The Contributions of Allergic Sensitization and Respiratory Pathogens to Asthma Inception

Childhood asthma is the most common chronic disease among grade school children, and is responsible for the greatest number of school days missed.  Fortunately, there are now efficient management strategies to minimize the effect of asthma for many children, but what are the factors that lead to its development in the first place?  In this month’s issue of JACI, Jackson and colleagues discuss the risk factors that contribute to the development of asthma (J Allergy Clin Immunol 2016; 137(3): 659-665) .

As the authors explain, asthma starts long before the first wheeze.  In the first few years of life, as young immune systems encounter the environment around them, children who are more likely to eventually develop asthma tend to develop sensitization to aeroallergens and have recurrent lower respiratory infections.  This can happen alone, but new evidence suggests that they feed off each other, leading to a mix where asthma becomes a likely outcome.

Nearly all wheezing illnesses in the first few years of life are due to respiratory viruses.  New molecular techniques have shown that there is a wide variety of viruses that can cause upper and lower respiratory tract infections.  Among these, respiratory syncytial virus (RSV) and rhinoviruses (RV) are the most common pathogens.  Indeed, one third of children who have had RSV bronchiolitis develop recurring wheezing episodes, and one study showed that passively immunization against RSV led to an 80% reduction in the risk of recurrent wheezing in nonatopic children.  Rhinovirus, which was previously thought to only cause upper respiratory tract infections, is now known to cause lower respiratory tract infections too.  And, at least in one Finnish study, 60% of children with RV who wheezed in the first two years of life continued on to develop asthma five years later.  Bacteria may also play a role, but the evidence is preliminary and mixed: some bacterial infections are associated with wheezing and asthma, but exposure to other bacteria may actually be protective.

Additionally, it’s been known for some time that environmental allergies are major contributors to asthma.  In addition, they increase the chance that children will get wheezing respiratory infections.  Part of it is because allergic sensitization leads to enhanced airway responsiveness due to respiratory viral infections.  Another important factor is that allergen exposure impairs antiviral responses, such as production of Interferons I & III.  Interestingly, the use of omalizumab, a medication targeting IgE, the type of antibody responsible for allergens, also leads to a decrease in virus-induced asthma exacerbations.

Of course, there is so much more to the story.  What makes certain children more susceptible to viral infections and allergies is still unknown.  17q21, CDHR3 and IL-33 polymorphisms offer possible answers, but they are only pieces of the puzzle.  The biggest question on the horizon is can we ward off asthma by preventing allergen sensitization or avoiding  severe respiratory infections.  More research is needed, but there’s at least some glimmer of hope that we can finally stop asthma before it actually sets in.