Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources
PubMed2004

Addition of montelukast versus double dose of inhaled budesonide in moderate persistent asthma.

BACKGROUND: Although current guidelines suggest the use of inhaled corticosteroids as the first line therapy in persistent asthma, the concerns about high-dose corticosteroids may limit their usage. We aimed to investigate the efficacy of inhaled budesonide plus oral montelukast versus a double dose of inhaled budesonide. METHODOLOGY: Thirty patients with moderate asthma took part in the study. Following a 2-week run in period, the patients were randomized into two groups to receive 400 microg/day of inhaled budesonide plus 10 mg/day of montelukast (BUD + M group) or 800 microg/day of inhaled budesonide (high BUD group). The patients were evaluated at 2-week intervals (during a total treatment period of 6 weeks) for symptom scores, asthma exacerbations, lung function, use of short-acting beta2 agonist, blood eosinophil counts and adverse events. RESULTS: At the end of the study, morning and daytime symptom scores were significantly reduced within the groups. Although there was a significant decrease in the frequency of short-acting beta2 agonist use in the BUD + M group, the decrease in the high BUD group was not significant. During the study period, no patient in either group experienced an asthma exacerbation. Blood eosinophil levels significantly declined in both the BUD + M (0.87 +/- 0.31%) and high BUD groups (0.67 +/- 0.29%) as compared with baseline levels (BUD + M = 2.60 +/- 0.65%, high BUD group = 2.60 +/- 0.47%; P < 0.05). CONCLUSION: Our results suggest that the addition of montelukast to low-dose inhaled budesonide is as effective as a double dose of inhaled budesonide in asthma control.

Acetates↗
PubMed1998

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines.

OBJECTIVE: To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler. DESIGN: This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months. SETTING: 646 general practices throughout the United Kingdom. SUBJECTS: 6614 patients with obstructive airways disease (1667 patient years of exposure). MAIN OUTCOME MEASURES: Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects. RESULTS: There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively). CONCLUSION: The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies.

Adult↗
PubMed1997

The ability of A&E personnel to demonstrate inhaler technique.

OBJECTIVE: To determine the ability of accident and emergency (A&E) personnel to demonstrate metered dose inhaler technique. METHODS: 25 senior house officers and 25 nurses working in A&E were individually interviewed and assessed on their knowledge of inhaler technique and competence in demonstrating the correct use of a metered dose inhaler. RESULTS: Demonstration of inhaler technique was generally poor by the staff assessed. Although 22 (88%) of the senior house officers were aware of the British Thoracic Society guidelines, only 10 (40%) routinely checked inhaler technique when discharging asthmatic patients. CONCLUSIONS: The A&E department offers an important opportunity for patient assessment and reinforcement of metered dose inhaler technique. Staff should be made aware of the British Thoracic Society guidelines and be competent at assessing and teaching inhaler technique.

Anti-Asthmatic Agents↗
PubMed1992

Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

BACKGROUND: The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. METHODS: The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 micrograms), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. RESULTS: In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had significant bronchodilator effects. The cough threshold was not altered by placebo or saline. CONCLUSIONS: These findings suggest that muscarinic receptor stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation might have no direct effect on the sensitivity of the cough receptors in normal subjects.

Adult↗
PubMed1988

Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation.

Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.

Acetylcholine↗
PubMedDate not supplied

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature.

