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PubMed2000

Guideline for the management of chronic asthma in children--2000 update. Allergy Society of South Africa Working Group.

OBJECTIVE: To increase awareness of asthma and diagnose asthma early in children. To make recommendations regarding management of chronic childhood asthma in a country with diverse cultural, socio-economic and educational characteristics. The guideline should be used by health professionals involved in the treatment of asthma at all levels of care. OPTIONS: Various management options were considered. Ideal treatment includes use of the new generation inhaled corticosteroids (fluticasone, budesonide), housedust mite intervention for asthma control using impermeable covers for pillows and mattresses, and if needed use of inhaled long-acting beta 2 agonists (LABAs) and leukotriene receptor antagonists (LRAs). Alternative therapeutic approaches for situations where resources are limited include simple housedust mite control measures (e.g. airing mattresses and bedding), avoidance of exposure to passive smoking, use of lower doses of beclomethasone than recommended by other guideline documents and/or sustained-release (SR) theophylline as preventer treatment and use of plastic bottles as cheap spacer devices. OUTCOMES: The main potential outcomes considered were: to reduce morbidity and mortality by correct diagnosis of asthma, to achieve the best quality of life for the child with asthma, to minimise side-effects from medication and to prevent development of permanently abnormal lung function. EVIDENCE: Current international guideline documents for diagnosis and management of childhood asthma were evaluated. Clinical studies before 1998 pertaining to the various aspects of management of childhood asthma were reviewed, including controlled studies on the use of inhaled corticosteroids in children with asthma, randomised controlled trials on the use of LRAs and two studies evaluating the efficacy of LABAs. Current data on the anti-inflammatory effects of SR theophylline were also reviewed as well as a randomised controlled trial on the benefits of SR theophylline as adjunct treatment in childhood asthma. The benefit of simple spacer devices, based on well-conducted local studies (published in an international peer-reviewed journal) was also considered. VALUES: The South African Childhood Asthma Working Group (SACAWG) committee members, appointed by the Allergy Society of South Africa (ALLSA), were selected to represent the interests of health professionals involved in the care of childhood asthma and to co-opt other colleagues with expertise relevant to the guideline. The committee was divided into six task groups headed by a chairperson--each task group had to review critically the previous SACAWG guideline (for deficiencies and obstacles to implementation), review current trends in asthma management (evidence-based where available) and submit proposals and recommendations to their respective chairperson. The chairperson then compiled a report for discussion by the SACAWG executive committee. The executive group convened a meeting to discuss the recommendations and obtain consensus. An editorial board was appointed to compile the final report. Cultural factors, patient preferences, cost, availability and education were considered important. BENEFITS, HARMS AND COSTS: Proper treatment should enable most children with asthma to lead normal or near-normal lives. The guideline could be implementable at all levels of care. The risk of systemic effects due to inhaled corticosteroids should be minimised in children with mild to moderate persistent asthma (risk of systemic effects is more likely at daily beclomethasone doses exceeding 400 micrograms or the equivalent dose of other inhaled corticosteroids). Promotion of simple environmental control measures and use of inhaled beclomethasone and/or SR theophylline should make treatment more widely available and more affordable and improve adherence to treatment. Alternative cheap plastic bottle spacer devices will increase availability and assist with overcoming the problem of incorrect inha

Adrenal Cortex Hormones↗
PubMed1999

Innovations and perspectives of metered dose inhalers in pulmonary drug delivery.

