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Friday, March 1, 2013

Phenotypic heterogeneity in COPD and asthma

It has come as small comfort for pulmonary clinicians that the two most prevalent obstructive lung diseases, COPD and asthma, are being characterized as phenotypically heterogeneous.  While it sheds light on the challenging clinical management of patients with these diagnoses, it dredges up more concerns about how exactly this variability in presentation should and could be addressed to mitigate the disease-related impairment.

This month’s Clinical Review from Carolan and Sutherland [Journal of Allergy & Clinical Immunology 2013; 131(3): 627-634] compiles important advances in understanding COPD phenotypes, current knowledge of asthma phenotypes, where they overlap and the focus of therapies.  The authors cover guidelines, clinical phenotypes, exacerbations and morbidity in both diseases.  They also discuss radiologic phenotypes in COPD and the promising predictive tool, the BODE index, which applies BMI, obstruction, dypsnea, and exercise capacity to predict disease progression with greater accuracy than decline in FEV1. 

Carolan and Sutherland note that COPD, unlike asthma, has not yet been sensitively correlated to any inflammatory biomarker, which has impaired programs for targeted drug development in COPD.  Phenotypic cluster analyses for both diseases are also covered in the authors’ review.  They comment that these efforts are creating alternative perspectives that may be useful for improving management of the variable clinical presentations.  Improved characterization of phenotype variability would permit development of personalized treatment regimens for both COPD and asthma. 

Dietary intervention for EoE remission

An article by Lucendo et al in this month’s issue [Journal of Allergy & Clinical Immunology 2013; 131(3): 797-804] provides convincing evidence supporting a drug-free therapy for eosinophilic esophagitis [EoE].  Noting that food elimination diets in children with EoE are being reported as successful for a majority of patients, the authors designed a six-food elimination diet [SFED] study involving adult EoE patients.  The six foods selected – cow’s milk, soy, cereals, eggs, nuts and legumes, and fish – were selected based on previous reports of their common association with EoE. 

Endoscopy, IgE and skin prick testing were performed to confirm diagnosis, determine EoE remission, and upon food rechallenge.  Lucendo et al report that 73% of subjects had clinical improvement and statistically significant reduction in esophageal mucosal eosinophilia.  Food challenge results showed that 1 food was the offender in approximately a third of the subjects, 2 foods in another third and 3 or more foods in the last third.  Cow’s milk was the most common food trigger affecting 62% of subjects, followed by wheat and eggs.  The authors report that among those who maintained the food avoidance at the 2 and 3 year follow up EoE remained in remission clinically and pathologically and that the subjects had not required medications for EoE during that period. 

Of particular interest, Lucendo et al report very low concordance and predictive power of IgE and skin prick testing with regard to food triggers.  They suggest that this may point to EoE as a delayed hypersensitivity response rather than an IgE-associated one. 

EoE may constitute a new, different type of food allergy, pathophysiologically closer to celiac disease than to food-triggered anaphylaxis. In fact, common IgE-based allergy tests are not sensitive in celiac patients for diagnosing the disease, even when this is also an immunologically mediated disorder. As a result, small bowel biopsies remain essential for diagnosing most patients. As in celiac disease, the mechanisms leading to EoE may be predominantly cell-mediated, but we lack specific peripheral markers that may help us in diagnosing and monitoring the disease in such as way as celiac serology does. Looking for new non-invasive markers of EoE that allow us to predict those exact food triggers and avoiding repeated endoscopies and biopsies are new challenges for EoE researchers.