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Biomedical subjects

P L Paggiaro

Publications and source records attributed to P L Paggiaro.

At least 19 recordsLinked to original sources
PubMed2006

Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma.

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.

Adult↗
PubMed2005

Minimal tolerance to the bronchoprotective effect of inhaled salmeterol/fluticasone combination on allergene challenge.

In order to assess whether the administration of salmeterol/fluticasone propionate combination (50/250 mcg by Diskus) for 1 week induces tolerance to the bronchoprotective effect of salmeterol on allergen challenge, a single-blind, cross-over study was carried out. We studied nine subjects (eight men and one woman; mean age+/-SD: 31.3+/-11.0 yr) with mild intermittent allergic asthma, never treated with regular beta2-agonists or inhaled corticosteroids. In a previous allergen challenge all subjects had shown a positive early airway response (EAR) to allergen. They underwent allergen challenge after 1-week treatment with placebo and a single dose of placebo immediately before allergen challenge (T1), or 1-week treatment with placebo and a single dose of salmeterol/fluticasone immediately before allergen challenge (T2), or 1-week treatment with salmeterol/fluticasone combination bid and a single dose of salmeterol/fluticasone immediately before allergen challenge (T3). EAR was evaluated both as maximum decrease in FEV1 (MaxDeltaFEV1 %) after allergen challenge and as area under FEV1 -time curve. MaxDeltaFEV1 % during allergen challenge protected by placebo (T1) was significantly greater than MaxDeltaFEV1 % during allergen challenges protected by single dose of salmeterol/fluticasone (T2) and by salmeterol/fluticasone 1-week treatment (T3). No difference was found in MaxDeltaFEV1 % between T2 and T3. The same results were observed also after computing the area under the curve for each challenge. When individually considered, all subjects were protected against EAR (protection index > or = 80%) at T2, while at 3 seven out of nine subjects were still protected against EAR. In conclusion, the simultaneous administration of salmeterol and fluticasone in the same device prevents in almost 80% of examined subjects the development of tolerance to the protective effect of salmeterol on allergen challenge. This observation may contribute to explain the positive interaction between inhaled beta2-agonists and corticosteroids in the long-term treatment of asthma.

Administration, Inhalation↗
PubMed2005

Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease.

BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a randomized, parallel-group, double-blind study on 114 patients with COPD of moderate-to-severe degree. The main outcome was the frequency of severe exacerbations over a 6-month period. Before and after treatment, respiratory symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group (19 vs. 34, p = 0.054); the number of patients experiencing at least one exacerbation during the study was also decreased (16 vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were significantly reduced by flunisolide (p = 0.044). In the placebo group, scores were higher than in the flunisolide group but nonsignificant for dyspnea, cough, sputum amount and purulence. FEV(1) was significantly increased compared to baseline in both groups, and the area under the FEV(1)-time curve during the 6-month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs. 2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle walking test distance and scores of the St. George's Respiratory Questionnaire, no significant difference between the baseline evaluation and the end of the study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD patients.

Aged↗
PubMed2005

Predictors of symptom recurrence after low-dose inhaled corticosteroid cessation in mild persistent asthma.

In order to identify predictors of recurrence of asthma symptoms after withdrawal of therapy in mild persistent asthmatics, asymptomatic on low-dose inhaled corticosteroids (ICS), we studied 87 asthmatic patients regularly treated with ICS for at least 6 months. At the enrollment visit (T1), 71 on ICS were asymptomatic over the past 3 months and discontinued asthma treatment. Symptoms and PEF were then monitored for up to 3 months or until symptoms recurred (T2). At T1 and T2, all subjects underwent methacholine challenge and sputum induction. Thirty nine out of 71 patients experienced symptom recurrence. At T1, clinical and functional data and sputum eosinophilia between patients with or without recurrence of symptoms were similar. Age > 40 yr, and disease duration > 5 yr were significantly associated with recurrence of asthma symptoms, while the presence of allergic rhinitis, low baseline FEV(1) and untreated time span > 60 months showed a trend to be associated with symptoms recurrence. At T2, symptoms, pulmonary function, bronchial hyperresponsiveness and sputum eosinophilia deteriorated in patients with symptom recurrence but not in patients without symptom recurrence. In conclusion, age and asthma duration were the best predictors of symptom recurrence in mild persistent asthmatics who withdrew pharmacological therapy, as recommended in the step-down of international guidelines.

Administration, Inhalation↗
PubMed2005

Effects of low doses of inhaled fluticasone propionate on inflammation and remodelling in persistent-mild asthma.

In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 microg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia >or=3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Delta) in FEV1 after treatment with FP negatively correlated with the Delta in sputum eosinophils, while the Delta in MMP-9 values positively correlated with Delta in TIMP-1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers.