The phase-out of chlorofluorocarbons (CFCs) has spurred the development of alternative pulmonary drug delivery systems to pressurized metered dose inhalers (MDIs), such as dry powder inhalers and pocket size nebulizers. Reformulation of CFC-MDIs with hydrofluoroalkanes (HFAs) 134a and 227 is also an opportunity to improve these widely accepted systems with respect to ease of handling, compliance, dosing, and more reliable and efficient lung deposition. MDIs have the advantage to protect the drug substance from external parameters such as temperature and humidity and to meter and de-agglomerate the drug independent from patients inspiratory flow rates. Novel formulation technologies combined with improved valves and actuators should help to overcome dose uniformity and priming problems and will increase the percentage of fine particles capable of reaching the deeper regions of the lungs. Spacer mouthpieces can reduce the cold freon effect and undesired oropharyngeal deposition caused by the rapid evaporation of the propellant and plume velocity of the aerosol cloud. More advanced delivery devices may allow the patient to inhale at predetermined flow rates (fast/slow) to target the deposition of fine drug particles (1-6 microm) to specific sites into the lungs. Breath-actuated devices make these systems more effective and patient friendly. The above features in combination with numerical counters showing the remaining number of shots, and built-in blocking mechanisms to avoid tail-off dependent dose uniformity problems of the last labeled shots, should help to improve both acceptance and compliance of pMDIs compared to other inhalation devices. However, only those inhalation systems, which are accepted and appreciated by patients and offering an ambulatory treatment at reasonable cost, will be successful in a more and more competitive market. These issues must be considered in the development of future devices and formulations.

Drug Delivery Systems↗
PubMed1990

[Corticosteroid--effects of beclomethasone dipropionate 800 micrograms/day].

The effects of beclomethasone dipropionate (BD) 800 micrograms on steroid-dependent adult asthmatics were examined. The study consisted of two groups; 20 patients on 800 micrograms and another 20 patients on 400 micrograms. In addition, 800 micrograms was administered to an additional 12 patients receiving 400 micrograms with insufficient effects. After two weeks of observation period, BD was administered for 12 weeks, and its effects adverse reactions were analyzed on the basis of asthma patients' diary etc. As the results, effects appeared earlier in the 800 micrograms group than in the 400 micrograms group and marked efficacy was seen. The 800 micrograms group was much better than the 400 micrograms group in the achievement of weaning from or of dose reduction of systemic steroid. A significant increase of serum cortisol levels which was considered to be due to the decrease of the systemic steroid usage was noted. Considerable efficacy was also observed in patients whose dosage had been increased from 400 micrograms to 800 micrograms. High dose administration usually increases topical side effects such as hoarseness and stomatitis, however the use of spacers was effective in the prophylaxis and treatment of those symptoms.

Administration, Inhalation↗
PubMed1989

Asthma.

Asthma is an extremely common disease that the emergency physician handles on a daily basis. Accurate clinical assessment from the history and physical examination is very important to assess the severity of the disease. Some measure of airway resistance of either FEV1 or PEFR should be done in every patient initially, at repeated intervals, and at discharge, to have a parameter to follow in therapy as well as a tool to use to warn the physician of a severe amount of airway obstruction. The inhaled beta agonists are the first line of therapy in acute asthma and can be delivered by either the nebulizer or the MDI with or without a spacer. Aminophylline will be continued to be used acutely even though it appears there is no improvement in bronchospasm in the first few hours of treatment when aminophylline is added to therapy. Anticholinergic agents will gain a wider role in acute asthma, especially when used in combination with a beta agonist. Corticosteroids continue to have a role in severe attacks of asthma, and earlier use may prevent relapse. Fatal asthma still occurs, however, and the emergency physician must use strict criteria to recognize status asthmaticus or the patient who is not doing well and admit them to the hospital. Using a stepwise, logical approach to the treatment of the asthmatic patient will lead to better patient satisfaction and fewer errors on part of the emergency physician.

Adult↗
PubMed2006

Bronchodilator effect of salbutamol from two different spacer devices.

Our aim was to compare the bronchodilator effect of salbutamol delivered via a new holding chamber (Volumatic Soft, VS) with that of an established device (Volumatic, V) in asthmatic children. Children with stable asthma were recruited. They inhaled 100 microg, and 10 min later, 300 microg of salbutamol aerosol delivered via VS or V on day 1, and vice versa on day 2. Spirometry was measured at baseline, 10 min after 100 microg, and 15 min after 300 microg of salbutamol were given. The preference for either device was assessed by visual analogue score. Forty-four children with a median age of 9.2 years (interquartile range, 8.0-10.7) completed the study. There were significant improvements in forced expired volume in 1 sec (FEV1) with time throughout the study period for both V and VS (linear and quadratic trend P < 0.001). There was a statistically significant difference in postbronchodilator FEV1 between V and VS (P = 0.013). VS gave an overall greater change in FEV1 than V, by 1.8%. The preference scores for V and VS were 7.0 (IQR 5.0-8.0) and 9.0 (IQR 8.0-10.0) (p < 0.0005), respectively. In conclusion, comparable clinical efficacy was found for V and VS with respect to changes in FEV1 after salbutamol. Patients also showed a strong preference for the new device.

