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At least 757 records · Page 42Linked to original sources
PubMed1999

Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect.

Insulin loaded PLGA nanospheres having weight mean diameters of 400 nm were prepared by the modified emulsion solvent diffusion method in water. The nanosphere recovery and the drug recovery in the nanospheres were 74.8%+/-4.71 and 46.8%+/-7.01, respectively. Eighty five percent of the drug was released from the nanospheres at the initial burst, followed by prolonged releasing of the remaining drug for a few hours in saline at 37 degrees C. The aqueous dispersions (6 mg/ml) of PLGA nanospheres were nebulized by a sieve type ultrasonic nebulizer to discrete droplets of 5 approximately 7 microm in mean diameters, 75% of which were successfully delivered into the alveolar fraction in a cascade impactor inhaled at 28.3 l/min. The nebulized PLGA nanospheres were administered via a spacer by using a constant volume respirator into the trachea of the fasted guinea pig for 20 min. After the administration of 3.9 I.U./kg insulin with the PLGA nanospheres, the blood glucose level was reduced significantly and the hypoglycemia was prolonged over 48 h, compared to the nebulized aqueous solution of insulin as a reference (6 h). This result could be attributed to the sustained releasing of insulin from the nanospheres deposited widely on to the whole of lung.

Administration, Inhalation↗
PubMed1990

An audit of inhaler technique among asthma patients of 34 general practitioners.

Doctors from 34 practices participated in an audit study which examined inhaler technique in up to 20 of their patients. A new scoring system, applicable to all forms of device, was used. Although the majority of the 422 patients (63%) was using metered dose inhalers, a broad range of other devices was included; most frequently Rotahalers (15%) and spacer devices (9%). For analysis, technique scores were rated as 'good' (score 4 out of 4), 'adequate' (score 3 or 4) and 'inadequate' (score 2 or less). Overall, 25% of patients had inadequate technique. Of all devices, the Turbohaler had the highest proportion of patients with good technique (78%), and metered dose inhalers the lowest (45%). This audit confirms that technique is unsatisfactory for a significant proportion of patients, regardless of the device used. A simple scoring system promotes consistent testing of technique within a practice.

Administration, Inhalation↗
PubMed1986

Comparison of two high dose corticosteroid aerosol treatments, beclomethasone dipropionate (1500 micrograms/day) and budesonide (1600 micrograms/day), for chronic asthma.

Twenty eight patients with chronic asthma took part in a double blind single crossover controlled trial of inhaled budesonide and inhaled beclomethasone dipropionate, using high doses of 1600 micrograms and 1500 micrograms daily respectively. Both drugs were administered by pressurised aerosol inhaler; the inhaler containing budesonide and its matching placebo were fitted with a collapsible spacer device. There was no significant difference in the control of asthma during the two six week treatment periods. There was no significant difference in FEV1 and forced vital capacity after four and six weeks of treatment or in mean morning and evening peak expiratory flow rates for the last 21 days of treatment. There was a small but statistically significant reduction in the daytime wheeze score while they were taking high dose budesonide but there was no difference for daytime activity, cough, and night symptoms. The mean basal cortisol concentrations were significantly lower after six weeks of high dose treatment than before treatment (budesonide p less than 0.01, beclomethasone p less than 0.05). There was no difference between mean basal cortisol values after six weeks of high dose treatment, and there was no effect on the rise of cortisol obtained after a short tetracosactrin test. High dose inhaled corticosteroids produced few side effects and were well tolerated.

Adult↗
PubMed1993

Inhaled corticosteroids in children. Is there a 'safe' dosage?

Inhaled corticosteroids are effective for the treatment of asthma. Because of the appreciation of the importance of airway inflammation in the pathogenesis of the disease, these drugs are being used more frequently not only in severe but also in moderate asthma. Treatment rarely has to be stopped because of topical adverse effects since oropharyngeal candidiasis and dysphonia are uncommon in children. However, paediatricians need to remain alert for the possibility of systemic adverse effects. With sensitive techniques, dose-dependent adrenal suppression has been documented in children treated with inhaled steroids but generally this effect has no clinical relevance. Although suppression of short term growth velocity has been reported, long term studies have shown that when growth impairment occurs in a child with asthma it is more likely to reflect poor asthma control than the administration of inhaled corticosteroids. Calcium supplementation may be necessary in children with asthma treated with inhaled steroids since this treatment may cause reduction in osteocalcin, a marker of osteoblast activity and bone formation. Other systemic adverse effects have been reported in case reports. The use of a large spacer device has been shown to reduce the incidence of both topical and systemic adverse effects from inhaled steroids and their use should be encouraged. In any child with asthma who really needs inhaled steroids, the lowest dose possible should be prescribed; however, the mistake of prescribing doses too low to be therapeutically effective should be avoided.

