Rational oral corticosteroid use in adult severe asthma: A narrative review

OCS play an important role in the management of asthma. However, steroid‐related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25–60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add‐on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS‐sparing interventions, such as improving guideline adherence and add‐on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS‐weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker‐based strategies.     

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

BACKGROUND: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. AIM: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. METHODS: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. RESULTS: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV(1)) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg (three of 11, 73%) compared to 2000 microg or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). CONCLUSIONS: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.     

The prevalence and disease burden of severe eosinophilic asthma in Japan

Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/μL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/μL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1?second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as ¥357,958/patient-year, and asthma exacerbations as ¥26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.     

儿童支气管哮喘发作相关影响因素分析

目的对照分析儿童哮喘急性发作的危险因素,为临床诊治提供依据。方法选择支气管哮喘患儿137例作为观察组与同期门诊113例健康体检患儿作为对照组,对两组资料进行对比分析,寻找发作的危险因素。结果对比两组患儿发现哮喘家族史、被动吸烟史、呼吸道感染史、有害气体接触史、母乳喂养、过敏性疾病史方面比较,差异有显著统计学意义(P0.05);Logistic多因素回归分析发现哮喘家族史(OR=2.353,P=0.001)、呼吸道感染史(OR=1.262,P=0.004)、过敏性疾病史(OR=5.527,P=0.003)是小儿支气管哮喘发作的危险因素,而母乳喂养(OR=0.429,P=0.017)是保护性因素。结论小儿哮喘发作是多因素综合作用的结果,应当根据相关因素采取有针对性措施,尽可能母乳喂养,对小儿哮喘的预防和控制具有重要作用。     

Epidemiology of colorectal cancer in Asia

The prevalence of colorectal cancer is increasing in Asia. However, the age‐standardized rate has reached a plateau in some countries. Some studies have shown a male predominance difference and increasing risk in the elderly, but not in the younger population. ‘Right shifting’ of colorectal cancer, not accountable by difference in age or the indications for endoscopic examination, has also been noted. Westernized diet is associated with colorectal cancer, but controversy remains on how it causes colorectal cancer. Alcohol consumption, obesity, diabetes mellitus, consumption of red and processed meat and cigarette smoking are linked to bowel cancer epidemiologically. Only high dietary calcium has a consistent negative (or ‘protective’) effect. The efficacy of fish oil, vitamin D, soy, phytoestrogens, folate, methionine, riboflavin and vitamin B6 has not been established. Aspirin and non‐steroidal anti‐inflammatory drugs use decrease risk of colorectal cancer after 5–10 years of use. There is no evidence for a detrimental effect of proton pump inhibitors or benefit of statins in colorectal cancer. In conclusion, there is a rising trend and prevalence of colorectal cancer in Asia. Dietary modification or supplementation may not be effective in preventing colorectal cancer. Surveillance of colorectal cancer in high‐risk groups, according to current recommendation, is probably most effective.     

Disease burden of mild asthma in China

Background and objective

The impact, treatment patterns and control of mild asthma are poorly understood for Chinese patients. This study describes the characteristics, therapeutic interventions and burden of mild asthma on patients residing in major cities of China.

Methods

The Respiratory Disease Specific Program 2015, a cross‐sectional survey, was conducted with Chinese physicians and their patients. The survey assessed clinical characteristics, asthma symptoms, exacerbations, rescue inhaler usage, treatment adherence, asthma control, work and activity impairments and healthcare utilization for patients prescribed Global Initiative for Asthma (GINA) Step 1 or 2 treatment defined mild asthma.

Results

From a total sample of 988 patients, 229 patients met the criteria for mild asthma, with 25.3% classified as Step 1 and 74.7% as Step 2. Overall, 12.6% of patients were considered of high adherence to prescribed treatment. Physicians reported that 75% of patients overall were well controlled, although well‐controlled asthma as defined by GINA was achieved in only 14.2% of patients. 26.5% of patients indicated daily use of as‐needed rescue medication in the last 4 weeks. 17.8% of patients experienced ≥1 exacerbations in the last 12 months and impaired work productivity was 27.2% overall.

Conclusion

Less than 15% of patients were well controlled according to GINA criteria despite physicians reporting the majority of patients were well controlled. Over one‐fourth of patients relied on daily rescue inhaler medication, while exacerbation frequency and work and activity impairment were higher than might reasonably be expected in a mild asthmatic population.

