[Double-blind study of clinical and functional respiratory effects of dexamethasone isonicotinate aerosol].
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Biomedical subjects
Publications and source records attributed to L Allegra.
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Proteolytic enzymes can act on the polymeric structure of the bronchial mucus, shortening the long chain of mucoproteins, DNA and other macromolecules, and thus reducing the viscosity of the mucus facilitating its expectoration. Seaprose (Flaminase, Puropharma) belongs to this class and is a proteinase from Aspergillus melleus and it is mainly used in traumatology, orthopaedics, gynaecology and pneumology. In the present study the in vitro activity of increasing concentrations (0.25, 0.5, 1%) of seaprose incubated with bronchial mucus samples (1 ml) was investigated by a rheological technique (transient test) that assesses changes in viscosity and elasticity. A dose-effect relationship between increasing concentrations of seaprose and the corresponding reductions in bronchial mucus viscosity was found. There was also a parallel reduction in elasticity after incubation with 0.5%, but an unfortunate distribution of values for 0.25 and 1% concentrations does not allow us to state whether there is a dose-effect relationship for elasticity.
BACKGROUND: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). OBJECTIVE: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. METHODS: Fourteen non-atopic patients (8 males, 20-42 years, forced expiratory volume in 1 s (FEV(1)) 97% SD +/- 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. RESULTS: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV(1) drop -10.75% SD +/- 1.89, p < 0.001) and UNDW induced (maximum FEV(1) drop -12% SD +/- 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV(1) drop following MC (maximum FEV(1) drop -33.22% SD +/- 1.42, p < 0.001) and UNDW challenge (maximum FEV(1) drop -30.02% SD +/- 0.4, p < 0.001). CONCLUSIONS: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.
Antibiotics not only reach the site of infection, but also penetrate cyclically, during a treatment, into polymorphonuclear leukocytes (PMNs) and may influence their functions positively or negatively. With reference to these aspects, the influence of brodimoprim (BMP), a dimethoxybenzylpyrimidine recently entered into clinical use, on human PMN phagocytosis and oxidant radical production (chemiluminescence) was investigated. PMNs from healthy adult donors were incubated for 50 min in medium alone or in medium containing increasing concentrations (3.7, 7.5, 15, and 30 micrograms/ml) of BMP and trimethoprim (TMP). In unwashed PMNs, phagocytosis was not modified by BMP, but was significantly reduced by 30 micrograms/ml TMP; chemiluminescence was significantly reduced by 15 and 30 micrograms/ml BMP and by all concentrations of TMP. When PMNs were washed after incubation, phagocytosis was unaffected and chemiluminescence was significantly restored. BMP at therapeutic concentrations did not influence PMNs and was less toxic than TMP.
Nesosteine, which is active on airway secretions, has been studied by assessment of the mucociliary clearance of the frog palate. Sputum was collected from patients admitted to hospital with acute exacerbations of chronic bronchitis with mucous expectoration. The relative speed of transport was measured for each patient before and after oral administration of 600 mg/day nesosteine. A significant increase in the mucus transport rate was found at the end of treatment.
Changes in production and in physico-chemical properties of bronchial mucus is a common denominator of many pulmonary diseases. A rheometer with innovative features aimed at bronchial mucus routine investigation in clinical practice at the bedside of the patient has been designed. Searle-type configuration with a coaxial cylinder sensor system and the Mooney-Ewart geometry has been adopted. Another new feature is that bob and cup are disposable. Dynamic viscoelasticity is calculated through a microprocessor with specific software and by means of a magnetic torque--motor electronically driven by the microprocessor. The self-zeroing procedure and the autorange greatly simplify the measuring-cycle which is driven by only one switch. Data (eta and G') are automatically printed on paper. The whole measuring-cycle at the bedside of the patient takes 3-5 min, so that in 1h about 12 samples can be investigated.