Administration, Inhalation↗
PubMed1993

Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion.

Allergen challenge is associated with an increased excretion of urinary leukotriene E4. The source of this increase is unknown, although the lack of effect of inhaled beta-agonists and sodium cromoglycate suggests that airway mast cells may not be involved. We investigated this further using a new and topically potent inhaled glucocorticoid, fluticasone propionate (FP). A group of 10 mild atopic asthmatic subjects (6 males; FEV1 > 60% of predicted; PC20 histamine < or = 8 mg/ml; and on inhaled beta 2-agonists only) were studied before and after a 2-wk period of FP (1,000 micrograms/day) or placebo administered by metered-dose inhalers as two puffs twice per day through a large-volume spacer. Treatments were assigned in a double-blind crossover fashion separated by a 3-wk washout period. The PC20 histamine was measured at the start and end of each treatment when subjects also received a bronchial allergen challenge. Urine was collected for 4 h after allergen challenge for determination of LTE4 using HPLC-RIA, and 2 h later the PC20 histamine measurement was repeated. The 2-wk treatment with FP significantly inhibited both early and late responses to allergen: the maximum % fall in FEV1 during the early (0 to 2 h) and late response (2 to 6 h) was 32.6 +/- 3.4 and 19.6 +/- 5.2, respectively, following placebo versus 19.5 +/- 4.5 and 3.6 +/- 2.6 following FP (both p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1998

In vitro comparison of beclomethasone and salbutamol metered-dose inhaler aerosols inhaled during pediatric tidal breathing from four valved holding chambers.

STUDY OBJECTIVES: To determine the amount of salbutamol or beclomethasone delivered from metered-dose inhalers (MDIs) in particle sizes appropriate for inhalational treatment with four common holding chambers (AeroChamber, OptiChamber, Space Chamber, E-Z Spacer) when used under simulated pediatric tidal breathing conditions. DESIGN: Five devices of each type were tested with salbutamol (100 microg, Glaxo-Wellcome) and beclomethasone (50 microg, Glaxo-Wellcome) MDIs. Each device was connected to face replicas representative of 7-month-old (infant), 2-year-old (toddler), and 4-year-old (child) children and aerosol inhaled into a cascade impactor (Anderson) using a valve system and simulated tidal breathing patterns representative of children of these ages. MEASUREMENTS AND RESULTS: Amounts of drug inhaled in fine particles varied significantly between devices and ages (p < 0.01), eg, for beclomethasone, from 4 microg (infant, Space Chamber) to 8 microg (toddler, OptiChamber), and for salbutamol, from 18 to 36 microg. The AeroChamber and OptiChamber behaved quite similarly, delivering more drug in the fine particles than the other two devices, and having insignificant variations in these amounts with age (p > 0.05). CONCLUSIONS: Amounts of drug inhaled in fine particles during pediatric tidal breathing from valved holding chambers are dependent on the holding chamber model, the drug used, and the breathing pattern, although dependence on the breathing pattern is relatively small for some of the devices tested.

Administration, Inhalation↗
PubMed2001

Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study.

Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but there are few studies evaluating their safety in young children. We, therefore, prospectively administered beclomethasone diproprionate (BDP) to 12 clinically stable young children with CF to examine the safety of this therapy with respect to adrenal suppression and airway infection. To determine potential mechanisms of corticosteroid action in CF, we also examined airway markers of inflammation before and after inhaled steroid treatment. BDP 210 microg twice a day was given via spacer for 2 months. Twelve-hour serum and urine cortisols and response to low-dose synthetic ACTH cortisol stimulation were assessed. Bronchoalveolar lavage fluid (BALF) was examined pre- and posttreatment with BDP by quantitative bacteriology and indices of airway inflammation, including levels of total neutrophils, neutrophil elastase-alpha-1 antiprotease complexes (NEAP), CA 19-9 mucin-associated antigen, interleukin-8 (IL-8), and macrophage IL-8 mRNA. Following 2 months of treatment, serum and urine cortisol levels were unchanged. Response to low-dose ACTH cortisol stimulation was not significantly decreased at 30 min. Posttreatment BALF bacterial density was not statistically different from pretreatment; however, one patient who was initially culture negative became culture-positive with Hemophilus influenzae. BALF total neutrophil counts, corrected for epithelial lining fluid dilution, were decreased to approximately one third of pretreatment values (P = 0.03). NEAP and CA 19-9 mucin-associated antigen demonstrated similar decreases. BALF IL-8 levels and macrophage IL-8 mRNA levels were not statistically changed. These findings suggest that treatment with BDP 420 microg per day for 2 months in young children with CF does not affect urine and blood cortisol, causes no decrease in adrenal reserve, and does not result in a clinically significant increase in airway infection. In addition, the fall in bronchoalveolar lavage fluid inflammatory markers following BDP suggests possible modulation of neutrophil influx into the CF airway and provides justification for further studies of inhaled corticosteroids in CF.

