Cardiovascular morbidity and the use of inhaled bronchodilators

We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS). End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease.In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents.We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.     

Co-administration of salbutamol and fluticasone for emergency treatment of children with moderate acute asthma.

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 microl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 microg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 microg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 mul/kg plus fluticasone at an accumulated dose of 1500 microg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.     

无创通气结合雾化吸入治疗COPD伴呼吸衰竭临床观察

目的:探讨应用多功能呼吸机无创通气结合雾化吸入支气管扩张剂治疗慢性阻塞性肺病(COPD)伴呼吸衰竭。方法:观察28例COPD伴呼吸衰竭患者在常规药物治疗的基础上应用无创通气结合雾化吸入治疗前后的血气分析变化,经统计学处理后比较通气前后各指标的差异。结果:所有患者治疗后血气分析有非常明显的改善,临床症状明显缓解。结论:COPD伴呼吸衰竭患者早期积极应用无创通气结合雾化吸入治疗是可行、有效的。     

Bronchodilator efficacy of tiotropium/formoterol (18/12 µg once daily via a Discair inhaler), tiotropium alone (18 µg by Handihaler) or combined with formoterol (12 µg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD

Abstract

Objectives: The bronchodilator efficacy of a once-daily fixed-dose combination of tiotropium/formoterol (18/12?µg administered via a dry-powder inhaler, Discair) [TIO/FORM_fixed group] vs a single-dose of tiotropium (18?µg) by Handihaler¹ alone [TIO_mono group], or combined with formoterol 12?µg twice-daily by Aerolizer² [TIO/FORM_bid group] was compared in patients with moderate-to-severe stable COPD.

Methods: COPD patients were randomized (28 patients/group) to receive TIO/FORM_fixed, TIO_mono, or TIO/FORM_bid. AUC for the changes in FEV₁ and FVC over a 24-h period; bronchodilator response (100?ml improvement in FEV₁) in the first 30?min; maximum changes in FEV₁ and FVC; and safety data were recorded. The primary endpoint was to confirm the non-inferiority of TIO/FORM_fixed vs TIO/FORM_bid in terms of the AUC for the changes in FEV₁ over a 24-h period.

Results: Changes in AUC_0–24h for FEV₁ and FVC were similar for TIO/FORM_fixed and TIO/FORM_bid, and were superior to TIO_mono (p?<?0.001). A positive bronchodilator response at 30?min was demonstrated in 50%, 64%, and 71% of patients in the TIO_mono, TIO/FORM_bid, and TIO/FORM_fixed groups, respectively (NS). Maximum FEV₁ and FVC changes were measured as 0.25/0.41?L, 0.32/0.49?L, and 0.37/0.53?L, for TIO_mono, TIO/FORM_bid, and TIO/FORM_fixed, respectively (FEV₁: TIO/FORM_fixed vs TIO_mono, p?=?0.0017 and TIO/FORM_fixed vs TIO/FORM_bid, p?=?0.4846); no differences were recorded between the combination groups.

Conclusions: The 24-h bronchodilator efficacy of TIO/FORM_fixed 18/12?µg once-daily by Discair³ was non-inferior to a combination of tiotropium 18?µg by Handihaler plus formoterol 12?µg twice-daily by Aerolizer, and superior to tiotropium 18?µg monotherapy by Handihaler.

Trial registration: ClinicalTrials.gov identifier: NCT02988869.     

Continuous bronchodilator therapy

Inhaled bronchodilators are first-line treatment for acute exacerbations of asthma. Continuous bronchodilator administration is a novel option for the treatment of bronchospasm, which may be more effective than intermittent therapy for patients with severe airflow obstruction. For 2007, coding and billing changes for this modality become effective. This article reviews clinical aspects and outpatient practice management of continuous bronchodilator therapy.     

Blood pressure lowering,cardiovascular inhibitory and bronchodilatory actions of Achillea millefolium

Achillea millefolium Linn. (Asteraceae) is used in folk medicine for the treatment of overactive cardiovascular and respiratory ailments. This study describes its hypotensive, cardio‐depressant, vasodilatory and bronchodilatory activities. The crude extract of Achillea millefolium (Am.Cr) caused a dose‐dependent (1–100 mg/kg) fall in arterial blood pressure of rats under anaesthesia. In spontaneously beating guinea‐pig atrial tissues, Am.Cr exhibited negative inotropic and chronotropic effects. In isolated rabbit aortic rings, Am.Cr at 0.3–10 mg/mL relaxed phenylephrine (PE, 1 µm ) and high K⁺ (80 mm )‐induced contractions, as well as suppressed the PE (1 µm ) control peaks obtained in Ca⁺⁺‐free medium, like that caused by verapamil. The vasodilator effect of Am.Cr was partially blocked by N_ω‐nitro‐l ‐arginine methyl ester in endothelium intact preparations. In guinea‐pig tracheal strips, Am.Cr inhibited carbachol (CCh, 1 µm ) and K⁺‐induced contractions. These results indicate that Achillea millefolium exhibits hypotensive, cardiovascular inhibitory and bronchodilatory effects, thus explaining its medicinal use in hyperactive cardiovascular and airway disorders, such as hypertension and asthma. Copyright © 2010 John Wiley & Sons, Ltd.     