In the first part of this two-part review it was noted that inhaled corticosteroids had become the mainstay of treatment for chronic asthma and yet the effects of long-term use of these compounds on the hypothalamic-adrenal-pituitary (HPA) axis were largely being determined by testing methods of limited reliability, especially by morning plasma cortisol measurements. It was established in our examination of the published literature and in our presentation of current knowledge of the structure and function of the HPA axis that safe, accurate and discriminating techniques to assess the functional status of the HPA axis were available. It was concluded that two state-of-the-art tests that have been insufficiently used were the ACTH stimulation test and measurement of the 24-hour integrated serial plasma cortisol concentrations. These two tests can detect adrenal suppression before the appearance of clinical effects. For part 2 of this review we conducted an exhaustive search of the English language clinical and pharmacological literature on the use of inhaled corticosteroids from 1988 until the present time to identify studies in which one or both of these testing methods have been used. We present our analysis of this limited number of studies to determine what accurately can be known of the HPA axis safety profile of three of the most commonly used and investigated inhaled corticosteroids - beclomethasone dipropionate, budesonide and fluticasone propionate. The first finding of significance was that only 50 reports were identified in which information on the HPA axis safety effects of orally inhaled steroids in asthma patients or in clinical pharmacological studies met our inclusion requirements. By analysis of the data presented in these reports we were able to reach the following conclusions: (1) inhaled corticosteroids administered chronically, and prudently, within recommended dose ranges do not endanger the functioning of the HPA axis, (2) the increasing tendency to use higher doses of inhaled corticosteroids on the assumption that there are clear dose-response benefits and no adverse HPA axis effects from long-term high-dose regimens is misguided and not supported by reliable published information, (3) the corollary - that higher corticosteroid potencies (as measured, for example, by skin-blanching activity) can have greater therapeutic effect in lung tissue without greater concomitant systemic activity - is a flawed concept, and (4) the limited clinical and pharmacological data support our part 1 conclusions that discriminating techniques to assess the functional HPA axis status should be an integral part of the drug development process and that further HPA axis function studies are required on existing inhaled corticosteroids - if they lack a rigorous testing history or long-term record of clinical safety.

Adrenal Cortex Hormones↗
PubMed2006

Effect of inhaled histamine on airway epithelial cell swelling in ozone-exposed Guinea pigs.

BACKGROUND: It has been reported that histamine stimulates ion channels on airway epithelial cells and induces changes in osmolarity and the ion composition of the periciliary field of airway epithelia. OBJECTIVE: To investigate the effect of inhaled histamine on epithelial cell swelling, we studied the role of airway epithelial cells under histamine inhalation challenge in an animal model of airway inflammation using ozone exposure. METHOD: After exposure to 3.0 ppm ozone for 2 h, guinea pigs were anesthetized and tracheostomized, and then, lung resistance (R(L)) was measured. Histamine inhalation challenge and histological examination were performed. RESULT: The values of R(L) before histamine inhalation in the control group and the ozone-exposed group were 0.26 +/- 0.11 and 0.45 +/- 0.34 cm H(2)O/s, respectively. R(L) increased significantly after histamine inhalation both in the control and the ozone-exposed groups. The threshold of histamine (PC(200)) in the ozone-exposed group was significantly lower than that in the control group. A significant swelling of the epithelial cells after histamine inhalation was observed both in the control and the ozone-exposed groups, with a greater increase in the ozone-exposed group compared with the control group. However, no change in wall thickness was observed in the histamine/antihistamine or the ozone/histamine/antihistamine group. CONCLUSION: Our results suggest the possibility that the airway epithelial cell swelling plays a role in the increase in R(L) after histamine inhalation, especially in the presence of airway inflammation.

Airway Resistance↗
PubMed1983

Bronchodilatory effect of inhaled versus oral salbutamol in bronchial asthma.

The bronchodilator effect of salbutamol inhalation was compared with the oral administration of the drug in 10 patients with bronchial asthma. The study consisted of treating each patient for 4 consecutive days with: (1) a combined regimen consisting of a 2-mg tablet of salbutamol and 10 puffs of salbutamol inhalation (100 micrograms in each puff) given in pairs of two puffs every 20 min (regimen 1); (2) salbutamol inhalation (regimen 2); (3) salbutamol tablet (regimen 3), and (4) placebo, tablet and inhalation (regimen 4). The bronchodilator effect was assessed measuring the forced expiratory volume in 1 s, the forced vital capacity and the peak expiratory flow rate. The bronchodilator response was significantly greater on the inhalation alone and the combined regimen than on the oral and placebo regimens. The combined regimen showed a better although not significant bronchodilatory response than the inhalation regimen. We conclude that the inhalation treatment with salbutamol is superior to the oral route of administration in treating bronchial asthma and that the oral treatment has an added effect.

Administration, Oral↗
PubMed1994

The influence of age, diagnosis, and gender on proper use of metered-dose inhalers.

