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What Is New In Small Airways Research

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By Ves Dimov, MD
Assistant Professor of Medicine and Pediatrics
University of Chicago

Biologic targeted therapy in allergic asthma – 2014 update

With more than 300 million people worldwide affected by asthma and with roughly 5% to 10% of this population living with severe, uncontrolled asthma, the need for new biologic therapies is significant.

The new therapies currently in trials are aimed at the following targets:

  • IgE
  • interleukin (IL)-4 and IL-4 receptor
  • IL-5 and IL-13
  • tumor necrosis factor-alpha (TNF-ɑ)
  • CRTh2
  • toll-like receptors (TLR) 7 and 9

Since the approval of omalizumab in 2003, the development of biologic asthma therapies has grown at a remarkable pace. With approximately 30 drugs currently in clinical trials and dozens more in development, the future of asthma biologic therapies seems as promising as ever. However, the outcome of many trials has led to disappointment. Despite several setbacks, researchers remain focused on elucidating the complex pathophysiology of asthma. Given the lack of overwhelming positive responses, these results have emphasized that asthma is a complex clinical syndrome with multiple underlying genotypes and clinical phenotypes.

The hope is that asthma biologic therapies will eventually be tailored to an individual's asthma phenotype. It is unlikely that there is one “magic bullet” to cure all patients with asthma.

Source: Bice JB, Leechawengwongs E, Montanaro A et al. Biologic targeted therapy in allergic asthma. Annals of Allergy, Asthma & Immunology 2014; 112(2):108-115.

Image Source: Airway during asthma symptoms, National Institutes of Health (NIH) and Wikipedia; public domain.

Safety of formoterol in asthma clinical trials: no increased risk of asthma-related deaths

Large safety trials on the use of long-acting beta-agonists (LABAs) in asthma, mandated by the FDA, are currently in progress.

This meta-analysis included 149 trials and 104,463 patients, 67,380 of whom were exposed to formoterol. There were no new asthma-related deaths in the dataset. Nonfatal asthma-related serious adverse events were reduced with formoterol (relative risk 0.63), as were discontinuations due to adverse events. Examining 40 trials with direct formoterol versus non-LABA comparisons, Mantel–Haenszel relative risk for asthma-related death was 2.75 (95% CI 0.52–14.4) and for serious adverse events 0.83.

The authors concluded that the large dataset indicated no increased risk of asthma-related deaths among patients exposed to formoterol compared with non-LABA treatments, although the wide confidence interval (0.52–14.4) precluded absolute certainty.

Source: Sears MR, Radner F et al. Safety of formoterol in asthma clinical trials: an update. European Respiratory Journal 2014; 43(1):103-114.

2014 ERS/ATS guidelines on severe asthma

Severe or therapy-resistant asthma is increasingly recognized as a major unmet need.

When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy.

Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma.

Increased resistance of small airways may be assessed noninvasively by spirometry, nitrogen wash out, body plethysmography, impulse oscillometry (IOS), and using imaging (high resolution computed tomography or conventional chest X-ray).

Specific recommendations are related to:

  • use of sputum eosinophil count and exhaled nitric oxide to guide therapy
  • treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents, and bronchial thermoplasty

Improved phenotyping may provide a biomarker-driven approach to severe asthma therapy.

Source: Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal 2014; 43(2):343-373.

Last updated: Thursday, May 14th, 2015