Adrenergic beta-Agonists↗
PubMed2000

Bronchodilator delivery with metered-dose inhaler during mechanical ventilation.

The delivery of bronchodilators with metered-dose inhaler (MDI) in mechanically ventilated patients has attracted considerable interest in recent years. This is because the use of the MDI has several advantages over the nebulizer, such as reduced cost, ease of administration, less personnel time, reliability of dosing and a lower risk of contamination. A spacer device is fundamental in order to demonstrate the efficacy of the bronchodilatory therapy delivered by MDI. Provided that the technique of administration is appropriate, MDIs are as effective as nebulizers, despite a significantly lower dose of bronchodilator given by the MDI.

Administration, Inhalation↗
PubMed2004

[Pharmacists' role in the management of asthma: a survey of 120 pharmacists in Bas-Rhin].

INTRODUCTION: The pharmacist plays an essential role in the management of the asthmatic patients on account of their frequent visits to the pharmacy to obtain their medication. METHODS: In order to evaluate the practice and knowledge of asthma among the pharmacists of the department of Bas-Rhin, 120 pharmacists were selected at random to reply to a standardised questionnaire. RESULTS: The 86 pharmacists who replied to the questionnaire had a good general understanding of asthma and its treatment. However, only 26.4% knew all the criteria of the severity of an attack of asthma. Among the 57 pharmacists who gave a demonstration of the use of inhaler devices, 16.3% showed all the steps in the use of a metered dose aerosol. These results are comparable to those of non-specialist doctors and nurses in whom poor techniques were found in 63-100% and 65-96% respectively. The mean scores of the pharmacists were 10.5/12 (+/- 1.2) steps for metered dose aerosols, 10.4/11 (+/- 1.0) for the Tubuhaler, 9.3/12 (+/- 1.7) for the Autohaler and 8.1/9 (+/- 0.9) for the Volumatic spacer. The asthmatic patient's main expectation of the pharmacist concerned the use of the prescribed systems (87.2%), underlining the lack of information received by the patient at the time of prescription. CONCLUSIONS: An improvement in the knowledge of the signs of severity of asthma and the use of inhaled devices could usefully be one of the objectives in the training of a dispensing pharmacist.

Adult↗
PubMed2001

Selecting an accessory device with a metered-dose inhaler: variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler.

Accessory devices reduce common problems with metered-dose inhalers (MDIs), namely high oropharyngeal deposition of aerosol and incoordination between actuation and inhalation by the patient. The objective of this study was to systematically compare the performance of various accessory devices in vitro. MDIs were tested alone or in combination with four spacers (Toilet paper roll, Ellipse, Optihaler, Myst Assist) and five holding chambers (Aerochamber, Optichamber, Aerosol Cloud Enhancer, Medispacer, and Inspirease). An Anderson cascade impactor was used to measure aerosol mass median aerodynamic diameter (MMAD) and fine particle dose (MMAD < 4.7 microm). In separate experiments, the influence of asynchronous MDI actuation on drug delivery was determined with a simulated spontaneous breathing model. Compared with the MDI alone, all of the accessory devices reduced aerosol MMAD and increased lung-throat ratio (fine particle dose/throat impaction; p < 0.05 for both parameters). The fine particle dose of albuterol was 40% higher with the Ellipse (p < 0.01), was equivalent with the Toilet Paper Roll, Aerochamber, Optichamber, and Medispacer, and was 33-56% lower with the Optihaler, Myst Assist, Aerosol Cloud Enhancer, and Inspirease (p < 0.03). MDI actuation in synchrony with inspiration produced highest drug delivery; when MDI actuation occurred 1-sec before inspiration or during exhalation, decrease in drug delivery with holding chambers (10-40% reduction) was less than that with spacers (40-90% reduction). Accessory device selection is complicated by variability in performance between devices, and in the performance of each device in different clinical settings. In vitro characterization of a MDI and accessory device could guide appropriate device selection in various clinical settings.

