US and European severe asthma cohorts: what can they teach us about severe asthma?

Asthma is a global health problem affecting around 300 million patients of all ages and ethnic groups in all countries around the world. In the majority of subjects with persistent, mild-to-moderate asthma (MA), the disease can be relatively well controlled by the use of currently available medications; however, five to ten per cent of patients suffer from a particularly severe disease that is poorly controlled clinically and often refractory to usual treatment. Improved care of severe asthma (SA) is a major unmet medical need and several international consortia aim at improving our understanding of mechanisms in SA. To manage SA better, standardized definitions and concepts of asthma severity, risk and level of control are critical. In the following sections, we present several guidelines approaches and definitions followed by an overview of U.S. (SARP) and European (ENFUMOSA, BIOAIR, U-BIOPRED) SA networks. Key findings regarding SA phenotypes, risk factors and pathophysiology are discussed. International cooperation in the area of respiratory diseases, including SA, across the Atlantic Ocean, will lead to a better understanding of asthma pathology, especially of those severe, not well controlled or difficult-to-treat cases.     

Work-related asthma: A case-based guide

Work-related asthma is common yet underdiagnosed. It is a significant cause of morbidity and socioeconomic loss. Diagnosis is often difficult, and requires a strong index of suspicion and careful investigation. The Canadian Thoracic Society has endorsed the recent American College of Chest Physicians consensus statement on work-related asthma. The present document illustrates the advised approach to diagnosis and management of work-related asthma using case-based examples of occupational asthma and work-exacerbated asthma. The main statements of advice from the American College of Chest Physicians consensus statement are reproduced with permission.     

改良哮喘日志在儿童哮喘临床控制中的应用

目的探讨改良哮喘日志在儿童支气管哮喘(简称哮喘)临床控制中的应用。方法选取在我院儿科哮喘门诊就诊的哮喘患儿96例,采用改良哮喘日志动态监测病情变化,随访1年后对患儿哮喘控制情况以及患儿病情变化进行分析。结果使用改良哮喘日志规范化治疗后,96例患儿临床控制水平有着明显的改善(P0.05),呼气峰流量(PEF)占预计值百分比随规范化治疗时间改变有着明显改善(P0.05)。结论改良哮喘日志为儿童哮喘临床控制提供动态、实用、易于实施、有效的检测方法。     

Predictors of Asthma Control in a Random Sample of Asthmatic Patients

The purpose of this study was to identify determinants of asthma control. Questionnaires were completed by a random sample of 570 members of a large managed care organization who were ≥35 years of age with utilization suggestive of active asthma. Asthma control was assessed buy the Asthma Control Test (ACT). Independent relationships were found between lower ACT scores and oral corticosteroid use (p < 0.0001), COPD (p < 0.0001), absence of regular specialist care (p = 0.006), higher BMI (p = 0.01), gastroesophageal reflux (p = 0.02), not being Caucasian (p = 0.04), and low income (p = 0.04).     

The Association Between Symptomatic Asthma and Neurobehavioral Comorbidities Among Children

Background. Asthma affects millions of children in the United States. The extent to which asthma and other medical conditions coexist, however, is largely unknown. Objective. This study aimed to determine associations between symptomatic asthma and neurobehavioral comorbidities among children in rural United States. Methods. This cross-sectional study used data from 406 parents/caregivers of children aged 16 or younger, who completed survey questionnaires assessing their child's health status. Symptomatic asthma was defined as parents’/caregivers’ report of physician diagnosed asthma and presence of night-time asthma symptoms in their children. The dependent variables were parents’/caregivers’ reported comorbidities in children. Results. Symptomatic asthma was present in 9% of the sample. Approximately 26% parents/caregivers reported their child had one or more mental health problems and 13% reported one or more neurological problems. In multivariable logistic regression analyses, a statistically nonsignificant 50% elevated odds of one or more mental health problems were observed for children with symptomatic asthma (adjusted odds ratio [OR] = 1.5, 95% confidence interval [CI] = 0.6–3.5). Of the individual comorbidities included in the mental health construct, more than 2-fold elevated odds of anxiety problems (adjusted OR = 2.6, 95% CI = 0.8–8.6) and attentional problems (adjusted OR = 2.4, 95% CI = 1.0–5.8) were observed for symptomatic asthma. The odds of reporting one or more neurological problems were 4-fold elevated (adjusted OR = 4.0, 95% CI = 1.6–10.0) for symptomatic asthma. Of the individual comorbidities included in the neurological construct a significantly elevated odds of hearing impairment or deafness was observed among children with symptomatic asthma (adjusted OR = 8.2, 95% CI = 1.5–45.3) as compared to the no asthma/no symptoms reference group. Conclusion. These data suggest significant associations between symptomatic asthma and neurological comorbidities.     

