Davidsen Jesper Romhild
Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C., Denmark.
Dan Med J. 2012 Aug;59(8):B4501.
This PhD thesis was performed during my employment at the Research Unit of General Practice in Odense, University of Southern Denmark. It comprises an overview of three papers, all published or submitted for publication in international peer-reviewed scientific journals.
Observational studies have revealed inadequate use of inhaled corticosteroids (ICS) among asthmatics. However, only limited data exist on whether ICS usage has changed over time. In addition, improved knowledge is needed on factors associated with ICS use and asthma control in order to identify subjects at risk of being inadequately treated.
Among young adult Danish asthmatics we aimed: To investigate trends in ICS use and factors associated with ICS use during 1997-2006 (Study I). To investigate associations between socioeconomic status (education and income) and ICS use, and whether these associations were consistent over time during 1997-2005 (Study II). To investigate whether particular prescribing patterns of anti-asthmatic drugs were associated with clinically uncontrolled asthma (Study III).
Three studies were carried out among Danish users of anti-asthmatic drugs aged 18-44 years. Study I (N = 106 757) and Study II (N = 97 665) were longitudinal studies based on repeated annual cross-sectional analyses on national register data. Study III (N = 357) was a cross-sectional study based on register and clinical data from a municipal cohort from Odense, Denmark.
Study I: We observed an annual increase in one year prevalence of ICS use from 67% in 2001 to 77% in 2006, occurring concurrently with the introduction of fixed dose combination therapy with ICS and inhaled long-acting beta-2-agonists. Still some 20-30% of subjects with a massive annual IBA consumption were not prescribed ICS. Factors associated with ICS use were high annual use of inhaled beta-2-agonists (IBA), female gender, age 18-24 years, use of leukotriene receptor antagonists, and use of drugs for rhinitis and specific immune therapy. Study II: High levels of education (OR 1.46, 95% CI 1.40-1.51) and income (OR 1.10, 95% CI 1.06-1.14) were found to be positively associated with ICS use with the most pronounced impact among 35-44 year-olds. Higher education showed an almost constant association with ICS use each year throughout the entire observation period, but high income did not demonstrate any statistically significant association with ICS use before 2001 (OR 1.10, 95% CI 1.02-1.18) with increasing ORs observed each year hereafter (OR 1.30, 95% CI 1.20-1.40 in 2005). Study III: A total of 96 of the clinically assessed subjects (26.9%) had uncontrolled asthma. An increasing association between uncontrolled asthma and an increasing annual quantity of inhaled short-acting beta-2-agonists (SABA) usage was demonstrated. Due to a substantial overlap in levels of SABA use among controlled and uncontrolled asthmatics this association was not strong enough to allow conclusions on individual asthma patients.
The results support previous findings by demonstrating a continuing inadequate use of ICS among young adult asthmatics with a consistent and high use of reliever therapy, which was associated with uncontrolled asthma. This apparent over-reliance on reliever therapy and possible non-adherence to ICS may indicate inefficient guideline implementation among patients and physicians, leaving room for further improvement. The clear indications of a socioeconomic gradient in ICS use further emphasizes that knowledge of patient-related factors associated with asthma treatment and asthma control is imperative for health care professionals to be able to identify subjects deserving special attention.
本博士论文是我在丹麦南部大学欧登塞全科医学研究室任职期间完成的。它包含三篇论文的概述,所有论文均已发表或已提交至国际同行评审科学期刊发表。
观察性研究表明哮喘患者吸入性糖皮质激素(ICS)使用不足。然而,关于ICS使用情况随时间的变化仅有有限的数据。此外,需要更多关于与ICS使用及哮喘控制相关因素的知识,以便识别治疗不足风险较高的患者。
在丹麦年轻成年哮喘患者中,我们旨在:调查1997 - 2006年期间ICS使用趋势及与ICS使用相关的因素(研究I)。调查社会经济地位(教育程度和收入)与ICS使用之间的关联,以及这些关联在1997 - 2005年期间是否随时间保持一致(研究II)。调查抗哮喘药物的特定处方模式是否与临床未控制的哮喘相关(研究III)。
对年龄在18 - 44岁的丹麦抗哮喘药物使用者进行了三项研究。研究I(N = 106757)和研究II(N = 97665)是基于对国家登记数据的年度重复横断面分析的纵向研究。研究III(N = 357)是基于丹麦欧登塞一个市政队列的登记和临床数据的横断面研究。
研究I:我们观察到ICS使用的一年患病率从2001年的67%逐年增加到2006年的77%,这与ICS和吸入长效β2受体激动剂的固定剂量联合疗法的引入同时发生。仍有大约20 - 30%每年大量使用吸入β2受体激动剂(IBA)的患者未被处方使用ICS。与ICS使用相关的因素包括每年高剂量使用吸入β2受体激动剂(IBA)、女性、年龄18 - 24岁、使用白三烯受体拮抗剂以及使用治疗鼻炎和特异性免疫疗法的药物。研究II:发现高教育水平(OR 1.46,95% CI 1.40 - 1.51)和高收入(OR 1.10,95% CI 1.06 - 1.14)与ICS使用呈正相关,在35 - 44岁人群中影响最为显著。在整个观察期内,高等教育与ICS使用的关联几乎每年都保持稳定,但高收入在2001年之前与ICS使用无统计学显著关联(OR 1.10,95% CI 1.02 - 1.18),此后每年的OR值逐渐增加(2005年为OR 1.30,95% CI 1.20 - 1.40)。研究III:在临床评估的受试者中,共有96人(26.9%)患有未控制的哮喘。未控制的哮喘与每年吸入短效β2受体激动剂(SABA)使用量增加之间的关联越来越明显。由于在控制和未控制的哮喘患者中SABA使用水平存在大量重叠,这种关联不够强,无法对个体哮喘患者得出结论。
结果支持先前的研究发现,表明年轻成年哮喘患者中ICS持续使用不足,同时缓解药物使用持续且频繁,这与未控制的哮喘相关。这种对缓解药物的明显过度依赖以及可能对ICS的不依从可能表明患者和医生在指南实施方面效率低下,仍有进一步改进的空间。ICS使用中社会经济梯度的明确迹象进一步强调,医疗保健专业人员必须了解与哮喘治疗和哮喘控制相关的患者因素,以便能够识别值得特别关注的患者。