Inhaled steroids are the most effective long-term treatment of persistent asthma but many children are unable to use correctly the available inhalers. Administration of nebulized corticosteroids has some advantages over the administration with pressurised metered-dose inhalers (pMDls). The objective of this multicenter randomised study was to compare the efficacy and tolerability of nebulized corticosteroids in paediatric patients with asthma. 127 patients aged > or = 6 and < or = 14 years with a diagnosis of mild to moderate persistent asthma (PEFR % predicted > 50% and < 85%) and positive response to the reversibility test were randomized. The patients were assigned by randomisation to one of the two treatment groups (4 weeks): beclomethasone dipropionate (BDP) 800 microg/daily b.i.d. (n = 66) or budesonide (BUD) 1000 microg/daily b.i.d. (n = 61) both administered by nebulizer. The primary efficacy end point was the final mean of PEFR measured at clinical visit (clinic PEFR). In the BDP group clinic PEFR increased from 177.5 +/- 80 L/min to 246.6 +/- 84.2 L/min (p < 0.001 vs baseline), while in the BUD group the increase was from 180.4 +/- 77.8/min to 260.9 +/- 84.1 L/min (p < 0.001 vs baseline) (NS between treatments). FEV1 (% predicted) increased from 77.8% to 92.7% (p < 0.001 vs baseline) and from 74.1% to 95.9% (p < 0.001 vs baseline) in BDP and BUD group respectively (NS between treatments). Patients reduced the use of salbutamol rescue medication by 76% and 81% in BDP and BUD group respectively (p < 0.001 vs baseline, NS between treatments). 4 patients in the BDP group and 2 in the BUD group reported adverse events (AEs). AEs were mild to moderate and never there was the need to discontinue the treatments. In conclusion the results of this study demonstrate that both BDP (800 microg/daily) and BUD (1000 microg/daily) administered by nebulization are effective and with a acceptable safety and tolerability profile.
The aim of our study was to verify if the type of nebulizer used could influence the results of aerosol therapy with beclomethasone dipropionate (BDP) in mild allergic asthma. We assigned 27 asthmatics allergic to grasses to 3 groups and treated them from May to July 1998 with aerosol therapy with BDP (800 microg) b. i. d. via nebulizer + pMDI salbutamol (200 microg) if necessary. Each group used a different type of nebulizer: jet nebulizer with glass ampoule (group JG); jet nebulizer with polycarbonate ampoule (group JP); ultrasonic nebulizer (group US). During the study patients underwent periodic lung function tests and methacholine bronchial challenges, recorded twice a day self-monitoring PEF and filled out a daily diary for the presence and intensity of asthmatic symptoms. At the end of the study the provocative dose of methacholine causing a 20% fall in FEV1 (PD20), the self-monitoring PEF and the clinical scores were all greatly improved, but without any statistically significant difference among the three groups. On the contrary, the variations during the study of basal spirometric parameters (specifically FEV1, PEF, FEF25) were significantly better in jet nebulizer groups than in group US. The results coming from the aerosol characterization that we carried out for each of the three nebulizers confirmed the clinical findings, since jet nebulizers showed greatly lower MMAD than the ultrasonic nebulizer (2.9 and 3.7 vs 5.8). Our data suggest that jet nebulizers are more appropriate than ultrasonic nebulizers for delivering BDP in aerosol therapy.
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Tiotropium is an anticholinergic drug for Chronic Obstructive Pulmonary Disease (COPD) patients, with a peak bronchodilator effect observed after 1.5 to 2 hours and a long duration of action. The aim of our study was to quantify the early protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in asthmatic patients with airway hyperresponsiveness. Ten subjects (7M, 3F), with history of asthma and a baseline FEV(1) (Forced Expiratory Volume 1 sec) > 80% of predicted, were enrolled in the study. Each subject performed three methacholine challenge tests, with a time of 72 hours between each challenge: Test A (methacholine challenge test), and successively, at random, Test B (methacholine 30 minutes after inhaled Tiotropium) and Test C (methacholine 30 minutes after inhaled Placebo). PD20 (Provocative Dose causing a 20% decrease in basal FEV(1) value) was reached to assess airways responsiveness. All the subjects showed in Test A and Test C a mild-moderate airway hyperresponsiveness. In Test B no PD20 was reached at the inhaled maximum dose of methacholine (1600 microg), FEV(1) before tiotropium was 88.6% +/- 4.4, beginning test FEV(1) 92.6% +/- 4.3, end test FEV(1) 85.7% +/- 4.6. Inhaled tiotropium bromide 18 microg has shown a protective effect against methacholine-induced bronchoconstriction in asthmatic patients, with mild-moderate airways hyperresponsiveness, already 30 minutes after its administration.
