosinophil counts in induced sputum and airway hyperresponsiveness (AHR) and therefore to explore the clinical significance of these parameters in severity assessment and medication adjustment in patients with mild to moderate asthma. METHODS: From February 2003 to June 2004, 35 outpatients with mild to moderate persistent asthma (mild: 9, moderate: 26) from Huaxi Hospital asthma clinic were treated with combined medications of inhaled corticosteroids (ICS) plus long-acting beta(2) agonist (LABA) for one year. The symptom scores were recorded, and AHR (represented by PC(35)sGaw), eosinophil counts and NO(3)(-)/NO(2)(-) concentrations in induced sputum were measured at regular intervals. Fifteen healthy volunteers served as control and eosinophil counts and NO(3)(-)/NO(2)(-) concentrations in induced sputum were measured. RESULTS: A total of 35 subjects were enrolled, of whom 26 completed one-year or longer follow-up. PC(35)sGaw of 26 subjects before treatment was 0.08 g/L, which became 1.40 g/L at the third months, and then maintained at a very low level (2.64 g/L) after the seventh month. NO(3)(-)/NO(2)(-) decreased from [(734 +/- 72) x 10(-3) g/L] to [(230 +/- 41) x 10(-3) g/L] by the third month (q = 6.26, P < 0.05), and [(137 +/- 27) x 10(-3) g/L] by the seventh month, which showed no significant difference with normal control (136 +/- 20) x 10(-3) g/L, q = 3.77, P > 0.05). Eosinophil counts decreased from (0.016 +/- 0.008) to (0.014 +/- 0.007) by the third month, which was not significantly different from normal control (q = 2.94, P > 0.05). In the first fifth months the concentration of NO(3)(-)/NO(2)(-) in induced sputum exhibited a significant negative correlation with PC(35)sGaw (r(1) = -0.872, r(2) = -0.653, r(3) = -0.639, r(4) = -0.656, all P < 0.05). But eosinophil counts had no correlation with PC(35)sGaw in the first three months (r(1) = 0.237, r(2) = 0.536, r(3) = 0.675, all P > 0.05). CONCLUSION: The parameters related to airway inflammation including PC(35)sGaw and sputum NO(3)(-)/NO(2)(-) may be useful in assessing asthma severity, evaluating the efficacy of treatment and adjusting medication regimens.

[The roles of interleukin-5 and eotaxin in signal transmission between lung and bone marrow of rat asthmatic models].

OBJECTIVE: To explore the roles of interleukin-5 (IL-5) and eotaxin in signal transmission between lung and bone marrow in rat asthmatic models and to investigate the effects of different interventions on the signal transmission. METHODS: Forty Wistar rats were randomly assigned to a control group and an asthma group (20 in each group). The asthmatic model were established by ovalbumin (OVA) sensitizing and challenging. The animals were sacrificed 30 min, 6 h, 12 h, 24 h, and 48 h after challenging, respectively. Slides were prepared from peripheral blood, bone marrow, and lung tissue respectively, and stained with HE. Then the total number and percentage of eosinophils (EOS) were counted. The concentrations of IL-5 and eotaxin in the lung homogenate at the different time points were determined by Enzyme-linked immunosorbent assay (ELISA). The bone marrow cells of the control rats and sensitized rats were incubated with lung homogenate of the different time points, and treated with dexamethasone (DXM), Galectin-3, anti-IL-5 polyclonal antibody, and montelukast, respectively. The bone marrow cell slides were stained with anti-IL-5 polyclonal antibody, anti-IL-5Ralpha polyclonal antibody, anti-eotaxin polyclonal antibody, anti-CD(34) polyclonal antibody, and anti-CCR(3) polyclonal antibody, respectively. The EOS and immunoactive cells were counted and represented as percentages of the total cells. RESULT: The percentages of EOS in peripheral blood, bone marrow, and lung tissue from the asthma group were 0.0200 +/- 0.0020, 0.023 +/- 0.003, 0.0250 +/- 0.0090, and those from the control group were 0.0100 +/- 0.0030, 0.009 +/- 0.003, 0.0090 +/- 0.0020 respectively. The differences were significant between the two groups (t = 2.547, 2.718, 2.718, all P < 0.05). The peak levels of IL-5 and eotaxin were (89.3 +/- 2.4) pg/ml at 6 h and (4.9 +/- 0.5) pg/ml at 12 h after allergy challenge, respectively, then the levels returned to the baseline value after 48 h (1.45 +/- 0.23) pg/ml. Except at 30 min, all other lung homogenate samples induced the increase of percentages of IL-5(+), IL-5Ralpha(+), eotaxin(+), CD(34)(+) and CCR(3)(+) immunoactive cells. After treatment with Galectin-3, the percentages of IL-5(+), IL-5Ralpha(+), eotaxin(+), CD(34)(+) and CCR(3)(+) immunoactive cells decreased to 0.021 +/- 0.005, 0.074 +/- 0.007, 0.138 +/- 0.014, 0.067 +/- 0.010, 0.040 +/- 0.005, 0.087 +/- 0.012. CONCLUSION: Galectin-3, a selective inhibitor of IL-5 mRNA transcription, potentially suppresses eosinophilic inflammation and might be a promising specific anti-asthma agent.

[Inhibitory effects of Galectin-3 on the inflammatory cytokines and chemokines in guinea pig asthma models].

OBJECTIVE: To elucidate the roles of interleukin-5 (IL-5), Eotaxin, and CCR-3 in eosinophilic inflammation in guinea pig asthma models and investigate the inhibitory effects of Galectin-3. METHODS: Thirty-two guinea pigs were randomly assigned to control group, asthma group, Galectin-3 intervention group, and dexamethasone (DXM) intervention group. Asthma models were established by sensitizing-challenging the animals with ovalbumin(OVA). The asthmatic animals were treated with Galectin-3 at 0.5 mg/kg, or DXM at 1 mg/kg, respectively,by peritoneally injection one hour before each aerosol challenge from the 14th day to 16th day after sensitization while the control animals were treated with normal saline. The specimens of peripheral blood, bone marrow, and lung tissue on slides were prepared respectively and stained with HE. Then the total number and percentage of eosinophils (EOS) were counted. The lung tissue slide was stained immunochemically with anti-IL-5 polyclonal antibody, anti-Eotaxin polyclonal antibody, and anti-CCR-3 polyclonal antibody, respectively. The immunoactive cells were counted and represented as percentages in total cells. RESULTS: The amounts of EOS in peripheral blood, bone marrow,and lung tissue as well as percentages of IL-5, Eotaxin,and CCR-3 immunoactive cells in the lung tissue from asthma group were increased significantly, compared to those from control group. DXM significantly decreased the amounts of EOS, percentages of IL-5, Eotaxin, and CCR-3 immunoactive cells (P < 0.05). Galectin-3 had an equivalent suppressive effects on the amounts of EOS and IL-5+ cells with DXM (P > 0.05) and down-regulated CCR-3 expression (P < 0.05) to a less extent when compared to DXM (P < 0.05), but had minimal effect on Eotaxin expression (P > 0.05). CONCLUSION: This study provides further evidence for an eosinophil recruitment from bone marrow to circulation blood to lung in asthmatic response, in which overexpression of IL-5, Eotaxin, and CCR-3 could be involved. Galectin-3, a selective inhibitor of IL-5 mRNA transcription, might potentially suppress eosinophilc inflammation and be a compromising specific anti-asthma reagent.