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D Giannini

Publications and source records attributed to D Giannini.

At least 37 records · Page 2Linked to original sources

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men.

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835

Adult↗

Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients.

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low-dose inhaled corticosteroids. Randomized, double-blind, placebo-controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run-in weeks, on treatment with low-dose inhaled beclomethasone dipropionate (BDP, 250 microgram b.i.d. in the last 3 months). At the end of the run-in, all patients underwent a methacholine challenge test and sputum induction (T1). They then stopped therapy and received either placebo (20 subjects, study group) or BDP at the same dose as in the previous 3 months (10 subjects, control group). They continued to monitor PEF and symptom score for 3 months, or until asthma symptoms recurred (diurnal and nocturnal symptom score >/=2 on two consecutive days). At the end of the study (T2), i.e., either within 5 days from the beginning of asthma symptoms or after 3 months in subjects without recurrence of asthma symptoms, all subjects repeated the methacholine challenge test and sputum induction. In the placebo-treated group, sputum eosinophils at T1 were significantly higher in subjects who subsequently developed recurrence of asthma symptoms (n = 7) after cessation of treatment than in subjects who remained asymptomatic for 3 months (8.2% [0-56.6] vs 0.9% [0-11], P < 0.05). At the time of recurrence of asthma symptoms, sputum eosinophil percentages significantly increased (from 8.2% [0-56.6] to 16.6% [5.8-73.6], P < 0.05). The positive predictive value of sputum eosinophils for the recurrence of asthma symptoms was 71%, while the negative predicting value was 84%. In the BDP-treated control group, none of the subjects experienced recurrence of asthma symptoms, and sputum eosinophil percentages measured at the beginning (T1) and at the end (T2) of the study were similar. Sputum eosinophil percentages may vary over a wide range in asthmatic subjects, although regularly treated and apparently well controlled. However, high sputum eosinophil percentages are related to early recurrence of asthma symptoms after cessation of inhaled corticosteroids.

Administration, Inhalation↗

Reproducibility of early and late asthmatic responses to allergen challenge in a large group of asthmatics.

The specific bronchial provocative test (sBPT) coupled with allergen is used to investigate asthma. Very few studies have examined the reproducibility of responses to allergen challenge. The aim of this study was to measure the reproducibility of PD20FEV1 allergen and late asthmatic response (LAR) in 53 asthmatics and to relate the reproducibility to the time interval between two allergen challenges. Fifty-three atopic asthmatics performed two allergen challenges not less than 2 and not more than 26 weeks apart. Randomly, 19 subjects were assigned to a short-interval group (14-35 days between the two tests) and 34 to a long-interval group (40-180 days). In each challenge, the PD20FEV1 was sought for and the maximum % fall in FEV1 from 3 to 7 h after the allergen challenge was evaluated as a measurement of magnitude of the LAR. High intraclass correlation coefficients (R(I)) were found for both PD20FEV1 (R(I) = 0.78) and LAR (R(I) = 0.77) in all subjects. PD20FEV1 allergen showed a high R(I) in the long-interval group (R(I) = 0.80), but a low R(I) in the short-interval group (R(I) = 0.63). In contrast LAR showed a lower R(I) in the long-interval group (R(I) = 0.68) than in the short-interval group (R(I) = 0.77). Moreover, the R(I) for PD20FEV1 was particularly low in subjects with a dual pattern to the allergen challenge and a short interval between the two allergen challenges. Our study confirmed that asthmatic responses induced by allergen challenge have a good reproducibility. Moreover, we have demonstrated that the interval between two allergen challenges can determine a change in reproducibility in asthmatic responses induced by allergen challenge.

Adolescent↗

Natural exposure to pollen reduces the threshold but does not change the pattern of response to the allergen in allergic subjects.

It is known that exposure to seasonal allergen in sensitized asthmatics increases non-specific bronchial responsiveness, but it is controversial if exposure to seasonal allergen influences the presence and the severity of the late asthmatic response (LAR) to allergen. Fifteen asthmatic subjects sensitized to grass pollen performed a specific bronchial provocative test (sBPT) with Phleum pratensis extract before and during the pollen season. Changes of methacholine were also assessed. Allergen PD20FEV1 significantly decreased during the pollen season with respect to outside (allergen PD20FEV1, geometric mean: 0.10 vs. 0.23 biological units; P < 0.05), but the pattern of specific airway response did not change. Particularly, a consistent LAR was observed in three subjects outside the pollen season and in two subjects during the pollen season. Seven subjects with isolated early asthmatic response (EAR) outside the season did not show LAR after allergen inhalation during the pollen season. However, four of five subjects with slight LAR outside the pollen season (deltaFEV1% between 15 and 20%) lost LAR during season. Methacholine sensitivity increased slightly but significantly from outside to during the pollen season. This increase was greater in subjects with LAR outside the pollen season. The natural exposure to pollen induces an increase in bronchial sensitivity to allergen in sensitized subjects, but it does not induce LAR in subjects without LAR outside the pollen season.

