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PubMedDate not supplied

Assessment of inhalation technique in primary care asthmatic patients using metered-dose inhalers with or without a spacer.

BACKGROUND: Asthma is a chronic disease with increasing morbidity and mortality. Although the development of metered-dose inhalers (MDIs) was a landmark in asthma management, their use is burdened by inappropriate training. Inadequate inhalation technique is reported in 24% to 89% of patients. We assessed how a sample of adult asthmatic patients seen in primary healthcare clinics (PHCs) in Riyadh used their metered-dose inhalers (MDI). PATIENTS AND METHODS: We conducted a cross-sectional survey of asthmatic adults â yen 18 years of age who attended PHCs and used an MDI with or without a spacer device. Patient inhalation technique was observed independently by the primary researcher and a respiratory therapist using a checklist based on US (National Heart, Lung and Blood Institute) asthma management guidelines. RESULTS: The mean age of the 191 patients in the survey was 40.64 years (range, 18 to 80 years). Fifty-nine percent were females and 41% were males. Most (77%) were illiterate and most (86%) had received previous education on MDI inhalation technique. Ninety-three percent were using an MDI without a spacer, but none could use their MDI without committing at least one error in both groups. In patients using an MDI without a spacer, the most common error was not tilting the head backward slightly and breathing out to residual volume (85%), followed by not breathing in slowly (84%). In patients using an MDI with a spacer, the most common errors were not tilting the head back slightly and breathing out slowly to residual volume (77%), and not holding the breath for 10 seconds (77%). CONCLUSION: Despite that MDIs are a mainstay in the management of our asthmatic patients, inhalation technique is very poor among our patients.

Journal Article↗
PubMed1989

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

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

Adult↗
PubMed1985

Terbutaline by metered-dose inhaler: conventional inhaler versus tube spacer for children with asthma.

We compared terbutaline administered through an 80-mL, 10 X 3.2-cm tube spacer versus a conventional metered-dose inhaler in 34 asthmatic patients, aged 8 to 16 years. In this double-blind, single-dose study, three groups of children (spacer active, conventional active, and placebo) were assessed clinically and with spirometry before and at one-half hour intervals for two hours after therapy. One investigator taught inhaler use and monitored patients' errors in technique. Compared with placebo, terbutaline delivered by either the tube spacer or the conventional inhaler significantly improved pulmonary function from one-half to two hours after treatment. Both the spacer and conventional inhaler were equally effective in improving pulmonary function from the baseline state. Only 4/34 (11.7%) children used both inhalers without any error. Adverse effects were mild, transient, and infrequent and did not differ between the groups. Terbutaline aerosol, whether delivered by the tube spacer or conventional actuator, provides effective bronchodilation for children with asthma, in spite of frequent errors in technique of inhaler use.

Aerosols↗
PubMed1994

Inhaled therapy in asthma: metered-dose inhaler experience.

Metered-dose inhalers are the most widely-used mode of administration of bronchodilators and anti-inflammatory agents in the treatment of asthma. However, their use is complex and about 50% of the patients do not use their metered-dose inhaler(s) properly. The most frequent errors include inadequate coordination between actuation and inspiration, rapid inspiration, absence of breathhold, and actuation of the aerosol on more than one occasion during the same inspiration. The misuse of metered-dose inhalers results in a loss of efficacy of the drug. It is, therefore, recommended that the patient be carefully trained in the proper use of metered-dose inhalers at the time of prescription. If a patient is unable to use a metered-dose inhaler properly, despite education, it may be advisable to employ a different inhalation system.

Aerosols↗
PubMed2005

Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit.

