Peter Le Souef (Perth Australia)
Asthma Phenotypes
For many years, asthma phenotypes used in clinical diagnosis or in research have been based on
either clinical features of asthma itself, basic physiological factors or laboratory features. Each of
these areas is very different and may not correlate with other features. In brief, clinical features
that have stood the test of time include: (1) doctor diagnosed asthma; (2) episodes of wheeze in
the last twelve months; (3) acute symptoms with “colds” or exercise; and (4) interval symptoms
with allergen exposure, exercise or sleep; and (5) use of asthma medications. Of these, the first
two are the most used in asthma research. Also useful for both clinical and research assessment
are physiological measurements of respiratory function, especially FEV1.0 in children old enough
to do spirometry. Airway responsiveness assessment has not proven to be useful in asthma
management in children and is now seldom done for clinical assessment and also less used for
research. Use of expired nitric oxide has inspired many publications, but not the clinicians who
read them. Laboratory features have proven to be more controversial, particularly in the case of
those associated with atopy (eg total and specific IgE, skin prick tests, blood eosinophils). While
many clinicians use them in their daily practice, many more don’t, although there are large regional
differences in these practices. The relative failure of allergen avoidance measures (1, 2) and
immunotherapy (3) to improve asthma has done little to convince clinicians that do not use them to
change their minds. Twenty years of asthma genetics studies has not helped to clarify
phenotypes. Indeed, as time has gone by, such studies use fewer and fewer phenotypes and
larger and larger populations to find a handful of genes (4). Interestingly, few of these genes are in
immunological pathways.
So, where to from here? One of the most important findings in asthma research in recent years
has been the identification of relative degrees of impairment of both Th1 and innate immune
responses in asthmatics (5). In addition, epithelial responses are also impaired in asthma.
Linked with these observations is the now convincing evidence that respiratory virus infections
are the most important cause of asthma exacerbations (5). Given that approximately 75% of
children have episodic asthma with few problems aside from these episodes and that almost all of
these exacerbations are due to respiratory viruses, the argument that viruses are the most
important factor producing the asthma phenotype in children is hard to refute. Since these viruses
remain the most important factor producing wheezy exacerbations throughout life, dividing asthma
in children into viral-induced wheeze of infancy and multi-trigger wheeze beyond this age group
would appear to be of little value. Using response to respiratory virus infections and the associated
defects in immune responses directed against viruses may be a better way to consider asthma
phenotypes.
REFERENCES
1.
Host A, Halken S, Muraro A, Dreborg S, Niggemann B, Aalberse R, et al. Dietary
prevention of allergic diseases in infants and small children. Pediatr Allergy Immunol. 2008
Feb;19(1):1-4.
2.
Piippo-Savolainen E, Remes S, Korppi M. Does early exposure or sensitization to inhalant
allergens predict asthma in wheezing infants? A 20-year follow-up. Allergy Asthma Proc. 2007 JulAug;28(4):454-61.
3.
Casale TB, Canonica GW, Bousquet J, Cox L, Lockey R, Nelson HS, et al.
Recommendations for appropriate sublingual immunotherapy clinical trials. J Allergy Clin Immunol.
2009 Oct;124(4):665-70.
4.
Zhang G, Goldblatt J, LeSouef P. The era of genome-wide association studies:
opportunities and challenges for asthma genetics. J Hum Genet. 2009 Oct 9;54:624-8.
5.
Johnston SL. Innate immunity in the pathogenesis of virus-induced asthma exacerbations.
Proc Am Thorac Soc. 2007 Jul;4(3):267-70.