     

The use of biologic therapies for the management of pediatric asthma

With better understanding of the role of type 2 inflammation in allergic asthma, there has been progress made in the development of new biologic therapies targeting these specific pathways. This review will consider diagnostic criteria for using biologic therapies for pediatric asthma with special emphasis on populations that are likely to benefit the most from particular therapies. With the exception of the anti‐immunoglobulin E, omalizumab, very few studies have been published on the efficacy and safety of biologic therapies in children, particularly anti‐interleukin‐5 (IL5) and anti‐IL4/IL13 therapies. The review will highlight the scarcity of published data in pediatric‐specific populations. In addition, we will consider the cost‐effectiveness as well as potential long‐term consequences of biologic therapies in pediatric asthma.     

昆明地区人群哮喘患病情况及相关危险因素的流行病学调查

目的了解昆明地区哮喘患病率情况及影响哮喘的危险因素,为哮喘的防治提供理论依据。方法对昆明市五华区、盘龙区、西山区、官渡区和东川区中,年龄4岁以上共15000例常住人口进行问卷调查,使用条件Logistic单因素与多因素分析,筛选哮喘发病的独立因素。结果本研究中总调查人数为15000人,收回问卷为14412份,应答率达到96.08%,累计哮喘患者174例,累计患病率为1.207%。不同性别、不同职业、教育程度和不同年龄患者之间患病率具有统计学差异(χ2=8.099,P0.05;χ2=112.054,P0.05;χ2=169.827,P0.05;χ2=404.875,P0.05)。影响哮喘患病的因素共9项(P0.05),分别为:吸烟、家族史、饲养宠物、反流性食管炎、湿疹、过敏性鼻炎、精神紧张、冷空气、药物过敏和接触粉尘。家族史、过敏性鼻炎、吸烟、接触粉尘和精神压力为哮喘发病的独立影响因素(P0.05)。结论本研究初步获得昆明地区的哮喘发病的流行病学特征,哮喘发病的独立影响因素为家族史、过敏性鼻炎、吸烟、接触粉尘和精神压力。     

136例支气管哮喘患者临床特点及相关危险因素分析

目的 探讨支气管哮喘发作的危险因素.方法 收集哮喘患者136例以及同期就诊的非哮喘人群,利用病例对照研究方法,对哮喘的临床特点以及发作危险因素进行分析.结果 支气管哮喘患者多在夜间及秋季发病,常反复发作,以轻、中度为主,超过患者曾被误诊,26.47%接受过健康教育,单因素分析发现支气管哮喘发作与过敏史、家族史、吸烟、感染、天气变化、室内装修、接触粉尘有害气体等因素有关,多因素分析家族史、感染、接触粉尘有害气体是支气管哮喘的独立危险因素.结论 积极预防避免接触各危险因素,对减少哮喘急性哮喘发作,改善患者的预后具有重要意义.     

The prevalence of asthma and related symptoms in Middle East countries

Objectives

Asthma is a chronic inflammatory airway disease characterized by reversible airway constriction and airway hyperresponsiveness. Asthma is a worldwide problem and its prevalence varies among different parts of the world. There are insufficient data about the prevalence and risk factors of this disease in Middle East countries.

Data source

The objective of this review article was to determine the prevalence of asthma in Middle East countries by searching EMBASE, Medline, Web of Science and Google Scholar for articles about asthma prevalence in children and adults in this region.

Study selection

The prevalence of asthma in different countries and different cities of each country in the Middle East was reviewed in children and adults of both sexes. The possible risk factors for asthma in different areas were also reviewed from 1985 to 2012.

Results

The highest asthma prevalence in children and adults was 35.4% in Tehran, Iran by ISAAC phase I and 15% in Kuwait by self‐designed questionnaire and the lowest prevalence was 1% in Kermanshah, Iran by ISAAC and 2% in Tehran, Iran by ECRHS questionnaire, respectively. Most studies showed that the prevalence of this common disease declines with increasing age.

Conclusion

The data showed that the prevalence of asthma varies among different countries and even among different cities of the same country. The common risk factors for this disease were genetic predisposition, cigarette smoking, family history of asthma and allergic diseases.     

