Unmet needs for assessment of small airways dysfunction in asthma will hopefully be met by the ongoing ATLANTIS study

An estimated 300 million people suffer from asthma worldwide. Asthma inflammation affects the entire bronchial tree. The small airways, i.e. less than 2 mm diameter, can be affected by inflammation and remodelling. However, their contribution to asthma control and exacerbations has been minimally investigated. Small airways function can be assessed with invasive and non-invasive techniques, including physiological and radiographic testing, in addition to direct and indirect assessments of inflammation. These tests are usually only available in specialised chest clinics. Unfortunately, there is no gold standard tool, or an easy-to-apply measure, available in which to assess small airways dysfunction (SAD). Thus, there is an unmet need to identify SAD easily and correctly across all severities of asthma, and to assess its role in the control of the disease.

The ATLANTIS study ((AssessmenT of smalL Airways involvemeNT In aSthma) aims to:

1) Determine the role of small airways abnormalities in the clinical manifestations of asthma.

2) Evaluate which (combination of) clinical methods best assesses the abnormalities of small airways and large airways dysfunction in asthma and best relates to asthma severity, control and future risk of exacerbations, both cross-sectional and longitudinal.

3) Further develop and validate the small airways dysfunction tool (SADT).

The ATLANTIS study started in 2014 and the first results are expected in 2016. The data gathered could improve our understanding of small airways pathobiology in asthma and provide a database and sample repository to answer future questions.

References: Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. Postma DS et al. Eur Respir J. 2015 Jun;45(6):1534-8. doi: 10.1183/09031936.00214314.
http://erj.ersjournals.com/content/45/6/1534.long
(free full text)

Thiazolidinediones may provide a new anti-inflammatory approach to asthma

Thiazolidinediones are oral diabetes medications that activate peroxisome proliferator-activated receptor gamma and have anti-inflammatory properties. Some studies have found improvements in pulmonary function in asthma patients treated with thiazolidinediones.



PPAR-alpha and -gamma pathways. Image source: Wikipedia, GNU Free Documentation License.

This cohort study included diabetic Veterans with asthma who were taking oral diabetes medications (2,178 patients were on thiazolidinediones). Thiazolidinediones were associated with reductions in risk of asthma exacerbation (OR = 0.79) and oral steroid prescription (OR = 0.73).

Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids.



Animation of thiazolidinediones mechanism of action and peroxisome proliferator-activated receptors (PPARs).

References:

Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study. Seppo T Rinne et al. Allergy, Asthma & Clinical Immunology 2014, 10:34 (free full text) http://www.aacijournal.com/content/10/1/34

Disclaimer: The editor of this website co-authored the first human study of thiazolidinediones in asthma which was cited in the article (Ann Allergy Asthma Immunol 2012, 109(1):75-77)

The microbiome in asthma

The concept of a “common mucosal immune system” relies on cross-talk between mucosal compartments. A balance must be struck that maintains homeostasis between the microbiome and the host. This balance is constantly challenged by a number of factors leading to “dysbiosis”(imbalance) in the microbial community, which is found in asthma. The microbiome (airway or gut) may play a role in the development of specific phenotypes such as allergic or nonallergic asthma and treatment-resistant asthma. Studies of oral or aerosol administration of the microbiota for the treatment and prevention of asthma are in planning stages.


References:

The microbiome in asthma. Yvonne J. Huang et al. JACI, January 2015, Volume 135, Issue 1, Pages 25–30 (free full text).
http://www.jacionline.org/article/S0091-6749(14)01649-2/fulltext

Asthma pathogenesis and new drugs for treatment - BMJ State of the Art Review

Asthma affects more than 300 million people worldwide. Of these, 10-15% have severe asthma, which is refractory to commonly available drugs. New drugs are needed because those that are currently available cannot control symptoms and exacerbations in all patients and can cause adverse reactions.

In the past 10 years, advances in asthma genetics, airway biology, and immune cell signaling have led to the development of small molecule therapeutics and biologic agents.

Several new classes of asthma drugs have been evaluated in randomized controlled trials:

- ultra long acting beta agonists
- modulators of the interleukin 4 (IL-4), IL-5, IL-13, and IL-17 pathways

Other new drug classes remain in earlier phases of development:

- dissociated corticosteroids
- CXC chemokine receptor 2 antagonists
- toll-like receptor 9 agonists
- and tyrosine kinase inhibitors

Despite some preliminary efficacy data, there is insufficient evidence to make strong recommendations about the use of these newer agents. Future research will focus on:

- clinical efficacy of the biologic agents
- effect of newer agents on severe asthma in pediatric patients
- biology of non-eosinophilic and corticosteroid resistant asthma

References:

Asthma: pathogenesis and novel drugs for treatment. BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g5517 (Published 24 November 2014)
Cite this as: BMJ 2014;349:g5517
http://www.bmj.com/content/349/bmj.g5517.long

Image source: Lungs, Wikipedia, public domain.

Lung Sound Analysis Predicts Airway Inflammation in Patients with Asymptomatic Asthma

The expiratory-inspiratory ratios of sound power in the low-frequency range (E-I LF) from 36 patients with asymptomatic asthma were compared with those of 14 healthy controls (here is the study link).

The mean E-I LF was higher in the patients with asthma and with increased sputum eosinophils than in those patients without increased sputum eosinophils (0.45 vs 0.20) or in the healthy controls (0.25). Sputum eosinophil ratio and exhaled nitric oxide were independently correlated with E-I LF.

For the prediction of increased sputum eosinophils and increased fractional exhaled nitric oxide levels, the E-I LF thresholds of 0.29 and 0.30 showed sensitivities of 0.80 and 0.74 and specificities of 0.83 and 0.77, respectively.

Lung sound analysis (LSA) could predict airway inflammation of patients with asymptomatic asthma.

References:

Prediction of Airway Inflammation in Patients with Asymptomatic Asthma by Using Lung Sound Analysis - The Journal of Allergy and Clinical Immunology: In Practice http://buff.ly/1zJK0CX
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