Administration, Inhalation↗
PubMed2004

One week treatment with salmeterol does not prevent early and late asthmatic responses and sputum eosinophilia induced by allergen challenge in asthmatics.

Salmeterol is an effective long-acting beta(2)-agonist bronchodilator, able to inhibit, as a single dose, asthmatic responses induced by several stimuli including allergen, and the subsequent increase in sputum eosinophilia. Aim of the present study was to investigate whether these effects of salmeterol persisted after 1 week of continuous treatment, or whether a loss of the bronchoprotective effects of salmeterol can occur over time. We investigated in a cross-over double blind placebo-controlled study, the protective effect of 1 week treatment with salmeterol on allergen-induced early and late responses and the associated airway inflammation in 15 atopic asthmatic subjects. Eosinophil percentage and Eosinophil Cationic Protein (ECP) concentration in peripheral blood and in hypertonic saline induced sputum were measured at baseline and 24 h after allergen inhalation. Salmeterol partially inhibited early asthmatic response, but it did not inhibit late asthmatic response in comparison with placebo. Salmeterol did not inhibit also the increase in sputum eosinophils percentage 24 h after allergen inhalation (E%, median: 22.7 and 15%, after placebo and after salmeterol respectively, p=n.s. between two post-allergen sputum samples). Also, the increase in blood eosinophils and both sputum and serum ECP at 24 h after allergen challenge was not affected by salmeterol pre-treatment. In conclusion, 1 week treatment with salmeterol causes a loss of its protective effect on allergen-induced airway bronchoconstriction, and does not prevent the subsequent increase in sputum and serum eosinophilic markers.

Adolescent↗
PubMed2004

Clinical assessment of asthma severity partially corresponds to sputum eosinophilic airway inflammation.

In the aim to evaluate the relationship between sputum eosinophil percentages and eosinophil cationic protein (ECP) concentrations, as markers of airway inflammation, and different Levels of asthma severity, we examined 223 patients consecutively observed in our asthma clinic. Diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms, FEV1, peak expiratory flow variability and level of asthma treatment needed to control asthma. Spontaneous or induced sputum was collected. Adequate sputum samples were obtained in 68 untreated subjects and in 117 subjects regularly treated with ICS. A control group of 14 normal subjects was also examined. In untreated subjects, mild intermittent asthmatics showed a lower sputum eosinophil percentage in comparison with other groups of asthma severity, while no difference in ECP levels was detected. In treated subjects, severe asthmatics showed higher levels of sputum eosinophils and ECP in comparison with other groups of asthma severity. Mild persistent and moderate persistent patients did not differ for sputum eosinophils or ECP in both untreated and treated subjects. Controls were significantly different from all groups of untreated and treated asthmatics. In conclusion, the assessment of asthma severity according to clinical and functional findings only partially corresponds to the severity of eosinophilic airway inflammation as assessed by induced sputum analysis.

Adult↗
PubMed2004

Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects.

The aim of this study was to assess whether hyperosmolarity affects granulocyte mediator levels in induced sputum of asthmatic subjects. A total of 32 mild-to-moderate asthmatics, who inhaled either hypertonic (HS; 4.5% NaCl) or isotonic (IS; 0.9% NaCl) solutions for 15 min, were studied. Selected sputum was used for analysis. Eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and free neutrophil elastase (NE) were measured in sputum supernatant. Sample weight, total and differential cell counts, as well as viability and squamous cell percentage were no different after the two tests. No significant differences in ECP, EPX, MPO or NE levels were observed between HS- and IS-induced sputum. Repeatability of the two tests was good for macrophages, neutrophils, eosinophils, ECP, EPX and NE, but not for lymphocytes and MPO. In conclusion, hyperosmolarity does not affect sputum cell counts and the levels of most granulocyte degranulation markers examined in this study, confirming that both hypertonic and isotonic solutions can be reliably used to induce sputum in asthmatics.

Administration, Inhalation↗
PubMed2003

Short-term effect of the addition of leukotriene receptor antagonists to the current therapy in severe asthmatics.

In a single blind study, the short-term efficacy of the addition of leukotriene receptor antagonists (LTRA: montelukast 10 mg o.d. in 15 subjects, zafirlukast 20 mg b.i.d. in 11 subjects) to the current therapy was evaluated in severe asthmatics, unstable under regular treatment with high dose inhaled corticosteroids, bronchodilators and, in seven of them, oral corticosteroids. Each subject monitored symptoms, PEF and rescue medication during two weeks with the addition of placebo, and during two following weeks with the addition of LTRA; clinic FEV1 was measured at the beginning and at the end of each 2 weeks period. There was no significant difference in the mean FEV1, PEF, symptom score and rescue medication use between two periods of placebo and LTRA treatments. When two subjects with asthma exacerbation during treatment with LTRA were excluded, FEV1 was higher after LTRA than after placebo treatment (p=0.055). An increase in FEV1>12% pred. at the end of LTRA treatment was observed in five out of 26 subjects (19%). We suggest that LTRA have no overall significant efficacy in severe asthmatics not controlled by high dose inhaled corticosteroids and bronchodilators, but that a minority of these patients could be particularly sensitive to the positive effects of these drugs. The detection of these 'responders' could be relevant in the treatment of severe asthma.

