Simultaneous treatment of rhinitis and asthma by nasal inhalation of corticosteroid from a spacer.
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Administration, Inhalation↗
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Preventing contamination of asthma spacer devices.
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Asthma↗
Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits.
OBJECTIVE: To assess whether paralysis alters pulmonary deposition of albuterol delivered by metered dose inhaler and spacer to small animals. DESIGN: A parallel group study of intubated and ventilated rabbits. INTERVENTIONS: Animals in group 1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rate of 30 breaths/ min. The animals in group 2 (n = 6) were ventilated at a rate of 10 breaths/min under light anesthesia without paralysis. In this latter group, spontaneous respiration continued at a rate of 40 to 50 breaths/min. Both groups were maintained at PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and other ventilatory settings were identical. MEASUREMENTS AND MAIN RESULTS: Technetium-99m labeled albuterol aerosol was delivered by metered dose inhaler via a spacer device to both groups. Pulmonary deposition of the aerosol, determined by measuring the radioactivity in the lung tissues at autopsy, was expressed as percent of the total radioactivity dispensed by the metered dose inhaler. Group 2 showed significantly greater lung deposition than group 1 (0.510 +/- 0.076 [SEM]% vs. 0.226 +/- 0.054%, p = .0094). Deposition in the airway, the endotracheal tube, and the ventilator circuit did not differ significantly. CONCLUSION: Metered dose inhaler delivery of aerosolized medications to ventilated rabbits is significantly enhanced if respiration is not controlled. This observation might have implications for the delivery of therapeutic aerosols to newborns and young infants receiving slow, intermittent, mandatory ventilation.
Aerosols↗
Long-term management of reversible obstructive airways disease in adults.
The goals of the long-term management of reversible obstructive airways disease (ROAD) are to find the minimum treatment that controls symptoms, allows resumption of normal life, prevents severe attack and death, and controls airflow obstruction. ROADs include asthma, chronic bronchitis, and emphysema. Although the differential diagnosis between these different entities may be difficult, they share the same possibilities of pharmacotherapy, including bronchodilator and antiinflammatory drugs. beta 2-agonists administered via inhaled route produce the best bronchodilator/side effects ratio, provided that the drugs reach the bronchi. This underlines the importance of a proper inhalation technique when using a metered-dose inhaler. In patients with hand-breath coordination problems, powder inhalers or spacer devices are useful to ameliorate the therapeutic efficacy of inhaled drugs. Anticholinergic agents are usually less potent bronchodilators than inhaled beta 2 agonists in asthma, but they may have additive effects when associated with beta 2 agonists. Only a therapeutic trial with peak-flow monitoring can demonstrate the efficacy of anticholinergic drugs in individuals. Theophylline's kinetics are characterized by a narrow therapeutic index with high inter- and intraindividual variabilities. Sodium cromoglycate and nedocromil sodium are antiallergic drugs, the efficacy of which has been demonstrated in controlled studies. Corticosteroids are the most efficient anti-asthma drugs. Inhaled corticosteroid dosing should be tailored to each individual. If inhaled corticosteroid therapy is used in an oral corticosparing attempt, patients should be followed-up during several months. The management of ROAD includes the diagnostic procedures, the identification of triggers and inducers of airways obstruction, the assessment of severity of the disease, and then the treatment and education of the patient. Strategy design to achieve proper use of drugs by patients is discussed.
Adrenergic beta-Agonists↗
Optimizing aerosol delivery by pressurized metered-dose inhalers.
The modern era of aerosol therapy began with the introduction of the Medihaler Epi in 1956, after a 13-year-old asthmatic told her father, an officer in the Riker company, that asthma medications should be as convenient to use as hair spray and she complained that the bulb atomizer leaked in her school bag. Since then, advances in technology have made aerosol delivery much more efficient, so that it is now the most widely used mode of medication delivery for chronic airways diseases. Today the pressurized metered-dose inhaler (pMDI) is a metal canister containing a mixture of propellants, surfactants, preservatives, and drug. However, pMDIs are underused in the United States. One barrier to use is the misconception related to pMDI effectiveness relative to small-volume nebulizers, especially among pediatricians. This is despite the strongest evidence of pMDI superiority, from well-controlled pediatric studies. In this manuscript we discuss ways to optimize the use of medications given via pMDI and examine recent changes in pMDI technology that will make drug delivery more efficient and consistent.
Administration, Inhalation↗
Force-dependent static dead space of face masks used with holding chambers.