Albuterol↗
PubMed2004

Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats.

BACKGROUND: Metered-dose inhalers (MDIs) are convenient, simple, inexpensive, and reproducible devices for administering aerosolized drugs through the pulmonary route, but methods have not been available for use of these devices in small animals. OBJECTIVE: We sought to test the efficacy of delivery of fluticasone through an MDI to rats with a rodent-adapted spacer chamber and to compare this treatment with systemic dexamethasone for the acute pulmonary allergic inflammatory response. METHODS: Changes in body and thymus weights were used as indicators for systemic steroid effects. Rats were sensitized to ragweed pollen extract 2 weeks before the experiment, and pulmonary allergic responses were evaluated 48 hours after a single aerosolized antigen challenge on the basis of bronchoalveolar leukocytes, lung tissue sections, total lung capacity, and forced expiratory volumes. RESULTS: Inhaled fluticasone caused dose-related systemic effects, indicating successful pulmonary drug delivery. Inhaled fluticasone was more effective than placebo but less effective than systemic dexamethasone in attenuating the increase in lung eosinophils and inflammatory infiltrates and the decrease in total lung capacity associated with the allergic inflammatory response. Inhaled fluticasone prevented airway obstruction and proximal inflammation, as did dexamethasone, but it appeared to have less effect in areas of lung served by the most distal airways. CONCLUSION: This is an effective method for use of MDIs to deliver inhaled drugs to small laboratory animals, and it should be valuable for investigations of treatment effects, as well as for in vivo testing of delivery devices.

Androstadienes↗
PubMed1999

Targeted delivery of inhaled drugs: current challenges and future goals.

Past success of topical delivery to the lung stems more from the therapeutic nature of drugs used rather than the delivery device. Both the pressurized metered dose inhaler (pMDI) and the dry powder inhaler (DPI) are inefficient, placing a small fraction of the dose at the site of action. Most of the drug deposits in the mouth and is swallowed. Modifications to the pMDI may redress this by improving the coordination of dose generation and inspiration, or by the use of spacers. The DPI can be improved by the use of special excipients. Nevertheless, fundamental weaknesses that limit improvements in targeting drugs to the lung remain. Ideally, a stationary or slow-moving cloud of a selected particle size distribution should be generated at the source by the device. The rate of cloud generation should be such that a patient can accommodate it during a slow inspiration. Many new devices are in development, harnessing one or more of these principles. Respimat (Boehringer Ingelheim, Ingelheim am Rhein, Germany), a soft mist inhaler, shows particular promise. It generates a fine slow-moving cloud over a period exceeding 1 second and incorporates many design features to win patient acceptance.

Administration, Inhalation↗
PubMed1999

Serum leptin in children with asthma treated with inhaled budesonide.

Leptin, a 167-amino-acid peptide, is a recently discovered hormone which is believed to play a major role in the regulation of body weight. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with asthma treated with inhaled budesonide 800 micrograms day-1. Ten boys and three girls with asthma, all adolescents aged from 12.9 to 16.6 years, were studied in a randomized double-blind two-period cross-over trial with 4-week treatment periods and a 1-week wash out. Placebo was given during one period and 800 micrograms budesonide during the other via a 750 ml volume spacer (Nebuhaler, Astra Draco, Lund, Sweden). On the last day of the placebo and budesonide periods blood samples were taken and serum leptin was measured by a specific radioimmunoassay. The difference in mean (SEM) leptin concentration between the budesonide and placebo period was 0.2 (0.4) microgram l-1 (P = 0.71; t = -0.4; df = 12, 95% confidence interval -0.9-0.7 microgram l-1). Inhaled budesonide 800 micrograms per day from a Nebuhaler does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected.

Administration, Topical↗
PubMed1992

Metered-dose inhalers and nebulizers in the acute setting.