Metered dose inhalers (MDIs) are widely used in clinical practice for administering pharmaceuticals targeted to the lung. It is well known that the inhalation technique used with MDIs can substantially influence the clinical response to inhaled medications. To determine the acceptability of MDI maneuvers, we studied 59 subjects (26 females and 33 males; age, 20 to 81 yr; mean age, 38 yr) to determine whether the MDI technique used by these individuals complied with published recommendations for acceptable inhalation technique. Measurements were made with an MDI adapter that contained an unobtrusive, lightweight, miniature sensing system. Inspiratory flow at the moment of MDI actuation (Va), the volume (integrated from airflow) at actuation as a fraction of total inspiratory volume (Va/VI), breath-holding time (tBH), and inspiratory volume as a fraction of FVC (VI/FVC) were determined from 59 uncoached inhalations. We defined an acceptable maneuver, based on published data, by four components: (1) inspiratory flow at actuation (Va) between 25 and 90 L/min; (2) actuation during early inspiration (0 < Va/VI < or = 0.20); (3) adequate breath-holding time (tBH > 4 s), and (4) a deep inhalation (VI/FVC > 0.50). For all subjects, only 25% of inhalation maneuvers met all four criteria for acceptability. We found that a significantly higher proportion of male than female subjects performed an acceptable MDI maneuver (43% versus 4%, p < 0.001). There were no significant differences in technique between younger and older subjects or between patients with a diagnosis of asthma or chronic obstructive pulmonary disease (COPD). We conclude that most patients use their MDIs incorrectly; females of all ages are much more likely to have improper MDI technique than are males.

Adult↗
PubMed1995

Importance of total serum IgE for improvement in airways hyperresponsiveness with inhaled corticosteroids in asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 < or = 8 mg/ml and FEV1 < 95% confidence interval of predicted normal. They were followed for 2.5 yr, during which one-third received inhaled corticosteroids. The independent influences of baseline FEV1/IVC, bronchodilator response, PC20, smoking habits, allergy, age, and sex on the improvement in airways hyperresponsiveness with inhaled corticosteroids were analyzed. Total serum IgE was taken as a parameter of allergy, next to specific IgE for house dust mite, skin tests, and blood eosinophils. Total serum IgE was found to be the most important and single independent predictor of change in PC20 with inhaled corticosteroids: patients with a higher IgE had a greater increase in PC20 when administered inhaled corticosteroids than those with lower IgE levels. Alternatively, patients with a higher IgE who did not receive corticosteroids had a decrease in PC20 compared with patients with a lower IgE. This effect was most prominent in asthma but was inconsistent in asthmatic bronchitis and COPD. The level of IgE cannot be used to predict the response to inhaled corticosteroids in individuals accurately. Total serum IgE is the single most important predictor of change in PC20 with and without inhaled corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency.

Using an in vitro model, we compared efficiencies of jet nebulizers and metered-dose inhalers (MDI) with actuator devices to deliver albuterol in various conditions of mechanical ventilation. Factors tested included influence of humidification, MDI actuator device (Aerovent spacer or Marquest 172275 MDI adaptor), and synchronization of MDI to the respiratory cycle. With the nebulizer (AeroTech II) filled with 2.5 mg albuterol sulfate in 3 ml water and run until dry, inhaled mass was 42 +/- 2.6% and mass median aerodynamic diameter (MMAD) was 1.3 microns on a nonhumidified circuit. With the MDI+ Aerovent, the inhaled mass percentage per 90 microgm puff was 15.4 +/- 0.2% with humidification and 25.1 +/- 3.7% without humidification, actuations being synchronized with the beginning of inspiration and separated by a 1-min pause. Failure to synchronize actuations with inspiration or to pause 1 min resulted in significant reductions in inhaled mass (by 35 and 72%, respectively). The Marquest adaptor was less efficient, with an inhaled mass of 7.2 +/- 0.7% under optimal conditions. Metered-dose inhaler actuation during expiration resulted in relatively large particles (MMAD = 2.0 microns). All other MDI actuations led to essentially biphasic distributions, with particles greater than 1 micron following a distribution similar to the nebulizer and the overall MMAD estimated to be 0.22 microns. The AeroTech II delivered a cumulative 1,000 micrograms of drug (2,500 x 0.40) over 40 min. To achieve that amount, the MDI connected to the Aerovent and used in its most efficient sequence would require 45 timed puffs (90 micrograms per puff, 25.1% mean inhaled mass) and take 45 min of an experienced therapist's time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1998

Endogenous nitric oxide inhibits bronchoconstriction induced by cold-air inhalation in guinea pigs: role of kinins.

