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Review
. 2022 Sep;52(9):1035-1047.
doi: 10.1111/cea.14207. Epub 2022 Jul 28.

Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms

Bronwyn K Brew  1   2 , Emma Caffrey Osvald  1   3 , Tong Gong  1 , Anna M Hedman  1 , Kirsten Holmberg  4 , Henrik Larsson  1   5 , Jonas F Ludvigsson  1   6 , Mwenya Mubanga  1 , Awad I Smew  1 , Catarina Almqvist  1   3
Affiliations
Review

Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms

Bronwyn K Brew et al. Clin Exp Allergy. 2022 Sep.

Abstract

It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.

Keywords: anxiety; asthma; children; comorbidity; depression; obesity; sleep.

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Conflict of interest statement

Jonas Ludvigsson has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG), which received funding from Janssen corporation. Henrik Larsson reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals, and Evolan Pharma AB; and sponsorship for a conference on attention‐deficit/hyperactivity disorder from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Results of MEDLINE and ePUB search 2016–2021, child and adolescent asthma and comorbidities: risk, symptom and mechanism studies.
FIGURE 2
FIGURE 2
Current knowledge on asthma and obesity in children. Summary of study factors measuring obesity as a risk of asthma, and a summary of currently proposed mechanisms explaining the comorbidity of asthma and obesity.
FIGURE 3
FIGURE 3
Current knowledge on asthma, depression and anxiety in children. Summary of study factors measuring depression/anxiety as a risk of asthma, and a summary of currently proposed mechanisms explaining the comorbidity of asthma and depression/anxiety.
FIGURE 4
FIGURE 4
Current knowledge on asthma and neurodevelopmental disorders in children. Summary of study factors measuring neurodevelopmental disorders as a risk of asthma, and a summary of currently proposed mechanisms explaining the comorbidity of asthma and neurodevelopmental disorders.
FIGURE 5
FIGURE 5
Current knowledge on asthma and sleep disorders in children. Summary of study factors measuring sleep disorders as a risk of asthma, and a summary of currently proposed mechanisms explaining the comorbidity of asthma and sleep disorders.
FIGURE 6
FIGURE 6
Current knowledge on asthma and autoimmune diseases in children. Summary of study factors measuring autoimmune diseases as a risk of asthma, and a summary of currently proposed mechanisms explaining the comorbidity of asthma and autoimmune diseases.
See this image and copyright information in PMC

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