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Biomedical subjects

C Terzano

Publications and source records attributed to C Terzano.

33 records · Page 2Linked to original sources
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Metered dose inhalers and spacer devices.

Easy to carry, highly effective and extremely safe, allowing accurate, consistent dose delivery, metered dose inhalers are the inhalation devices doctors and patients choose most readily the world over. Clinical response, however, may be affected by the inhalation technique used and the precise formulation in the canisters. The purpose of this review is to consider metered dose inhalers, add on devices and training issues related to the proper coordination of drug delivery with inhalation, and to report on new technology and recent studies into non ozone depleting propellants, in compliance with the Montreal protocol.

Aerosol Propellants↗
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State of the art and new perspectives on dry powder inhalers.

Modern local therapy for lung diseases is now largely based on pressurized metered-dose inhalers (MDIs). The research of alternatives to MDIs has recently accelerated, primarily due to environmental concerns related to the use of chlorofluorocarbon (CFC) propellants. The most recent and attractive solution to this problem is represented by the development of dry powder inhalers (DPIs), particularly designed to avoid the use of propellants. DPIs have been developed for specific products, therefore they possess a reduced versatility in term of application of the same device to different drugs. However, they did introduce new concepts in pulmonary drug delivery, solving some disadvantages of the pressurized devices. They are in their infancy and the efforts of researchers are now impressive. The future will certainly see many other devices containing additional innovative features for the effective respiratory delivery of drug. The goals still remain the delivery of precise and uniform drug doses and increasing the respirable fraction in relation to the dose emitted from the device.

Administration, Inhalation↗
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Beclomethasone dipropionate versus budesonide inhalation suspension in children with mild to moderate persistent asthma.

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.

Administration, Inhalation↗
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Effectiveness of beclomethasone dipropionate aerosolized through different nebulizers to asthmatic patients.

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.

Administration, Inhalation↗
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Nebulized tobramycin in patients with chronic respiratory infections during clinical evolution of Wegener's granulomatosis.

Aminoglycosides are effective against Pseudomonas aeruginosa but with intravenous administration there are only very low concentrations achieved in sputum; therefore in order to obtain therapeutic levels in patients with endobronchial infections should be administered high doses with increased likelihood to produce both nephrotoxic and ototoxic effects. Direct aerosol delivery of aminoglycosides to the lower respiratory tract has the advantage to achieve high antibiotic sputum concentrations in the infected area with reduced risk of systemic toxic reactions because of minimal absorption into the circulation. Nowadays, except for patients suffering from cystic fibrosis and bronchiectasis, the administration of antibiotics through inhalers is not very much in use. The aim of this study was to administer nebulized tobramycin in chronic respiratory infections developed during the evolution of Wegener's Granulomatosis in order to obtain data concerning the safety and efficacy of inhaled aminoglycosides. The results obtained underlined an improvement in FEV1, FEF75 and PaO2. The aerosolized tobramycin administered in 300 mg doses three times per day for four weeks, showed itself to be effective and safe, not causing any undesirable clinical or microbiological side-effects. Moreover, a long term treatment has been shown to control the Pseudomonas aeruginosa infection on the bronchial system in Wegener's granulomatosis and reduce the frequency of exacerbations in chronic patients.

Administration, Inhalation↗
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The smooth muscle and airway hyperresponsiveness.

Airway hyperresponsiveness, excessive airway narrowing caused by stimuli that normally elicit limited or no response, is one of the cardinal features of asthma. The length-dependence of smooth muscle contractility has been recognized for decades, and it forms an essential foundation for many aspects of the physiological regulation of airway contractility in vivo. This review summarizes the structural and functional alterations of airway smooth muscle in asthma and chronic obstructive pulmonary disease, that underlie pathophysiological conditions of airway hyperresponsiveness.

Airway Resistance↗
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Brittle asthma.

Brittle asthma is a rare form of severe asthma characterized by a wide variation of Peak Expiratory Flow (PEF), in spite of heavy doses of steroides. Brittle asthmatic patients had very serious and often, life threatening, attacks. Type 1 brittle asthma is characterized by a mantained PEF variability despite therapy, and it affected mostly female, aged between 15 and 55 years. Type 1 is associated to skin prick tests positivity and food intolerance. Several studies have referred a correlation with personality disorders. The patients affected with type 1 have high morbidity, and frequently they have hospital admission for assessment and stabilitation their asthmatic condition. Type 2 brittle asthma is characterized by acute attacks that are very severe and could led to death or mechanical ventilation for respiratory insufficiency. Brittle asthma is very difficult to recognize and to treat. In type 1 brittle asthma, the therapy is based on inhaled and/or oral steroids, and beta2-agonists, used with an inhaler or with subcutaneous infusion. The patients affected with type 1 had to be nearly monitered and treated. Patients affected with type 2 brittle asthma, are mostly free by simptoms, but they have severe attacks that led them to emergency treatment. Brittle asthma is a rare form of severe asthma, that the clinicians may recognize and treat very strictly, because of high morbidity and mortality.

Adrenergic beta-Agonists↗
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Early protective effects of tiotropium bromide in patients with airways hyperresponsiveness.

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.

Administration, Inhalation↗
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The influence of ipratropium bromide in the recovery phase of methacholine induced-bronchospasm.

