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Bronchodilator delivery by metered dose inhaler (MDI) to treat airflow obstruction is considered to be less expensive and as effective as nebulized therapy.
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Wearing a noseclip leads to an increase of 113% (SEM 23.5) in drug delivery and improves the inspiratory versus expiratory ratio (ratio 2.07 versus 0.75).
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Chronic obstructive pulmonary disease is a major health burden. Evidence that childhood lower respiratory tract infection (LRTI) is associated with reduced adult lung function and thereby with chronic obstructive pulmonary disease comes from 3 sources. First, studies of children hospitalized with specific LRTIs, for example, as a result of respiratory syncytial virus, show reduced lung function 7 to 10 years later, but many have diagnostic and referral biases. Second, population studies show that adults reporting childhood LRTI have reduced lung function, but retrospective ascertainment of LRTI is unreliable. Finally, in the largest study of adults with independent ascertainment of childhood LRTI, those with pneumonia before age 7 years had a 6% to 7% lower unadjusted mean forced expiratory volume in 1 second and forced vital capacity. The deficits in adjusted lung function persisted after albuterol was administered and were neither due to wheezing illness nor diminished after results were controlled for confounders. Loss of lung function was no greater in those with pneumonia at age <2 years than in those with pneumonia at age 2 to 7 years. This and similar studies strongly support an association between childhood pneumonia and a reduction in adult lung volume, whereas follow-up studies of children with specific LRTIs show an obstructive defect. Ongoing studies that have ascertained premorbid lung function should help determine whether pneumonia causes this deficit or is commoner in those with poorer premorbid lung function.
To investigate the utility of the determination of airway responsiveness to inhaled adenosine 5'-monophosphate (AMP) and exhaled nitric oxide (ENO) levels as markers for safely reducing the dose of inhaled corticosteroids (ICS) in patients with asthma well controlled with a moderately high ICS dose.
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Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ).
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In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV₁) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV₁ at 5 minutes post-dose.
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Once-daily tiotropium add-on to medium-dose inhaled corticosteroids reduces airflow obstruction and improves asthma control in patients with moderate symptomatic asthma. Patterns of response with both tiotropium doses were similar to those of salmeterol, and all active compounds had good safety and tolerability. Tiotropium is a safe and effective bronchodilator, and an alternative to salmeterol in this patient population.
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The aim of the study was to compare clinical efficacy of two variants of broncho- and mucolytic therapy for patients with mild or moderately severe chronic obstructive pulmonary disease (COPD). It included 49 patients in the phase of exacerbation divided into 2 groups. Group 1 (n = 25) received ascoril (10 ml tid), group 2 salbutamol (200 mcg two inhalations tid) plus bromhexin (8 mg tid) for 10 days. The efficacy of therapy was estimated from dynamics of clinical symptoms (cough, spiting patterns, PEFmorn/REV1, number of inhalations). Therapy decreased the intensity and frequency of daytime and especially night-time coughing. The effect of ascoril on these symptoms was more pronounced than that of two other drugs that practically did not reduce expectoration. PEFmorn/REV1 in group 1 significantly increased 80% of the patients in this group ceased using salbutamol "on demand" whereas all patients of group 2 continued to inhale it once or twice daily. It is concluded that ascoril is most efficacious and safe for the treatment of mild or moderately severe COPD and elimination of its exacerbation. The early prescription of this therapy permits to avoid hospitalization and expensive therapy.
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Salbutamol and adrenaline had approximately equivalent airway smooth muscle relaxant potencies in vitro and bronchodilator potency in vivo. However, their effects on histamine induced contraction in vitro were significantly different from their effects on histamine reactivity in vivo. Salbutamol was less potent in vitro producing a mean (SE) 2.4 (0.15) doubling dose increase in the histamine EC20 and adrenaline a 5.2 (0.18) doubling dose increase (mean difference between salbutamol and adrenaline 2.8 doubling doses; 95% CI 1.1 to 4.5). Salbutamol had no effect on the maximal response to histamine whereas adrenaline reduced it by 54%. In contrast, salbutamol was more potent in vivo producing a mean (SE) increase in PD20 histamine of 1.84 (0.5) doubling doses whereas adrenaline was without effect increasing PD20 by only 0.06 (0.47) doubling doses (mean difference between adrenaline and salbutamol 1.78, 95% CI 0.26 to 3.29 doubling doses).