Acetates↗
PubMed2003

Fifty microg b.i.d. of inhaled fluticasone propionate (FP) are effective in stable asthmatics previously treated with a higher dose of FP.

Twenty-seven subjects with moderate asthma at the time of diagnosis, well controlled under regular fluticasone propionate (FP) (250 microg b.i.d.) for 6 months at least, were randomized to receive in double-blind fashion: FP 125 microg b.i.d. (Group 1) or FP 50 microg b.i.d. (Group 2) or placebo (Group 3) for 3 months or until symptom recurrence. Daily symptom score and peak expiratory flow were monitored. At the beginning and at the end of the study subjects underwent methacholine challenge and sputum induction. Recurrence of symptoms occurred shortly after randomization in all subjects receiving placebo. None from Group 1 or 2 experienced symptom recurrence during the study. No significant difference in clinical and functional data, and in sputum eosinophil percentages was observed between the beginning and the end of the study in both Groups 1 and 2. Subjects from Group 3 showed a significant increase of sputum eosinophils (P<0.05) and a significant decrease in provocative dose of methacholine (P<0.05) when asthma symptoms recurred. Therefore, very low doses of FP (50 microg b.i.d.) are effective in maintaining for 3 months a good control of the disease in asthmatics already stable under high-dose fluticasone, considering both clinical and functional outcomes and markers of airway inflammation.

Adult↗
PubMed2002

Diagnosis of flour-induced occupational asthma in a cross-sectional study.

The diagnosis of occupational asthma is usually performed in epidemiology using a combination of symptoms and bronchial hyperresponsiveness, while in a clinical setting the 'gold standard' for the diagnosis of occupational asthma is the specific bronchial challenge test in the laboratory The aim of this study was to detect new cases of flour-induced occupational asthma (OA) in a group of workers exposed to grain and/or flour dust, by means of a step-by-step approach, as used in a clinical setting. In an epidemiological study, III millers and 186 bakers were examined by means of questionnaire, pulmonary function tests and skin-prick tests (SPT) to common allergens and to wheat flour dust extracts. From the whole sample, 82 subjects who showed asthma-like symptoms in the questionnaire and/or low forced expiratory volume in 1 sec (FEV1) were selected. Selected subjects underwent methacholine challenge test, and hyperreactive subjects underwent specific bronchial challenge with flour dust in the laboratory. Sixty-two of the selected subjects performed the methacholine challenge test, and 22 (33 8%) were hyperreactive (PD20 FEV1 <1 mg of methacholine). Fifteen of 22 hyperreactive subjects underwent specific bronchial challenge test (s BCT) with flour dust; a positive response was elicited in six subjects. These subjects can be diagnosed as having flour-induced occupational asthma. Atopy and skin sensitivity to flour was partially related to the response to flour bronchial challenge. Bronchial hyperreactivity can be observed in a small percentage of subjects with asthma-like symptoms and/or low FEV1, and a positive response to s BCTwas observed in a subgroup of hyperreactive subjects.Therefore, using these selection criteria, a diagnosis of flour-induced OA, as commonly performed in a clinical setting, can be performed in few previously undiagnosed subjects.This approach could be relevant for an early diagnosis ofoccupational asthma.

Adult↗
PubMed2002

Quality evaluation of samples obtained by spontaneous or induced sputum: comparison between two methods of processing and relationship with clinical and functional findings.

The aim of the study was to assess, on a large group of spontaneous or induced sputum samples, the difference in quality between slides processed by two different methods, and the relationship between quality assessment and some clinical and functional characteristics of the examined subjects. We examined 631 sputum samples obtained from 337 subjects with proven (n = 291) or suspected bronchial asthma. Of these, 467 samples were processed using the whole-sample method (Group I), while 164 samples were processed using the plug method (Group II). Salivary contamination, cell distribution on the slide, and cell borders were evaluated, and samples were classified as inadequate, adequate, or good. Inadequate samples were equally represented in both groups, while good samples were represented more in Group II. No significant difference in most clinical and functional findings was observed between the different quality categories of both groups. A higher proportion of inadequate samples was observed in Group I samples spontaneously collected. Mild intermittent asthmatics produced a better quality of slides in comparison with other groups of asthma severity. In conclusion, sputum quality partially depends on the different methods of sputum collection and/or processing, although the percentage of inadequate samples is similar for the two methods of processing. Sputum quality is only marginally affected by clinical and functional characteristics of asthma, or by asthma severity.

