Pressurized Aerosol Research Articles

Excess mortality in patients with asthma on long-acting 2-agonists

Asthma ranks among the most common of chronic diseases in the Western world. Although modern therapy has improved patient care, asthma still affects 5–10% of the population and, according to the World Health Organization, claims the lives of some 12,000 patients per year in Western Europe 1. β2-Agonists are potent bronchodilators and are the most widely prescribed drugs for asthma worldwide. National and international guidelines recommend short-acting β2-agonists as as-needed therapy for symptomatic relief in all stages of asthma. Long-acting β2-agonists (LABAs) have been recommended as controller medication for moderate and severe asthma. Nevertheless, the safety profile of short-acting β2-agonists has been questioned due to possible detrimental effects on asthma control 2–5. Recent evidence and meta-analysis suggest an increased risk for cardiovascular complications in patients using β2-agonists 6–8 and, in addition, there is evidence suggesting that the frequent use of these drugs might increase the risk of premature death 9–11. The hypothesis that β2-agonists can have fatal adverse effects was first demonstrated in the late 1960s 12. Inman and Adelstein 12 reported a 30–700% increase, depending on age, in asthma death in patients using pressurised aerosols containing, most often, isoprenaline. The excess mortality in patients with asthma at that time was attributed to overdosing (metered-dose aerosols were not widely available at the time). β2-Agonists came into focus again in the 1980s, when more selective β2-agonists were introduced in metered-dose inhalers. However, in the 1990s, case–control studies showed that the use of these drugs was associated with an increased risk of fatal asthma, even when inhaled from a metered-dose inhaler. A dose-dependent risk of death from asthma was reported, which increased up to 20-fold with …

In Reply: Aerosol Delivery Devices

Teaching patients correct inhaler technique and reinforcing this technique with each subsequent office visit are indeed key steps to the successful implementation of aerosol therapy, as aptly stated by Drs. Barnes and Crompton. In 1982, Crompton 1 Crompton GK Problems patients have using pressurized aerosol inhalers. Eur J Respir Dis. 1982; 63: 101-104 Google Scholar identified the difficulties patients had when using their metered-dose inhalers; and this article, along with eight others, were discussed in the introduction to our meta-analysis. 2 Dolovich M Ahrens R Hess D et al. Device selection and outcomes of aerosol therapy: American College of Chest Physicians /American College of Asthma, Allergy and Immunology Evidence-based guidelines. Chest. 2005; 127: 335-371 Abstract Full Text Full Text PDF PubMed Scopus (649) Google Scholar In addition, the take-home message from the meta-analysis was that for patients unable to master the required inhalation technique for a specific delivery device, other choices for inhalers delivering equivalent drug doses and providing the same clinical efficacy were often available. The importance of correct inhaler technique to successful therapy was stressed throughout the body of the text, with the points made in the Abstract re-emphasized in the concluding paragraphs, in which we restated that competence in the use of an inhaler needed to be confirmed by the physician or health-care worker when choosing an aerosol delivery device for their patient. Aerosol Delivery DevicesCHESTVol. 129Issue 5PreviewThe conclusions reached by Dolovich and colleagues1 in a special report of meta-analyses of randomized controlled clinical trials of aerosol delivery devices and inhaled therapy for patients with asthma and COPD are concise and show that devices used for the delivery of bronchodilators and steroids can be equally efficacious. However, we believe that when selecting a delivery device, much more prominence should be given to a patient's ability to use the selected device correctly. The conclusion that all devices can be equally efficacious was obviously obtained from analyses of randomized controlled clinical trials in which patient participation required the ability of patients to use the devices being studied correctly. Full-Text PDF

The development of a novel high-dose pressurized aerosol dry-powder device (PADD) for the delivery of pumactant for inhalation therapy.