Adolescent↗

Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations.

BACKGROUND: Leptin is thought to represent a peripheral signal involved in the regulation of energy balance. Its action has been studied in animals and obese subjects. Little is known about leptin's role during negative energy balance. OBJECTIVE: The objective was to evaluate the relation between energy turnover, body composition, and plasma leptin concentrations in anorexia nervosa (AN). DESIGN: Sixteen weight-stable women with AN were compared with 22 control subjects and 14 rehabilitated AN patients (R-AN). Basal metabolic rate (BMR) was measured by indirect calorimetry; fat-free mass (FFM) and fat mass (FM) were calculated according to a 4-compartment model. Plasma leptin was determined by radioimmunoassay. RESULTS: The BMR of AN patients (2.73 +/- 0.37 kJ/min) was significantly lower than that of control subjects (3.45 +/- 0.34 kJ/min) (P < 0.001), even after adjustment for FFM (2.92 +/- 0.33 kJ/min in AN patients and 3.30 +/- 0.26 kJ/min in control subjects; P < 0.004). Plasma leptin concentrations in AN patients were 76% lower than in control subjects, even after body fat was controlled for. In R-AN patients, BMR was not significantly different from that of control subjects and leptin concentrations were generally close to normal. Plasma leptin concentrations correlated significantly with FM (r(2) = 0.53, P < 0.0000) and BMR, even after adjustment for FFM (r(2) = 0.21, P < 0.0003). CONCLUSIONS: BMR and plasma leptin concentrations are depressed in patients with AN; this is not explained by body-composition changes. The relation between leptin and BMR suggests that leptin plays a role in the energy sparing response to exposure to chronic energy deficiency. The return of BMR to normal and the significant increase in leptin concentrations in R-AN patients suggests a full reversibility of this adaptation mechanism.

Adolescent↗

Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750.

Candida tropicalis is less commonly isolated from clinical specimens than Candida albicans. Unlike C. albicans, which can be occasionally found as a commensal, C. tropicalis is almost always associated with the development of fungal infections. In addition, C. tropicalis has been reported to be resistant to fluconazole (FLC). To analyze the development of FLC resistance in C. tropicalis, an FLC-susceptible strain (ATCC 750) (MIC = 1.0 microg/ml) was cultured in liquid medium containing increasing FLC concentrations from 8.0 to 128 microg/ml. The strain developed variable degrees of FLC resistance which paralleled the concentrations of FLC used in the medium. The highest MICs of FLC were 16, 256, and 512 microg/ml for strains grown in medium with 8.0, 32, and 128 microg of FLC per ml, respectively. Development of resistance was rapid and could be observed already after a single subculture in azole-containing medium. The resistant strains were cross-resistant to itraconazole (MIC > 1.0 microg/ml) and terbinafine (MIC > 512 microg/ml) but not to amphotericin B. Isolates grown in FLC at concentrations of 8.0 and 32 microg/ml reverted to low MICs (1.0 microg/ml) after 12 and 11 passages in FLC-free medium, respectively. The MIC for one isolate grown in FLC (128 microg/ml) (128 R) reverted to 16 microg/ml but remained stable over 60 passages in FLC-free medium. Azole-resistant isolates revealed upregulation of two different multidrug efflux transporter genes: the major facilitators gene MDR1 and the ATP-binding cassette transporter CDR1. The development of FLC resistance in vitro correlated well with the results obtained in an experimental model of disseminated candidiasis. While FLC given at 10 mg/kg of body weight/day was effective in reducing the fungal burden of mice infected with the parent strain, the same dosing regimen was ineffective in mice infected with strain 128 R. Finally, the acquisition of in vitro FLC resistance in strain 128 R was related to a loss of virulence. The results of our study elucidate important characteristics and potential mechanisms of FLC resistance in C. tropicalis.

Animals↗

Interactions between triazoles and amphotericin B against Cryptococcus neoformans.

The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue. A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively. Antagonism (FIC >2.0) was not observed. When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination. To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro. Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug. On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed. In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene. However, this apparent antagonism was not observed in vivo. Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed. Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.

Amphotericin B↗

The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction.