Inhalation of cold air in guinea pigs increases total pulmonary resistance (RL), an effect that is mediated by kinins and tachykinins. Bronchoconstriction induced by bradykinin (BK) inhalation in guinea pigs is markedly inhibited by nitric oxide (NO) release from the airway epithelium. We investigated whether endogenous NO modulates the increase in RL induced by inhalation of cold air. In anesthetized and artificially ventilated guinea pigs pretreated with atropine, cold-air inhalation (13 degrees C in the trachea) for 5 min did not increase RL. Pretreatment with intravenous N(G)-nitro-L-arginine methyl ester (L-NAME) (but not with its inactive enantiomer, D-NAME) increased RL, an effect reversed by L-Arg. The increase in RL induced by cold air after L-NAME was abolished by the tachykinin NK2-receptor antagonist SR 48968 or the kinin B2-receptor antagonist, HOE 140. After administration of SR 48968, inhalation of cold air reduced baseline airway tone. However, after HOE 140, cold-air inhalation did not affect baseline airway tone. L-NAME exaggerated the bronchoconstriction induced by BK. However, L-NAME did not affect capsaicin-induced bronchoconstriction. BK increased cyclic guanosine monophosphate (cGMP) levels in strips of guinea pig trachealis muscle in vitro, whereas the selective tachykinin NK2-receptor agonist [betaAla8]neurokinin A (4-10) was without effect. The present data suggest that bronchoconstriction induced by cold-air inhalation and mediated by kinin and tachykinin release is inhibited by endogenous NO, and that kinins, but not tachykinins or cold air alone, release bronchorelaxant NO.

Air↗
PubMed1976

Airway visualization by tantalum inhalation bronchography.

A novel technique for the generation of tantalum aerosols (aerodynamic mass median diameter, 5.8 mum; sigma g, +/-2.14) for inhalation bronchography via the mouth was applied in 26 anesthetized dogs. Ventilatory patterns during periods of aerosol inhalation were controlled by either bilateral electrophrenic stimulation of the diaphragm (EPS), or by intermittent, negative pressure at the body surface (INPV). We studied patterns of tracheobronchial deposition with regard to both the sites of particle deposition longitudinally along airways within lobes, and the topographic distribution of aerosol among the lung lobes. Bronchographic patterns were accordingly studied after inhalations by either (1) EPS and INPV in the supine posture with constant tidal volumes, but varied inspiratory flow (30 to 90 liter per min); or (2) EPS with constant tidal volume and peak inspiratory flow in the prine, right, and left lateral decubitus body positions. Under all airflow conditions, the aerosol was deposited on the surfaces of ciliated airways. Deposition was nearly entirely confined to subsegmental bronchi and above with vigorous inspirations, but extended distally to subsegmental bronchi in greater proportion with decreases in the inspiratory flow. Airways among the basal lung lobes were particularly subject to distal subsegmental and bronchiolar deposition with low rates of inspiratory airflow. Regionally, the aerosol was deposited preferentially in dependent lung lobes after inhalations with EPS in the right and left lateral decubitus positions, and in the basal lung lobes with EPS in the supine posture. A greater caudocranial uniformity in lobar aerosol distribution occurred with inhalations by INPV in the supine posture, and by EPS in the prone posture. The canine model strongly suggests that for clinical inhalation bronchography, nonhomogeneities in lobar deposition may be averted by inhalations in multiple body positions, and that deposition of the aerosol may be confined to ciliated airway surfaces by inertial impaction accompanying high rates of inspiratory airflow.

Aerosols↗
PubMed1979

Impaired alveolar macrophage chemotaxis in patients with acute smoke inhalation.