The performance of a novel dry powder inhaler designed to deliver exceptionally high doses was investigated using pumactant as a model powder. Pumactant (a synthetic lung surfactant consisting of a phospholipid mixture), with a 90th percentile particle size of 2.92 microm is highly cohesive, has a high moisture affinity (6.2% w/w at 45% RH), and is predominantly amorphous. The device (pressurized aerosol dry-powder delivery [PADD]) utilizes pressurized gas to aerosolize a powder bed from a reservoir and delivers it through a conventional mouthpiece. The influence of loaded dose on dry powder delivery and can pressure on aerosolization efficiency was investigated. Analysis of the delivered dose studies suggested a linear relationship between loaded dose and delivered dose (R(2) = 0.96, for loaded doses of 0-250 mg), with a delivery efficiency of 70%. Analysis of the aerosolization efficiency using a Marple Miller type impactor suggested fine particle fractions (particles with an aerodynamic diameter of <5 microm) of approximately 30% using canister pressures of 8-14 bars. These results indicate that the PADD device may be a useful tool in delivering high-dose medicaments, as a carrier-free formulation, to the deep lung.

Comparative Study of Different Inhaler Devices in Asthmatic Children

The inhaler is an important drug delivery system in the treatment of asthma, but inhaler technique is often inadequate. We assessed technique in children diagnosed with asthma, comparing the performance of three devices. In a cross-sectional survey, 523 children (271 boys, 252 girls, ages 5 to 12 years; mean+/-SD 7.53+/-1.79 years) demonstrated inhalation technique according to Netherlands Asthma Foundation criteria during a first visit to a primary care clinic in Abha, Saudi Arabia. Patients used the device with which they were most familiar (either pMDI, Turbuhaler or Diskus). Two hundred children (38% of total population) used a pMDI, while 323 (62% of total population) used one of the dry powder inhalers 173 (58%) the Turbuhaler and 150 (47%) the Diskus. Only 49 children (25% of the total population) completed the assessment without making a mistake. The remaining 474 (75% of the total population) performed one or more manuevers poorly. Only 80 children who used an MDI (40% of those using the device) completed 50% or more of the maneuvers correctly compared with 111 (69% of those using the device) and 100 (67% of those using the device) of those using the Turbuhaler and Diskus, respectively (P=0.001 for comparison of MDI with dry powder inhalers). Children whose mothers had intermediate school or higher education performed better than those whose mothers had less education (P=0.001). The father's education had no bearing on performance with the inhaler. The inhaler technique of most asthmatic children is poor, but technique is better in children who use a dry powder compared a metered-dose inhaler. The level of the mother's education is positively associated with better inhalation technique in the child.

Comparison of the efficacy of beclometasone dipropionate and fluticasone propionate suspensions for nebulization in adult patients with persistent asthma

The use of nebulization for the administration of inhaled steroids plays an important role in asthma patients who are unable to use pressurized aerosol or dry-powder inhalers effectively. Moreover, the type of nebulizer used may affect how much drug is delivered to the lungs. The objective of this multinational, multicentre, randomized, active controlled, parallel-group study was to compare the efficacy and safety of nebulized corticosteroids in adult patients with chronic asthma. Following a 1-week placebo run-in period, 205 patients, aged 18–65 years, with moderate persistent asthma were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 2400 μg day −1 b.i.d. ( n=103), or fluticasone propionate (FP) suspension for nebulization 2000 μg day −1 b.i.d. ( n=102), both administered by a jet nebulizer. Comparable efficacy in controlling asthma was demonstrated by the two treatments at study end, as evident when evaluating various efficacy parameters (pulmonary function tests, asthma exacerbations and symptoms, and the use of rescue salbutamol). The primary efficacy endpoint was the variation in the pulmonary expiratory flow (PEF) at treatment end over the baseline visit. For the intent-to-treat popoulation, in the BDP group mean PEF values increased statistically significantly from 5·2 ± 1·31 s −1 to 5·7 ± 1·61 s −1, while in the FP group the increase was from 5·2 ± 1·21 s −1 to 5·8 ± 1·81 s −1. Mean PEF values as per cent of predicted also increased in a statistically significant way, from 71% to 77·1% in the BDP group, and from 70·1% to 76·9% in the FP group. The two treatments were equally well tolerated. A total of 23 and 32 patients in the BDP and FP groups, respectively, reproted adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP 2400 μg day −1 and FP 2000 μg day −1, both suspensions for nebulization administered via a jet nebulizer, are equally effective, with an acceptable safety and tolerability profile, when used in adult patients with moderate persistent asthma.

