Steroid-resistant asthma

Steroid-resistant asthma (SRA) refers to patients with symptoms consistent with asthma who show very poor or no response at all to high doses of inhaled or even of systemic corticosteroids. The current article reviews the SRA related literature focusing on the problems associated with the definition of SRA (especially its association with difficult to control, or severe asthma), its various phenotypes, its molecular basis, and the potential treatment options. The article also discusses the limitations of some of the key criteria used for the determination of SRA and proposes a modified set of criteria that are more applicable to children.     

Childhood asthma

The concept of chronicity in asthma, as emphasized by recent definitions of the disease, rests on the major characteristics of inflammatory response of the airways and progressive development of irreversible structural and functional alterations, or so-called airway remodeling. In childhood, however, such characteristics as chronicity and irreversibility are debatable. Various clinical phenotypes with variable degrees of severity of persistence are found in children. Furthermore, many patients with a history of recurrent wheezing in early infancy do not develop asthma later in life. The prevalence of asthma, especially in its mild forms, has increased markedly in recent years. Although the trend has stabilized in Italy, it continues to rise in other Western countries. Our research has shown that increased cutaneous response to histamine determines a major prevalence of positive skin tests. The rise in clinical forms of the disease accompanied by gastrointestinal symptoms is partly attributable to the dietary intake of food and beverages processed from environmentally engineered products. The features of the new forms of asthma demand accurate clinical and functional assessment. In addition to pulmonary function tests, determinations for eosinophils and inflammation markers in the blood and sputum, noninvasive methods have recently become available to assess airway inflammation. Among these, particularly useful studies include test for nitric oxide in exhaled air, along with tests for other markers of allergic inflammation and oxidative stress in the droplets of the exhaled air. Because in paediatric age, prolonged use of inhaled steroids increase the risk of growth impairment, asthma therapy should be guided by clinical criteria and examinations, rather than by rigid treatment guidelines. Moreover, to secure successful treatment, the parents and the child as well should be involved in monitoring the course of the disease.     

Exercise-induced asthma

Exercise-induced asthma (EIA) is common in asthmatic children and adolescents. Since it may cause limitations to daily life activities in up to 30%, mastering EIA is important in asthma management. EIA consists of bronchial obstruction occurring immediately, or soon after, physical exercise as a result of increased respiratory water and heat loss due to increased ventilation during exercise, with the subsequent release of mediators and stimulation of airways receptors. Diagnosis is best made by standardised exercise tests, preferably running on a treadmill for 6-8 minutes at an exercise load of 95% of maximum. The sensitivity of the test may be increased by cold air inhalation. EIA is best treated by inhaled steroids in addition to pre-treatment before exercise by inhaled beta(2)-agonists, short or long acting, and/or leukotriene antagonists. Physical training may improve physical fitness and quality of life in asthmatic children but baseline lung function and bronchial responsiveness are not improved.     

Difficult asthma

Children with asthma who are not well controlled in spite of optimum therapy outlined in Asthma Management Guidelines are said to have 'difficult-to manage asthma' or 'difficult asthma'. Several phenotypes of this subset of asthma have been described. However, before any child is labeled as difficult asthma a thorough search for an alternative diagnosis should be made. Thus, one should look for recurrent aspiration pneumonia, tuberculosis, foreign body aspiration, tracheomalacia, bronchomalacia, cystic fibrosis etc. Causes of treatment failure range from unidentified exacerbating factors, noncompliance, inappropriate inhalers and spacers and true steroid dependence or resistance. Economics of the treatment and social beliefs should also be taken into consideration at the time of finalizing the management plan. Management involves recognizing and correcting the above factors. However, steroids form the main pillar of treatment. Majority of the patients can be controlled by optimizing inhaled steroid therapy and possibly adding steroid sparing agents. Thus, long acting bata-2 agonists, long acting theophyllines and leukotriene inhibiters may be useful. A few children will require continuous oral steroid therapy and an occasional one may be actually steroid steroid resistant. Such children are best managed at asthma specialist centers where experimental drugs like, methotrexate cyclosporin or IVIG may be tried on an individual basis under close monitoring.     

Brittle asthma

Asthma is recognised as a heterogeneous disease and, within this heterogeneity, brittle asthma is identified as a distinct phenotype. Two types of brittle asthma have been recognised in adults: type 1, showing more than 40% diurnal variability in PEF rate on most days over long periods and type 2, with acute severe attacks on a background of apparently good asthma control. The exact incidence of these phenotypes in adults is unknown but both seem to carry an increased risk of death and considerable morbidity. Adults with brittle asthma are generally atopic, with a high degree of psychosocial morbidity. This phenotype has not been recognised to the same degree in children, although we believe that such children exist and probably present the same management problems as their adult counterparts. The management of brittle asthma is, as for all patients with complex disease, holistic, with the removal of important causal factors ensuring compliance and providing adequate education. Steroid therapy remains the mainstay of treatment but the balance has to be struck between the benefits and side-effects of both inhaled and oral corticosteroids. Continuous subcutaneous terbutaline has been shown to be effective in controlling PEF variability but there are side effects and it must be used with due caution.     