Development and Preliminary Validation of the Asthma Intensity Manifestations Score (AIMS) Derived from Asthma Control Test,FEV1, Fractional Exhaled Nitric Oxide,and Step Therapy Assessments

Objective. Inherent asthma severity is difficult to assess clinically. The purpose of this study was to develop an Asthma Intensity Manifestations Score (AIMS) as a surrogate for asthma severity. Methods. Three hundred and four patients treated with inhaled corticosteroids completed the Asthma Control Test (ACT), underwent spirometry, and fractional exhaled nitric oxide (FENO) testing, and reported their current medications. These parameters (defined as ACT < 16, forced expiratory volume in 1 second [FEV₁] < 80% predicted, FENO > 50 ppb, and Expert Panel Report [EPR3] step care level >3) were related to prior year outcomes to develop the AIMS and to follow-up year outcomes to validate it. Results. FENO was independently related to prior year short-acting beta agonist (SABA) ≥ 7 (odds ratio [OR] 2.9); ACT (OR 4.9), FEV₁ (OR 3.3), and step care (OR 3.9) were independently related to prior year systemic corticosteroid (SCS) ≥ 2. Thus, all the four items were chosen for the AIMS (0–4 points). AIMSs were linearly related to follow-up year SABA ≥ 7, any SCS, SCS ≥ 2, and emergency hospital care (all p < .01). Compared to patients with AIMSs <2, patients with AIMSs ≥2 were at more than a fourfold greater risk of requiring ≥2 SCS in the following year and were at a 2–2.8-fold greater risk of experiencing other adverse outcomes during that time period. Conclusions. The AIMS is linearly related to future year adverse asthma outcomes. Further studies will be necessary to confirm its utility as a surrogate for asthma severity in clinical practice and clinical research.     

Evaluation of Risk Factors and Health Outcomes among Persons with Asthma

Objective: To examine risk factors associated with healthcare utilization in Arizona Medicaid patients with asthma. Methods: Data were obtained from Arizona Medicaid between 1/1/2002 and 12/31/2003. Inclusion criteria consisted of persons with an asthma diagnosis (ICD9-CM 493.XX), 5 to 62 years of age; and were new users of inhaled-corticosteroids (ICS), combination ICS+long-acting beta-agonist, or leukotriene-modifiers. Factors examined included age, geographic location (urban/rural), race/ethnicity (White, non-Hispanic Black, Hispanic, other), medication adherence, pre-period short-acting beta-agonist use (SABA), and co-morbidities. Utilization measures examined included SABA use; exacerbations measured by hospital visits; and asthma-related and total healthcare costs. Analyses for utilization measures were performed using negative binomial, logistic regression, and generalized linear modeling gamma-family, log-link, respectively. Results: A total of 3,013 subjects met inclusion/exclusion criteria and had a mean age (±SD) of 24.7 ±13.7 years. Urban residents were 55% more likely to have an exacerbation than rural residents (odds ratio-OR 0.45, 95%CI: 0.27–0.78). Age (years 18 to 62) was a significant predictor for SABA use (incidence rate ratio-IRR 1.22, 95% CI: 1.06–1.41); and exacerbations (OR 2.07, 95% CI: 1.28–3.38). Mean predicted asthma cost was $530 (95% CI: $461–608) for ages 5 to 17, $702 (95% CI $600–822) for ages 18 to 39), and $583 (95% CI $468–726) for ages 40 to 62. Males were 46% less likely to have an exacerbation than females (OR 0.54, 95% CI: 0.31–0.94). Exacerbations were not different between race/ethnicity categories. Predicted mean asthma-related costs were not different between Whites ($591, 95% CI: $509–686), Blacks ($638, 95% CI: $499–815), or Hispanics ($535, 95% CI: $466–614). Conclusions: Results of these analyses found urban areas had higher rates of asthma-related hospital visits compared to rural counties, but no difference in asthma-costs between urban and rural areas which may suggest rural exacerbations may be more costly or severe. Persons with asthma aged 18 to 62 had higher rates of asthma-related emergency-room visits/hospitalizations than those aged 5 to 18. Persons 18 to 39 years of age had higher costs than person 5 to 17 or 40 to 62. Race/ethnicity in this population was not a significant predictor of outcomes or asthma-related costs.     

