9 Distinct Trajectories Identified in Children with Asthma, Allergy

Daniil Lisik, MD

Credit: ResearchGate

A new study identified 9 trajectories of asthma and allergy in children with distinct differences in parental report and medication use, longitudinal patterns, and classes and frequency of dispensed medications.¹

“The present study was strengthened by the use of combined parental report and register data, enriching disease characterization with personal experience and medication utilization,” investigators wrote, led by Daniil Lisik, MD, from Krefting Research Centre at Sahlgrenska Academy, University of Gothenburg, in Sweden.

Asthma and allergies have various underlying pathophysiological pathways and clinical presentations caused by complex interactions between genetic and environmental factors. The most well-known developmental pattern of atopic diseases is the “atopic march”—early-life eczema followed by food allergy and later allergic rhinitis and asthma.² However, several reports indicate the atopic march may only apply to a fraction of allergic disease trajectories.

Characterizing asthma and allergy trajectories is important because it helps inform disease progression, prognosis, pathophysiological mechanisms, and risk factors.¹ Traditionally, disease subtypes and trajectories were defined based on clinical experience, but this approach can lead to bias and fail to identify relevant subgroups. A data-driven approach not only removes assumptions but has the potential to discover latent patterns in complex datasets.

Many studies used latent class analysis to identify patterns in categorical data and subsequently trajectories of asthma and allergy, but no study evaluated a combination of survey responses and healthcare utilization register data to identify asthma and allergy trajectories.

Thus, investigators conducted a study to identify trajectories of asthma and allergy in children based on longitudinal data of parental-reported disease and medication use from a national register. Children in the Swedish population-based birth cohort, Children of Western Sweden, initiated in 2003 in Västra Götaland county which comprises 1-6th of the Swedish population.

The team randomly selected 8176 (~50%) families to participate in this study. Among these families, 5654 participants (69%), nearly half female (48%), were followed up with postal surveys from 6 months old until 12 years old. Survey responses were collected at ages 1, 4.5, 8, and 12 years, and the team linked these responses with dispensed medication register data for 2 – 12 years.

The postal surveys included data on parental-reported disease, medication, symptoms, sociodemographic or lifestyle factors, and environmental exposures. The National Medical Birth Register included information on antenatal, delivery, and neonatal care. Moreover, the National Prescribed Drug Register, which included data on dispensed prescription medication, was created in mid-2005 and included participants aged 2 – 13 years.

More than half of the sample (64%) had ≥ 1 family member with asthma, allergic rhinitis, or eczema. Eczema was the most common allergic disease in early childhood, reported by roughly 20% of parents at 1 year. Children had an increase in asthma (6%) and later allergic rhinitis (9%) by 12 years old. Although concomitant diseases increased over time, they never exceeded 5% of the sample.

When participants were around 2 years old, data revealed the most dispensed medication was for asthma, followed by eczema. However, by the time the children were 5 years old, allergic rhinitis medication was the most common.

Investigators identified 9 trajectories of asthma and allergy in children:

Asthma-dominated

1. Early-onset remitting (3.3%)
2. Late-onset (2.1%)
3. Persistent (2.6%)

Eczema-dominated

1. Persistent (3.4%)
2. Remitting (7.6%)

Allergic rhinitis-dominated

1. Late-onset (4.6%)

Multimorbidity

1. Mild-childhood asthma and late-onset allergic rhinitis (2.5%)
2. Persistent eczema and late-onset allergic rhinitis (1.6%)

Other

1. Low-disease burden trajectory (72.2%)

The team saw substantial complexity was found in the trajectories, but this was not a surprise since asthma and allergic diseases are heterogeneous. The trajectories had similarities to previously described longitudinal phenotypes. For instance, early transient asthma resembled Trajectory 1.

Moreover, many of the trajectories consisted of infection-related asthma symptoms and not chronic asthma. Late-onset asthma or wheezing is a common trajectory found in previous studies and is similar to Trajectory 2 in this study. This study did not identify a trajectory identical to the atopic march, but Trajectory 3 and Trajectory 7 had similar characteristics.

Investigators wrote the study was limited by relying on medication use for diagnoses. Although an asthma diagnosis can be validated by dispensed asthma medication, the same is not the case for allergic rhinitis and eczema since Sweden offers medication for milder diseases over the counter and not as prescriptions. Also, medications can be used for other purposes, such as antihistamines, which are also used in the management of urticaria.

The team also wrote how the study was limited by not performing clinical investigations in SWS, so the trajectories could not be related to lung function, allergic sensitization, eosinophilia, or other markers of atopy and health.

“Our work highlights the value of combining healthcare utilization register and parental-reported data, but also the need to validate the presence and generalizability of the derived trajectories,” investigators wrote. “There is a need to further investigate the underlying mechanisms, associated risk factors, as well as risk of hard clinical endpoints for the derived trajectories, in order to ascertain their clinical utility.”

References

1. ^{Lisik D, Wennergren G, Kankaanranta H, et al. Asthma and allergy trajectories in children based on combined parental report and register data. Pediatr Allergy Immunol. 2024;35(10):e14254. doi:10.1111/pai.14254}
2. ^{Maiello N, Comberiati P, Giannetti A, Ricci G, Carello R, Galli E. New Directions in Understanding Atopic March Starting from Atopic Dermatitis. Children (Basel). 2022;9(4):450. Published 2022 Mar 23. doi:10.3390/children9040450}