Adrenal Cortex Hormones↗
PubMed2002

Sputum induction.

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Administration, Inhalation↗
PubMed2002

Comparison of anti-inflammatory and clinical effects of beclomethasone dipropionate and salmeterol in moderate asthma.

Inhaled corticosteroids and long-acting beta2-agonists effectively control asthma symptoms and improve airway function. The effects of beclomethasone were compared with those of salmeterol on markers of eosinophilic inflammation in induced sputum in steroid-naive asthmatic subjects with moderate asthma. Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 microg b.i.d.) or salmeterol (50 microg b.i.d.) for 4 weeks, according to a randomised, double-blind, parallel-group study design. All patients underwent spirometry, methacholine test, sputum induction, and blood sampling before and after 2 and 4 weeks of treatment. They also recorded daily symptoms and peak expiratory flow (PEF). Sputum eosinophils, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and blood eosinophils, as well as the forced expiratory volume in one second (FEV1) and morning PEF, significantly improved after beclomethasone but not after salmeterol. PEF variability, the symptom score and rescue beta2-agonist use significantly improved after both treatments, although the improvement in the symptom score tended to be greater after beclomethasone. After 2 and 4 weeks of beclomethasone treatment, both serum ECP and EPX decreased. With salmeterol, only serum EPX decreased, after 4 weeks. Bronchial hyperresponsiveness to methacholine did not change after either treatment. The authors conclude that beclomethasone, but not salmeterol, substantially improves airway inflammation in asthma. Beclomethasone also had an overall greater clinical effect, although the improvement in symptoms and peak expiratory flow variability was similar after both treatments.

Adrenergic beta-Agonists↗
PubMed2001

Budesonide reduces neutrophilic but not functional airway response to ozone in mild asthmatics.

Ambient ozone concentration is related to asthma exacerbation, but few findings are available regarding the effects of pharmacologic asthma treatment on this relationship. The purpose of this study was to investigate whether inhaled corticosteroids inhibit ozone-induced airway neutrophilic inflammation, as detected in induced sputum, and reduce functional response to ozone exposure. Eleven subjects with mild persistent asthma were exposed for 2 h, on separate days, to 0.27 ppm ozone and to air in random order, before and after 4 wk of treatment with budesonide (400 microg twice daily). Before exposure, 1 and 2 h after the beginning of exposure, and 6 h after the end of exposure, pulmonary function was measured, and a total symptom score questionnaire was completed; 6 h after exposure, sputum was induced with hypertonic saline. Budesonide treatment did not inhibit the functional response to ozone exposure, as determined by reduction in FEV(1) and increase in total symptom score, but it significantly blunted the increase in the percentage of sputum neutrophils and interleukin-8 concentrations in the supernatant (p < 0.05). Therefore, 4 wk of inhaled budesonide blunted the airway neutrophilic inflammatory response but did not prevent the functional impairment of the airways after ozone exposure.

Administration, Inhalation↗
PubMed2001

Effects of inhaled corticosteroids on cough threshold in patients with bronchial asthma.

In asthmatic subjects cough can be related to the degree of airway inflammation. The aim of this study was to evaluate the effect of treatment with high dose inhaled beclomethasone dipropionate (BDP) on cough threshold in asthmatic subjects. Cough threshold to inhaled capsaicin (one breath of 10(-8)-10(-4)M solution) and to citric acid (one breath of 10(-4)-1 M), expressed as provocative concentration of two (PC2) and four coughs (PC4), was measured in 16 normal and 36 asthmatic subjects. After baseline evaluation, asthmatic subjects were randomized in two groups: (a) Group A, n=20: treated with salbutamol (200 microg t.i.d.) plus BDP (500 microg t.i.d.); (b) Group B, n=16: treated with salbutamol plus placebo in the same doses. After 1 month, cough threshold and clinical and functional evaluation were repeated. After treatment, asthmatics of group A showed a significant improvement in PC4 citric acid, in total symptom and cough scores, and in PD20FEV1 methacholine. In asthmatics of group B, treatment caused no improvement in symptoms, PD20FEV1 methacoline and cough threshold. In addition, cough threshold was not different between normal and asthmatic subjects and, in asthmatics, cough threshold did not correlate with PD20FEV1 methacholine. These data confirm that cough in asthma can be partially related to airway inflammation.

Administration, Inhalation↗
PubMed2000

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↗