Asthma is a chronic, non-communicable disease with a major morbidity impact to those affected (1) as well as a high economic burden, with billions going into healthcare costs and missed workdays yearly. (2) Due to the heterogenous nature of asthma, where both genetic and environmental conditions play a role in the disease and patient response to treatment, patient-level treatment decisions are key (3). Across the years, efforts have been made to phenotype asthma and personalize treatment (4).
The TAHS (Tasmanian Longitudinal Heath Study) is comprised of a population of children born in 1961 and attending school in Tasmania, Australia in 1968 (5) which followed the trajectories of “asthma and allergic diseases” over a long follow-up period. This study aimed to characterize phenotypes of asthma between the first and sixth decades of life in a cohort study using this patient population database. Respiratory questionnaires were used for data collection, first obtained at age 7 as a baseline. Follow-up questionnaires were then subsequently obtained at ages 13, 18, 30, 43, 50, and 53 years. The study sample was composed of patients who had “ever asthma” status. Group- Based Trajectory Modeling was used to identify five longitudinal phenotypes within the “ever-asthma” sample (compromised of 1,506 patients); early-onset adolescent-remitting (40%), early-onset adult remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). Childhood exposures were assessed through parents’ responses to the baseline questionnaire. When compared to the never-asthma population, all 5 phenotypes were independently associated with maternal asthma and childhood bronchitis. Apart from late onset remitting asthma, they were also associated with childhood eczema, allergic rhinitis, and food allergies. Additionally, while all phenotypes showed pre-and post- bronchodilator spirometry changes consistent with obstructive pathology, the extent of the deficits were higher in the early-onset persistent asthma (OR, 8.73; 95% CI, 4.10 to 18.55) and late-onset persistent asthma (OR, 6.69; 95% CI, 3.81 to 11.73) groups. Increased risk of spirometrically defined COPD at age 53 was also noted in all phenotype groups except late onset remitting asthma. Late-onset persistent asthma was also associated with numerous comorbidities at age 53 which included diabetes (OR, 1.81; 95% CI, 1.16-2.82), high cholesterol (OR, 1.42; 95% CI, 1.07-1.89), GERD (OR, 1.89; 95% CI, 1.31-2.71), anxiety (OR, 1.62; 95% CI, 1.20-2.18), and depression (OR, 1.69; 95% CI, 1.28-2.23).
Previous studies have limited asthma phenotyping to the mid-20s, but this is the first study to include longitudinal asthma phenotypes to the mid-50s. Using respiratory histories collected at seven different time points, five phenotypes were characterized by the age of asthma onset and remission. This study also included two novel phenotypes of early-onset adult-remitting and late-onset remitting asthma.
Although there were similarities between the five phenotypes of asthma, this study noted differences when it came to familial factors, childhood allergies, and childhood lung conditions in the trajectory of early-onset and persistent phenotypes. It also showed, like prior studies, that remitted asthma is often an overlooked cause of lung pathologies in adulthood (6-8). All three remitting phenotypes were shown to be associated with an increased risk of established COPD. Early onset remitting phenotypes showed an increased risk of established COPD. These results warrant looking into when these patients should follow up with their provider as they represented greater than 30% of the general population at age 53 years in TAHS. This study reinforced the importance of smoking cessation and good asthma control with early onset and late onset phenotypes showing worse lung function with adult personal smoking.
Advantages of the study are its’ novelty in including patients beyond the mid 20s. Phenotype-specific prevalence of current asthma at each time point was examined looking at a range of childhood, lifetime and adult characteristics because of the population-based nature of TAHS. This study did have multiple limitations. One, there were small sample sizes for some phenotypes and contribute to a lack of power in this study. Between-phenotypes were not analyzed. Secondly, there was no statistical adjustment for multiple testing in the analyses which affects the studies generalizability and stability. Third, asthma status was self-reported although these definitions have been validated for specificity and sensitivity in prior studies (9). Fourth, causality was not able to be determined between asthma phenotypes and clinical outcomes as phenotypes were characterized at different time points. Lastly, individuals who followed up in between could have been misclassified into a specific phenotype as specific time points were used. The interval follow up times were also longer than in previous studies.
Using group-based trajectory modeling, this is the first study to characterize asthma into longitudinal phenotypes from the first to sixth decade of life in a population- based cohort. Two new remitting phenotypes were included, and the ultimate goal of phenotyping was to better analyze the effects of different phenotypes on development of chronic obstructive pulmonary disease. These phenotypes were stratified based on age of asthma onset and asthma remission. Clinically remitted asthma has been shown to be a risk factor in the development of COPD later in life, but all asthma should be appropriately treated. More research is needed to see if there are genetic differences between each phenotype and if preventative efforts and smoking cessation can impact clinical outcomes and the course of asthma.
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