STUDY OBJECTIVE: To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine. DESIGN: Randomized, double-blind, cross-over, placebo-controlled study. PATIENTS: Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 microg bid, and inhaled beclomethasone dipropionate, 250 microg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV(1) [PD(20)] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique. METHODS AND MEASUREMENTS: After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 microg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD(20), and expressed in terms of doubling doses of methacholine in comparison with placebo treatment. RESULTS: The PD(20) was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD(20) was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean +/-SEM) were obtained with doubling doses of methacholine (pMDI, 2 +/- 0.47; pMDI + spacer, 3 +/- 0.35; and Autohaler, 2.4 +/- 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered. CONCLUSIONS: Our data show that the protective effect of salbutamol, 100 microg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient's inhalation technique.

Adolescent↗

Body-fat distribution and responsiveness of the pituitary-adrenal axis to corticotropin-releasing-hormone stimulation in sedentary and exercising women.

Excess upper-body (android) fat is considered an health hazard. Exercise training is known to have the potential to modify body composition and to induce a preferential loss of abdominal fat. We studied and compared the composition of whole body and major body regions using dual-energy X-ray absorptiometry (DEXA) in 21 exercising (3-4 hours of intense physical activity/day) and 21 sedentary eumenorrhoic women of similar ages, body mass index (BMI), waist-to-hip ratio (WHR) and age of menarche. In a small number of women in each group (6 out of 21), the ACTH and cortisol response to CRH test and the 24-h urinary cortisol excretion was evaluated. Exercising women had 10% higher total and leg lean mass (p<0.05), and 38% lower total fat mass (p<0.01) than sedentary women. Furthermore, the proportion of android fat was 22% lower in exercising than sedentary women (p<0.01), while the proportion of lower-body (gynoid fat) was unchanged. BMI and WHR were not different between the two groups, while the android/gynoid fat ratios were 16% lower in exercising than in sedentary women (p<0.01). In the exercising women, ACTH and cortisol plasma levels, as well as the 24-h urinary cortisol excretion, were significantly (p<0.01) higher than in the sedentary women studied. In these subjects, a direct relationship between the peak delta percentage increases of ACTH and cortisol after the CRH test and the proportion of android fat was found (r=0.60, p<0.05 and r=0.69, p<0.02, respectively). These results demonstrate that in women who practise intense exercise there are significant differences in body fat distribution in comparison to sedentary women, with a marked less amount of android fat, and suggest that this difference may be related to a reduced response of the pituitary-adrenal axis to CRH.

Absorptiometry, Photon↗

Airway inflammatory response to ozone in subjects with different asthma severity.

The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting beta2-agonists (group B). All subjects were exposed, in a randomized cross-over design, to air or O3 (0.26 parts per million (ppm) for 2 h with intermittent exercise); subjects in group B withdrew from regular treatment 72 h before each exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test, and a questionnaire was completed to obtain a total symptom score (TSS). Six hours after the end of the exposure, hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages, eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the sputum supernatant were measured. TSS significantly increased and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) significantly decreased after O3 exposure in comparison with air exposure in group A, whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O3 exposure. Sputum neutrophil percentage was significantly higher after O3 exposure than after air exposure in both groups (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus 27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O3 exposure than after air, only in group A. No change due to O3 has been found in sputum eosinophil percentage and ECP concentration in both groups. In conclusion, the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity. The available data do not allow elucidation of whether this difference depends on the severity of the disease or on the regular anti-inflammatory treatment.

Adolescent↗

Salbutamol pretreatment does not change eosinophil percentage and eosinophilic cationic protein concentration in hypertonic saline-induced sputum in asthmatic subjects.

BACKGROUND: Sputum induction by inhalation of hypertonic saline (HS) is usually preceded by beta2-agonist pretreatment, to prevent severe bronchoconstriction. OBJECTIVE: To evaluate whether salbutamol pretreatment may influence cell counts and concentrations of soluble mediators in induced sputum. METHODS: We studied 22 patients who randomly underwent HS sputum induction after pretreatment with either 200 microg salbutamol or placebo. Sputum was induced by means of HS inhalation (3, 4, 5% NaCl, 10 min each), measuring FEV1 every 5 min until it fell >/= 20% from baseline. Collected sputum was diluted 1 : 1 with 0.1% DTT, incubated at 37 degrees C for 20 min, and total and differential cell counts were measured. ECP and histamine levels were measured in the supernatant. RESULTS: Sputum volume, percentages of inflammatory cells, squamous cell counts and quality of the slides were not different after the two pretreatments, while sputum total inflammatory cells after salbutamol tended to be higher than after placebo (8.3 [1-41] 10(6) vs 6.3[0.2-40] x10(6); P = 0.09). Eosinophilic cationic protein (ECP) did not significantly change (260 [8-900] microg/L after salbutamol vs 200 [8-800] microg/L, n = 19), while histamine levels tended to be lower after salbutamol (140.9 [39.9-236.5] nm) than after placebo (190.4 [72. 2-322.6] nm, P = 0.09, n = 17). The airway response to HS inhalation was significantly greater after placebo and the duration of the test was significantly different (median: 15 min after placebo and 30 min after salbutamol). Similar results were obtained when patients who differed for more than 15 min in the duration of HS-inhalation in the two tests were selected (n = 11). CONCLUSION: Salbutamol pretreatment reduces the severity of bronchoconstriction induced by HS inhalation without significantly affecting the percentages of inflammatory cells and the levels of soluble mediators in induced sputum.

