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Sympathomimetics in acute severe asthma: inhaled or parenteral, nebulizer or spacer?

It is accepted today that all patients with acute asthma should be treated with a sympathomimetic, irrespective of previous therapy. This short review addresses the question of the optimal mode of administration of these drugs in acute severe asthma. Inhaled sympathomimetics are as effective as subcutaneous adrenaline, or intravenous salbutamol or terbutaline, and, as they produce fewer side-effects, are recommended as the best mode of administration. However, self-medication with a ready to use subcutaneous preparation may be indicated in those patients prone to very abrupt attacks. The conventional mode of inhalation therapy in acute asthma is nebulization, but equally effective bronchodilatation may be obtained with metered-dose inhalers combined with valved spacers. Tachypnoeic patients unable to perform a conventional inhalation manoeuvre can use one-way valve inhalation devices with repeated tidal breaths. Finally, sequential or even continuous inhalation techniques have recently been advocated, particularly in patients with impending respiratory failure.

Administration, Inhalation↗

Lung deposition of aerosol--a comparison of different spacers.

AIMS: To investigate (1) aerosol lung deposition obtained from two small volume conventional spacers (Babyhaler and Aerochamber) and a home made spacer (modified 500 ml plastic cold drink bottle); (2) the effect of using a face mask or mouthpiece; and (3) the relation between age and pulmonary deposition. METHODS: Lung deposition of aerosolised technetium-99m DTPA inhaled via spacer was measured in 40 children aged 3-7 years with stable asthma. Each patient performed sequential randomly assigned inhalations using two spacers. Three studies were performed: Babyhaler compared to Aerochamber (with facemasks); Babyhaler with facemask compared to Babyhaler with mouthpiece; and Babyhaler with mouthpiece compared to a 500 ml bottle. RESULTS: Median lung aerosol deposition from a Babyhaler and Aerochamber with masks were similar (25% v 21%, p = 0.9). Aerosol lung deposition from a Babyhaler with mask compared to a Babyhaler with mouthpiece was equivalent (26% v 26%, p = 0.5). Lung deposition was higher from a 500 ml bottle compared to a Babyhaler in both young (25% v 12.5%, p = 0.005) and older children (42% v 22.5%, p = 0.003). A notable reduction in pulmonary deposition occurred at 50 months of age. CONCLUSION: A Babyhaler or Aerochamber produce equivalent lung deposition of aerosol. There is no difference in lung deposition when a mask or mouthpiece is used. A modified 500 ml plastic bottle produces greater pulmonary aerosol deposition than a conventional small volume spacer.

Administration, Inhalation↗

A comparison of large volume spacer, breath-activated and dry powder inhalers in older people.

AIMS: To see if elderly people can use the breath-activated (Easi-breathe) and dry powder (Turbohaler) inhalers as effectively as the metered-dose inhaler and Volumatic system. METHODS: 102 inhaler-naive patients (aged 75-101, mean 84 years), without cognitive impairment, were randomly allocated one of Easi-breathe, Turbohaler or metered-dose inhaler and Volumatic placebo inhalers. Standardized tuition was done on enrolment and at 6 h review. Inhaler technique was assessed immediately after enrolment tuition and at 6 and 24 h. Assessment was by scoring (0 = poor, 1 = moderate, 2 = perfect) five aspects of technique. RESULTS: Mean total scores were significantly (P < 0.005) higher for Turbohaler and Easi-breathe than metered-dose inhaler and Volumatic on enrolment and 6 h and at 24 h (P < 0.045). Fewer patients achieved excellent scores of 9 or 10 when using metered-dose inhaler and Volumatic. The main difficulties were in assembling the metered-dose inhaler and Volumatic and detecting when the metered-dose inhaler and Volumatic or Easi-breathe was empty. CONCLUSIONS: Breath-activated and dry powder inhalers were more likely to be used correctly than metered-dose inhalers with large volume spacers.

Administration, Inhalation↗

Relative lung bioavailability of generic sodium cromoglycate inhalers used with and without a spacer device.

The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) microg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) microg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method.

Administration, Inhalation↗

Comparison of patient preference and ease of teaching inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers.

