Long-Term Natural History of Severe Asthma Exacerbations and Their Impact on the Disease Course

Lee, Tae Yoon; Petkau, John; Sadatsafavi, Mohsen

doi:10.1513/annalsats.202012-1562oc

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…Similarly, the severity and number of AEs have a prognostic capability in riskstratification [131], but only one GWAS of the annual number of exacerbations has been conducted [75], and no study has assessed temporal distance among events and/or the time-to-first exacerbation. Moreover, although bioinformatic tools have been used to evaluate the functional impact of potential susceptibility variants, many of these resources do not include data from tissues/cells obtained from asthma patients, across several asthma-relevant tissues, or diverse ethnic backgrounds.…”

Section: Discussionmentioning

confidence: 99%

Asthma Exacerbations: The Genes Behind the Scenes

Luis¹,

Forno²,

Celedón³

et al. 2023

J Investig Allergol Clin

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The clinical and socioeconomic burden of asthma exacerbations (AEs) represents a major public health problem. In the last four years, there has been an increase in ethnic diversity in candidate-gene and genome-wide association studies (GWAS) of AEs, which in the latter case has led to the identification of novel genes and underlying pathobiological processes. Pharmacogenomics, admixture mapping analyses, and the combination of multiple “omic” layers have contributed to prioritizing genomic regions of interest and/or understanding the functional consequences of genetic variation. Despite this, the field still lags behind the genomics of asthma, where a vast compendium of genetic approaches has been used (e.g., gene-environment interactions, next-generation sequencing, or polygenic risk scores). Furthermore, the roles of the DNA methylome and histone modifications in AEs have been scarcely investigated, and microRNA findings remain to be validated in independent studies. Likewise, the most recent transcriptomic studies highlight the importance of host-airway microbiome interaction in the modulation of AEs risk. Leveraging -omics and deep-phenotyping data from sub-types or homogenous subgroups of patients will be crucial to overcome the inherent heterogeneity of AEs, and boost the identification of potential therapeutic targets and the implementation of precision medicine in clinical practice for AEs.

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Section: Discussionmentioning

confidence: 99%

Asthma Exacerbations: The Genes Behind the Scenes

Luis¹,

Forno²,

Celedón³

et al. 2023

J Investig Allergol Clin

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“…We used those values as the shape parameter α for a Dirichlet distribution to generate a preliminary vector of probabilities W pre , for the severity levels. We then incorporated the effect of very severe exacerbations on subsequent very severe exacerbations (Lee et al, 2022b). If an individual labeled as asthmatic had a past history of very severe exacerbation, the probability for the very severe level increased by a factor of 1.79 if less than 14 years of age and 2.88 otherwise.…”

Section: Model Componentsmentioning

confidence: 99%

Development and Validation of an Asthma Policy Model for Canada: Lifetime Exposures and Asthma outcomes Projection (LEAP)

Lee,

Petkau,

Johnson

et al. 2024

Preprint

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Purpose: To develop Lifetime Exposures and Asthma outcomes Projection (LEAP), a reference policy model for evaluating health outcomes and costs of asthma interventions and policies for the Canadian population. Methods: Following the best practice guidelines for development, we first created a conceptual map with a steering committee of clinician experts and economic modelers through a modified Delphi-process. Following the committee's recommendations and given the multidimensionality of risk factors and the need for modeling realistic aspects (e.g., gradual market penetration) of adopting health technologies, we opted for an open-population microsimulation design. For the first version of the model, we concentrated on several key risk factors (age, sex, family history of asthma at birth, and exposure to antibiotics in the first year of life) from the concept map. The model consists of five intertwined modules: 1) demographic, 2) risk factors, 3) asthma occurrence, 4) asthma outcomes, and 5) payoffs. The demographic module, including birth, mortality, immigration, and emigration, was based on sex- and age-specific estimates and projections from Statistics Canada. The distributions of risk factors, including family history of asthma and exposure to antibiotics, were estimated from population-based administrative databases and a population-based longitudinal birth cohort. To estimate parameters in the asthma occurrence (prevalence, incidence, reassessment) and asthma outcomes (severity, symptom control, exacerbations) modules, we performed quantitative evidence synthesis. Costs and utility weights were obtained from the literature. We conducted multiple face and internal validation assessments. Results: LEAP is capable of modeling asthma-related health outcomes at the individual and aggregate levels from 2001 onwards. Face validity was confirmed by checking the structure, equations, codes, and results. We calibrated and internally validated the age-sex stratified demographic projections to the estimates and projections from Statistics Canada, the age-sex stratified asthma prevalence to the administrative data, and the asthma control levels and exacerbation rates to the estimates from the literature. Conclusions: LEAP is the first reference Canadian asthma policy model that emerged from identified needs for health policy planning for early interventions in asthma. As an open-source and open-access platform, LEAP can provide a unified framework under which different interventions and policies can be consistently compared to identify those with the highest value proposition.

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“…The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item yes/no composite asthma control tool. It was designed to assess symptoms over the past two weeks and exacerbations over the past 12 months [10][11][12]. It also predicts exacerbations in the coming 12 months and the probability of time to first exacerbation [13].…”

Section: Introductionmentioning

confidence: 99%

Validation of the German version of the Asthma Impairment and Risk Questionnaire (AIRQ)

Kanniess,

Defosse,

Lommatzsch

et al. 2024

Pneumologie

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Background The Asthma Impairment and Risk Questionnaire (AIRQ), a 10-item, equally weighted, yes/no tool assessing symptom impairment and risk of exacerbations in patients with asthma aged ≥12 years, was developed and validated in a US patient population to evaluate varying levels of asthma control. This study aimed to validate the German language version of the AIRQ in patients aged ≥12 years with different levels of asthma control. Methods A cross-sectional, observational, multi-centre study comprising a single visit was conducted in multiple specialised asthma centres and general practices in Germany. A total of 300 patients completed the following measures: 1) Patient Sociodemographic and Clinical Questionnaire, 2) AIRQ, 3) Asthma Control Test (ACT), and 4) Asthma Control Questionnaire (ACQ-6). Logistic regression analyses were conducted to assess the AIRQ score cut points with the greatest predictive validity in discriminating between different control levels relative to a standard of ACT plus prior-year exacerbations or ACQ-6 plus prior-year exacerbations. Results The German version of the AIRQ demonstrated a robust capability to correctly identify well-controlled versus not well- or very poorly controlled (AUC values of 0.90 or higher) and well- or not well-controlled versus very poorly controlled asthma (AUC values of 0.89 or higher). Conclusions The German version of the AIRQ is a suitable tool to identify adults with varying levels of asthma control, which in turn can help to accurately identify patients with uncontrolled asthma in clinical practice.

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Long-Term Natural History of Severe Asthma Exacerbations and Their Impact on the Disease Course

Cited by 5 publications

References 44 publications

Asthma Exacerbations: The Genes Behind the Scenes

Asthma Exacerbations: The Genes Behind the Scenes

Development and Validation of an Asthma Policy Model for Canada: Lifetime Exposures and Asthma outcomes Projection (LEAP)

Validation of the German version of the Asthma Impairment and Risk Questionnaire (AIRQ)

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