BACKGROUND: Pressurized metered-dose inhalers with valved holding chambers and masks are commonly used for aerosol delivery in children. Drug delivery can decrease when the dead-space volume (DSV) of the valved holding chamber is increased, but there are no published data evaluating force-dependent DSV among different masks. METHODS: Seven masks were studied. Masks were sealed at the valved holding chamber end and filled with water to measure mask volume. To measure mask DSV we used a mannequin of 2-year-old-size face and we applied the mask with forces of 1.5, 3.5, and 7 pounds. Mask seal was determined by direct observation. Intra-brand analysis was done via analysis of variance. RESULTS: At 3.5 pounds of force, the DSV ranged from 29 mL to 100 mL, with 3 masks having DSV of < 50 mL. The remaining masks all had DSV > 60 mL. At 3.5 pounds of force, DSV percent of mask volume ranged from 33.7% (Aerochamber, p < 0.01 compared with other masks) to 100% (Pocket Chamber). DSV decreased with increasing force with most of the masks, and the slope of this line was inversely proportional to mask flexibility. Mask fit was 100% at 1.5 pounds of force only with the Aerochamber and Optichamber. Mask fit was poorest with the Vortex, Pocket Chamber, and BreatheRite masks. CONCLUSION: Rigid masks with large DSV might not be not suitable for use in children, especially if discomfort from the stiff mask makes its use less acceptable to the child.
Administration, Inhalation↗
Spacers and nebulisers for the delivery of beta-agonists in non-life-threatening acute asthma.
BACKGROUND: In asthma exacerbations, higher doses of inhaled beta-agonists are used to overcome acute bronchoconstriction. Traditionally, wet nebulisation has been used, but metered-dose inhaler with a spacer device is an alternative delivery method. OBJECTIVE: To compare the clinical outcomes in adults and children with acute asthma, presenting in emergency departments or in the community, who have been randomised to beta-agonists given by two different delivery. METHODS: a metered-dose inhaler with spacer or a nebuliser. RESULTS: A Cochrane review has found no important differences between the two delivery methods in adults. Children may suffer fewer side effects with spacer delivery. CONCLUSIONS: Individual response to treatment cannot be predicted, but many studies overcame this problem by using frequent repeated doses of beta-agonists (one respule via nebuliser or four separate actuations of a metered-dose inhaler through a spacer) every 10-15 min, titrated against the clinical response of the patients. This approach is advocated in clinical practice.
Acute Disease↗
Inhaled budesonide in acute asthma.
OBJECTIVE: To evaluate the efficacy of aerosolized budesonide therapy (with metered dose inhaler and spacer) early in the emergency room treatment of acute moderate exacerbations of bronchial asthma in children. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Paediatric Emergency Service of an urban teaching hospital and a tertiary case referral centre. STUDY POPULATION: Sixty children between 3 and 12 years of age with an acute moderate exacerbation of asthma. INTERVENTION: All patients received humidified oxygen (5-8 L/min by Venturi(R) mask; Hudson Respiratory Care, Temecula, CA, USA), nebulized salbutamol (0.15 mg/kg in 3 mL saline) and were randomized to receive either budesonide (400 microg) or placebo inhalation (MDI and spacer) at half hourly intervals for three doses. If there was an inadequate response or no response to treatment at the end of 2 h, oxygen and salbutamol therapy were continued and the patient was given one of dose intravenous hydrocortisone and was started on an aminophylline infusion. If there was no response at the end of a further 4 h, the patient was hospitalized. INITIAL EVALUATION AND MONITORING: Colour, respiratory rate (RR), heart rate, accessory muscle usage, chest retraction, wheeze, oxygen saturation (by pulse oximetery) and peak expiratory flow rate (PEFR) was recorded at admission and thereafter at hourly intervals for 3 h or until till the child recovered. The need for oxygen therapy after 2 h and need for hospitalization were recorded. MAIN RESULTS: Both groups showed a significant improvement in respiratory status at the end of 2 h. However, children in the intervention group showed greater improvements in RR and PEFR (P < 0. 05) and respiratory distress score (P < 0.1). A significantly lower proportion of the intervention group patients required oxygen therapy for more than 2 h (23% vs 50%; P < 0.05) and aminophylline infusion and systemic corticosteroid therapy (7% vs 27%; P < 0.05). None of the children in the budesonide group, in contrast to 23% of those in the placebo group, required hospitalization (P < 0.05). The length of hospital stay (i.e. time taken to recover from acute asthma) was significantly shorter in the intervention group (3.2 +/- 2.5 h) than in the placebo group (7.8 +/- 11.3 h; P < 0.01). CONCLUSION: Aerosolized budesonide therapy (with MDI and spacer) together with nebulized salbutamol early in the emergency room treatment of acute moderate exacerbations of asthma helped in early recovery and decreased the need for hospitalization. It may be worthwhile calculating this regimen for home-based early treatment of acute exacerbations.