ICU sedation poses many problems. The action and side-effects of intravenous drugs in the severely ill patient population of an ICU are difficult to control. The incidence of post-traumatic stress disorder after long-term sedation is high. The recent focus on propofol infusion syndrome entails restrictions in the use of this drug. On the other hand, volatile anaesthetics very selectively suppress consciousness but leave many autonomic functions intact. In the absence of perception and disturbed information processing the number of adverse experiences should be lower, leading to a better psychological outcome. Respiration and intestinal motility are not depressed, facilitating modern therapeutic concepts such as early enteral feeding and augmentation of spontaneous breathing. Awakening after inhalational ICU sedation is quick and predictable, extubation can be planned and organized, and the time during which the patient needs very close observation will be short. Technological advances have greatly simplified the application of inhalational anaesthetics. New anaesthesia ventilators offer ventilatory modes and high flow generation comparable to ICU ventilators. However, they are not yet licensed for stand-alone use. The introduction of a volatile anaesthetic reflection filter for the first time enables the concept of inhalational sedation to be performed with very little effort by many ICUs. This 'anaesthetic conserving device' (AnaConDa) is connected between the patient and a normal ICU ventilator, and it retains 90% of the volatile anaesthetic inside the patient just like a heat and moisture exchanger. In this chapter possible advantages of the new concept and the choice of the inhalational agent are discussed. The technical prerequisites are explained, and the practice and pitfalls of inhalational ICU sedation in general and when using the AnaConDa are described in detail.

Anesthesia, Inhalation↗
PubMed1998

Effects of inhaled fluticasone propionate administered with metered dose inhaler and spacer in mild to moderate croup: a negative preliminary report.

Beneficial effects of treatment of viral croup with inhaled corticosteroids and administered with a jet-nebulizer have been reported in recent years. To facilitate such therapy at home and avoid hospitalization, the administration of inhaled corticosteroids with a metered dose inhaler (MDI) with a holding-chamber was studied as a potential alternative. In a hospital-based prospective, double-blind, randomized study, 17 children admitted with croup were treated with either fluticasone propionate MDI (2,000 microg with the Babyhaler spacer) or placebo. The primary outcome variable was the croup symptom score recorded from 0 up to 24 hours. Secondary outcome variables were the need for administration of nebulized corticosteroids with a nebulizer, the need for intubation, and the duration of hospitalization. The administration of the drug with an MDI and spacer was well tolerated in each child. In all children the clinical course was favorable, without any significant differences between the actively treated and placebo-treated group. One child needed additional use of inhaled corticosteroids with a jet nebulizer, despite treatment with fluticasone. Mean duration of hospitalization was 2.6 (1-4) and 2.4 (1-4) days for treatment with fluticasone and placebo, respectively. No undesirable side effects of treatment were reported. In conclusion, this study did not demonstrate therapeutic benefits of fluticasone propionate when administered with an MDI and a spacer compared with placebo. We hypothesize that the lack of effect is probably due to the inadequate deposition of adequate inhaled corticosteroids in the upper airways.

Administration, Inhalation↗
PubMed2003

Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys.

Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.

Administration, Inhalation↗
PubMed1995

Effects of inhaled prostacyclin as compared with inhaled nitric oxide on right ventricular performance in hypoxic pulmonary vasoconstriction.

OBJECTIVE: Recently, inhalation of prostacyclin (PGI2) has been shown to cause selective pulmonary vasodilation. However, the effects of inhaled PGI2 on right ventricular (RV) performance are still unknown and therefore were compared with those of inhaled nitric oxide (NO). DESIGN: Reported measurements design. SETTING: Animal research laboratory. ANIMALS: Six anesthetized, ventilated dogs (28 +/- 2 kg). INTERVENTIONS: Pulmonary hypertension was induced by decreasing FIO2 to 0.09-0.11 ('hypoxic pulmonary vasoconstriction', HPV). Subsequently, a single dose of either NO (50 ppm) or PGI2-aerosol (0.9 +/- 0.3 ng/kg/min) was randomly added to the inspired gas. MEASUREMENTS AND MAIN RESULTS: Measurements were performed before induction of HPV and 10 minutes after application and withdrawal of each drug. Central hemodynamics, global RV function, and local RV function (n = 5, sonomicrometry) were assessed. HPV resulted in an increase of pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), RV stroke work, right coronary artery flow, maximal rate of RV pressure increase (RV dP/dtmax), and maximal velocity of shortening of contractile elements (Vmax). In contrast, RV ejection fraction, RV end-diastolic volume, RV end-diastolic fiber length, and systolic fiber shortening were unchanged. Both PGI2-aerosol and NO attenuated the HPV-induced increase in PAP and PVR without affecting arterial pressure. NO, but not PGI2, resulted in an increase of RV ejection fraction from 42 to 46% (p < 0.05). Right coronary flow dropped from 29 to 21 mL/min during PGI2 (p < 0.05). RV stroke work, RV dP/dtmax, and Vmax decreased subsequent to both NO and PGI2, whereas local RV function was not affected. CONCLUSIONS: In pulmonary hypertension induced by HPV, PGI2-aerosol and inhaled NO reduced RV afterload and, hence, RV oxygen demand, with only minor changes of stroke volume and cardiac output, indicating an improvement of overall efficiency of RV contraction. RV ejection fraction increased on NO, but not with PGI2. This might be explained by the fact that the reduction of pulmonary vascular resistance during PGI2 amounted to only 65% of the effect of NO. In summary, both inhaled NO and PGI2-aerosol showed beneficial effects on RV performance and may prove helpful in the treatment of acute pulmonary hypertension.

