Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study

Dai, Ruixue; Miliku, Kozeta; Gaddipati, Sirisha; Choi, Jihoon; Ambala, Amirthagowri; Tran, Maxwell; Reyna, Myrtha E.; Sbihi, Hind; Lou, Wendy; Parvulescu, Paula; Lefebvre, Diana L.; Becker, Allan B.; Azad, Meghan B.; Mandhane, Piush J.; Turvey, Stuart E.; Duan, Qingling; Moraes, Theo J.; Sears, Malcolm R.; Subbarao, Padmaja

doi:10.1016/j.jaci.2021.10.039

Cited by 27 publications

(35 citation statements)

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“…A similar risk and lower lung function were also found in children born at term with rapid weight gain in early life [ 139 , 140 ]. Some longitudinal studies have investigated the relationship between overweight and respiratory diseases in toddlers and older children [ 141 , 142 , 143 , 144 ]. A prospective cohort study of 731 children aged three to eight found that increased body mass index (BMI) at three and five years of age was associated with a higher risk of recurrent wheezing with no differences between girls and boys [ 142 ].…”

Section: Resultsmentioning

confidence: 99%

“…Data analysis from the combination of eight different prospective birth cohort studies, including 12,050 children, demonstrated that children with rapid BMI gain in the first two years of life were at higher risk for incident asthma up to age 6 compared with children with less pronounced weight gain slope in early childhood [ 143 ]. In the CHILD Cohort Study including 3154 children followed up from three months to five years of age, higher BMI at one year of age remained an independent risk factor for all the wheeze trajectories (transient wheeze, intermediate-onset wheeze and infantile-onset persistent wheeze) after adjustment for other factors [ 144 ].…”

Section: Resultsmentioning

confidence: 99%

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Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

Grandinetti

Fainardi

Caffarelli

et al. 2022

JCM

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Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children’s exposure to risk factors that may permanently affect respiratory health.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

Grandinetti

Fainardi

Caffarelli

et al. 2022

JCM

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“… 6 Nonetheless, a widely held belief that preschool wheeze is a benign condition has been refuted in recent years because persistence of preschool wheezing symptoms to school age, even if associated with subsequent remission, is linked to lower lung function and chronic lung disease. 7 …”

Section: Introductionmentioning

confidence: 99%

Development of a Symptom-Based Tool for Screening of Children at High Risk of Preschool Asthma

et al. 2022

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ImportanceDespite advances in asthma therapeutics, the burden remains highest in preschool children; therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings.ObjectiveTo develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden.Design, Setting, and ParticipantsThe cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022.ExposuresThe CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age.Main Outcomes and MeasuresWithin the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values.ResultsAmong 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years; 1324 [52.7%] male; 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94; 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73; 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70; 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82; 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87; 95% CI, 0.80-0.94).Conclusions and RelevanceIn this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.

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“…In this issue of the Journal of Allergy and Clinical Immunology, Dai et al present data from the CHILD birth cohort, wherein they identify wheeze trajectories and examine environmental and genetic factors associated with those trajectories, lung function, and outcomes through age 5 years in more than 3000 Canadian children. 4 Subjects completed detailed high-frequency questionnaires from the ages of 3 to 60 months; food and aeroallergen testing at 1, 3, and 5 years; and measurement of blood eosinophil counts at 1 and 5 years. Group-based trajectory models (GBTMs) were used to classify subjects into wheeze trajectories, whereas most prior studies used latent class analysis approaches.…”

mentioning

confidence: 99%

“…However, the CHILD study has likely collected data to support future investigations of the impact of the microbiome on asthma evolution. Finally, paternal asthma was associated only with intermediate-onset wheeze, which Dai et al 4 speculate might reflect airway hyperresponsiveness (AHR) given that AHR has previously been associated with paternal asthma. 7 Now that the CHILD cohort has matured to school age, future follow-up visits will ideally include AHR testing and a GRS enriched for variants associated with AHR.…”

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confidence: 99%

Preschool wheeze phenotypes from birth cohorts: Where do we go from here?

Debley

2022

Journal of Allergy and Clinical Immunology

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Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study

Cited by 27 publications

References 53 publications

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

Development of a Symptom-Based Tool for Screening of Children at High Risk of Preschool Asthma

Preschool wheeze phenotypes from birth cohorts: Where do we go from here?

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