News Beyond Our Pages

Asthma phenotypes dictate therapy 

The widely accepted view of asthma is that it is a TH2-driven disease mediated by the TH2 cytokines, including IL-4, IL-5, and IL-13. Recent studies, however, have suggested significant heterogeneity in asthma phenotypes. Microarray and PCR analyses were conducted by Woodruff and collaborators (Am J Respir Crit Care med 2009;180:388-95) on bronchial epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects to assess the role of TH2 cells in asthma. Only half (n = 22) of the asthmatic subjects proved to have increased levels of IL-13–inducible genes. These high-TH2 asthmatic subjects had similar demographics, lung function, and response to bronchodilators as the low-TH2 group; however, they had higher IgE levels, were more often sensitized to indoor allergens, and had increased eosinophil counts in their bronchoalveolar lavage fluid compared with the low-TH2 group. When treated with inhaled corticosteroids, 9 of 10 of the high-TH2 group responded compared with only 1 of 6 of the low-TH2 group. The results of this study suggest the potential importance of assessing asthma phenotypes and individualizing asthma therapy.

Swimming pool chlorine increases atopy risk 

A study by Bernard and colleagues at the Catholic University of Louvain, Belgium, presented evidence of a link between teenagers who swim in chlorinated pools and asthma/allergy risk. The effect was exposure dependent, with longer exposures associated with increased risk. The authors reported that swimming more than 1000 hours increased the odds of allergic rhinitis and asthma in children at risk.

Catching the culprit before the crime 

Duke University researchers, in collaboration with the Department of Defense, are studying the possibility of presymptom detection of viral infections. Lead investigator Geoffrey Ginsburg, MD, PhD, and his colleagues are studying flu transmission in college dormitories. What better place? Using RNA “fingerprinting,” the researchers were able to separate the participants into those who would have symptoms and those who would not. The Department of Defense clearly has a vested interest in pre-empting flu breakouts in crowded barracks.

Sex and hay fever 

A father-son research team, Michael and Ryan Benninger, published preliminary results from quality-of-life surveys taken by participants with allergic and nonallergic rhinitis, as well as persons with no nasal problems. There was 1 question on the survey about sex problems, and participants with allergic rhinitis were most likely to report that their allergies had a negative effect on their sex lives. Of all participants with allergic rhinitis, 17% reported that their allergies “almost always” or “always” affected their sexual activity. The authors stated that responses to a single question do not give enough information to determine whether allergy or other causes are related to the decrease in sexual activity in allergic subjects.

A bad allele 

A report by Tachdjian et al (J Exp Med 2009, doi:10.1084/jem.20091480) provided evidence that a known genetic variant in the IL-4 receptor α chain is a causative event. The authors replaced the mouse IL-4 receptor α gene with the good and bad version of the human gene. The Q576R polymorphism of the IL-4 receptor gene directly enhanced airway inflammation in both an antigen-dependent and antigen–independent way when inserted into mice. The allele expression was associated with higher eosinophil load, increased mucus production, and stepped-up fibrosis. The Q576R polymorphism has been associated with severe asthma in human subjects and is more common in African American persons with asthma.

Senior author Talal Chatila, MD, provided this comment: “This is the first study of its kind to demonstrate that a human genetic polymorphism associated with asthma promotes allergic airway inflammation when introduced in mice. The polymorphism in question, a glutamine-to-arginine substitution in the IL-4 receptor α chain, is specifically associated with severe and fatal/near-fatal asthma. It is especially common in the African American population, which is at increased risk for asthma and its complications. . . . Finally, it illuminates mechanistic aspects of the polymorphism action, most notably the potentiation of several IL-4 receptor responses by activating alternative signaling pathways, such as mitogen-activated protein kinases.”

Gene mutation identified in a variant of combined immunodeficiency 

Researchers at the National Institute of Allergy and Infectious Diseases made a major step toward characterizing the cause of a variation of combined immunodeficiency that presents as chronic upper respiratory tract and cutaneous viral infections (Zhang et al, N Engl J Med 2009, 7:10.1056/NEJMoa0905506). Patients with this new syndrome have severe atopy, chronic sinusitis, and persistent extensive infections with herpes viruses and molluscum contagiosum. The primary finding was the association of mutations in dedicator of cytokinesis 8 protein (DOCK8) genes with impaired lymphocyte development and function. Zhang et al reported disabled CD8 T-cell activation and expansion and suggested this might account for the apparent increased risk of malignancy in the patients affected.

In a press release from the National Institute of Allergy and Infectious Diseases, Dr Su, the senior author, commented about the similarity of this new immunodeficiency disease with hyper-IgE syndrome (HIES): “Even though these individuals were diagnosed with a more uncommon form of HIES, they were still considered to have a mystery disease, because they had severe allergies and had developed cancers.” According to Dr Su, these findings indicate that DOCK8 is essential for defense against viral infections and for preventing the development of cancer and allergies.

From one omega fatty acid to another 

G.E. Rainger

Dr G. E. Rainger, the senior author, stated that “these findings . . . support the idea that the metabolites of omega-6 fatty acids, in particular arachidonic acid, are proinflammatory and are important regulatory agents required to sustain a normal inflammatory response, without which we would be prone to serious infection and tissue damage. However, they also provide mechanistic evidence that supports the anti-inflammatory role of omega-3 fatty acids. Understanding these mechanisms could help us control the exaggerated or unwanted responses associated with inflammatory disease.”

Most news items are written by Sherri Gabbert, PhD.