Escaping asthma’s choke hold

Spring is a season for rejuvenation. But if you are one of the 25 million Americans suffering from asthma, you may dread this time of the year. The Asthma and Allergy Foundation of America designates May as National Asthma and Allergy Awareness Month because higher pollen count and air pollution, combined with increased outdoor activity, cause an increased number of asthma-related hospitalizations during spring and summer. Asthma incidence has increased by 28 percent in the past decade and continues to rise, particularly among children. Identifying the physiological causes of asthma can help develop more targeted and comprehensive therapies.

What is asthma?

Asthma is a chronic immune system disorder in which the airways constrict and the mucous lining in the lungs becomes inflamed in response to environmental factors such as pollen, mold, dust mites, viruses and air pollutants. Symptoms include coughing, wheezing, congestion and shortness of breath.

How is the immune system involved?

Upon first exposure to an allergen, Th2 cells, a type of T cell, secrete interleukin-4 and interleukin-13, which stimulate B cells to produce immunoglobulin-E antibodies. The IgE antibodies bind to mast cells, which regulate inflammation. This process is called sensitization. Upon re-exposure to the same allergen, the mast-cell-bound IgE antibodies crosslink and set off the release of inflammatory mediators, like histamines and prostaglandins, that cause sneezing, shortness of breath and coughing. Next, white blood cells, like eosinophils and neutrophils, infiltrate the airways and release cytokines, lipids and proteases that cause congestion and constriction.

What are researchers investigating now?

Microorganisms in the gut and lung, which can regulate the immune system, now are linked to asthma. Helicobacter pylori, an intestinal bacteria, can protect indirectly against asthma by modulating global immune response. This protective effect is achieved by activating CD4 and CD25 regulatory T cells and increasing the production of intestinal hormones like leptin, ghrelin and gastrin, which have immunomodulatory effects.

An analysis of 16S ribosomal bacterial RNA revealed a greater variety and abundance of pathogenic bacteria in the airways of asthma patients. Resistance to anti-inflammatory corticosteroid treatments is a phenomenon observed in some asthma patients. The resistance emerges from the activation of the p38 mitogen-activated kinase phosphatase pathway in macrophages by the pathogen Haemophilus parainfluenzae. Inhibiting transforming growth factor-β–associated kinase-1, an upstream activator of the MAPK pathway, can restore sensitivity to the treatments.

Indumathi Sridharan Indumathi Sridharan earned her bachelor’s degree in bioinformatics in India. She holds a Ph.D. in molecular biochemistry from Illinois Institute of Technology, Chicago. She did her postdoctoral work in bionanotechnology at Northwestern University.