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At least 19 recordsLinked to original sources
PubMed1991

Effect of terbutaline on mucociliary clearance in asthmatic and healthy subjects after inhalation from a pressurised inhaler and a dry powder inhaler.

BACKGROUND: beta Agonists have been shown to increase mucociliary clearance in some studies but not all. Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases. METHODS: The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second (FEV1) was assessed in 10 patients with asthma and 10 healthy subjects. Terbutaline (1 mg) was administered through a metered dose inhaler with a spacer (Nebuhaler) or a dry powder inhaler (Turbuhaler), or both treatments were given, in a four way double blind, double dummy trial. Mucociliary clearance was measured by bronchoscintigraphy. RESULTS: Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32% after terbutaline was given by metered dose inhaler and 55% after a combined dose of 2 mg from both inhalers (1 mg from each) compared with placebo but by only 9% after 1 mg of terbutaline was given by a dry powder inhaler. In the healthy subjects mucociliary clearance increased by 51% when terbutaline was given by a dry powder inhaler, by 66% when given by a metered dose inhaler, and by 66% when given by both inhalers combined. The effect of terbutaline on FEV1 was the same with each of the inhalers. CONCLUSION: Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects. The reason for the difference in asthmatic subjects is unclear, but may be associated with differences in the deposition of terbutaline.

Administration, Inhalation↗
PubMed1991

Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler.

BACKGROUND: High doses of inhaled corticosteroids are absorbed systemically and may cause long term side effects. As rinsing the mouth out after use and inhaling through a spacing device may reduce systemic absorption this has been further investigated. METHODS: Three crossover studies were carried out to assess the effect of budesonide given by dry powder inhaler (Turbuhaler) with and without mouth rinsing and beclomethasone dipropionate given by metered dose inhaler with or without a spacing device (Volumatic) on serum cortisol concentrations and urinary cortisol excretion in patients with asthma taking an inhaled corticosteroid. Each treatment period was two weeks with in a two week washout period. Serum cortisol concentrations at 0800 hours on day 14 and the 24 hour urinary excretion of cortisol were measured. In study 1 24 patients taking beclomethasone dipropionate 500 micrograms twice a day inhaled with (n = 10) or without (n = 14) a Volumatic spacing device were switched to a budesonide dry powder inhaler, 600 micrograms to be taken twice a day without mouth rinsing. In study 2 10 patients took budesonide 800 micrograms twice a day with and without mouth rinsing and without swallowing the rinsing water. In study 3 17 patients took budesonide 800 micrograms twice daily with mouth rinsing and beclomethasone dipropionate 500 micrograms twice daily with the spacing device and mouth rinsing. RESULTS: In study 1 no difference was seen between budesonide without mouth rinsing and beclomethasone dipropionate without a spacer: beclomethasone with spacer caused less suppression of cortisol (mean (SD) serum cortisol concentration: beclomethasone and spacer 487(148), budesonide 368(145) nmol/l). In study 2 mouth rinsing caused less suppression of morning serum cortisol concentrations (rinsing 440(63), no rinsing 375(56) nmol/1). In study 3 there was no difference in serum or urinary cortisol concentrations between twice daily beclomethasone dipropionate 500 micrograms inhaled by Volumatic spacer or budesonide by Turbuhaler 800 micrograms twice daily, both with mouth rinsing. Individual serum cortisol values were within the normal range in all patients except one in study 1. CONCLUSION: Systemic absorption of a corticosteroid inhaled from a metered dose inhaler is reduced by using a spacing device and that from a dry powder inhaler by mouth rinsing.

Administration, Inhalation↗
PubMed1992

Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes.

1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of inhalation using the terbutaline TBH in 10 stable asthmatic subjects, who were tested on 5 consecutive days. 2. Measurement of 10 different parameters of pulmonary function indicated that the full bronchodilatory effect of an inhaled dose was already achieved at 5 min after the inhalation. Inspiratory flows through the TBH varying from 34 to 88 l min-1 resulted in comparable bronchodilation, and a previous exhalation to residual volume proved of no value. However, if, prior to inhalation, an exhalation through the device was performed, a substantially reduced effect was seen. 3. Reducing the inspiratory flow to approximately 34 l min-1 produced slightly reduced side effects and lower plasma terbutaline concentrations.

Adult↗
PubMed1991

Clinical efficacy of two beta 2-sympathicomimetics in different inhalers in children with asthma. Comparison of pirbuterol in a breath-actuated inhaler and salbutamol in a customary metered-dose inhaler.