成人支气管哮喘患者吸入糖皮质激素治疗的依从状况及其影响因素

目的探讨成人支气管哮喘患者应用糖皮质激素治疗的治疗依从性,并分析与其相关的影响因素。方法选取2014年3月至2015年6月我院收治的成人支气管哮喘患者160例,应用哮喘用药依从性量表对患者吸入糖皮质激素治疗依从性进行测评,并应用Logistic回归分析对于吸入糖皮质激素治疗相关的影响因素进行分析。结果 160例患者中,吸入糖皮质激素治疗依从性好的患者有60例,依从率为37.5%,治疗依从性较差的患者有100例;经影响吸入皮质激素治疗依从性的单因素分析显示,患者病情严重程度及吸入技术掌握程度及哮喘知识掌握程度与患者吸入糖皮质激素治疗依从性存在相关性,差异有统计学意义(P0.05);经Logistic多因素分析显示,哮喘知识的掌握程度、疾病严重程度及吸入技术掌握程度是影响支气管哮喘患者吸入糖皮质激素治疗依从性的影响因素。结论成人支气管哮喘患者应用糖皮质激素吸入治疗的依从性不高,应加强患者吸入技术及哮喘知识的宣教,以提高治疗依从性。     

The relationships between patients'' related variables in asthma: Implications for asthma management

OBJECTIVE: Understanding patients' personal characteristics is essential for better asthma management. This study assessed the relationships between patients' related variables in asthma and identified key associations relevant to asthma management. METHODOLOGY: Subjects were recruited from the Alfred Hospital Asthma and Allergy Clinic (Melbourne, Victoria, Australia) and general practices. Their clinical and demographic characteristics, asthma knowledge, impact of asthma on their quality of life, their self-management skills and attitudes to asthma were assessed. RESULTS: One hundred and sixty-nine subjects participated in the study. Fifty-seven per cent had one or more previous hospital admissions, 94% had either moderate or severe asthma, and 51% reported nocturnal symptoms in the last 6 weeks. Patients who spoke only English, had been admitted to an intensive care unit, had a peak flow meter, and an asthma action plan had significantly better asthma knowledge than those who did not. The impact of asthma was greatest in patients who had a peak flow meter, used oral steroids, had exercise limitation, and developed asthma between the ages of 31-45 years. Female patients had better self-management skills than males. Patients with asthma-related distress were more likely to use oral steroids or theophylline and to have a history of previous hospital admissions. Patient self-confidence was negatively correlated with age. CONCLUSIONS: There are significant relationships between many of patients' variables related to asthma, including their personal clinical, demographic and psychological characteristics. The findings have implications for optimizing asthma management.     

Long-term corticosteroid use,adrenal insufficiency and the need for steroid-sparing treatment in adult severe asthma

Secondary adrenal insufficiency (AI) occurs as the result of any process that disrupts normal hypothalamic and/or anterior pituitary function and causes a decrease in the secretion of steroid hormones from the adrenal cortex. The most common cause of secondary AI is exogenous corticosteroid therapy administered at supraphysiologic dosages for ≥ 1 month. AI caused by oral corticosteroids (OCS) is not well-recognized or commonly diagnosed but is often associated with reduced well-being and can be life-threatening in the event of an adrenal crisis. Corticosteroid use is common in respiratory diseases, and asthma is a representative condition that illustrates the potential challenges and opportunities related to corticosteroid-sparing therapies. For individuals with severe asthma (approximately 5%–10% of all cases), reduction or elimination of maintenance OCS without loss of control can now be accomplished with biologic therapies targeting inflammatory mediators. However, the optimal strategy to ensure early identification and treatment of AI and safe OCS withdrawal in routine clinical practice remains to be defined. Many studies with biologics have involved short evaluation periods and small sample sizes; in addition, cautious approaches to OCS tapering in studies with a placebo arm, coupled with inconsistent monitoring for AI, have contributed to the lack of clarity. If the goal is to greatly reduce and, where possible, eliminate long-term OCS use in severe asthma through the increasing adoption of biologic treatments, there is an urgent need for clinical trials that address both the speed of OCS withdrawal and how to monitor for AI.     

Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma

Objectives: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). Methods: A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. Results: There is a statistically significant increase of 0.369 kg/m² in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m² in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m² per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05). Conclusions: The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.     

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.