Patient Handling of a Dry-Powder Inhaler in Clinical Practice

Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Delivery of salbutamol pressurized metered-dose inhaler administered via small-volume spacer devices in intubated, spontaneously breathing rabbits.

Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles <5.8 microm in diameter (NES-spacer = Babyhaler > Aerochamber-Infant; p < 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52-5.40% of the delivered dose) but greater with the NES-spacer than with the Aerochamber-Infant or the Babyhaler (5.40 +/- 2.40%, 2.91 +/- 0.86%, 0.52 +/- 0.46%, respectively; p = 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants.

Deposition of fenoterol from pressurized metered dose inhalers containing hydrofluoroalkanes

The imaging technique of gamma scintigraphy has been used to quantify the total amount of drug deposited in the lungs and the pattern of regional lung deposition, for formulations of Berodual (Boehringer Ingelheim GmbH) delivered from pressurized metered dose inhalers formulated with chlorofluorocarbons, and with hydrofluoroalkane-134a or -227. Data were expressed as the mass of fenoterol deposited in the lungs from the Berodual formulations. All the formulations tested gave a whole lung deposition less than 20% of the metered (exvalve) dose. The mass of fenoterol deposited in the lungs for a solution formulation containing hydrofluoroalkane-134a was inversely proportional to the actuator nozzle diameter. The data suggest that the total and regional lung deposition of hydrofluoroalkane-based pressurized aerosol formulations is highly product-specific and that changes in bioavailability can be brought about by varying both the constituents of the formulation and the design of the actuator. (J Allergy Clin Immunol 1999;104:S253-7.)

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.

Burns de to aerosol can explosions

This report describes one burn service's experience with burn injuries sustained by 18 patients over a 5-year period as a result of the explosion of pressurized aerosol cans. The burns were predominantly superficial flash burns and involved from 5 to 45 per cent of the body surface area. There were no deaths in the series. Heightened public awareness of the fire and explosive hazards of these cans, as well as a more prominent warning label on the can should aid in decreasing the incidence of these injuries.

Evaluation of a non-chlorofluorocarbon formulation of cromolyn sodium (Intal) metered-dose inhaler versus the chlorofluorocarbon formulation in the treatment of adult patients with asthma: A controlled trial

Background: Cromolyn sodium is a nonsteroidal inhaled antiinflammatory agent for the treatment of asthma. As with other pressurized aerosol medications, the metered-dose inhaler (MDI) formulation currently contains chlorofluorocarbon (CFC) propellants. Because of their harmful effects on the environment CFCs are now generally banned from production and use. Alternative propellants under production for MDIs include derivatives of hydrofluoroalkane (HFA). This study uses HFA-227 in an MDI formulation of cromolyn sodium. Objectives: The objectives of the study were (1) to examine the efficacy and safety of an HFA formulation of cromolyn sodium (Intal) MDI and (2) to compare the HFA formulation with the CFC formulation. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel study with two active groups (HFA-cromolyn sodium [ n = 113] and CFC-cromolyn sodium [ n = 107] ) and a placebo-treated group ( n = 105). Results: Patients treated with either formulation of cromolyn sodium MDI showed a statistically significant ( p < 0.05) improvement of 12% to 18% compared with placebo in symptom summary score, daytime asthma symptoms, and albuterol use. No statistically significant differences were observed in pulmonary function. Patient and physician opinions of overall effectiveness favored HFA-cromolyn sodium over placebo ( p = 0.01), with no other significant between-treatment differences. No statistically significant differences existed among groups in the incidence of treatment-related adverse events. Conclusion: The HFA formulation of cromolyn sodium MDI is a well- tolerated and active alternative treatment for asthma patients aged 12 years and more.(J Allergy Clin Immunol 1998;101:7-13.)