Administration, Inhalation↗
PubMed2000

Improved delivery of ipratropium bromide using Respimat (a new soft mist inhaler) compared with a conventional metered dose inhaler: cumulative dose response study in patients with COPD.

Respimat (RMT) is a reusable, propellant-free, soft mist inhaler (SMI), a novel device for inhalation therapy. We conducted a three-period cross-over study to evaluate the safety and efficacy of cumulative doses of ipratropium bromide inhaled from RMT (Two dose levels) or from a pressurized metered dose inhaler (MDI), in 36 patients with chronic obstructive pulmonary disease (COPD). The bronchodilator effect of ipratropium bromide was greater when administered via RMT (10 or 20 microg per puff, given double-blind within device, to total doses of 160 or 320 microg) than via MDI (20 microg per puff, total dose 320 microg). The bronchodilator effects of the 160 and 320 microg doses delivered via RMT were similar. Cumulative ipratropium bromide doses of 320 microg given via MDI or RMT and 160 microg given via RMT produced similar safety profiles. Between 45 min after the first drug inhalation and 45 min after the final dose, greater bronchodilatory effect was obtained from half the cumulative dose of ipratropium (RMT 10 microg per puff) when compared with the MDI (20 microg per puff). Therefore, ipratropium bromide delivered by RMT is as safe as, and can be more effective than, the MDI on acute administration in patients with COPD.

Administration, Inhalation↗
PubMed1999

Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.

BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on-off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. RESULTS: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group. CONCLUSIONS: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.

Administration, Inhalation↗
PubMed1999

Metered dose inhaler add-on devices: is the inhaled mass of drug dependent on the size of the infant?

Limited cooperation and low tidal volumes in infants make aerosol therapy difficult. We measured the amount of drug delivered from two baby spacer devices especially developed for use in infants. Designed as a randomized crossover study, aerolized budesonide from a pressurized metered dose inhaler (pMDI) was collected in the inspiratory filter interposed between the face mask and the spacer in 13 infants aged from 2 to 19 months old. The study was performed in connection with pulmonary function testing with a plethysmograph, and the children were sedated with cloral hydrate. Two small-volume baby spacer devices were used: a Babyhaler spacer (GlaxoWellcome, Hertfordshire, UK) made of polycarbonate with a volume of 350 mL and a built-in dead space of 40 mL and a NebuChamber spacer (AstraZeneca, Lund, Sweden) made of stainless steel with a volume of 250 mL and no dead space. Budesonide delivery from the NebuChamber was significantly higher than from the Babyhaler: 38.2% (range, 28.3%-47.5%) of the nominal dose versus 12% (range, 3.3%-21.25%) of the nominal dose of 400 micrograms of budesonide (P = 0.002). The inhaled mass of budesonide from the Babyhaler correlated significantly with skin surface area (r = 0.68, P = 0.018), weight (r = 0.66, P = 0.019), height (r = 0.69; P = 0.017), tidal volume (r = 0.82; P = 0.004), and minute volume (r = 0.67; P = 0.019). No correlations were found between these variables and the inhaled mass of budesonide from the NebuChamber. The results indicate that the design of the NebuChamber spacer affords stable drug delivery in infants and that a large variability in the inhaled mass of drug may be found when infants are inhaling from different baby spacers.