To compare the bronchodilator effectiveness of albuterol reformulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing.
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The results of treatment carried out with salbutamol, erythromycin and fluidifiers in 20 children with whooping cough are reported. Results in all cases were much superior to those that have been obtained up to the present with the use of antibiotics alone or associated with hyperimmune gammaglobulins and/or sedatives. A speedier and more complete resolution of symptomatology was observed in the group where treatment was instituted earlier.
Two prospective randomized controlled trials have demonstrated increases in bronchodilation with ipratropium when added to maintenance tiotropium therapy, suggesting potential benefits during short-term, combined use. One study reported significantly higher peak forced expiratory volume in 1 second (FEV(1)) responses with both ipratropium (230 mL) and fenoterol (315 mL) compared to placebo (178 mL) when added to maintenance tiotropium. The peak response with fenoterol was significantly higher than with ipratropium (FEV(1) difference = 84 mL). Another study reported a mean difference in FEV(1) of 81 mL (95% CI 27 to 136) with albuterol versus placebo and a mean difference in FEV(1) of 68 mL (95% CI 3 to 132) with ipratropium versus placebo. The difference between albuterol and ipratropium when added to maintenance tiotropium was not significant. One large observational study reported a significantly higher risk of acute urinary retention in individuals receiving combination therapy with a short- and long-acting anticholinergic agent compared to those receiving monotherapy (OR 1.84; 95% CI 1.25 to 2.71). Individuals at highest risk were men and those with evidence of benign prostatic hypertrophy.
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It has been suggested that obesity adversely influences both the severity and the therapeutic responsiveness of chronic asthma. However, it is unclear if it also impacts acute situations.
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Exercise in healthy subjects is usually associated with progressive bronchodilatation. Though the decrease in vagal tone is deemed to be the main underlying mechanism, activation of bronchial β(2)-receptors may constitute an additional cause. To examine the contribution of β(2)-adrenergic receptors to bronchodilatation during exercise in healthy humans, we studied 15 healthy male volunteers during maximum exercise test at control conditions and after a non-selective β-adrenergic blocker (carvedilol 12.5mg twice a day until heart rate decreased at least by 10beats/min) and inhaled β(2)-agonist (albuterol 400μg). Airway caliber was estimated from the partial flow at 40% of control forced vital capacity (V˙(part40)) and its changes during exercise from the slope of linear regression analysis of V˙(part40) values against the corresponding minute ventilation during maximal exercise until exhaustion. At control, V˙(part40) increased progressively and significantly with exercise. After albuterol, resting V˙(part40) was significantly larger than at control increased but did not further increase during exercise. After carvedilol, V˙(part40) was similar to control but its increase with exercise was significantly attenuated. These findings suggest that β(2)-adrenergic system plays a major role in exercise-induced bronchodilation in healthy subjects.
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In an initial study with six lung perfusions the pharmacokinetic properties of the β(2)-agonists were determined. We then investigated the influence of an induced bronchoconstriction on the pulmonary absorption in six lung lobes for each drug. Therefore, methacholine (MCh) challenge agent was nebulised prior to administration of the β(2)-agonists.
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To compare the effectiveness of (1) fluticasone propionate, 100 microg, and salmeterol, 50 microg; (2) fluticasone propionate, 100 microg; and (3) montelukast, 10 mg, as first-line maintenance treatment for persistent asthma.