In a controlled clinical crossover trial, the therapeutic effect of pirbuterol (CAS 38677-81-5) in the Autohaler was compared to that of salbutamol in a customary metered-dose aerosol in 17 children with asthma. Each child was randomized to both treatments with a washout period of at least 1 day and at most 13 days. Ten children commenced with salbutamol and then switched over to pirbuterol, and the other 7 vice versa. The main criterion to evaluate efficacy was the forced expiratory volume after 1 s (FEV1). Other efficacy criteria were forced vital capacity (FVC) and peak expiratory flow (PEF). The patients were given detailed instructions on how to use the inhalers. Each treatment was applied in the morning with one shot (0.2 mg pirbuterol or 0.1 mg salbutamol). FEV1, FVC and PEF were measured in all patients 10 min before and 10 min after medication with the whole-body plethysmograph; further measurements were carried out in most patients 60 and 240 min after application. There was a mean increase of 47% in the FEV1 compared to baseline with pirbuterol in the Autohaler compared to a mean increase of only 30% with salbutamol in the customary metered-dose inhaler. The difference is statistically significant (p = 0.036). A linear crossover analysis showed a significant treatment effect 10 min after application in favour of pirbuterol with no significant period effects or interactions (p = 0.020). The increases of FVC and PEF after pirbuterol treatment were also remarkably higher than after salbutamol. No side effects were observed.

Administration, Inhalation↗
PubMed1990

Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.

Administration, Inhalation↗
PubMed1992

Effect of inhaled furosemide on the bronchial response to lysine-aspirin inhalation in asthmatic subjects.

It has been demonstrated recently that inhaled furosemide inhibits bronchoconstriction induced by cold air, physical exercise, various antigens, and metabisulfite. The goal of the present study was to determine if the inhalation of furosemide would inhibit the bronchoconstriction resulting from the inhalation of lysine-aspirin in aspirin-sensitive asthmatics. Six female subjects with known hypersensitivity to aspirin participated in this crossover study comparing 20 mg of inhaled furosemide and placebo. The volunteers inhaled increasing concentrations of lysine-aspirin after the inhalation of furosemide or placebo. The geometric mean provocative dose causing a 20 percent decrease in the FEV1 (PD20) after the inhalation of placebo was 30.4 mg/ml and the PD20 was equal or below 90 mg/ml in all patients. In contrast, the FEV1 did not decrease by 20 percent in any of the patients pretreated with furosemide when the inhaled concentration was increased to 360 mg/ml. From this study, we conclude that the administration of furosemide blocks the bronchospasm induced by the inhalation of lysine-aspirin in aspirin-sensitive asthmatics.

Administration, Inhalation↗
PubMed1992

Increased inhaled bronchodilator vs increased inhaled corticosteroid in the control of moderate asthma.

Undertreatment of chronic asthma may reflect uncertainty as to how it may be best controlled. We compared the effects of increased inhaled corticosteroid vs regular inhaled bronchodilator in 32 adult asthmatics. During three 16-week treatment periods, comprising baseline inhaled corticosteroid (mean 505 micrograms daily) and on-demand beta-agonist, baseline inhaled corticosteroid and increased (regularly scheduled four times daily) beta-agonist, and increased inhaled corticosteroid (mean 1478 micrograms daily) and on-demand beta-agonist, subjects recorded symptoms, morning and evening peak flow, and additional medication. Of 25 subjects whose control differed significantly between treatments with baseline vs increased corticosteroid, 22 (88 percent) favored the increased dosage (p < 0.001). Of 28 subjects whose control differed between treatments with regular beta-agonist vs increased corticosteroid, 24 (86 percent) were better controlled with increased inhaled corticosteroid and were worse with regular beta-agonist (p < 0.001). Only one quarter the number of exacerbations were experienced during treatment with increased inhaled corticosteroid. Upper airway adverse effects were minor and easily controlled. Hence, asthma with persistent symptoms was better controlled by increased inhaled corticosteroid therapy than by increased use of inhaled beta-agonist.

Administration, Inhalation↗
PubMed1989

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?

To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.

Administration, Inhalation↗
PubMed1991

The effect of inhalation flow on the performance of a dry powder inhalation system.