Administration, Inhalation↗
PubMed2006

The effect of inhaled nitric oxide and inhaled iloprost on hypoxaemia in a patient with pulmonary hypertension after pulmonary thrombarterectomy.

Acute pulmonary hypertension with life-threatening right heart failure may complicate the postoperative course following cardiothoracic surgery. Both inhaled nitric oxide and inhaled iloprost, a stable analogue of prostacyclin, have been used frequently for this purpose in acute pulmonary hypertension of various origins. We present a case of a patient with acute pulmonary hypertension and severely impaired gas exchange following pulmonary thrombo-endarterectomy. Therapy with one inhaled vasodilator alone did not satisfactorily abort a postoperative pulmonary hypertensive crisis and low-output syndrome due to right heart failure. Combined inhaled nitric oxide and inhaled iloprost, however, showed additive effects. Hence, the combination of both drugs may be reasonable in cases where the standard therapy fails. The effect has been demonstrated by means of continuous blood gas monitoring.

Administration, Inhalation↗
PubMed2003

Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma. METHODS: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks. RESULTS: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated. CONCLUSION: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.

Acetates↗
PubMed2003

Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects.

BACKGROUND: All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects. METHODS: The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma. RESULTS: Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI -11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI -1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI -1026 to 1339) pg/ml (p=0.8). CONCLUSIONS: Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.

Administration, Inhalation↗
PubMed1996

Effect of inhaled thiorphan, a neutral endopeptidase inhibitor, on the bronchodilator response to inhaled atrial natriuretic peptide (ANP).

BACKGROUND: The hormone atrial natriuretic peptide (ANP) causes bronchodilation and partially protects against direct and indirect bronchial challenges. Both in vitro and in vivo studies have found that the protective effect of ANP against bronchoconstriction is enhanced by inhibition of the enzyme neutral endopeptidase (NEP). It was hypothesised that pretreatment with thiorphan, an NEP inhibitor, might enhance the bronchodilator response to inhaled ANP. METHODS: In a randomised double blind placebo controlled crossover study, six asthmatic patients (one woman) of mean (SD) age 47.3 (3.8) years and forced expiratory volume in one second (FEV1) 1.91 (0.42) 1, 55 (3.8)% predicted, were studied. All were shown at screening to have at least a 25% improvement in FEV1 to inhaled salbutamol. On five study visits the patients received either thiorphan 1 mg (in 2 ml) followed by ANP 5 mg or placebo (saline), or placebo (saline) followed by ANP (5 mg), placebo or salbutamol 5 mg. Spirometric parameters were measured after each inhalation and thereafter for the next two hours. RESULTS: ANP alone caused a bronchodilator response up to 15 minutes when compared with placebo or thiorphan alone with a mean (SE) change in FEV1 of 16.8 (8.1)% and 16.1 (6.8)% at 10 and 15 minutes from baseline, respectively. Prior inhalation of thiorphan prolonged the duration of the bronchodilator effect of ANP up to 60 minutes with a mean (SE) change in FEV1 of 23.1 (3.4)% at 60 minutes. There was no difference in the maximum degree of bronchodilation following the administration of ANP alone compared with the combination of thiorphan and ANP. The degree and duration of the bronchodilator response produced by ANP, or the combination of the NEP inhibitor and ANP, were less than that produced by salbutamol. CONCLUSIONS: These results confirm that, at least in part, the bronchodilator response to inhaled ANP is modulated by NEP. Analogues of ANP which are stable to NEP may have greater bronchodilator activity than ANP in the treatment of asthma.

Administration, Inhalation↗
PubMed2000

Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients.

