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.