Articles
Trajectories of asthma and allergies from 7 years to 53 years and associations with lung function and extrapulmonary comorbidity profiles: a prospective cohort study

https://doi.org/10.1016/S2213-2600(20)30413-6Get rights and content

Summary

Background

Longitudinal trajectories of asthma and allergies from childhood to adulthood might be differentially associated with lung function and chronic obstructive pulmonary disease (COPD), but associations with extrapulmonary comorbidities have not been well investigated. We aimed to assess these trajectories and examine their associations with lung function outcomes and profiles of comorbidities.

Methods

In this prospective cohort study, data for asthma and related allergic conditions (ie, eczema, hay fever, and food allergy) were prospectively collected from the Tasmanian Longitudinal Health Study for participants aged 7–53 years originally recruited in Tasmania, Australia. All surviving individuals in the database with contact details were invited in the most recent follow-up (mean age 53 years). There were no exclusion criteria. With use of latent class analysis, we identified longitudinal trajectories of asthma and allergic conditions from 7–53 years, and profiles of self-reported extrapulmonary conditions recorded at 53 years. The associations between asthma and allergy trajectories and morbidity profiles and lung function at 53 years were investigated with regression models.

Findings

Between Sept 3, 2012, and Nov 8, 2016, of 6128 individuals invited, 3609 (58·9%) individuals were enrolled. We identified five asthma and allergy trajectories: minimal and least asthma and allergies (n= 1767 [49·0%]); late-onset hay fever, no asthma (n=1065 [29·5%]); early-onset remitted asthma and allergies (n=236 [6·5%]); late-onset asthma and allergies (n=317 [8·8%]); and early-onset persistent asthma and allergies (n=224 [6·2%]); and four profiles of extrapulmonary morbidities: minimal or least disease (n=2206 [61·1%]); dominant mental health disorders (n=861 [23·9%]); dominant cardiovascular diseases or risks (n=424 [11·7%]); and multiple disorders (n=117 [3·2%]). The late-onset asthma and allergies trajectory was predominantly associated with the multiple disorders profile (relative risk ratio 3·3 [95% CI 1·9–5·9]), whereas the other asthma and allergy trajectories were associated only with the dominant mental health disorders profile. Both spirometrically defined and clinical COPD were most strongly associated with the early-onset persistent asthma and allergies trajectory (odds ratio [OR] 5·3 [95% CI 3·2–8·6]) and also with the late-onset asthma and allergies trajectory (OR 3·8 [2·4–6·1]).

Interpretation

Distinct longitudinal trajectories of asthma and allergic disease from childhood to 53 years are associated with different profiles of extrapulmonary comorbidities and varying risk of COPD. These findings can inform a personalised approach in clinical guidelines and management focusing on treatable traits. Comorbidity profiles are a new target for early identification and intervention.

Funding

National Health and Medical Research Council of Australia, EU's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

Introduction

Asthma and related allergic diseases are important personal and public health challenges, given their high prevalence and burden, with asthma affecting more than 339 million people worldwide as of 2018.1 Asthma is heterogeneous in its natural history with variable age of onset, severity, persistence, and relationships to other allergic diseases. Asthma often coexists with other allergic diseases (ie, hay fever, eczema, and food allergies), in both children and adults, with hay fever being especially prevalent with cases exceeding 50% in individuals with asthma.2, 3 Such heterogeneity might create diverse longitudinal trajectories of asthma and allergies over the life course.

The burden of lifetime asthma stems from both long-term lung function deficits and comorbidities. Asthma is associated with numerous comorbidities, some of the most prevalent being gastro-oesophageal reflux disease (GERD), cardiovascular, metabolic, musculoskeletal, and psychological conditions.1 Extrapulmonary comorbidities compound the already substantial burden of asthma on the health-care system, patients, and carers.1 Extrapulmonary comorbidities are also gaining increasing interest in the context of so-called treatable traits, a new paradigm for management of chronic airway diseases.4 It is quite possible that profiles of comorbidities could vary depending on longitudinal trajectories of asthma and allergies, but we currently have a poor understanding of such potential relationships.

Research in context

Evidence before this study

Asthma is heterogeneous in its natural history with a variable age of onset, severity, persistence, and relationship to other allergic diseases (eg, eczema, hay fever, and food allergy) and chronic obstructive pulmonary disease (COPD). Asthma is also frequently a component in individuals with multimorbidities, particularly in older individuals aged 60 years and older. Understanding of longitudinal trajectories of asthma in combination with other allergies, and the link between these trajectories and comorbidities, is essential for tailored treatment and management of asthma itself, as well as for reducing the burden of multimorbidity. We searched for articles in PubMed from database inception until Feb 10, 2020, using the search terms “asthma”, “allerg*”, “comorbidit*”, “multimorbidit*”, “pattern*”, and “trajector*”. We included studies that identified longitudinal trajectories of asthma and allergic diseases based on repeated measurements and investigated comorbidities among these trajectories. There were no language restrictions. We found no studies that have investigated profiles of comorbidities and their associations with longitudinal trajectories of asthma and allergic disease.