Administration, Inhalation↗
PubMed1989

[Pillars of therapy of chronic obstructive bronchitis].

While bronchial asthma is defined on the basis of pulmonary function, emphysema has a patho-anatomic substrate. Chronic bronchitis on the other hand is defined clinically: productive cough of three months duration per year occurring in two successive years. Complete abstinence of smoking is a prerequisite for a meaningful anti-obstructive therapy. Beta-2-adrenergic stimulation and corticosteroids represent the treatment of choice. Beta-2-agonists are effectively complemented by anticholinergic drugs. Oral or parenteral corticosteroids should be used liberally for exacerbations. For prolonged treatment topical steroids are prescribed exclusively in order to prevent systemic side effects. The type of inhalation therapy (electric nebulizer, aerosol spray, insufflator) has to be adapted to the individual patient. Correct application of inhalation-technique is important. Topical steroids should be administered by means of a spacer chamber. Physical therapy is the most important adjuvant treatment. Selective respiration-training, a correction of breath-technique and autogenic bronchial drainage manoeuvres have to be learned in the setting of a rehabilitation program and are controlled frequently by the treating physician. The integration of all these measures into a treatment and rehabilitation plan is facilitated in a specialized clinic.

Administration, Inhalation↗
PubMed1999

Use of gamma scintigraphy to evaluate the performance of new inhalers.

Many new inhaler devices and formulations involving pressurized metered dose inhaler (pMDI), dry powder inhaler (DPI), and liquid spray technologies are currently being developed. Some of these novel drug delivery products deposit a greater percentage of the drug dose in the lungs than a conventional chlorofluorocarbon (CFC)-based pressurized aerosol, hence providing better drug targeting to the required site of drug action. The noninvasive imaging technique of gamma scintigraphy provides an accurate quantification of the amount of drug deposited in the lungs from inhaler devices together with an assessment of deposition in different lung regions. Respimat (Boehringer Ingelheim, Ingelheim am Rhein, Germany) is a novel liquid spray "soft mist inhaler" that more than doubles deposition in the lungs compared with a pMDI and reduces oropharyngeal deposition, thus providing a degree of drug targeting comparable to that from a spacer device. These data suggest that Respimat should be a valuable addition to the range of devices available for inhalation therapy.

Administration, Inhalation↗
PubMed2003

Use of a paper disposable cup as a spacer is effective for the first-aid management of asthma.

OBJECTIVE: There are many settings in which a spacer device is not available for the administration of bronchodilator. Therefore, we tested whether a paper disposable cup is as effective as a commercially produced spacer to administer bronchodilator. METHODOLOGY: Randomised controlled trial. 50 subjects aged 16-50 years who had wheeze and a greater than 10% decrease in FEV1 after histamine inhalation test (HIT). Subjects were randomised to either the 150 ml paper disposable cup group (CUP) or the commercially produced spacer group (SPACER). Twenty minutes after 400 microg salbutamol was administered FEV1 was measured. The recovery index measured post-bronchodilator FEV1 as a percentage of baseline FEV1. Also, analysis of covariance tested whether recovery of FEV1 was related to the magnitude of the fall following the HIT. RESULTS: There were no statistically significant differences between CUP and SPACER groups in any characteristics. There was no difference for the recovery index (t48=1.14, P=0.26). Regression analyses showed that the relation between the magnitude of the fall in FEV1 during the HIT and the percent recovery was not different between the CUP and SPACER groups (t=-1.2, P<0.23). CONCLUSIONS: A paper disposable cup was effective for the reversal of mild to moderate bronchoconstriction. Therefore, a paper disposable cup can be used for the first-aid management of asthma when there is concern about cross-infection and a commercially produced spacer is not available.

Adolescent↗
PubMed1996

Trial of beclomethasone dipropionate by metered-dose inhaler in ventilator-dependent neonates less than 1500 grams.

