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The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.

Background: Adult-onset asthma is an important but relatively understudied asthma phenotype and little is known about its natural course and prognosis. The remission rate is believed to be low, and it is still obscure which factors predict remission or persistence of the disease. Objective: This study sought to determine the remission rate and identify predictors of persistence and remission of adult-onset asthma. Methods: Two hundred adult patients with recently diagnosed ( = 1 year and no asthma medication use for >= 1 year. Descriptive statistics and logistic regression analysis were performed. Results: Five-year follow-up data of 170 patients (85%) was available. Of these, 27 patients (15.9%) experienced asthma remission. Patients with asthma persistence were older, had worse asthma control, required higher doses of inhaled corticosteroids, had more severe airway hyperresponsiveness, more often nasal polyps, and higher levels of blood neutrophils as compared to patients who experienced clinical remission. In a multivariable logistic regression analysis, only moderate to severe bronchial hyperresponsiveness and nasal polyps were independent predictors of asthma persistence. Patients with these 2 characteristics had

Background: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. Objective: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. Methods: One hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross-sectional study. C pneumoniae –specific serum IgG and IgA were measured by means of ELISA. The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV 1 /vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. Results: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients ( P = .001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV 1 /vital capacity (2.3% vs 0.5% predicted per year of asthma duration). Conclusion: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma. It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways. (J Allergy Clin Immunol 2001;107:449-54.)

Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways. The most prominent abnormalities include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. In the absence of definite evidence on how different remodeling features affect lung function in asthma, the working hypothesis should be that structural alterations can lead to the development of persistent airway hyperresponsiveness and fixed airway obstruction. It is still unanswered whether and when to begin treating patients with asthma to prevent or reverse deleterious remodeling, which components of remodeling to target, and how to monitor remodeling. Consequently, efforts are being made to understand better the effects of conventional anti-inflammatory therapies, such as glucocorticosteroids, on airway structural changes. Animal models, in vitro studies, and some clinical studies have advanced present knowledge on the cellular and molecular pathways involved in airway remodeling. This has encouraged the development of biologicals aimed to target various components of airway remodeling. Progress in this area requires the explicit linking of modern structure-function analysis with innovative biopharmaceutical approaches.

Background A proportion of patients with adult-onset asthma have severe disease. Risk factors for an increase in asthma severity are poorly known. Objective We sought to identify predictors for the development of severe asthma in adults. Methods A cohort of 200 adults with new-onset asthma was prospectively followed for 2 years. At baseline, patients underwent a comprehensive assessment of clinical, functional, and inflammatory parameters. After 2 years, change in asthma severity was assessed by using the Global Initiative for Asthma score (range, 1-4), which is based on asthma control (Asthma Control Questionnaire), lung function (FEV 1 ), and inhaled corticosteroid requirement. ANOVA and multiple regression equations were used in the analysis. Results One hundred twenty-eight patients completed 2 years of follow-up. Seventeen (13.3%) patients had an increase in asthma severity, whereas 53 (41.4%) patients had a decrease. A lower postbronchodilator FEV 1 /forced vital capacity ratio and a higher number of cigarette pack years smoked at baseline were significantly associated with an increase in asthma severity at follow-up. Multiple regression equations showed that only the number of cigarette pack years smoked was independently associated with an increase in asthma severity, with an odds ratio of 1.4 (95% CI, 1.02-1.91) for every 10 pack years smoked. Conclusion A history of cigarette smoking in patients with new-onset adult asthma predicts an increase in asthma severity during the first 2 years of the disease in a dose-dependent manner.