Dry powder inhalation systems are composed of a small amount of active ingredients and a larger amount of filler. The drug particles are believed to be bound by the filler crystals. The complexes are too large to be inhaled and need to be separated before they enter the lungs. This is done by the air patients inhale through the inhaler. Asthmatics can show low inhalation flows and the performance of a dry powder inhaler at low flows was investigated. It was shown, that small particles (less than 5 microns) separate swiftly at low flows and larger particles (greater than 5 microns) will need higher flows. The conclusion is that dry powder inhalation preparation do not show a simple separation pattern.

Administration, Inhalation↗
PubMed1979

[Experimental studies of long-term aerosol inhalation. An inhalation apparatus for long-term exposure with concentration regulation facilities (author's transl)].

A "multipurpose" inhalation system for long-term experiments was developed to study health effects of the exposure to various kinds of aerosols appearing in general working environments as well as in the ambient atmosphere. In order to carry out a continuous inhalation study on animals for their life-span, at least two essential conditions should continuously be fulfilled. (1) Steady maintenance of the appropriate sanitary conditions for the animals placed in the inhalation box. (2) Constant feeding of aerosol at an appropriately regulated concentration level. The developed system described in the present paper has been proved to be satisfactory from the above viewpoints. This inhalation system was applied to an experimental study attempting to simulate the polluted lungs in the urban dwellers. Heavy oil combustion products were chosen as the inhalation material, which were made to be inhaled by the male rats of SD-JCL strain for their life-span. The present report is mainly concerned with the construction of the inhalation system including a newly devised regulation facility of the aerosol concentration. Operating characteristics and actual data obtained are described. Details of the exposure conditions and pathological findings obtained will be described in the succeeding reports.

Aerosols↗
PubMed1990

[A new inhalation system for bronchodilatation. Study of the acceptance of the Ingelheim M inhaler in chronic obstructive respiratory tract diseases].

The aim of this study was to investigate the acceptance and convenience of a new inhalation system for the treatment of chronic obstructive pulmonary disease. The Ingelheim M inhalator, an inhalation system with a supply magazine for six powder-filled capsules represents a further development of the Ingelheim inhalator in which only a single capsule can be utilized. The study was designed as an open, randomized, crossover trial involving 60 ambulatory adult patients. Each treatment period lasted two weeks. The medication tested was Berodual Inhaletten. The success of treatment was checked on the basis of peak flow metering each morning prior to and after initial inhalation. The results of the study show a highly significant preference on the part of the patients for the new inhalation system. The advantage most emphasized by the patients was the fact that they were able to carry with them their entire daily dose. Differences in the symptomatology of chronic obstructive pulmonary disease were not observed with these inhalation systems.

Adolescent↗
PubMed1989

Effects of chelating on organ distribution and excretion of manganese after inhalation exposure to 54MnCl2. II: Inhalation of chelating agents.

The effect of 1, 2-cyclohexylene-aminetetraacetic acid (CDTA) and diethylenetriaminepentaacetic acid (DTPA) on Min distribution and excretion in rats was examined after 1 hr exposure to 54MnCl2 (0.3 micrograms Mn/m3). Both chelating agents were inhaled independently, by nose only, for 30 min for the four following days, starting immediately after cessation of Mn exposure. During the experiment, the mean concentrations of CDTA and DTPA aerosols were 508 mg/cm3 and 517 mg/cm3, respectively. The activity of 54Mn was determined in lung, liver, kidney and brain 24 hrs after the last treatment, and in urine and faeces collected for 24 hrs on days 1-4 after Mn exposure. The CDTA inhalation appeared to be more effective than DTPA in mobilizing the inhaled manganese: about a twofold decrease of 54Mn was observed in all excised organs: lung, liver, kidney and brain, as compared to the controls. The DTPA inhalation resulted in about a twofold decrease of 54Mn in the lung, but was not effective in removing the metal from the liver, kidney and brain. As it can be seen from the comparison of these results with our previous data (6), the CDTA inhalations were more effective than its i.p. injections mobilizing manganese additionally also from the lung; but generally less effective in the case of DTPA, which decreased 54Mn levels in the lung only. On the first day after 54Mn exposure, manganese levels in the urine of rats inhaling CDTA and DTPA were respectively more than 200 and 30 times higher than in the control group. Excretion of Mn in faeces was not affected significantly in this experiment. Our data show that the effectiveness of removing inhaled Mn depends not only on the chelating agent, the time of its administration (see Part I) but also on the method of its administration.

Animals↗
PubMed1992

Treatment with inhaled steroids in asthma and chronic bronchitis: long-term compliance and inhaler technique.