OBJECTIVE: This article evaluates the current literature comparing beta-adrenergic agonists administered via metered-dose inhalers (MDIs) with nebulizer devices in adult and pediatric patients. These studies focus on the acute treatment of asthma or chronic obstructive pulmonary disease in the emergency department and other acute care settings. DATA SOURCES: English-language journal articles published between 1980 and 1991. STUDY SELECTION: Eight studies that compared beta-adrenergic agonists administered via an MDI or an MDI with a spacing device versus a nebulizer were identified. All of the studies were either poorly designed or had few subjects. By consensus of the authors, all were included in the review. DATA EXTRACTION: Studies were assessed according to methodologic strength (e.g., prospective, comparative). DATA SYNTHESIS: Five studies found no differences between administration methods, one study found metered-dose inhalation to be superior, and another found nebulization to be superior based on observed improvements in pulmonary function tests. There were no significant differences in adverse-reaction rates. When surveyed, subjects preferred MDIs to nebulizers. There were marked variations in doses administered within and between studies. There was no consideration given to doses potentially delivered to the lungs. CONCLUSIONS: There is no significant difference between nebulizers and MDIs plus a spacer with regard to the administration of beta-agonists in the treatment of acute asthma. There are insufficient data to conclusively support the role of spacers in this setting. The choice of a specific delivery method at this time must be determined on an individual basis, taking into account the issues of cost, timeliness of administration, and personnel availability.

Administration, Inhalation↗
PubMed1988

An inexpensive spacer for use with metered-dose bronchodilators in young asthmatic children.

A 1-liter soft drink plastic bottle was modified as a spacer for use with a metered-dose bronchodilator. Its efficacy was tested on 22 children aged 3.9-7.5 years who had acute asthma. They were randomly selected to receive aerosolized salbutamol or placebo via the plastic bottle. Children who received the salbutamol showed significantly greater degree of bronchodilation than those who received the placebo. No significant adverse effects were observed. Cylindrical plastic bottles of 1-liter capacity may thus be used as a convenient and cheap spacer to effectively deliver metered-dose bronchodilators to children during acute asthma.

Administration, Inhalation↗
PubMed1992

Rapid onset of action of inhaled formoterol in asthmatic patients.

Twelve patients with stable asthma (mean age, 39 years; asthma duration, 11 years; mean forced expiratory volume in 1 s, 65 percent of predicted; and reversibility, 31 percent) were studied in a double-blind crossover trial. The patients were studied during three test days. Airway resistance and specific airway conductance (Raw and SGaw) were measured using a body plethysmograph and pulse rate, blood pressure, tremor, and subjective effects were recorded before and 1, 3, 5, 10, 15, 30, 60, and 120 min after the test doses. A baseline Raw variability of +/- 20 percent was allowed between the test days. Formoterol 12 micrograms, 24 micrograms, and terbutaline 500 micrograms were given in a spacer (Nebulator) in a randomized double-blind crossover manner as two puffs with a 30-s interval in between. The effect of formoterol 12 micrograms on Raw was significantly better than terbutaline after 3, 5, 10, 60, and 120 min. Formoterol 24 micrograms was significantly better than terbutaline as soon as 3 min after inhalation and at every point in time after that. Formoterol 24 micrograms tended to be better than formoterol 12 micrograms but the differences were not significant at any point in time. All three treatments were well-tolerated. No differences were observed for pulse rate, blood pressure, tremor, or palpitations. The overall onset of bronchodilatation after formoterol 12 and 24 micrograms was faster than after terbutaline 500 micrograms. The tolerability of formoterol was good.

Administration, Inhalation↗
PubMed2001

Therapeutic equivalence study of two formulations (innovator v. generic) of beclomethasone dipropionate in adult asthmatic patients.