Acute Disease↗
A large volume spacer significantly reduces the effect of inhaled steroids on bone formation.
Inhaled steroids are increasingly advocated as first line treatment for mild asthma. Some studies suggest that inhaled steroids suppress bone formation as reflected by a fall in plasma osteocalcin. Spacers have been shown to increase the proportion of inhaled aerosol that is deposited in the lungs and to reduce the amount swallowed. We measured plasma osteocalcin levels to determine the effect on bone formation of inhaled beclomethasone dipropionate (BDP) with and without a 750 ml spacer in a double-blind, randomised, placebo-controlled, cross-over study. Twenty-six healthy male volunteers took BDP 500 micrograms (two puffs of Becloforte) together with two puffs of placebo, inhaled twice daily for seven days. One inhaler was taken directly while the other was inhaled through a 750 ml spacer. After a two week washout period, the inhalers were exchanged so that BDP was taken by the alternate route for a further seven days. Fasting plasma osteocalcin levels were measured at 09.00 h before and at the end of each week. After a week of BDP taken directly (without a spacer), osteocalcin levels fell from 11.8 (SEM 0.6) ng/ml to 9.5 (SEM 0.5) ng/ml (p < 0.001). After a week of BDP taken through a spacer, osteocalcin levels fell from 12.1 (SEM 0.5) ng/ml to 11.1 (SEM 0.5) ng/ml (p < 0.001). The fall in osteocalcin when a spacer was used was significantly less than when BDP was taken directly (p < 0.005). This is likely to be because the systemic effects on bone are caused by swallowed rather than inhaled BDP, and this is limited by the use of a spacer. Spacers should be more widely prescribed with inhaled steroids. Further prospective studies are indicated to evaluate whether spacers protect bone mass.
Administration, Inhalation↗
Emitted doses of salbutamol pressurized metered-dose inhaler from five different plastic spacer devices.
In a recent clinical study we have demonstrated that the bronchodilator effect of 200 microg salbutamol (Ventoline) was spacer device-dependent in 100 tested asthmatic children, with the Babyhaler providing greater efficacy for improving peak expiratory flow rate compared to Aeroscopic, Nebuhaler, Aerochamber and Volumatic. The aim of this present study was to correlate our clinical results to in vitro determinations of the emitted dose (ED) of Ventoline administered via these five different plastic spacer devices. ED was determined from the mean of single doses collected in unit dose sampling tubes using a constant suction flow of 28.3 L/min. Three pressurized metered-dose inhalers and three sets of spacer devices were used to obtain a total of 30 measurements per group. Inter-group results were compared by RM-ANOVA or Student-Newman-Keuls method when indicated. Babyhaler delivered significantly (P < 0.05) more salbutamol than Nebuhaler, Aerochamber and Aeroscopic (mean +/- standard deviation: 63.6 +/- 2.9 microg/100 microg actuation for Babyhaler vs. 59.4 +/- 8.6 for Nebuhaler, 50.8 +/- 5.0 for Aerochamber and 47.5 + 2.5 for Aeroscopic). The ED from Volumatic (61.5 +/- 7.9 microg/100 microg actuation) was similar to that from the Babyhaler. The variability in the ED was greatest with the large volume spacers. Despite a greater ED from the Babyhaler, in vitro results do not fully explain the in vivo results. However, the previously described clinical improvement seen with the Babyhaler may be due to the quantitatively different aerosol production in a more 'useful' size range, as well as the different breathing patterns of the children tested. The results of this present study question the relevance of mouthpiece filter collection studies using a constant sampling in predicting clinical or physiological outcomes.
Albuterol↗
Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma.
The aim of this study was to compare the response to inhaled albuterol after administration by nebulizer with the response after administration by a metered-dose inhaler and spacer device (MDI-spacer) to children with acute asthma. In a double-blind fashion, 33 children (6 to 14 years of age) with forced expiratory volume in 1 second (FEV1) between 20% and 70% of predicted values, and who were seen in the emergency department with acute asthma, were studied. They were treated with aerosolized albuterol or placebo by MDI-spacer, followed immediately by albuterol or placebo administered by nebulizer with oxygen. The dose ratio for albuterol by MDI-spacer versus nebulizer was 1:5. Outcome measures included a clinical score, respiratory rate, arterial oxygen saturation, and FEV1, measured before and 10, 20, and 40 minutes after treatment. With the exception of heart rate (which increased in the nebulizer group and decreased in the MDI-spacer group (p < 0.05), no difference in the rate of improvement of clinical score, respiratory rate, arterial oxygen saturation, or FEV1 was noted during the 40-minute study period between children who received albuterol by nebulizer and those who received it by MDI-spacer. We conclude that spacers and nebulizers are equally effective means of delivering beta 2-agonists to children with acute asthma.