We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis.

Administration, Inhalation↗
PubMed1989

Dosimetric principles for extrapolating results of rat inhalation studies to humans, using an inhaled Ni compound as an example.

Dose-effect relationships of inhaled substances are complicated by the interrelationship between inhaled dose, deposited dose, and retained dose. Deposited and retained doses are most important for evaluating dose-effect relations; however, inhaled dose and exposure concentration that are not representative of the actual dose to target sites are widely used for this purpose. For extrapolating results of animal inhalation studies to humans, several factors have to be considered for calculating a human equivalent dose to the respiratory tract and for estimating a human equivalent exposure concentration. Among these factors are separate deposition in nasopharyngeal, tracheobronchial, and alveolar regions, both total regional deposition and deposited dose per unit surface area. Predictive particle deposition models for the respiratory tract can be used for calculating these. The retained dose is another factor that takes into account respiratory tract retention and determines the long-term dose to the respiratory tract. A rat inhalation study using Ni3S2 exposure (concentration, 970 micrograms m-3; duration, 78 wk; exposure, 6 h d-1, 5 d wk-1) resulted in bronchogenic and alveologenic tumors. Extrapolation modeling of rat data was performed based on dose factors discussed above, and assuming different conditions of pulmonary retention for Ni3S2 with half-times of 36 d for rats and 103 d for humans. Model calculations showed that deposited surface area dose was greater for the tracheobronchial than for the pulmonary region in both rat and man. The retained dose per gram of lung was greater in rat than in man under resting conditions. An equivalent exposure concentration would be lower in humans than in the rat if it is based on the retained dose expressed per square centimeter of alveolar surface area. However, inhaled equivalent concentration in man can be considerably higher when the tracheobronchial surface area dose is considered. The most sensitive region of the respiratory tract--for example, with regard to tumor induction--should be selected for estimating human equivalent exposure.

Administration, Inhalation↗
PubMed1989

The bronchodilator response from inhaled terbutaline is influenced by the mass of small particles: a study on a dry powder inhaler (Turbuhaler).

This study was carried out to investigate if particles approximately less than 5 microns are optimal when delivered from a dry powder inhaler. It was performed as a cumulative dose response study of twelve asthmatic adults. Three different versions of a dry powder inhaler, Bricanyl Turbuhaler, were studied. Each inhaler delivered 0.5 mg of pure terbutaline sulphate with each dose. Out of this 0.5 mg, they delivered 90 micrograms, 40 micrograms and 5 micrograms, respectively, of particles approximately less than 5 microns with each dose at an inspiratory flow rate of 28 l.min-1. Terbutaline 0.5 mg, 0.5 mg, 1.0 mg and 2.0 mg was inhaled with a 30 min interval between the doses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured 5 and 20 min after each dose. The bronchodilator response was greater with the inhaler delivering 90 micrograms of small particles with each dose than with the inhaler delivering 5 micrograms, thus confirming the importance of small (approximately less than 5 microns) particles.

Adult↗
PubMed1992

Acute resistant asthma caused by excessive beta-2-adrenoceptor agonist inhalation and reversed by inhalation of beclomethasone.

With the aim of devising an improved beta 2-agonist treatment regimen for patients presenting with acute severe resistant asthma, a double-blind, placebo-controlled randomised study of the effect of fenoterol and beclomethasone inhalations was done in 40 patients. Fenoterol inhalations had minimal effect in acute resistant asthma, but significant improvement was obtained when beclomethasone inhalations were given before fenoterol inhalations. Sequential beclomethasone and fenoterol inhalations can therefore be used as a preliminary emergency treatment for these patients.

Administration, Inhalation↗
PubMed1975

[The inhalation of beta stimulators. Effect of the inhaled aerosol deposited in the oropharynx and in the bronchial tree].

Inhaled aerosols are predominatly deposited in the oropharynx and only a minor portion penetrates into the sublaryngeal airways. The effectiveness of both components of an orciprenaline aerosol was tested in 12 asthmatics. For this purpose they were given an inhalation on one day and, on the next, the entire oropharynx was sprayed with the inhalant. Evaluation of the corresponding bronchodilator effects was based on repeated measurements of specific airway conductance. The results show that the inhalation is about 6 times as effective as the spray, and thus prove the superiority of inhalation therapy over oral or peroral medication with beta-stimulants in the treatment of bronchial asthma.

Adult↗