Lung Delivery of Salbutamol Given by Breath Activated Pressurized Aerosol and Dry Powder Inhaler Devices

Poor inhalation technique is prevalent in asthmatics using standard metered dose inhalers (MDI). Both dry powder inhalers (DPI) and breath activated MDIs offer a solution to this problem. Our aim was to compare the lung delivery of salbutamol from two DPIs, Diskhaler and Diskus (Accuhaler), and the Easi-Breathe breath activated MDI. Ten healthy volunteers mean (SEM) age 24.0 years (1.7) were studied in a randomized single (investigator) blind crossover design. Single 1200 μg nominal doses of salbutamol via Diskhaler and Diskus (6 sequential 200 μg puffs) and Easi-Breathe (12 sequential 100 μg puffs) were given over 6 min. Mouth rinsing was performed after every inhalation sequence. Lung delivery was evaluated by measuring the early lung absorption profile of salbutamol at 5, 10, 15 and 20 min after inhalation, with calculation of peak (Cmax) and average over 20 min (Cav) concentration (ng/ml). Both the Diskhaler and the Easi-Breathe produced significantly greater salbutamol Cmaxand Cavthan Diskus (as mean and 96% CI for difference vs. Diskus): [Cmax] Diskus 3.22 vs. Diskhaler 4.35 (95% CI 0.19 to 2.08), vs. Easi-Breathe 3.98 (95% CI −0.18 to 1.71). [Cav] Diskus 2.62 vs. Diskhaler 3.95 (95% CI 0.52 to 2.14), vs. Easi-Breathe 3.52 (95% CI 0.09 to 1.71). For Cavthis amounted to a 1.51-fold difference (95% CI 1.35 to 1.68) between Diskhaler vs. Diskus, and a 1.36-fold difference (95% CI 1.03 to 1.69) for Easi-Breathe vs. Diskus. In conclusion we found that, in vivo, the Diskus DPI produced significantly lower lung delivery for the same nominal dose of salbutamol than either Diskhaler DPI or the Easi-Breathe pressurised aerosol. This shows that breath activated inhaler devices may have different in vivo deposition characteristics for delivering the same drug.

The Spacehaler ™ for delivery of salbutamol: a comparison with the standard metered-dose inhaler plus Volumatic ™ spacer device

The Spacehaler ™ is a new, compact, pressurized aerosol device that uses the same canister as a conventional metered-dose inhaler (MDI). Its design, however, reduces the velocity of the aerosol cloud that emerges from the inhaler, thereby reducing the amount of the non-respirable fraction of the drug delivered to the patient. Large volume spacers achieve a similar effect, but they are bulky and therefore inconvenient to use and carry around. This study compared the bronchodilator effect of 200 μg salbutamol delivered by the Spacehaler ™ to that of an MDI used with a Volumatic ™ spacer (MDI plus spacer) in patients with reversible obstructive airways disease. Twenty-five patients with asthma, having a forced expiratory volume in 1 s (FEV 1) between 50 and 90% predicted and a reversibility of ≥15% to 200 μg salbutamol given by the conventional (standard) MDI entered the study. On two separate study days, they inhaled 200 μg salbutamol either via the Spacehaler ™ or the MDI plus spacer. To maintain blinding, they received placebo on both study days via the alternate device. Their FEV 1, forced vital capacity (FVC) and peak expiratory flow (PEF) were measured before and at regular intervals for 6 h after inhalation. Assessment of equivalence between the two devices was based on whether the 90% confidence interval for the difference between the weighted mean FEV 1 was within ±0·251. Patient preference was assessed by a questionnaire at the end of the second study day. Twenty-four patients completed the study. Both devices produced a significant improvement in FEV 1 ( P<0·02). The upper and lower 90% confidence limits for the difference in weighted mean FEV 1 between the devices was ±0·041, and the 99% confidence limits were +0·061 and −0·071. The weighted means for FVC and PEF, and the duration of effect and peak responses for FEV 1, FVC and PEF also showed no difference between the two devices. Patients found no difficulty in using the Spacehaler ™, and 20 out of 24 patients (83·3%) preferred it to the MDI plus spacer. The bronchodilator effect of 200 μg salbutamol administered by a Spacehaler ™ was equivalent to that produced by an MDI plus spacer in this group of patients with reversible airways obstruction. The majority of patients preferred it to a large volume spacer.

Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler ( n = 30) or pMDI + Nebuhaler ( n = 28). Dose-dependent effects were demonstrated on asthma symptoms ( p = 0.0001), daily peak expiratory flow ( p = 0.02), blood eosinophils ( p = 0.0001), urinary cortisol output per day ( p = 0.0001), serum cortisol ( p = 0.006), serum osteocalcin ( p = 0.0001), and the oropharyngeal Candida colony count ( p = 0.0007, analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found ( p ≥ 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler. (J Allergy Clin Immunol 1997;99:186-93.)

A CLINICAL COMPARISON OF INTRANASAL BUDESONIDE WITH BECLOMETHASONE DIPROPIONATE FOR PERENNIAL NON‐ALLERGIC RHINITIS: A 12 MONTH STUDY

SUMMARY To evaluate possible differences in efficacy and safety between budesonide and beclomethasone dipropionate when used intranasally in the treatment of perennial non‐allergic rhinitis, a 12‐month open study was undertaken in 24 patients suffering from perennial non‐allergic rhinitis. Both drugs were applied intranasally from pressurised aerosols at a daily dosage of 400 μg. On entry and at visits after 1, 2, 4, 6, 9 and 12 months, rhinoscopy was performed and the severity of nasal symptoms graded according to a four‐point rating scale. All nasal symptoms were reduced from baseline during the treatment period in both groups. Tachyphylaxis was not observed. No clinically significant changes in haematology or blood chemistry parameters were observed in either group, and analysis of plasma cortisol levels revealed no influence of either drug on the hypothalamic‐pituitary‐adrenal axis. Local adverse reactions were uncommon and mild. Budesonide and beclomethasone dipropionate used intranasally at 400 μg per day were found to be safe, and budesonide was found to have a significantly higher (p&lt;0.05) efficacy than beclomethasone dipropionate in alleviating symptoms of perennial non‐allergic rhinitis.

A novel aerosol inhalation device for pressurized metered dose inhalation aerosols: Gammascintigraphic evaluation of pulmonary deposition profiles and comparison with commercial inhalation devices

A cylindrical shape prototype aerosol inhalation device that was previously shown to enhance pulmonary deposition from a nebulizer was evaluated for its performance in conjunction with a pressurized metered dose inhalation aerosol (MDI). Gammascintigraphic studies in human volunteers using radiolabeled technetium Tc 99m sulfur colloid (TSC) MDI showed this prototype to enhance sulfur colloid deposition in the lungs and minimize oropharyngeal deposition. A second in vivo study conducted with a new compact prototype designed for commercial development showed similar pulmonary deposition profiles with the radiolabeled TSC MDI. Data from these studies with the radiolabeled MDI show that both the prototypes enhanced pulmonary deposition and minimized oropharyngeal deposition in comparison with commercial inhalation devices.

Present state of the controversy about regular inhaled beta-agonists in asthma

A possible association between the use of β-agonists and mortality from asthma was postulated for the first time during the so-called epidemic of asthma deaths, which was observed in England and Wales in the 1960s [1]. With reference to this epidemic, INMAN and ADELSTEIN [2] reported a rise and fall of asthma mortality paralleling an increase and decrease, respectively, in the use of pressurized aerosols. However, SPEIZER et al. [1], the authors of the first report, pointed out that Accounts of the excess use of aerosols have been obtained in some cases, but decisive evidence to incriminate them is lacking. Other studies based on the same approach have yielded different results. In New Zealand, from 1979 to 1987, asthma mortality showed a trend to decline, whereas fenoterol and salbutamol use had a further increase [3]. In Sweden, asthma mortality remained quite stable from the beginning of the 1960s, whereas there was a marked increase in the use of inhaled β-agonists [4]. In the UK, prescription of β-agonists increased threefold during the 1980s, without any appreciable change of asthma mortality in this decade [4]. In Italy, no correlation was apparent between asthma mortality in three age classes (5–34, 35–54, and more than 55 yrs) and the number of β-agonist canisters sold in the period 1980– 1989, since against an increase in the sale of metereddose inhalers there was a trend for asthma mortality firstly to level-off and then to decline [5]. Ecological studies of this type, which are based on correlations, at a regional level, between rates of asthma death and sales of inhaled β-agonist bronchodilators, may be used only to generate or support cause-effect hypotheses, which then require other methodological approaches to be tested [6]. Case-control studies

Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations

The aim of the study was to assess the prevalence of throat and voice symptoms in asthma patients using pressurized aerosol, metered-dose, inhaled corticosteroid preparations. A questionnaire was administered to hospital out-patients in an asthma clinic and to a control group attending a diabetic clinic. Two hundred and fifty five consecutive out-patients using pressurized aerosol inhaled corticosteroids and 100 controls were surveyed. One hundred and forty seven (58%) patients taking inhaled steroids reported voice dysphonia or throat symptoms compared with 13% of control patients. Women admitted to symptoms more frequently than men. Throat symptoms were more prevalent in patients using higher doses of inhaled steroid. Aerosol inhaler-induced cough was reported by 87 (34%) patients. Local side-effects were equally prevalent both with beclomethasone dipropionate and budesonide aerosol inhalers. The use of a large volume spacing device with either steroid aerosol did not appear to protect against these symptoms. Local side-effects are common in asthmatics taking pressurized aerosol, metered-dose, inhaled steroids.

The quantitative determination of aspirin and its degradation products in a model solution aerosol

Formulation of pressurized aerosol solutions in propellants for inhalation requires the use of high quantities of surfactants to solubilize the drug. Due to the lipophilic nature of these surfactants, analytical difficulties are created for those wishing to quantify the drug and its degradation products. In order to quantify drug and degradation products by LC it is necessary to separate surfactant and analytes prior to chromatography. To illustrate a typical situation, a method was developed for the analysis of acetylsalicyclic acid (≈2.5 × 10 −3 M) and its major degradation products (salicylic acid, acetylsalicylsalicylic acid and salicylsalicylic acid) solubilized in trichloromonofluoromethane (CFC-11) containing 10 −2 M sorbitan trioleate (Span 85 ®). Surfactant extraction problems were reviewed experimentally. The presentation of all analytes and the surfactant, dissolved in hexane, to silica solid phase extraction columns, followed by elution in a polar solvent, was found to be an efficient way of separating this lipophilic surfactant from the analytes. The final assay employed propellant evaporation, reconstitution of the non-volatiles in hexane, normal phase solid phase extraction (recoveries of 100 ± 10% were observed for all analytes), elution and dilution with mobile phase, and reversed-phase liquid chromatography (Econosphere ® C 8 5 μm, 4.6 × 250 mm). The assay utilized a mobile phase of water, methanol, tetrahydrofuran and 1 M phosphoric acid with ultraviolet detection at 275 nm. Using external standards, linear calibration curves of peak height versus concentration were obtained for all analytes in the expected concentration ranges ( r > 0.991). As it is described, the assay had a relative standard deviation of ≤3.7% for all analytes.

State of the Art in Asthma Education: The US Experience

Formal development of asthma education programs began in the early 1970s. More powerful inhaled medications had become available, yet their benefits were not being fully realized. 1 Parker SR Asthma self-management: a second generation of research programs (Editorial). Health Educ Q. 1988; 14: 265-266 Crossref Scopus (3) Google Scholar Patients’ technique in using metered-dose inhalers, upon which so much of the current pharmacologic management depends, was seriously inadequate. 2 Paterson JC Crompton GK Use of pressurized aerosols by asthmatic patients. BMJ. 1976; 1: 76 Crossref PubMed Scopus (174) Google Scholar , 3 Crompton GK Problems patients having using pressurized aerosol inhalers. Eur J Respir Dis. 1982; 63: 101-104 Google Scholar High rates of nonadherence to medication regimens were documented for several chronic health problems, and adherence was poorer for more complex regimens and for medications that had to be used when the person was not having symptoms 4 Sackett DL Haynes RB Compliance with therapeutic regimens. Johns Hopkins University Press, Baltimore, Md1976 Google Scholar —both of which were typical of asthma regimens. Environmental control practices of patients were notoriously problematic and, although somewhat less prevalent than among nonasthmatics, active smoking was, and is, an issue for many persons with asthma. These observations suggested that the asthma education occurring in the course of clinical contacts was not as effective as it needed to be.