哮喘治疗的演变与哮喘能否控制

随着对支气管哮喘发病机制研究的进展,特别是支气管镜对呼吸道组织活检、病理、病理生理、细胞生物学科对哮喘基础研究所取得的成果,使我们对其认识得到不断修正、提高,随其治疗亦在不断修正完善中。40年代前仅认识到哮喘有平滑肌痉挛,因此治疗就是解痉。当支气管平滑肌发生痉     

Assessment of asthma severity and asthma control in children

National and international guidelines for asthma recommend the assessment and documentation of severity as the basis for patient management. However, studies show that there are problems with application of the severity assessment to children in clinical practice. More recently, asthma control has been introduced as a method to assess the adequacy of current treatment and inform asthma management. In this article we review the application and limitations of the severity assessment and the asthma-control tools that have been tested for use in children. A system of using asthma severity for disease assessment in the absence of treatment and using asthma-control assessment to guide management decisions while a child is receiving treatment appears to be a promising approach to tailor treatment to improve care and outcomes for children with asthma.     

Effect of asthma intervention on children with undiagnosed asthma

OBJECTIVE: To measure the effect of an asthma intervention on the functional status and morbidity of children with undiagnosed asthma. STUDY DESIGN: Data from a randomized trial were used to compare outcomes at baseline and follow-up for children with undiagnosed and diagnosed asthma. We studied 510 symptomatic children with diagnosed asthma (diagnosed) and 299 children with symptoms but no diagnosis (undiagnosed). Baseline functioning and morbidity were similar for undiagnosed and diagnosed patients classified as moderate-severe. RESULTS: There were fewer undiagnosed reported allergies, seasonal symptoms, and other respiratory diagnoses (all P < 0.01). Among the moderate-severe, functional status, for example, symptom-days ( P = .02), symptom-nights ( P < .01), and days of restricted activity ( P < .01), was significantly reduced at follow-up for the undiagnosed in the intervention group but not for undiagnosed control subjects. Findings were similar for children with diagnosed asthma. CONCLUSIONS: Children with undiagnosed asthma were generally nonatopic, although some had symptoms at a level comparable to children with a diagnosis. The intervention successfully improved functional status for children with undiagnosed asthma as well as for children with diagnosed asthma. These results can be applied to ongoing discussions related to case detection.     

Relationship of exercise-induced asthma to clinical asthma in childhood.

Thirty-three asthmatics were followed up for a mean of 8 1/2 years in prospective study in order to observe the clinical course of the disease. The severity of asthma was graded according to the treatment each required to keep him in reasonable health. Regular exercise tests were performed so that a comparison could be made between the degree of exercise-induced asthma and the severity of the disease. In this group of severe perennial childhood asthmatics profound exercise-induced asthma was found to exist throughout the entire clinical spectrum of the disease with no appreciable difference until the patient became symptom-free. Exercise-induced asthma then disappeared only to return if clinical asthma recurred. This study showed that exercise-induced asthma is a sensitive indicator of clinical asthma but has no prognostic significance in the symptom-free patient.     

Adverse asthma outcomes among children hospitalized with asthma in California

OBJECTIVE: To use administrative data to determine whether adverse asthma outcomes for pediatric asthma hospitalizations are related to specific clinical and nonclinical patient characteristics. DESIGN: Cross-sectional study. SETTING: All pediatric (0 to 17 years of age) asthma-related hospital discharges, 1986 to 1993, in California. PATIENTS: A total of 113 974 eligible patients with asthma-related discharges. MAIN OUTCOME MEASURE: Adverse asthma outcomes (intubation, cardiopulmonary arrest, and death). RESULTS: Adverse asthma outcomes occurred in 0.48% of subjects. The frequency of adverse asthma outcomes increased during the 1990s compared with 1986. After controlling for differences in gender, age, specific comorbid conditions, year, race, and insurance type, adverse asthma outcomes were more likely to occur in the 5- to 11-year-old group (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.13-1.69) and in the 12- to 17-year-old group (OR: 4.48; CI: 3.20-6.21) compared with those children in the 0 to 4-year-old age group. Asian Pacific-American children were more likely (OR: 1.59; CI: 1.24-2.59) than were white children to experience an adverse asthma outcome. Children who had a secondary diagnoses of pneumonia (OR: 1.54; CI: 1. 19-2.00) also were more likely to experience an adverse asthma outcome. The odds of an adverse outcome increased progressively after 1986, becoming significant after 1989. Gender and insurance type were not associated with increased odds of experiencing an adverse asthma outcome. CONCLUSIONS: Adverse asthma outcomes among hospitalized children are increasing in the 1990s and are associated with specific clinical and nonclinical patient characteristics.