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Biomedical subjects

Daniel K C Lee

Publications and source records attributed to Daniel K C Lee.

At least 19 recordsLinked to original sources
PubMed2006

A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma.

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.

Adult↗
PubMed2006

Long-acting beta2-agonists in asthma: not so SMART?

Asthma is a worldwide chronic disorder that is characterised by airway inflammation and hyper-responsiveness, which results in intermittent airflow obstruction and subsequent perception of symptoms and exacerbations. Inhaled corticosteroids are a fundamental component in the prevention of the short- and long-term complications associated with inadequately controlled asthma. However, many individuals experience persistent symptoms and exacerbations despite receiving low-to-medium doses of an inhaled corticosteroid (400-800 microg/day of beclometasone or equivalent). In these symptomatic asthmatic patients, guidelines advocate the initiation of a long-acting beta2-adrenoceptor agonist (LABA) as additional second-line controller therapy. The recent SMART (Salmeterol Multi-centre Asthma Research Trial) study was designed to compare the effects of add-on salmeterol 42 microg (ex-actuator) twice daily with placebo over 28 weeks in a randomised, double-blind, parallel-group fashion, with the intention to enrol 60,000 asthmatic patients. However, the study was halted prematurely because preliminary data revealed an increased mortality associated with regular use of salmeterol. Moreover, concerning rates of respiratory-related deaths, asthma-related deaths and life-threatening events were observed among African Americans, who constituted up to 18% of the study population. This in turn prompted the US FDA to announce important safety information regarding inhalers containing LABAs and advise that new labelling be produced outlining the "small but significant risk in asthma-related deaths" associated with their regular use. This evidence-based review discusses the data from SMART and highlights potentially important drawbacks with regular use of LABAs in persistent asthma.

Administration, Inhalation↗
PubMed2005

Effects of tiotropium and other long acting bronchodilators in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) accounts for a major workload in both primary and secondary care. It is characterised by progressive airflow obstruction which does not fully reverse to inhaled or oral pharmacotherapy. The diagnosis should be considered in any current or former smoker who has symptoms of breathlessness, wheeze, cough, sputum production and impaired exercise tolerance. From a pharmacological perspective, short-acting bronchodilators (anti-cholinergics and beta(2)-agonists) play a vital role in immediate relief of symptoms. However, in patients with persistent symptoms and exacerbations, long-acting bronchodilator therapy is advocated for regular use. Tiotropium is a newly introduced long-acting anti-cholinergic which facilitates once daily administration. This evidence based review article discusses the use of long acting bronchodilators in COPD with a particular emphasis on the putative benefits of tiotropium.

Administration, Inhalation↗
PubMed2005

Effects of dual therapy with corticosteroids plus long acting beta2-agonists in asthma.

Asthma is a common condition characterised by inflammation, airway hyperresponsiveness and reversible airflow obstruction. Effective pharmacotherapy must therefore be aimed at attenuating these underlying hallmark features. Despite the use of regular low-to-moderate doses of inhaled corticosteroids, many patients remain symptomatic and require further 2nd line controller therapy. The addition of a concomitant long acting beta2-agonist provides an effective means in which to alleviate symptoms and reduce exacerbation frequency. Moreover, both agents can be combined in a single inhaler, and provide patients with a more convenient and effective way in which to deliver treatment to the endobronchial tree. This evidenced-based review article discusses the effects of such combination inhalers upon a variety of outcome parameters and their effects upon asthmatics across a range of severities.

Adrenergic beta-Agonists↗