OBJECTIVE: To study the therapeutic equivalence of two formulations (innovator v. generic) of beclomethasone dipropionate (BDP) 400 micrograms twice daily administered per metered dose inhaler (MDI), in adults with moderate to severe asthma. METHODS: A double-blind randomised parallel-group trial was performed with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult asthmatics on a mean daily dose of 750 micrograms inhaled corticosteroids during run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted normal and a mean histamine concentration provoking a 20% reduction in FEV1 (histamine PC20) of 0.11 mg/l were randomised to one of the two treatment groups. Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine PC20. Secondary variables were beta 2-agonist use, symptom score and nocturnal awakening. The Schuirmann two one-sided tests procedure was used for the statistical analysis. Ninety-five per cent confidence intervals (CIs) were calculated for the differences in means. RESULTS: The mean differences end of treatment to baseline for the two formulations (Becotide and Beclate) respectively were: mPEF 5.6 l/min (CI - 16.4-27.6) and -22.3 l/min (CI -35.6(-)-9); FEV1 -2.9% (CI -11-5.2) and 0.2% (CI -4.8-5.2); Histamine PC20 -0.04 mg/ml (CI -0.15-0.06) and 0.02 mg/ml (CI -0.37-0.4). Changes in clinical variables were not conclusive. The mean differences with CIs for primary variables were contained within the limits set for equivalence. The sample size was sufficient to differentiate the groups for mPEF, but this was not of clinical significance. CONCLUSION: After 8 weeks of treatment the two formulations of BDP, delivered by MDI through a large-volume spacer, were therapeutically equivalent in moderate-to-severe asthmatic adults.

Administration, Inhalation↗
PubMed1994

Clinical efficacy and safety of Turbuhaler as compared to pressurized MDIs-beta 2-agonists.

Beta 2-agonists are one of the cornerstones in the management of patients with obstructive lung diseases. The Turbuhaler containing terbutaline has been available in several countries for a few years only but has proven to have effects comparable to those of the conventional metered dose inhaler (MDI) and other powder inhalers in the treatment of obstructive lung diseases. Even in acute severe asthma, treatment with terbutaline via the Turbuhaler has proven as effective as treatment with the conventional MDI in combination with the 750ml spacer. These results indicate that the conventional MDI containing terbutaline can be exchanged by the Turbuhaler for most clinical purposes. Thereby this new method of treatment can contribute to the reduction of chlorofluorocarbon (CFC) pollution of the atmosphere. Furthermore, CFC-provoked bronchoconstriction can be avoided.

Aged↗
PubMed1998

Clinical adverse effects of inhaled corticosteroids: results of a questionnaire survey of asthma specialists.

BACKGROUND: Inhaled corticosteroids are recognized as the mainstay of prophylactic anti-inflammatory therapy in patients with persistent asthma. In large multiclinic trials, the clinical adverse event profiles have been not significantly different than patients treated with placebo or other medications; however, in small studies evaluating very sensitive in vitro measurements of the hypothalamic pituitary adrenal axis there have been adverse laboratory events noted with moderate and high doses of inhaled steroids. OBJECTIVE: To survey asthma specialists in North America with regard to their personal clinical experience of adverse events with the use of inhaled corticosteroids. METHODS: Two hundred thirteen physicians specializing in the treatment of asthma responded to questionnaires asking their experiences with specific adverse clinical events that have the potential to occur after the use of inhaled corticosteroids (see appendix A for questionnaire). RESULTS: There was a 67% response rate for the questionnaire. Eighty percent of the respondents were allergists/immunologists and 20% were pulmonologists. The average length of time they had been in practice was 16 years. In general, side effects from inhaled steroids were seen very infrequently in the hands of these physicians in spite of the fact that they were primarily secondary or tertiary referral physicians for the treatment of asthma. The local oropharyngeal adverse events were seen 48% of the time on an occasional basis but only 3% of the time on a frequent basis. When spacers were used the oropharyngeal symptoms were reduced significantly. Skin changes such as bruising or thin skin were seen frequently 6% of the time and occasionally 24% of the time only. In general, these skin changes were found in elderly or middle-aged individuals. Weight gain was very unusually seen, as were adverse effects on bone (osteoporosis, fractures, growth problems, etc.). Hypothalamic pituitary axis abnormalities were seen quite infrequently and primarily in patients who had also received oral corticosteroids. CONCLUSIONS: This study shows that inhaled corticosteroids are generally safe in the treatment of asthma and are rarely associated with systemic side effects, as detected in routine clinical practice.

Administration, Inhalation↗
PubMed1999

Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.

Administration, Inhalation↗