Adrenergic beta-Agonists↗

Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects.

BACKGROUND: The long acting beta2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property. METHODS: The protective effect of a single dose of salmeterol (50 microg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation. RESULTS: Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24 hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol. CONCLUSIONS: A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

Adolescent↗

Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of salmeterol on allergen challenge.

STUDY OBJECTIVE: One week of regular treatment with salmeterol can induce tolerance to the protective effect of a beta2-agonist on early airway response to allergen (EAR). The objective was to assess whether inhaled corticosteroids revert tolerance to salmeterol. STUDY DESIGN: The study had a randomized, double-blind, placebo-controlled design. PATIENTS AND METHODS: Twelve subjects with mild allergic asthma and positive result of specific bronchial provocation test (sBPT) to allergen underwent three sBPTs, separated by 1 week. sBPT was done in all subjects after a single dose (T1) and after 1 week of regular treatment with inhaled salmeterol (50 microg bid) (T2) in order to induce tolerance. Subjects were then randomized to receive either the same dose of salmeterol + beclomethasone dipropionate (BDP, 500 microg bid) (group 1, n = 6) or placebo + BDP (group 2, n = 6) for 1 week before sBPT (T3). RESULTS: After a single dose of salmeterol (T1), all subjects were protected against EAR, whereas after 1 week of regular treatment, the protective effect of salmeterol was totally or partially lost (T2). Maximum FEV1 percent fall (MaxdeltaFEV1%) after allergen inhalation was significantly higher at T2 than at T1. All subjects except one of group 1 were protected against EAR after salmeterol + BDP (T3), and MaxdeltaFEV1% at T3 (median, 12%; range, 4 to 6%) was significantly lower than T2 (median, 22%; range, 12 to 43%; p < 0.05 by Wilcoxon test). Subjects of group 2 did not show any significant protection against EAR after placebo + BDP treatment (T3) MaxdeltaFEV1% at T2 (median, 31%; range, 9 to 40%) and T3 (median, 31%; range, 3 to 42%; not significant). CONCLUSIONS: In conclusion, the addition of inhaled BDP partially restored the bronchoprotective effect of salmeterol on allergen challenge that was lost after 1 week of regular treatment with salmeterol alone. This ability of BDP in reverting tolerance cannot be ascribed to a direct effect of corticosteroids per se on allergen challenge in this group of asthmatics.

Administration, Inhalation↗

Comparison of different long-term asthma treatments in subjects with mild-to-moderate asthma.

In order to compare the efficacy of different asthma treatment in subjects with mild-to-moderate asthma, three groups of 11 patients were treated with nedocromil sodium (NS), beclomethasone dipropionate (BDP) and beclomethasone dipropionate plus salmeterol (BDP + S) in an open, randomized study. Symptom score, peak expiratory flow (PEF) maximal amplitude, forced expiratory volume in one second (FEV1), and methacholine reactivity were measured at the baseline and at intervals of 3 months up to 12 months. After 3 months, symptoms reduced significantly in all treatment groups, while PEF variability improved in BDP and BDP + S groups; FEV1 and bronchial responsiveness to methacholine were significantly improved in comparison with baseline value in the BDP + S group only. No significant difference was observed after 6 and 12 months of treatment in PEF variability, FEV1 or bronchial hyperreactivity in the NS group compared with baseline values, while a significant difference was observed in symptom score. BDP group showed a significant improvement in FEV1 and bronchial reactivity to methacholine after 6 and 12 months of treatment. In the BDP + S group, the improvement in symptoms and pulmonary function persisted until the end of the study. In conclusion, the combination of beclomethasone dipropionate and salmeterol improved pulmonary function and bronchial reactivity earlier than beclomethasone dipropionate alone, while nedocromil sodium improved symptoms but not pulmonary function. Assuming that bronchial reactivity could be an indirect measurement of airway inflammation, overtreatment of asthma in relationship with the classification of asthma severity of the International Guidelines could improve both airway inflammation and the prognosis of airway obstruction.

Adolescent↗