BACKGROUND: Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) but they do not affect disease progression. FEV1, as single parameter, showed limits in describing the heterogeneity of COPD population. Combination therapy, with long-acting Beta2-agonist and corticosteroid, showed a more beneficial effect on lung function, exacerbations, and health status than single inhaled drug. The aim of this study was to assess, in stable COPD, which stage (mild, moderate, severe) shows the best response after 12 weeks inhaled treatment, and which starting functional parameters show a correlation with the response. METHODS: 170 stable COPD patients (38 mild, 66 moderate, 66 severe) were enrolled. Patients received salmeterol/fluticasone 50/500 microg Metered Dose Inhaler (MDI) bid for 12 weeks. Pulmonary function tests and clinical data were performed. Results were subdivided, on functional and clinical data, in "responders (R)" and "no-responders (NR)". RESULTS: A FEV1 improvement (+ 12% and 200 ml) was achieved in 21 mild, 28 moderate and 17 severe COPD patients, respectively 55.3%, 45.9%, and 30.9% of each group. Statistical analysis of starting functional parameters showed a correlation with the therapeutic response for FEV1/FVC, MEF50 and DLCO/VA% (p < 0.05). CONCLUSIONS: Salmeterol/fluticasone improves FEV1% in mild and moderate more than in severe COPD patients. The study confirmed the difference in response between early and advanced stage. Starting FEV1/FVC and MEF50 were significant predictors in mild and moderate stages, and starting DLCO/VA% resulted a significant predictor in moderate and severe stages.
We studied the effects of sobrerol treatment on airway mucus secretion. Normal sheep and sheep with airways sensitized to Ascaris suum antigen were treated in vivo with sobrerol, 1 mg.kg-1 i.m., twice a day for five days. Composition and secretion of mucus macromolecules, and fluxes of ions and water were subsequently measured in tracheal tissues in vitro, and were compared to values from untreated (normal and sensitized) sheep. Macromolecules were radiolabelled with 35SO4 and 3H-threonine and we measured the secretion of macromolecule-bound radiolabel on to the mucosa. We also measured secretion of total protein and of sialic acid. Unidirectional fluxes of Cl-, Na+ and water were measured with radioactive tracers. Net fluxes were calculated from appropriately paired tissues. Sobrerol treatment decreased total protein secretion in both normal and sensitized sheep. Specifically, it decreased secretion of sialylated but not sulphated macromolecules. Sobrerol had no effect on tracheal ion or water fluxes in normal sheep, but in sensitized sheep it significantly decreased net Na+ absorption and induced secretion of water. These changes are likely to alter the physical properties of the mucus, and may alter its transportability by airway cilia and/or by gas-liquid two-phase flow.
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The purpose of this study was to analyze changes in respiratory resistance (Rrs) and breathing pattern in normal and asthmatic subjects after exposure to ultrasonically nebulized distilled water (UNDW). After measurement of baseline Rrs and breathing pattern, ten normals inhaled UNDW for 30, 60, 120, 240 and 480 s administered at 15 min intervals. After the 480 s exposure, subjects inhaled two puffs of metaproterenol. Rrs was measured immediately before and after each exposure to UNDW and after metaproterenol while breathing pattern was continuously monitored. Ten asthmatics were exposed to UNDW and metaproterenol in a similar time sequence, but the durations of exposure to UNDW were 15, 30, 60, 120 and 240 s. Mean (+/- SD) and frequency histograms of minute ventilation (VE), tidal volume (VT), frequency, inspiratory time, fractional inspiratory time, mean inspiratory flow (VT/TI) and end-expiratory level at baseline were compared to values after each exposure to UNDW and after metaproterenol. All subjects experienced laryngeal irritation or cough during the exposure. In normals, there were no changes in Rrs or any of the components of breathing pattern. In asthmatics, 15 and 30 s exposures produced no changes in Rrs or breathing pattern. With subsequent longer exposures, mean Rrs showed a stepwise significant increase, along with parallel increases of VT/TI and end-expiratory level. VE increased after 60 and 120 s exposure, but reached a plateau after 240 s exposure despite continued increase in Rrs.(ABSTRACT TRUNCATED AT 250 WORDS)
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