Pulmonary infection is a leading cause of death in patients with smoke inhalation; however, few studies have evaluated the effects of inhaled smoke on the host defense mechanisms of the lung. In this study we investigated the effects of acute smoke inhalation on the random and chemotactic (stimulated unidirectional) migration of human pulmonary alveolar macrophages. Fiberoptic subsegmental pulmonary lavage was performed in 19 normal subjects (12 nonsmokers and 7 smokers) and 7 patients with smoke inhalation. After quantification of lavaged cell populations, random and chemotactic migration was measured using modified Boyden chambers. Zymosan-activated serum was used as a chemotactic stimulant. Mean +/- SE random migration was 6.2 +/- 0.8 cells per 20 microscopic fields in smoking control subjects, 5.7 +/- 0.7 in nonsmoking control subjects, and 5.2 +/- 0.7 in patients with smoke inhalation. These values are not significantly different. In contrast, the mean directed (chemotactic) migration of pulmonary alveolar macrophages was 26.5 +/- 1.9 in smoking control subjects, 22.7 +/- 3.0 in nonsmoking control subjects, and 11.4 +/- 1.4 in patients with smoke inhalation; the latter response was significantly different from that of the smoking (P less than 0.001) and nonsmoking (P less than 0.025) control subjects and the combined average of the 2 control groups (P less than 0.001. In vitro exposure of pulmonary alveolar macrophages to nontoxic doses of smoke produced similar impairment of chemotaxis. These findings may partially explain the enhanced susceptibility of patients with smoke inhalation to pulmonary infection.

Adult↗
PubMed1986

Inhalation of 0.30 ppm nitrogen dioxide potentiates exercise-induced bronchospasm in asthmatics.

Epidemiologic studies support an association among elevated levels of nitrogen dioxide (NO2), increased respiratory symptoms, and alterations in lung function. To determine if low level NO2 inhalation potentiates exercise-induced bronchospasm, 15 asthmatic subjects, defined by airway constriction with cold air provocation, inhaled 0.30 ppm (560 micrograms/m3) NO2 for 30 min. All asthmatics inhaled either air or 0.30 ppm NO2 via a mouthpiece for 20 min at rest followed by 10 min of exercise on a bicycle ergometer at a workload of 300 kpm/min, producing a 3-fold or greater increase in minute ventilation. Our studies showed 72 +/- 2 (SE)% deposition of inhaled NO2 at rest and 87 +/- 1% deposition with exercise (p less than 0.001). Nitrogen dioxide inhalation at rest resulted in no significant change in pulmonary function. Nitrogen dioxide inhalation plus exercise compared to control (air) exposure plus exercise produced significantly greater reductions in FEV (p less than 0.01) and partial expiratory flow rates at 60% of total lung capacity (p less than 0.05). One hour after completion of NO2 exposure and exercise, pulmonary function had returned to baseline values. To determine if NO2 exposure caused increased reactivity to a known bronchoconstrictor, asthmatic subjects inhaled cold air (range: -11 +/- 2 degrees C) at 3 successive rates of isocapnic ventilation. The response to cold air was expressed as the respiratory heat exchange required to reduce the FEV by 10% (PD10RHE). Prior NO2 exposure potentiated the fall in FEV, PD10RHE, and specific airway conductance (p less than 0.05) after isocapnic cold air hyperventilation, compared to the control exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Deposition of inhaled particles in the mouth and throat of asthmatic subjects.