BACKGROUND: The protective effect of Ipratropium Bromide (IB) in the methacholine-induced bronchospasm is well known from some time. The objective of the present study was to assess whether a pretreatment with IB may influence the subsequent phase of methacholine-induced bronchospasm relief. METHODS: Sixteen patients with bronchial hyper-reactivity (PD20 FEV1 < 200 microg) were randomly assigned to three methacholine challenge tests at a 48 to 72 hours interval apart. In the first test IB was inhaled before the challenge (pre-IB), in the second IB was administered soon after the PD20 FEV1 (post-IB), and in the third no treatment was given (control). RESULTS: The pre-IB PD20 FEV1 (695 +/- 587.6 microg) was significantly greater (p < 0.0001) than that of post-IB (82.2 +/- 49.18 microg) and of control (73.9 +/- 41.8 microg). The dose response slope (DRS) (decline percentage of FEV1/cumulative methacholine dose), in pre-IB was greatly lower (p < 0.0001) than that in post-IB and in control. During the bronchospasm relief phase, the increase of FEV1 measured after 5, 10, 15, 30 and 60 minutes from the PD20 FEV1 was significantly greater in post-IB (p < 0.05) compared with the other two conditions. Conversely, the recovery slope (RS) (increase percentage of FEV1 at 60 minutes after PD20 FEV1 x cumulative methacholine dose) was significantly more efficient (p < 0.001) in pre-IB than in post-IB and in control. CONCLUSION: In conclusion, ipratropium bromide confirmed to have a good protective activity against methacholine-induced bronchospasm; the pre-administration of ipratropium bromide showed also a positive effect on the recovery phase.

Administration, Inhalation↗
PubMedDate not supplied

Combination therapy in COPD: different response of COPD stages and predictivity of functional parameters.

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.

Administration, Inhalation↗
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Time course of methacholine induced bronchoconstriction during drugs and spontaneous resolution.

We examined the resolution of the bronchial spasm induced by methacholine after administration of a dose sufficient to provoke PD20 to study, in patients with bronchial asthma, how spontaneous resolution (as opposed to bronchodilator-induced resolution) takes place. According to a randomization criterion, the patients were divided into four groups: 1) resolution induced by salbutamol (S), 2) by ipratropium bromide (I), 3) after placebo (P) and 4) spontaneous resolution (R). In brief, we observed that variations in FEV1 after methacholine PD20, reach statistically significant levels after 15 minutes in patients from groups (S) and (I), after 30 minutes in patients from groups (P) and (R) (p < 0.05). Comparing the phenomenon at various intervals in the four experimental situation, we found a pairing trend: groups (S) and (I) on the one hand, and groups (P) and (R) on the other. On the whole, this phenomenon shows that pharmacological treatment accelerates the process of spontaneous resolution of the bronchial spasm induced by methacholine which, in our experience, beings to show after 15 minutes, and that after 60 minutes, there are no statistically significant differences in the four groups. It is our opinion that closer examination of this phenomenon may provide greater knowledge of the mechanisms that come into play during the phase after stimulation of the muscarinic receptors and that reasonably involve the system to eliminate the muscarinic drug.

Adolescent↗
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Sensitivity of FEV1 and indices of flow volume curve in the methacholine test.

Our aim was to asses the association between the decrease of FEV1 and the modifications of the indices (PEF, MEF25, MEF50 and MEF75% of FVC) during methacholine challenge. 105 patients of both sexes with mild bronchial asthma were included in this study and were subjected to methacholine test according to ATS standards. The results were analysed using analysis of variance (MANOVA), discriminant stepwise and multiple regression. The reduction of FEV1 induced by increasing dosage of methacholine was associated with a significant decrease of the other flow-volume curve indices but we can observe a different flow behaviour. The MEF50 was more significant during the first level of variations and the MEF75 and MEF25 being more significant during the subsequent phases. We conclude that the evaluation of the flow volume indices can be important for better study the site of action of methacholine.

Adult↗
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Respiratory allergy to Cupressus sempervirens in Rome.

Mediterranean Cypress pollen is the major aerospore component in winter and early spring. Several recent studies have assessed the incidence of respiratory allergy to this pollen. A personal series of patients encountered in 1994-96 revealed a 9.33% incidence of positive prick-test responses to Cypress pollen among a population with atopical status. That series included 16 (19.05%) single and 68 (80.95%) multiple allergy sufferers. Among the former the symptoms encountered were rhinitis (62.5%) and asthma (37.5%). Given the ever-increasing incidence of Cypress pollen allergy, there is a need to restrict the planting of the tree for ornamental purposes, especially in areas with a high pollen count.

Adult↗
PubMedDate not supplied

Ipratropium bromide in the recovery phase after methacholine PD20: is there more than an antagonist effect?

Aim of the study was to discover whether the recovery phase after methacholine challenge might be influenced by the administration of an antimuscarinic drug and to verify the mode and timescale of restored receptor activity. 16 patients with severe bronchial hyperreactivity were selected and subjected to methacholine test in order to assess: the preventive bronchodilatory effect of ipratropium bromide (40 mcg) inhaled before the test and the bronchial spasm spontaneous recovery after PD20 at 15, 30 and 60 minutes. Data were subjected to variance and Tukey test analysis. The results confirm that ipratropium bromide raises the methacholine dose response threshold by a factor of about 10 and also demonstrate that the anti-muscarinic drug modified the FEV1 PD20 and influenced the recovery phase by intensifying and making the bronchial spasm resolution faster. Thus results moreover suggest that the receptor activity restoration depends also on the elimination of the muscarinic mediator.

Adult↗