长期小剂量克拉霉素治疗支气管扩张的疗效观察

目的 观察长期低剂量服用克拉霉素治疗不同阶段非囊性纤维化支气管扩张的临床效果.方法 选择处于不同阶段的支气管扩张患者50例,按病情轻重分成两组,均口服克拉霉素0.25 g,1/d,4个月,进行前瞻性研究,对比观察研究起点以及终点时两组患者在痰液量、气促指数以及肺功能相关指标方面的改变,并统计在治疗期间因急性加重而住院患者的住院时间及住院费用与以往住院时的差异.结果 两组患者治疗后痰液量均显著减少（P〈0.01）,轻症患者治疗后的气促指数、肺功能指标FVC、FEV1及PEF均有改善（P〈0.05）,但重症患者除PEF外其他改善均不明显.此外,两组中因急性加重而住院的患者,住院时间及住院费用较以往有明显减少（P〈0.05）.结论 长期低剂量克拉霉素治疗对于减少支气管扩张患者的痰液量、改善轻症患者肺功能相关指标有明显益处,住院患者联合应用该药物可减少住院时间及住院费用.     

Clinical characterization of children with resistant airflow obstruction,a multicenter study

Objective: To characterize a cohort of children with airflow limitation resistant to bronchodilator (BD) therapy. Methods: Pulmonary function tests performed in children 6–17 years of age at 15 centers in a clinical research consortium were screened for resistant airflow limitation, defined as a post-BD FEV₁ and/or an FEV₁/FVC less than the lower limits of normal. Demographic and clinical data were analyzed for associations with pulmonary function. Results: 582 children were identified. Median age was 13 years (IQR: 11, 16), 60% were males; 62% were Caucasian, 28% were African-American; 19% were obese; 32% were born prematurely and 21% exposed to second hand smoke. Pulmonary diagnoses included asthma (93%), prior significant pneumonia (28%), and bronchiectasis (5%). 65% reported allergic rhinitis, and 11% chronic sinusitis. Subjects without a history of asthma had significantly lower post-BD FEV₁% predicted (p = 0.008). Subjects without allergic rhinitis had lower post-BD FEV₁% predicted (p = 0.003). Children with allergic rhinitis, male sex, obesity and Black race had better pulmonary function post-BD. There was lower pulmonary function in children after age 11 years without a history of allergic rhinitis, as compared to those with a history of allergic rhinitis. Conclusions: The most prevalent diagnosis in children with BD-resistant airflow limitation is asthma. Allergic rhinitis and premature birth are common co-morbidities. Children without a history of asthma, as well as those with asthma but no allergic rhinitis, had lower pulmonary function. Children with BD-resistant airflow limitation may represent a sub-group of children with persistent obstruction and high risk for life-long airway disease.     

Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy

What is known and objective: Inhaled combination therapy composing of long‐acting β2‐agonist and corticosteroid has been widely applied in the management of asthma, but observed treatment responses vary. The aim of this study was to evaluate the pharmacogenetic effect of the adenylyl cyclase type 9 (ADCY9) gene polymorphism on combination therapy. Materials and methods: Eighty‐six mild to moderate Korean asthmatics were enrolled in this clinical trial. After the 2‐week ‘run‐in’ period, patients received budesonide (an inhaled corticosteroid) and formoterol (long‐acting β2‐agonist) during the following 12‐week active treatment period. Forced expiratory volume in 1 s (FEV₁) and maximum mid‐expiratory flow (MMEF) levels were measured at all visits as primary outcome. ADCY9 (Ile772Met, 150127 C/T, 150130 C/T, 150397 C/T, 150479 C/T, TTTA _5/4) and β2‐adrenergic receptor (ADRB2, Arg16Gly) gene polymorphisms were genotyped. Results: Significant associations were observed between the ADCY9 single nucleotide polymorphisms and percent changes in FEV₁ (Ile772Met T/C, P = 0·030) and MMEF (150397 C/T, P = 0·016) after 8 weeks of combination therapy. Haplotype associations were also observed with respect to percent changes in FEV₁ after 8 weeks of therapy (Ht3[TTCC], P = 0·017). Additive therapeutic effect was observed in those with the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms in terms of percent change in FEV₁ after 8 and 12 weeks of therapy (P = 0·002 and P = 0·027 respectively). What is new and conclusion: Our results suggest that ADCY9 gene polymorphisms may alone, and in combination with ADRB2 gene polymorphisms, contribute to individual response to combination therapy in mild to moderate asthmatics.