Beclomethasone dipropionate administered by metered-dose inhaler to ventilated infants with early chronic lung disease was evaluated in a double-blind, placebo-controlled study to determine the feasibility and safety of administration. Patients selected for study were less than 1500 g birthweight, had previous radiographic evidence of respiratory distress syndrome with early changes of bronchopulmonary dysplasia (BPD), were greater than 2 weeks of age, and had failed attempts at extubation. The metered-dose inhaler was connected to the respirator circuit by an in-line spacer device and either saline placebo or beclomethasone was delivered for 7 days or until extubated. Beclomethasone was delivered in a dose calculated to be approximately 1 mg/kg/day in three divided doses. Nineteen infants were enrolled. Nine received placebo and 10 received beclomethasone. No adverse effects on blood pressure, heart rate, respiratory rate, ventilator settings, concentration or duration of oxygen therapy, incidence of retinopathy of prematurity (ROP) or infections, blood glucose, daily weight, or serum cortisol levels before and after adrenal stimulation tests were observed in the beclomethasone group compared with the placebo group. One infant in the placebo and six infants in the steroid group were extubated during the study period (p = 0.03). These data indicate that beclomethasone dipropionate may be administered safely to intubated neonates without adverse effects of hypertension, hyperglycemia, diminished weight gain, or adrenal suppression frequently seen with systemic steroid administration. Beclomethasone may enhance extubation in infants with early BPD, however, further data are required to substantiate this preliminary observation.

Anti-Inflammatory Agents↗
PubMed1990

[Aerosol generators and the determination of their aerosol size distribution].

To determine aerosol size distribution of several particle generators for the inhalation therapy we employed a laser scattering method and QCM cascade impactor method. The particle size distribution measured by the latter method showed MDI less than Diskhaler less than Jet nebulizer, the smaller in order. Our model analysis also suggests that an usage of a spacer (especially the size of around 150 ml) enable to increase the total amount of aerosol inhalation into the lungs, when MDI is applied as an aerosol generator.

Aerosols↗
PubMed2000

Aerosol delivery from spacers in wheezy infants: a daily life study.

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.

Aerosols↗
PubMed1992

Randomised cross-over comparison of five inhaler systems for bronchodilator therapy.

The pharmacological efficacy of beta-2 agonists such as bronchodilators is well established, yet many patients fail to obtain optimum benefit from conventional metered-dose inhalers. This is usually because of difficulty in achieving adequate co-ordination between activation of the aerosol and inhalation. To some extent this problem can be alleviated by detailed personal instruction and re-instruction, but the medical or paramedical staff needed to do this may be unavailable and in any case their time is expensive. To increase the benefit obtained from bronchodilators, therefore, pharmaceutical companies have produced a variety of devices, eg, large-volume (750 ml) spacers (Nebuhaler, Volumatic) which enclose a cloud of aerosol, obviating the need for actuation-inhalation co-ordination, and breath actuated dry-power inhalers with (Rotahaler, Diskhaler) or without (Turbohaler) carrier powders. Subsequent compliance with treatment is dependent upon the acceptability of the inhaler device to the patient.

Adolescent↗
PubMed1999

A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler.

Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.

Administration, Inhalation↗
PubMed1992

[Correct inhalation technique--an integral part of rational treatment of bronchial asthma].

In the rational treatment of asthma bronchiale in recent years a marked increase can be observed as regards prescription of beta-2-agonists and glucocorticoids. They are administered almost exclusively from metered dose inhalers (MDI) with an adjustable valve. Almost half the users do not know the correct inhalation technique. Unless that is used, the effect of drugs is markedly reduced. The author deals therefore in his review in detail with all aspects of a correct inhalation technique; above all he emphasizes slow inhalation with subsequent breath retention which is the only way how to achieve maximum penetration of particles to the final branches of the bronchial tree. The author mentions also spacers which improve in some patients the effectiveness of aerosol treatment.

Administration, Inhalation↗
PubMed1987

A dose-response study of inhaled terbutaline administered via Nebuhaler or nebuliser to asthmatic children.

In 12, symptom-free, asthmatic children, aged 5-10 years, responses (increases in FEV1) were measured to cumulative doses of inhaled terbutaline delivered by two methods: a) 5 breaths from a 750 ml spacer (Nebuhaler) attached to a metered dose aerosol (doses were 0.5, 1, 2 and 4 mg); and b) by face mask attached to a Bennett twin-jet nebuliser containing terbutaline solution (doses were 1, 2, 4 and 8 mg in 2 ml). Responses were dose-related by both methods and the log dose-response lines were parallel. Twice the dose of nebulised terbutaline was required to give responses equivalent to those seen with the Nebuhaler (significant difference between the lines, ANOVA, P = 0.05). The highest doses given by either method resulted in achievement of at least 80% of the maximum possible improvement in respiratory function (i.e. predicted FEV1 (50th centile) minus basal FEV1) with no effects on pulse rate. Thus, the use of the Nebuhaler with terbutaline metered dose aerosol is at least as effective as administration of the same total dose by nebuliser in children who are not in acute respiratory difficulty. Also, it produces a dose-related bronchodilator effect, without pulse-rate effects, for doses of terbutaline between 0.5 to 4 mg (2 to 16 puffs of the metered dose (0.25 mg) aerosol).

Administration, Inhalation↗
PubMed2004

A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.

Administration, Inhalation↗