We previously studied the deposition of inhaled particles in the mouth and throat of asthmatic patients, and found large, reproducible differences among subjects. In the present study, we examined whether anatomical and/or functional differences in the pharynx and larynx could underlie this interindividual variation. Deposition in the mouth and throat, and in the lung was estimated in 16 asthmatic subjects after inhalation of 3.6 microns (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. The particles were inhaled at a flow rate of 0.5 l.s-1 with maximally deep breaths. Radioactivity was measured by external scanning over head and neck, lungs and stomach, immediately after the inhalation. Radioactivity in the lungs was also measured 24 h later. A measure of the total amount of particles deposited in the mouth and throat was obtained from the added activities in mouthwash, head and neck, and stomach, immediately after the inhalation of the test particles. Pharynx and larynx function was examined by fibreoptic laryngoscopy performed during a corresponding inhalation procedure. Deposition in the mouth and throat varied widely among the subjects, ranging 9-76% (median 12%). We found two subpopulations, 13 subjects in the range 9-34%, and 3 subjects with > 70% deposition. Deviations in pharyngeal configuration during inhalation were significantly related to high mouth and throat deposition, whereas functional differences in the larynx were not. Our study shows that mouth and throat deposition may be extremely high in some asthmatics, and that pharyngeal configuration affects deposition of particles in the mouth and throat.

Adult↗
PubMed2005

Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids.

BACKGROUND: Once-daily dosing with an inhaled corticosteroid (ICS) may simplify asthma management and improve patient compliance. Since asthma is frequently worse at night, evening dosing appears to be a more obvious choice to accommodate the chronobiology of asthma than morning dosing. OBJECTIVE: The primary study objective was to compare the efficacy and safety of mometasone furoate (MF) dry powder inhaler (MF-DPI) 400 microg qd PM (one 400 microg inhalation) with placebo for the treatment of asthma in patients previously dependent on twice a day (bid, bis in die) ICS therapy. We also compared different regimens of MF-DPI with each other and with placebo. METHODS: This 12-week, multicenter, double-blind, placebo-controlled study evaluated lung function and asthma symptoms in 400 subjects with persistent asthma randomized to MF-DPI 200 microg qd (once a day, quaque die) PM, 400 microg qd PM as one inhalation from a 400 microg device, 400 microg qd PM as two inhalations from a 200 microg device, 200 microg twice daily (bid), or placebo. Evening doses were to be taken in the late afternoon or early evening, preferably before dinner time. RESULTS: Mean changes from baseline at endpoint in FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 microg qd PM (one inhalation; 0.41 L), MF-DPI 400 microg qd PM (2 inhalations; 0.49 L), MF-DPI 200 microg qd PM (0.41 L), and MF-DPI 200 microg bid (0.51 L); and all were significantly improved compared with placebo (0.16 L; p < 0.001). Secondary efficacy variables, including nocturnal awakenings and use of rescue albuterol, were also significantly improved with MF-DPI treatment compared with placebo. All treatments were generally safe and well tolerated, with adverse events of mild to moderate severity. CONCLUSIONS: Once-daily evening dosing of MF-DPI at doses of 400 and 200 microg restored lung function and improved nocturnal and daytime symptom control in subjects with asthma previously dependent on bid ICS therapy. Comparable effectiveness of a total daily dose of 400 microg was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 microg qd PM, the lowest dose studied.

Adolescent↗
PubMed1993

A comparative study of the efficacy of beclomethasone dipropionate delivered from a breath activated and conventional metered dose inhaler in asthmatic patients.

In order to overcome the problem of poor co-ordination with the use of the conventional press and breathe metered dose inhaler, a breath-activated inhaler ('Autohaler' inhalation device) has been developed. The clinical response to equal doses of beclomethasone dipropionate administered from the 'Autohaler' device and the conventional metered dose inhaler was compared in 36 stable asthmatic patients receiving regular inhaled beclomethasone dipropionate. The study was performed using a double-blind, double-dummy crossover design. Each treatment was given for 4 weeks. Objective and subjective measures of asthma severity were compared in the second 14 days of each treatment period, with clinical equivalence defined as a difference of 20% or less in the adjusted mean values for the 30 patients with data from both treatment periods. Equivalence at the +/- 5% level was found in the objective measures of pre-bronchodilator FEV1 (p < or = 0.001); post-bronchodilator FEV1 (p < 0.001); morning and evening peak expiratory flow rate (both p < or = 0.001). Patient diary cards established there was equivalent usage of inhaled bronchodilator, and equivalent symptom scores for daytime disability and daytime and night-time breathlessness. The results show that, in stable asthmatics, treatment with beclomethasone dipropionate is clinically equivalent when delivered by the 'Autohaler' device or the conventional metered dose inhaler used efficiently.

Adult↗