Acute Disease↗
The effects of inhaled albuterol and salmeterol in 2- to 5-year-old asthmatic children as measured by impulse oscillometry.
The functional assessment of the response to bronchodilators in 2- to 5-year-old asthmatic children is technically difficult. For this reason, there have been no reports on the effects of long-acting bronchodilators, such as salmeterol, in this age group. Of the several techniques available for measuring resistance to airflow, forced oscillation remains the most adaptable to young children and the most practical for research and clinical use. In this stud we used the Jaeger MasterScreen Impulse Oscillometry System to assess the response of 2 to 5 year-old asthmatic children to an inhaled long-acting bronchodilator, salmeterol, by comparing it to the effect of a standard dose of the short-acting bronchodilator, albuterol. We performed a placebo-controlled, randomized, crossover study in 10 children aged 2 to 5 years who had a history of physician-diagnosed asthma and who were not on regular controller therapy. At weekly intervals after baseline measurements of reversibility, each child received two inhalations from an albuterol metered-dose inhaler (MDI) with a spacer (200 microg), or placebo MDI with spacer, or two inhalations from a salmeterol MDI (50 microg), or 50 microg from a salmeterol Diskus. Measurements were obtained at 5, 30, 60, 360, and 540 min, the last time interval only on the salmeterol days. Based on previous studies, total respiratory system reactance at 5 Hz (X5), calculated by the MasterScreen computer from mouth pressure and flow data, was used as the primary efficacy variable. The mean intra-individual variability in X5 was 10.5% (range 3.6% to 17.9%). The mean (SE) changes from baseline X5 at each time point were as follows: for placebo, 9.6 (3.0), 10.1 (2.6), 5.1 (2.9), 6.1 (3.5), p=0.36 vs. baseline; after treatment with albuterol, 32.7 (3.8), 53.9 (1.2), 47.3 (5.4), 18.1 (5.8), p<0.01 vs. baseline at all time points; after salmeterol MDI, 16 (6.4), 28.9 (5.2), 32.7 (3.9), 34.6 (4.4), 31.2 (4.8), p<0.05 at 60, 360, and 540 min; and after salmeterol Diskus, 16.4 (4.0), 16.9 (6.6), 27.8 (5.9), 28.6 (5.6), 33.8 (4.0), p<0.05 at 540 min. No significant adverse events or electrocardiographic changes were noted at any time. Impulse oscillometry is an acceptable method of assessing airway responses to bronchoactive drugs in this age group. Compared to albuterol and to its effect in older children and adults, the response to salmeterol Diskus appears to be somewhat blunted in this age group. The MasterScreen system is well suitedfor pharmacodynamic studies and clinical investigations in pre-school-aged children.
Administration, Inhalation↗
Asthma medications and their potential adverse effects in the elderly: recommendations for prescribing.
The incidence of drug-induced adverse effects is likely to increase as a result of advanced age and exposure of elderly patients to polypharmacy. Therefore, pharmacological therapy of asthma and chronic obstructive pulmonary disease (COPD) in the elderly patient can be potentially hazardous. beta(2)-agonists, administered as therapy for asthma and COPD, have recognised systemic sequelae, such as hypokalaemia and chronotropic effects, which may be life-threatening in susceptible patients. Adverse effects such as hypokalaemia can be aggravated by concomitant treatment with other drugs promoting potassium loss including diuretics, corticosteroids and theophyllines. In addition, relatively minor adverse events associated with the administration of beta(2)-agonists, such as tremor and blood pressure changes, may be of significance to the elderly patient leading to impairment in the quality of life. However, long-term treatment with beta(2)-agonists may reduce the incidence of drug-induced adverse effects as a result of beta-receptor subsensitivity. Oral and inhaled corticosteroids have been used for the treatment of acute asthma and COPD in the elderly patient. Long-term treatment with oral corticosteroids can result in serious systemic adverse effects such as suppressed adrenal function, bone loss, skin thinning and cataract formation. In contrast to beta(2)-agonists, oral corticosteroids can upregulate beta(2)-adrenoceptors and thereby potentiate the systemic sequelae of beta(2)-agonists. Hence, oral corticosteroids should be administered with caution for as short a duration as possible. Inhaled corticosteroids appear to be relatively well tolerated when administered at doses below approximately 1000 microg. However, larger doses of inhaled corticosteroids may affect hypothalamic-pituitary-adrenal function and bone turnover. In the case of inhaled corticosteroids, spacer devices, often used in older patients who cannot operate metered dose inhalers, can potentiate the systemic sequelae of both corticosteroids and beta(2)-agonists. The use of theophyllines in the treatment of COPD or chronic asthma is controversial. Theophyllines have a wide adverse effect profile and are prone to drug-drug interactions. The adverse effects may be mild or life threatening and include nausea and vomiting or sinus and supraventricular tachycardias. Therefore, theophyllines should be prescribed with extreme caution to elderly patients with asthma or COPD. In contrast, inhaled anticholinergic drugs such as ipratropium bromide and oxitropium bromide are generally safe in elderly patients and have useful bronchodilator function. Commonly reported adverse effects are an unpleasant taste and dryness of the mouth. When used as first-line therapy, anticholinergic drugs may optimise the bronchodilator effects of low-dose inhaled beta(2)-agonists in patients with chronic airflow obstruction, and hence obviate the need for higher doses.