Japanese guidelines for adult asthma 2017

Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management by therapeutic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high levels. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonist are recommended as add-on drugs, while anti-immunoglobulin E antibody and oral steroids are considered for the most severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by choosing treatment steps for asthma in accordance with the severity of exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-induced asthma, and pregnancy are also important issues that need to be considered in asthma therapy.     

Food Allergy Is Associated With Potentially Fatal Childhood Asthma

Background. Risk factors for potentially fatal childhood asthma are incompletely understood. Objective. To determine whether self-reported food allergy is significantly associated with potentially fatal childhood asthma. Study design. Medical records from 72 patients admitted to a pediatric intensive care unit (PICU) for asthmatic exacerbation were reviewed and compared in a case-control design with 2 randomly selected groups of 108 patients admitted to a regular nursing floor for asthma and 108 ambulatory patients with asthma. Factors evaluated included self-reported food allergy, gender, age, poverty area residence, race/ethnicity, inhaled steroid exposure, tobacco exposure, length of hospital stay, psychologic comorbidity, and season of admission. Results. At least one food allergy was documented for 13% (38/288) of the patients. Egg, peanut, fish/shellfish, milk, and tree nut accounted for 78.6% of all food allergies. Children admitted to the PICU were significantly more likely to report food allergy (p = 0.004) and 3.3 times more likely to report at least one food allergy compared with children admitted to a regular nursing floor, and significantly more likely to report food allergy (p < 0.001) and 7.4 times more likely to report at least one food allergy compared with children seen in the ambulatory setting. Children admitted to either the PICU or the regular nursing floor were significantly more likely be African-American (p < 0.001) and to be younger (p < 0.01) compared with children seen in the ambulatory setting. Conclusions. Self-reported food allergy is an independent risk factor for potentially fatal childhood asthma. Asthmatic children or adolescents with food allergy are a target population for more aggressive asthma management.     

A winter to remember! Extracorporeal membrane oxygenation for life‐threatening asthma in children: A case series and review of literature

Progressive refractory near‐fatal asthma requiring intubation and mechanical ventilation can lead to death. Data on outcomes in children requiring extracorporeal membrane oxygenation (ECMO) support for status asthmaticus is sparse. We describe our experience of three patients in the winter of 2018 to 2019 successfully rescued with ECMO. We also report our novel use of extubation while still being on ECMO support. Awareness and use of ECMO in refractory asthma can help lower the mortality for this very common disease in children. We also review the current literature on the use of ECMO and other extracorporeal therapies in asthma.     

Extracorporeal and advanced therapies for progressive refractory near‐fatal acute severe asthma in children

Asthma is the most common chronic illness and is one of the most common medical emergencies in children. Progressive refractory near‐fatal asthma requiring intubation and mechanical ventilation can lead to death. Extracorporeal membrane oxygenation (ECMO) can provide adequate gas exchange during acute respiratory failure although data on outcomes in children requiring ECMO support for status asthmaticus is sparse with one study reporting survival rates of nearly 85% with asthma being one of the best outcome subsets for patients with refractory respiratory failure requiring ECMO support. We describe the current literature on the use of ECMO and other advanced extracorporeal therapies available for children with acute severe asthma. We also review other advanced invasive and noninvasive therapies in acute severe asthma both before and while on ECMO support.     

Japanese guidelines for adult asthma 2020

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.     

