Combination of B-type natriuretic peptide and minute ventilation/carbon dioxide production slope improves risk stratification in patients with diastolic heart failure.

BACKGROUND: Recent studies demonstrated that the minute ventilation/carbon dioxide production (VE/VCO(2)) slope more powerfully predicted mortality, hospitalization, or both than peak oxygen consumption (VO(2)) in systolic heart failure. However, the prognostic values of these two parameters in diastolic heart failure remained unclear. METHODS: The patients with diastolic heart failure were recruited from April 2006 to May 2007, and underwent cardiopulmonary exercise testing. Plasma BNP concentration was measured using Triage BNP immunoassay method. RESULTS: Of the 224 patients enrolled, mean values for age and New York Heart Association (NYHA) class were 68.8 ± 9.0 years and 2.38 ± 0.53, respectively. During the mean follow-up of 30 months, 57 patients died (36 from cardiovascular death). Univariate Cox regression analysis showed that age, NYHA class, atrial fibrillation, diabetes mellitus, left ventricular diastolic dysfunction, peak VO(2), VE/VCO(2) slope, and plasma BNP were significantly associated with mortality. Multivariate analysis revealed that plasma BNP, VE/VCO(2) slope, and age remained independent predictors for cardiovascular and all-cause mortalities, with the strongest prognostic power of plasma BNP (χ(2) ≥ 31.4, P < 0.001). In addition to plasma BNP and clinical predictors, the VE/VCO(2) slope could provide independent and incremental prognostic value of cardiovascular (χ(2) = 60.6 vs 51.7; P = 0.009) and all-cause mortalities (χ(2) = 62.8 vs 54.2; P = 0.015) with increased χ(2) value of Cox regression model. CONCLUSION: In diastolic heart failure, plasma BNP is the strongest predictor of mortality, and VE/VCO(2) slope provides independent and additive prognostic information, which suggests that combination of plasma BNP and VE/VCO(2) slope can improve risk stratification.

[The clinical significance of noninvasive inflammatory markers in exhaled breath condensate and induced sputum in persistent asthmatic patients].

OBJECTIVE: To assess the clinical significance of three different noninvasive airway inflammatory indices in induced sputum and exhaled breath condensate (EBC) from persistent asthmatic patients. METHODS: Moderate and severe asthmatic patients were prescribed inhaled corticosteroids combined with long-acting beta(2) agonists for a month. The symptom scores and percentage of predicted value of forced expiratory volume in one second (FEV(1)) (FEV(1)%pred) were measured while the concentrations of H(2)O(2), NO(3)(-)/NO(2)(-), and cysteinyl-leukotriene E(4) (LTE(4)) in induced sputum and EBC were detected before and after therapy. RESULTS: A total of twenty-five subjects with moderate and severe asthma were enrolled. By combined therapy for one month the asthma symptoms relieved and FEV(1)%pred improved significantly (P < 0.01). The concentrations of H(2)O(2), NO(3)(-)/NO(2)(-) and LTE(4) in induced sputum and EBC declined significantly (P < 0.01) although the concentrations were still higher than those at normal baseline. More marked reduction of H(2)O(2) and NO(3)(-)/NO(2)(-) compared to LTE(4) was observed. It was revealed that the concentrations of H(2)O(2)and NO(3)(-)/NO(2)(-) but not of LTE(4) in EBC were negatively correlated with FEV(1)%pred (P < 0.01) and positively with symptom scores. Such correlations were also found in H(2)O(2) in induced sputum with FEV(1)%pred and symptom scores as well as NO(3)(-)/NO(2)(-) in induced sputum with FEV(1)%pred. The improvement of FEV(1)%pred after treatment was positively correlated with the reduction of H(2)O(2) and NO(3)(-)/NO(2)(-) both in induced sputum and EBC. Correlation analysis also demonstrated three inflammatory indices were equivalent in induced sputum and EBC (correlation coefficient of H(2)O(2), NO(3)(-)/NO(2)(-) and LTE(4), 0.759, 0.826 and 0.653, respectively. P < 0.01). CONCLUSIONS: (1) Combined therapy with inhaled corticosteroid plus long-acting beta(2) agonist significantly improves the clinical symptoms and lung function of patients with moderate and severe asthma companies with marked suppression of airway inflammation. (2) Both of EBC and induced sputum sampling are valuable noninvasive procedures for detecting asthma airway inflammation, however, EBC technique is superior in safety and reproducibility. (3) H(2)O(2) and NO(3)(-)/NO(2)(-) seem to be more sensitive indices in diagnosis and monitoring asthma compared to LTE(4).

[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.