Life Cycle Sessions: They'll Grow Out Of It... Or Will They?

This is Part 2 in the Life Cycle Sessions series, providing an overview of research presented at Asthma Canada’s Breathe Easy: The Life Cycle of Asthma conference in Toronto, Ontario, on October 21, 2017. However, these posts don’t have to be read in order—you can find part 1 here.

The Canadian Healthy Infant Longitudinal Development Study, or CHILD Study, is a massive research undertaking in asthma and allergy. The CHILD study has enrolled over 3500 families, following children from birth through age 5, collecting environmental and biologic samples, and completing lab tests including pulmonary function measurements, and clinical assessments, using this information to form a greater understanding of immune system development. ¹ Dr. Subbarao chairs the Lung Function & Allergy and Infection working groups, and is a member of the Genetics, Immunology, and Epidemiology & Statistics working groups for the CHILD Study.

In her presentation “Asthma in Kids: They’ll Outgrow It, Right?”, Dr. Padmaja “PJ” Subbarao from the Hospital for Sick Children in Toronto, presented on what is currently understood about childhood asthma, whether children will outgrow asthma, and other data gathered from her work with the CHILD Study. A focus that transitioned nicely from Dr. Aaron’s prior presentation, was that of measuring lung function in infants.

Diagnosing asthma in children

Yep, you can do pulmonary function tests (PFTs) on babies—who knew! Dr. Subbarao notes that to do spirometry on children (or anyone!), they must be verbal and able to follow instructions accurately to provide PFTs. However, even infants can perform what is known as the Multiple Breath Washout Test (MBWT), which determines lung function by measuring gases as they are transferred in the lungs.²

The MBWT has been available since the 1960s, and while it can even be done on sleeping infants, it is seldom used. The gases measured determine the Lung Clearance Index (LCI), a measure of lung function, determining how well the lungs are able to ventilate by means of how efficiently the tracer gas is exhaled. Even in young children—from sleeping babies to preschoolers—the MBWT’s LCI measurement is able to detect early signs of airways disease, like asthma and cystic fibrosis (which it is more routinely used in assessment of).³ Unfortunately, most clinics do not have access to multiple breath washout testing equipment, making this potentially important test impractical in administration in many areas. ²

Implementing testing and findings

In the CHILD Study, Dr. Subbarao used MBWT/LCI testing in tandem with biologic data (blood, gut microbiome/flora, and documentation of viral infection), and samples collected from the home environment (dust samples), to assess phenotypes of children with and without wheezing. ²

In comparative testing between children with wheeze (suspected asthma), cystic fibrosis (CF), and healthy controls, children with asthma actually scored worse than children with CF on the LCI. ² In the CHILD Study, 3 wheeze phenotypes were noted that mapped consistently with PFT (LCI) scores—“no wheeze”, “recurrent wheeze” and “transient (infrequent) wheeze”. Children with recurrent wheeze scored worst on the LCI.²

In the follow-up at pre-school age, 90% of children remained in the study, and pulmonary function differences were found.² It was found that there is a ciruclar relationship between wheeze and PFT scores: wheeze correlated with lower PFT scores, and lower PFT scores indicated wheezing to be present. ² Dr. Subbarao notes the importance of checking actual PFTs in young, by way of Multiple Breath Washout Testing.

In the Q&A session, Dr. Subbarao noted some important “fast facts” about asthma and atopy (allergy) in childhood:

• Atopy is far more common in children than asthma. ² (I think we may just not hear parents talking as much about their child’s seasonal allergies if they are not severe!)
• Not all children with allergy develop asthma.
• Lung function changes are far more predictive of developing asthma, rather than allergy.
• Lung function changes may not be driven by allergy.
• About 10% of children with wheezing are difficult to treat. Wheezing was a risk factor for receiving an asthma diagnosis by age 5.
• There are other causes of lung disease in childhood, like alpha-1 antitrypsin deficiency, however this usually presents as liver disease in pediatrics, with lung disease coming later. ²

Questions for future research

Dr. Subbarao parted with questions for further research, namely, “Are changes in lung function modifiable?”
In addition, she posed the following:

• What factors are associated with asthma that does go into remission?
• What do early physiologic changes (ie. poorer scores on lung clearance index testing) represent?
• What is different between children whose asthma goes into permanent remission vs. those who relapse at another stage in life?

Final thoughts

If you have interest in pediatric asthma, you can watch the entirety of Dr. Subbarao’s presentation on YouTube. As someone diagnosed with asthma a month before I turned seventeen, I am still classified as having “pediatric onset asthma”, which feels weird since I did not have asthma—or wheeze—as a young child.

The reality is, no matter what age you are diagnosed with asthma, it is a possibility that these early physiologic changes that Dr. Subbarao discusses are present even in those of us who are diagnosed with asthma a bit later—or a lot later—in life. Only continued research can unlock the clues that will hopefully one day lead us to being able to prevent asthma before it starts—and maybe after that, even reverse it. But I’m not holding my breath—and I’m unsure if I intended that pun or not!