A multicenter, randomized, open-label, crossover study with two 4-week evaluation periods compared patient preference and ease of teaching correct inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers (pMDIs). Patients 18 to 65 years of age with stable, mild to moderate asthma, who required or were eligible for inhaled corticosteroid therapy, were randomized to treatment sequences consisting of 4-week evaluation periods with Pulmicort Turbuhaler (budesonide inhalation powder) two puffs (400 microg) bid and one of three inhaled corticosteroids via pMDI: Aerobid-M (flunisolide) four puffs (1 mg) bid, Flovent (fluticasone propionate) two puffs (440 microg) bid, or Vanceril Double Strength (beclomethasone dipropionate) five puffs (420 microg) bid. Patients indicated device preference at study end and completed the Patient Device Experience Assessment (PDEA) questionnaire after each evaluation period. Ease of teaching, time required to master use of the device, percentage of patients demonstrating mastery on the first attempt, and the number of attempts required to demonstrate mastery were assessed. Despite previous use of pMDIs by most patients, Pulmicort Turbuhaler was significantly preferred (p < 0.001) and required significantly less time to master than pMDIs (p < 0.001). Median times to device mastery were 3.67 min for Pulmicort Turbuhaler versus 5.33 min for pMDIs. Patients rated Pulmicort Turbuhaler significantly better than pMDIs on PDEA ease of use (p = 0.0005) and overall satisfaction (p < 0.0001) single-item scales and all four multi-item scales (pharyngeal symptoms, oral sensation, operational use, and inhaler attributes; p < 0.05). Overall, patients preferred Pulmicort Turbuhaler over pMDIs and required less time to be taught how to correctly use Turbuhaler trade mark.

Administration, Inhalation↗

Comparison of inhaled corticosteroids.

OBJECTIVE: To review the comparative studies evaluating both efficacy and safety of inhaled corticosteroids in the management of asthma. Specifically, comparative clinical trials are evaluated that allow clinicians to determine relative potencies of the various inhaled corticosteroids. METHODS: A critical review was performed of the published clinical trials, either as articles or abstracts, comparing the clinical efficacy or systemic activity of inhaled corticosteroids. No a priori criteria were applied, as this was not a meta-analysis. FINDINGS: In vitro measures of antiinflammatory activity of corticosteroids consistently demonstrate potency differences among the various corticosteroids. Traditionally, these in vitro measures have been used to develop new corticosteroids with greater topical activity. While no accepted direct measure of antiasthmatic antiinflammatory activity exists, clinical trials using surrogate measures (e.g., forced expiratory volume in 1 second, peak expiratory flow, bronchial hyperresponsiveness, symptom control) indicate that in vitro measures provide a relatively accurate assessment of antiasthmatic potency. The relative antiinflammatory potency of the inhaled corticosteroids is in the following rank order. flunisolide = triamcinolone acetonide < beclomethasone dipropionate = budesonide < fluticasone. Studies of systemic activity appear to confirm this relative order of potency. Currently, no evidence exists for greater efficacy for any of the inhaled corticosteroids when administered in their relative equipotent dosages. The preponderance of current data suggests that when administered in equipotent antiinflammatory doses as a metered-dose inhaler plus spacer or as their respective dry-powder inhaler, the existing inhaled corticosteroids have similar risks of producing systemic effects. CONCLUSIONS: Delivery systems can significantly affect both topical and systemic activity of inhaled corticosteroids. More direct comparative studies between agents are required to firmly establish comparative topical to systemic activity ratios. The preponderance of evidence suggests that the agents are not equipotent on a microgram basis.

Administration, Inhalation↗

Improvement of inhaler efficacy by home-made spacer.

The delivery of aerosol from a metered dose inhaler (MDI) was reported to be more efficient with a spacer. Hence, a home-made spacer modified from a 950 ml low cost plastic bottle, was compared with a MDI and with a 750 ml imported spacer (Nebuhaler). On three consecutive days, at the same time of day, 20 adult patients with chronic asthma inhaled two puffs of terbutaline sulphate (0.5 mg), delivered from MDI alone, MDI with a 750 ml Nebuhlaer and MDI with a home-made spacer. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate. These measurements were carried out immediately before and at 5, 20, 60 min after inhalation of terbutaline. FEV1 was significantly increased (P < 0.05) at 5, 20 and 60 min after administration of terbutaline with MDI via either spacers than with MDI alone but no significant difference was observed between Nebuhaler and the home-made spacer. FVC and pulse rate showed no significant change with each method of administration. In conclusion, terbutaline delivered by MDI and home-made spacer was more effective in bronchodilatation than by MDI alone and was just as effective as MDI and Nebuhaler. The home-made spacer therefore offers a simple, inexpensive and more effective method for delivering aerosol drug.

Adolescent↗

[Effectiveness of treatment of bronchoobstruction in children with acute respiratory infections using home-made spacer].

A metered-dose inhaler (MDI) with spacer is the best way to deliver bronchodilator therapy for treatment of bronchoobstructive syndrome, especially in children. In developing countries, commercially produced spacers are generally unavailable or are too costly. Hence, a home-made spacer modified from a 500 ml plastic bottle, was compared with imported spacer (AeroChamber) in 80 children with spastic bronchitis. Clinical score, PEF and oximetry were recorded at baseline and 15 min after treatment. A beta-2- agonist (Ventolin) was given via MDI and two spacers (home-made and conventional spacers). PEF and oxygen saturation were significantly increased at 15 min after administration of the ventolin in both groups. No significant difference was observed between Aerochamber and the home-made spacer. In conclusion, ventolin delivered by MDI with AeroChamber was as effective in bronchodilatation as MDI with home-made spacer. The home-made spacer therefore offers a simple, inexpensive and effective method for delivering aerosol drug.