This study investigated the effect of chronic methylprednisolone treatment on the ability of albuterol and aminophylline to inhibit methacholine-induced airway constriction in Basenji-Greyhound (BG) dogs in vivo. Pulmonary responsiveness to methacholine was measured in five untreated BG dogs and in the same dogs pretreated with albuterol or aminophylline (which has been shown in this model to release endogenous catecholamines). Each dog was studied before, during, and after daily subcutaneous methylprednisolone for 6 wk. Changes in pulmonary resistance and dynamic compliance with methacholine aerosol challenge were measured. Neither baseline pulmonary function nor pulmonary responsiveness to aerosolized methacholine was significantly altered by albuterol, aminophylline, or chronic methylprednisolone administration alone. However, pretreatment with albuterol or aminophylline significantly attenuated airway responses to methacholine in BG dogs chronically receiving methylprednisolone. Because the reduced sensitivity to albuterol and aminophylline was restored by chronic methylprednisolone treatment, we conclude that at least part of the beneficial effects of corticosteroids on airways in BG dogs is through modulation of beta-adrenergic function.
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This was a retrospective medical record review at six pediatric emergency departments (EDs) of otherwise healthy children 2 to 17 years of age discharged with acute asthma. Data were extracted on history, disease severity, and pharmacotherapy used in the ED and at discharge. The primary outcome was the proportion of children prescribed "comprehensive therapy," i.e., albuterol via metered dose inhaler (MDI) with oral and ICS.
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773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.
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Intervention consisted of the salmeterol/fluticasone propionate combination (SFC) product (50/250 microg bid via the Diskus inhaler) or placebo for 3 months.
Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.
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Tabulation and classification of drugs and dietary supplement inquiries.
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The placebo response in patients with asthma is important in understanding the limitations of clinical research studies and in maximizing safe and effective therapies. This article confirms the existence of a strong placebo response in an objective and clinically relevant measure of disease activity.
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There is concern that long-acting beta agonist (LABA) drugs may increase the risk of asthma mortality.
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A total of 53.1% of participants were women and 46.1% were men; most of the population (72.5%) was <65 years of age. Canister use for HFA patients was consistently lower (2.7+/-3.2 vs 5.4+/-6.7) than for CFC MDIs for the entire cohort over the 20-month assessment period. This difference was consistently observed for albuterol canister use in patients with and without concomitant ICS use (3.3+/-3.8 HFA vs 7.2+/-7.5 CFC for ICS users and 2.1+/-2.1 HFA vs 4.1+/-5.7 CFC for non-ICS users). Time to next prescription also was longer for HFA patients than for CFC patients (61.6+/-50.9 days HFA vs 47.3+/-40.8 days CFC). When duration of therapy and physician samples associated with product launch were controlled for, similar differences were consistently observed. CFC patients used, on average, 1.3 more canisters per year than did HFA patients (P < 0.001), averaging 10.7 canisters (95% CI, 10.6 to 10.7), compared with 9.4 canisters used by HFA patients (95% CI, 8.9 to 9.9). Further analyses indicated that this finding was consistent when ICS use was controlled for (CFC plus ICS mean, 11.9 canisters vs HFA plus ICS mean, 10.4 canisters; P < 0.001).
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Salbutamol (SAL) has systemic effects that may adversely influence ventilation in asthmatic patients. The authors sought to determine the magnitude of this effect and mechanisms by which i.v. SAL affects ventilation.
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Sixteen healthy male high-performance nonasthmatic athletes with a mean age of 23.2 years participated in the study.
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A total of 111 children was evaluated; 21% of those treated with dexamethasone required hospitalization, compared with 31% of those treated with prednisone (P = .26). A significantly greater proportion of dexamethasone-treated children were discharged home within 2 hours (23% versus 7%, P = .02). In the dexamethasone group, 8% who received the drug by mouthpiece were hospitalized compared with 33% who received it by face mask (P = .06). Fewer children treated with dexamethasone vomited (0% versus 15%, P = .001) and fewer relapsed within 48 hours of ED discharge (0% versus 16%, P = .008).
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Serum GH was measured in duplicate by immunoradiometric assay.