Paternal Asthma is a Predictor for Childhood Asthma in the Consanguineous Families from the United Arab Emirates

Consanguinity is known to increase the burden of genetic disorders among offspring. However, the effect of consanguinity on a complex disorder like childhood asthma has not been studied previously. Therefore, we explored this relationship by studying the asthma prevalence in children between 6 and 14 years of age among the local Arab families of the United Arab Emirates (UAE) where consanguinity is known to be highly prevalent. A total of 1136 children from 295 families met our inclusion criteria. The prevalence of childhood asthma was higher among children in consanguineous families (43.3%) compared to non-consanguineous (22.6%, p < 0.001). There was a significant correlation between the degree of consanguinity and the number of asthmatic children per family (p = 0.0002). Girls from consanguineous families had proportionately more asthma (42.9%, p < 0.001) compared to boys (23.1%, p = 0.539).

Paternal asthma in consanguineous families increased asthma risk for both boys and girls (p = 0.021 for boys, p < 0.001 for girls), while maternal asthma had no significant impact on asthma in offspring. Prevalence of childhood asthma was significantly higher in consanguineous families. The significant asthma predictors for girls from the consanguineous families were the degree of consanguinity and paternal asthma. The only predictor for boys was paternal asthma. These interesting observations merit further studies on both larger samples and in other consanguineous communities for confirmation.     

A Population-based Clinical Study of Allergic and Non-allergic Asthma

Background. The aim of this study was to describe differences between allergic and non-allergic asthma in a large community-based sample of Danish adolescents and adults. Methods. A total of 1,186 subjects, 14 to 44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms, and furthermore skin test reactivity, lung function, and airway responsiveness were measured. Results. A total of 489 individuals had clinical asthma of whom 61% had allergic asthma, whereas 39% had non-allergic asthma. Subjects with non-allergic asthma were more likely to be females, OR = 2.24 (1.32–3.72), p = 0.003, and to have cough as the predominant symptom, OR = 1.96, (1.19–3.23), p = 0.008, but were less likely to have AHR, OR = 0.40, (0.24–0.66), p < 0.001, food allergy, OR = 0.28, (0.11–0.73), p = 0.009, and symptoms of rhinitis, OR = 0.08 (0.05–0.14) compared with subjects with allergic asthma. Subjects with non-allergic asthma had had persistent symptoms within the last 4 weeks more often than subjects with allergic asthma (68% vs. 53%), p = 0.001. Conclusions. Non-allergic asthma accounts for two in every five cases of asthma in adults and constitutes symptomatically, and in terms of lung function, a more severe form of disease than allergic asthma.     

Childhood asthma in the United States: urban issues.

The prevalence and morbidity of asthma are growing problems that appear to affect urban populations and particularly impoverished centers disproportionately. Poor children are more likely to be hospitalized for asthma than nonpoor children, and are more likely to experience clinical and social dysfunction due to asthma. While guidelines exist for best care of childhood asthma, the neediest children are least likely to encounter the benefits of these recommendations. The relationship between host and environment in both primary causation and disease exacerbation is an area of research and debate. Allergen exposure in early life appears to correlate with sensitization and expression of atopy and asthma. Impoverished households are more likely to be reservoirs for dust mite and cockroach antigen in high concentrations than more affluent settings. Lifestyle factors, including diet and ambient air quality, may be disease modifiers. Suboptimal systems for delivery of healthcare to high-risk populations are obvious targets for blame. Poor children are more likely than nonpoor children to receive sick care in emergency rooms that lack a connection to chronic care providers. Besides the method of delivery, the quality of care is questionable, as poor children are less likely to receive the anti-inflammatory maintenance medications for asthma that evidence-based guidelines recommend. Efforts to correct these problems must take into account such issues as explaining the nature of the disease and the best intervention strategies to people who have a diverse array of cultural backgrounds, belief systems, and life stressors. Efforts to improve the status quo are underway in many communities. Environmental control measures to reduce dust mite and cockroach exposure have met with some success. Models to improve access to care and acceptance of care may improve community outreach maneuvers that connect the medical establishment with families and patients. Examination and assessment of new approaches to facilitate this sort of communication hold promise and are receiving attention as well as research dollars.