Adrenal Cortex Hormones↗
Asthma and COPD. Inhalation therapy--clarity or confusion?
BACKGROUND: Inhalation therapy is the most effective drug administration route for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The range of available inhaler devices is wide and choosing the right one for your patient can be difficult. OBJECTIVE: This article reviews the available evidence on the pros and cons of various inhaler devices, in order to encourage a more tailored choice. DISCUSSION: Of the currently available devices, we believe the Autohaler is probably the most clinically effective and user friendly. Although nebulisers are also clinically effective, they are costly and less easily portable. For most situations, the acceptable alternative to a nebuliser is an aerosolised metered dose inhaler attached to a spacer. Regardless of inhaler device choice, your patient must be able to use the device easily, maintain it, and derive clinical benefit. The cornerstone of good asthma and COPD management is continual clinical reassessment, including inhaler technique.
Asthma↗
[Role of inhalation therapy in the management of childhood asthma].
Inhaled drugs became of great interest in the treatment of childhood asthma. They must be adapted now to age and each form of the disease. The primarily interest of an organ therapy is to lead to a maximal efficacy by bringing locally an optimal quantity of drug without or with very few side effects. The choice of the device depends upon age which determines drug tolerance and quality of the inhalation technique. In infants and young children the use of nebulizers appears to be the most suitable technique; preschool children are capable to use metered-dose inhalers (MDI) with spacers; in older children the use of MDI, without spacers, or dry powder inhalers is allowed. During attacks of asthma, inhaled therapy appears to be effective in most cases using either B2 agonists alone in moderate forms, or B2 agonists associated with oral or parenteral corticoids in more severe forms. For the preventive treatment of asthma, in order to prevent attacks, some inhaled drugs also belong to a first line therapy against either allergy or on specific bronchial hyperreactivity: cromolyn or nedocromil are often used in mild to moderate forms (in association with oral anti-histamine drugs in some cases); in more severe forms we can start with a bronchodilator B2 agonist long-term treatment (associated with sustain-released theophylline in some cases), except in infants before twelve or eighteen months of age; in the most severe forms of chronic asthma an anti-inflammatory long-term treatment with inhaled corticosteroids may be prescribed even in young children.
Administration, Inhalation↗
Assessment of care of patients with asthma in a family practice training program.
To determine if primary care physicians have been adhering to guidelines set forth by the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel Report Guidelines for the Diagnosis and Management of Asthma, the author gauged the use of peak flow meters in a hospital family training program. Specifically investigated were the physicians' response to results from the peak flow meters and their prescribing practices regarding the beclomethasone dipropionate metered-dose inhaler. Overall, the use of peak flow meters among the 20 patients included in this study averaged 70%, up from 10% in earlier studies. Similarly, 45% of these patients received prescriptions for beclomethasone metered-dose inhalers with spacer devices. Although these results appear to indicate that physicians are following the aforementioned guidelines, the author cautions that the peak expiratory flow rate measurement is not a perfect indication of asthma severity. Likewise, the spacer devices are not indicated for all patients with asthma who are taking inhaled corticosteroids. Finally, the author emphasizes that anti-inflammatory agents should be effectively used when indicated.
Asthma↗
[The inhalational therapy of respiratory pathology].
The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.
Administration, Inhalation↗
[The effects of changed spacer tubes of the convergent beam irradiator].
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Carmustine↗