Acute Disease↗

Inhaled terbutaline administered via a spacer fully prevents exercise-induced asthma in young asthmatic subjects: a double-blind, randomized, placebo-controlled study.

The effects of inhaled terbutaline, a beta 2-adrenergic agonist, administered via a 750-ml spacer device were studied in young asthmatic subjects with exercise-induced asthma. A double-blind, randomized, placebo-controlled study of the effects of inhaled 0.5 mg terbutaline and placebo was conducted in 10 asthmatic children (age range 6-16 years) with documented exercise-induced asthma. Forced expiratory volume in 1 s (FEV1) was measured at baseline, 15 min after inhaling terbutaline or placebo, and at intervals up to 60 min after exercising. Subjects exercised using a cycle ergometer for 5 min at a submaximal, constant work-load while breathing dry air at room temperature. Terbutaline induced bronchodilation at rest in all subject and fully prevented exercise-induced asthma in nine out of the 10 subjects; the exercise-induced fall in FEV1 was markedly reduced in the remaining subject. It is concluded that exercise-induced asthma can be inhibited by pretreatment with inhaled terbutaline, administered via a spacer, in a majority of young asthmatics.

Administration, Inhalation↗

Nebulized wet aerosol treatment in emergency department--is it essential? Comparison with large spacer device for metered-dose inhaler.

OBJECTIVE: To determine the efficacy of a metered-dose inhaler (MDI) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: University Hospital Department of Emergency Medicine (DEM). PATIENTS: Fifty patients, referred to the DEM between October 1, 1994 and March 31, 1995 with a severe, acute obstructive pulmonary event. Thirteen patients were diagnosed as having COPD; 37 patients were diagnosed as having asthma. INTERVENTION AND RESULTS: Patients received either placebo MDI through a 750-mL cone-shaped spacer (Glaxo) [2 puffs] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution (group 1, n=25) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above (group 2, n=25). The above treatment was repeated three times every 15 min, unless side effects appeared. Upon enrollment into the study, the FEV1 in group 1 was 0.78+/-0.7 L (mean+/-SD), 32% of predicted, and in group 2, 0.74+/-0.51 L, 29% of predicted (p=0.83). The FEV1 values after the first, second, and third interventions were as follows: in group 1, 1.18+/-0.99 L, 1.40+/-0.8, and 1.47+/-0.79, respectively, and in group 2, 1.17+/-0.99 L, 1.46+/-1.01, and 1.54+/-0.79 (p=0.83, 0.36, and 0.48, respectively). We observed no difference in spirometric measurements between the two groups at any time. CONCLUSION: Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation, the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery: MDI with a large spacer vs aerosol nebulization.

Aerosols↗

Delivery of beclomethasone dipropionate from a spacer device: what dose is available for inhalation?

BACKGROUND: It is common for inhaled steroids to be delivered through a large volume spacer device. Comparatively little is known about how this practice affects the dose of drug received by patients compared with drug delivered directly from a metered dose inhaler. METHODS: The amount of beclomethasone dipropionate, contained in particles of various size, available for inhalation from a 750 ml polycarbonate spacer (Volumatic) was determined by impinger measurement and high performance liquid chromatography. Three strengths of metered dose inhalers were studied (50 micrograms, 100 micrograms, and 250 micrograms/actuation). The effect of multiple actuations of beclomethasone dipropionate into a Volumatic spacer, and increasing residence times of drug within the spacer before inhalation, on the amount of drug available to the patient for inhalation was determined. RESULTS: The amount of beclomethasone dipropionate in particles < 5 microns when delivered by a spacer device or directly from a metered dose inhaler was similar. The total amount of beclomethasone dipropionate available for inhalation per actuation decreased by 20 micrograms with the 50 micrograms inhaler, 48 micrograms with the 100 micrograms inhaler, and 161 micrograms with the 250 micrograms inhaler, when given via the spacer compared with delivery directly from a metered dose inhaler. There was a progressive decrease in drug available for inhalation per actuation as the number of actuations into the spacer increased, for all strengths of beclomethasone dipropionate tested. A progressive decrease in drug recovered per actuation was also seen with increasing residence times of drug within the spacer before inhalation. CONCLUSIONS: Use of the spacer device significantly reduced the amount of nonrespirable beclomethasone dipropionate available for inhalation. The amount of beclomethasone dipropionate within respirable particles decreased considerably following multiple actuations into the spacer and with increasing residence times within the spacer before inhalation. When given via a spacer device beclomethasone dipropionate should be inhaled immediately after actuation and multiple actuations into the device should be avoided.

Beclomethasone↗

Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma.

The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.

Administration, Inhalation↗