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Measures of asthma control

Purpose of review: Over the past decade, the concept of asthma control as distinct from asthma severity has been clearly defined. Well controlled asthma is the goal of therapy in all asthma patients. This review is a comprehensive description of the tools currently available for a methodical assessment of different aspects of asthma control in clinical practice and research. Recent findings: Several questionnaires for assessing asthma control have been extensively validated in adults. In children, validation data are less extensive. Considerable overlap exists between asthma control measures and measures of asthma-specific quality of life. Asthma-specific quality-of-life questionnaires have been used as primary outcome measures in major clinical trials evaluating asthma therapy. Biomarkers that reflect eosinophilic inflammation of the airways are used as intermediate outcome measures to reflect the biological basis of asthma control. There is some controversy, however, over which biomarkers are best incorporated into therapeutic algorithms that attempt to achieve maximal asthma control while minimizing treatment intensity. Summary: In designing clinical studies to evaluate different asthma therapies, researchers will find this review to be a useful resource in terms of choosing the appropriate tool for assessing asthma control. This is also a valuable resource for a methodical assessment of response to asthma therapy in routine clinical care.

Appraising the small airways in asthma

Purpose of review: The small airways play an important yet poorly targeted role in asthma pathophysiology, leading to increased morbidity in asthma patients. Assessing inflammation and remodeling in these airways, determining the contribution of small airways to lung dysfunction and enhancing drug delivery to the distal regions of the lung remain challenging. The purpose of this review is to highlight recent advances in our understanding of small airways involvement in asthma. Recent findings: Inflammation in the small airways can be evaluated through exhaled gas measurements, most often nitric oxide. However, additional exhaled biomarkers have recently been described. Considerable infiltration of mast cells in the distal lung and extensive structural changes to the small airways have also been demonstrated. Advances have been made in the functional assessment of small airways, particularly in the measurement of small airway compliance and ventilation defects and in studies investigating the impact of small particle inhaled corticosteroid treatment on lung function. Summary: Experimental assessments of small airways inflammation, remodeling and function have provided novel insights into the importance of the distal regions of the lung in asthma pathology. Further advances in drug delivery to the small airways have the potential to improve asthma control.

Systemic effects of inhaled corticosteroids

Purpose of review: Although inhaled corticosteroids (ICSs) are the mainstay of therapy in asthma, their use raises certain safety concerns. We review the articles appearing in the last year which have addressed the safety of ICSs when used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Recent findings: Recent studies suggest that patients with asthma as opposed to COPD do not experience an excess risk of pneumonia with ICS use. Patients with respiratory diseases are at increased risk of developing active tuberculosis and this excess risk is exacerbated by the use of high doses of ICSs. ICSs have systemic effects and one result appears to be an increase in the risk of diabetes onset and progression, especially at high doses of ICSs. When examining cases of glaucoma requiring therapy, there was no increase in risk with ICSs even at high current and cumulative doses. Finally, use of even high doses of ICSs during pregnancy does not appear to affect foetal adrenal function. Summary: ICSs are a highly effective therapy in asthma and have an excellent safety profile at the low doses usually required in asthma. Adverse effects appear mostly at higher doses.

Genetic and genomic approaches to asthma: new insights for the origins

Purpose of review: The aim is to update current understanding of the genes identified by the recent genome-wide association studies (GWASs) of asthma and its associated traits. The review also discusses how to dissect the functional roles of novel genes in future research. Recent findings: More than 10 GWAS aimed at identifying the genes underlying asthma and relevant traits have been published in the past 3 years. The largest of these was from the GABRIEL consortium, which discovered that the IL18R1, IL33, SMAD3, ORMDL3, HLA-DQ and IL2RB loci were all significantly associated with asthma. Many novel asthma genes, including those previously identified by positional cloning, are expressed within the respiratory epithelium, emphasizing the importance of epithelial barriers in causing asthma . The genes controlling IgE levels have surprisingly little overlap with the genes mediating asthma susceptibility, suggesting that atopy is secondary to asthma rather than a primary driver of the disease. The next challenge will be the systematic analysis of the precise functions of these genes in the pathogenesis of asthma. Summary: GWAS have uncovered many novel genes underlying asthma and detailed functional dissection of their roles in asthma will point the way to new therapies for the disease.

Stepping down asthma treatment: how and when

Purpose of review: Guidelines suggest that asthma medication should be reduced once asthma control is sustained. Moderate-dose inhaled corticosteroids (ICS) can typically be reduced, but questions remain about the lowest effective ICS dose and the role of non-ICS controllers in treatment reduction. Long-acting beta agonist (LABA) safety concerns have created controversy about how to step down patients on ICS/LABA therapy. This review will focus on the current status of these issues. Recent findings: Intermittent ICS treatment, often in fixed combination with short-acting beta agonist, is an emerging strategy for control of mild asthma. Addition of leukotriene modifiers, LABAs, and omalizumab to ICS can allow for reduced ICS dosing. Doses of ICS that control symptoms may be inadequate to control exacerbations. Reducing ICS dose before discontinuing LABAs may be the more effective approach for patients on combination therapy. Summary: Use of non-ICS controllers allows for ICS dose reduction with superior outcomes. Tapering of ICS prior to LABA discontinuation may be the favored approach for patients on ICS/LABA therapy, but an understanding of long-term outcomes and further safety data are required. The lowest ICS dose that adequately controls both asthma impairment and risk remains to be determined.

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