Understanding Genomics

Abstract

In 2015, a 7-year-old African-American boy presents in your emergency department with a 2-day history of cough and wheeze. The symptoms began in the setting of a mild upper respiratory tract infection and were worsened by exercise. He is known to have chronic asthma as do his father and younger sister. His respiratory rate is 32 breaths per minute, and he is wheezing bilaterally and diffusely with moderate retractions. How will your evaluation and management begin? If recent trends in other fields are predictive, you will begin with a review of your patient’s genetic profile. Although that profile may guide a portion of or your entire approach, some facts about asthma will remain the same. It will still be a multifactorial chronic disorder,1–3 highly prevalent among children and adolescents,4,5 with a strong environmental component1,2,4,6–8 and genetic predilection.9–11 In addition, the pathophysiology will likely not have changed. As Sir William Osler wrote more than 100 years ago in The Principles and Practice of Medicine, “Asthma is a term which has been applied to various conditions associated with dyspnea. Of the numerous theories, the following are most important: (1) that it is due to spasm of bronchial muscles, (2) that the attack is due to swelling of the bronchial mucous membrane, (3) and that, in many cases, it is a special form of inflammation of the smaller bronchioles.”12 During the past century, our understanding of the pathophysiology of asthma has advanced slowly, without significant change in Sir Osler’s basic paradigm. Now, however, with a completed “map” of the human genome in hand, new developments in the field of asthma pathobiology are arriving more quickly and often involve the identification of specific “asthma genes.” Some of these asthma genes hold promise as potential predictors of the clinical variability of disease and even response to therapy. The advanced technologies used to make these discoveries will continue to slowly find their way into clinical practice.