Added value of this study

To our knowledge, with use of data-driven techniques, we are the first to characterise four profiles of extrapulmonary comorbidities. The comorbidities were differentially associated with longitudinal trajectories of asthma and allergies based on repeated measurements from the first to the sixth decade of life for an unselected community population sample. The late-onset asthma and allergies trajectory was associated with multiple comorbidities and dominant cardiovascular comorbidity profiles, highlighting new inflammatory paradigms responsible for asthma and multimorbidities. The other asthma and allergy trajectories were solely associated with the dominant mental health comorbidity profile. The identified trajectories also had specific associations with lung function deficits and risk of COPD. Although the early-onset persistent asthma and allergies trajectory was associated with the highest risk of COPD, the late-onset asthma and allergies trajectory also had an increased risk but to a lesser extent.

Implications of all the available evidence

Our findings are important from a clinical perspective. They can inform a personalised approach in clinical guidelines and management focusing on treatable traits. Longitudinal phenotypes, comorbid allergic diseases, and other extrapulmonary comorbidities should be considered together in the management of individuals with asthma. The findings also highlight avenues with the potential to reduce the burden of COPD and multimorbidity in the general population.

Trajectories of asthma and lung function outcomes have been previously reported, but have mainly focused on trajectories from childhood to the mid-20s. Some of these early life studies have used a manual classification to identify asthma trajectories,5, 6 while others7, 8 have used data-driven approaches that recognise dynamic changes in disease status and have helped identify new longitudinal patterns of wheeze and asthma. To our knowledge, only two respiratory studies spanning from childhood to the sixth decade of life have investigated changes in asthma or wheeze status. The WHEASE study9, 10 followed up a small number of participants (n=330) at four timepoints until the age of 61 years, after initially recruiting three groups of children (ie, children with asthma, wheezy bronchitis, and controls) aged 10–15 years. The MESCA followed five small groups of children (n=484; children with mild wheezy bronchitis, wheezy bronchitis, asthma, severe asthma, and controls) up to the age of 50 years.11, 12, 13 Both MESCA and WHEASE were seminal longitudinal studies on asthma and they have provided insights into the long-term outcomes of childhood asthma and wheeze, especially when severe. However, these studies focused on the change of asthma or wheeze status (persistence and remission) from baseline to each follow-up for predefined recruitment groups (appendix p 1). They did not use latent modelling techniques, which include variable sequential phenotype changes over time to develop longitudinal asthma or wheeze trajectories for the whole population. Moreover, while asthma and allergies are closely linked and known to occur frequently together or manifest sequentially, longitudinal trajectories of asthma and concurrent allergic diseases over the life course are not well defined.

Understanding longitudinal trajectories of asthma and allergic diseases from childhood to adulthood will help in several ways. Different trajectories might have different underlying causes, pathophysiological processes and prognoses, and might need specific preventive treatment, or management strategies. While childhood asthma, especially severe asthma, has been associated with reduced adult lung function,9, 11 investigation of longitudinal trajectories of asthma and allergic diseases could provide more insight into the phenotypic influence of lifetime asthma and allergy on the causes of lung function deficits and chronic obstructive pulmonary disease (COPD). Exploring the potential association of longitudinal trajectories of asthma and allergic diseases with specific profiles of extrapulmonary comorbidities in later life can help untangle the burden of multimorbidity that starts to increase in the sixth decade of life.

These investigations could help identify at-risk groups, and guide optimal primary care, clinical surveillance, and clinical interventions. Addressing these knowledge gaps requires large cohorts with comprehensive data over the life course. The Tasmanian Longitudinal Health Study (TAHS) provides a unique opportunity given that it has extensive data for respiratory health and related factors at different life stages. In this study, we aimed to identify and characterise longitudinal trajectories of asthma and related allergic diseases from childhood to middle-age (7–53 years); examine their associations with lung function outcomes, especially COPD, and with profiles of common extrapulmonary comorbidities at 53 years.

Section snippets

Study design and participants

In this prospective cohort study, we used data from the TAHS, collected at ages 7, 13, 45, and 53 years (appendix p 10). Study methods have been reported in detail elsewhere.14 In brief, TAHS began in 1968 when 8583 Tasmanian children born in 1961 (probands) and attending school in Tasmania were enrolled in a respiratory health study. Parents completed a questionnaire for the child who then underwent a clinical examination and pre-bronchodilator spirometry. The next follow-up was in 1974 when

Results

Between Sept 3, 2012, and Nov 8, 2016, of 6128 individuals invited, we analysed data from 3609 participants who attended the last follow-up at 53 years and previously also had three follow-ups done at ages 7, 13, and 45 years. Just more than half (1845 [51·1%]) of the participants were women (appendix p 6). By age 7 years, 627 (17·4%) participants had self-reported asthma, 509 (14·2%) had eczema, 490 (13·8%) had hay fever, and 270 (7·5%) had food allergy. At 53 years, more than half (2029

Discussion

To our knowledge, this study is the first to investigate associations of profiles of extrapulmonary comorbidities with different longitudinal trajectories of asthma and allergic diseases from childhood to middle-age. With use of a data-driven method, we identified five trajectories. We found associations between individual trajectories and specific profiles of extrapulmonary comorbidities. The late-onset asthma and allergies trajectory was associated with multiple comorbidities independent of

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