BACKGROUND: Respimat, a possible alternative to the conventional metered dose inhaler (MDI), is a novel, reusable, propellant-free, multidose soft mist inhaler. Respimat slowly releases a metered dose of active substance as a soft mist with a high proportion of the dose in the fine particle fraction, leading to improved lung deposition following inhalation when compared with the conventional MDI. OBJECTIVES AND METHODS: The equipotent bronchodilating efficacy and safety of a combination of fenoterol hydrobromide and ipratropium bromide (F/I) in cumulative doses delivered by either Respimat or pressurised MDI was assessed in a randomised, controlled, double-blind (within device) 4-way crossover study. Forty-three patients with stable asthma (mean FEV(1) 62% predicted) responsive to F/I inhaled cumulatively 16 puffs on each of 4 test days (1 + 1 + 2 + 4 + 8 puffs at 50-min intervals) via Respimat delivering 50/20, 25/20 or 25/10 microg F/I per puff or via MDI delivering 50/20 microg F/I per puff. RESULTS: Cumulative doses of 400/160 and 400/320 microg F/I via Respimat produced bronchodilation (evaluated by average increase in FEV(1) 45-245 min after first inhalation) equivalent to that achieved with a cumulative 800/320 microg F/I via MDI (mean increase in FEV(1) above baseline 0.76, 0.73 and 0.71 litres, respectively). The tolerability of the F/I combination via Respimat was also comparable to that of twice the dose delivered via MDI. CONCLUSION: Therefore, a fenoterol hydrobromide/ipratropium bromide combination delivered by Respimat is as safe and effective as the MDI at half the cumulative dose, on acute administration to patients with asthma.

Administration, Inhalation↗
PubMed2000

No effect of inhaled budesonide on the response to inhaled ozone in normal subjects.

Inhalation of ozone in normal subjects causes a neutrophilic inflammatory response in the airways. Pretreatment with inhaled corticosteroids reduces the inflammatory response to inhaled ozone in dogs. We undertook a double-blind, randomized, placebo-controlled, crossover study to investigate the effects of 2 wk of treatment with inhaled budesonide 800 microg twice daily or placebo prior to ozone exposure in humans. Fifteen (six male; mean age, 31.1 +/- 2.1 yr) healthy nonsmokers were exposed to 400 parts per billion (ppb) ozone for 2 h with intermittent exercise. Spirometry, exhaled carbon monoxide (CO) and nitric oxide (NO) levels, measurement of methacholine reactivity, and collection of exhaled air condensate and induced sputum samples were performed at baseline, preexposure, and at intervals up to 24 h postexposure. Ozone exposure led to significant decreases in spirometry and increased methacholine reactivity and sputum neutrophils and myeloperoxidase (MPO). There were no changes in exhaled NO and CO levels, or exhaled breath nitrite after ozone exposure. There were no differences in any of the parameters after treatment with budesonide compared with placebo, and no differences in the response to ozone between treatment groups. We conclude that a high dose of inhaled corticosteroid does not protect against the effects of ozone exposure in normal subjects.

Administration, Inhalation↗
PubMed1995

Inhaled salmeterol and albuterol in asthmatic patients receiving high-dose inhaled corticosteroids.

Salmeterol may be useful in the treatment of asthmatic patients requiring high-dose inhaled steroids, and there have been debates about its anti-inflammatory action. We have compared the efficacy and effects on serum inflammatory markers, including soluble interleukin 2R (sIL-2R), eosinophil cationic protein (ECP), and tryptase of salmeterol and albuterol in 20 patients with moderate to severe asthma who were all receiving high-dose inhaled corticosteroids and inhaled beta 2-agonist on demand. After a 2-week run-in period, they received, in a randomized, crossover, double-blind and placebo-controlled manner, either salmeterol, 50 micrograms twice a day, or albuterol 400 micrograms, four times a day, from a powder inhaler during two 2-week treatment periods, separated by a 2-week washout. Compared with albuterol, salmeterol treatment was associated with better morning and mean peak expiratory flow (p = 0.013 and 0.016, respectively), less daytime and nocturnal symptoms (p = 0.008 and 0.01, respectively), reduced requirement of rescue albuterol (p = 0.04), and better efficacy rating by patients (p = 0.04). However, serum concentration of sIL-2R was significantly higher during regular albuterol treatment (p = 0.014) but no differences were seen in the concentrations of ECP and tryptase between the two treatment periods. We conclude that inhaled salmeterol, 50 micrograms twice daily, confers a better control of asthma than albuterol, 400 micrograms four times daily, in patients with moderate to severe disease, and the latter treatment may be associated with increased T-lymphocyte activation.

Administration, Inhalation↗