The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort

Abstract

Background Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised. Objectives To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort. Methods K-Means Cluster analysis was undertaken among 309 currently wheezing subjects at 18-years in the Isle of Wight Birth Cohort ( N=1456). Thirteen disease characterising clustering variables at 18-years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18-years of life. Results Six wheeze clusters were identified. Cluster 1 (12.3%) male-early-childhood-onset-atopicwheeze-with-normal-lung function had male predominance, normal spirometry, low BDR (bronchodilator reversibility), intermediate BHR (bronchial hyper-responsiveness), high atopy prevalence, and more admissions. Cluster 2 (24.2%) early-childhood-onset-wheeze-with-intermediate-lung-function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female-early-childhood-onset-atopic-wheeze-with-impaired-lung-function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent onset non-atopic wheeze, low BDR and BHR, impaired but non-obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female-late-childhood-onset-wheeze-with-normal-lung-function showed no specific atopy association, normal spirometry, low BDR, BHR, and symptom severity. Cluster 6 (9.7%) male-late-childhood-onset-atopic-wheeze-with-impaired-lung-function had high atopy and rhinitis prevalence, elevated BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy. Conclusions & Clinical Relevance Young adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking associated undiagnosed-wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health.

The prevalence of atopic diseases and the patterns of sensitization in adolescence

“…This indicates that having asthma or AD as a single disease may not be driven by IgE. A cluster analysis of wheeze in 18‐year‐olds from the IoW cohort showed that 25% of children with wheezing fell within the adolescent‐onset low‐atopy wheeze cluster that was predominated by females . We included asthma and not only wheezing, but the asthma‐only group shared some of the same characteristics: low frequency of sensitization, predominance of girls, and the majority with a late onset.…”

“…A study from MeDALL (Mechanism of the Development of ALLergy) published in 2014 stated that coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance irrespective of IgE sensitization . Studies have shown that the presence of sensitization has a major influence on the development and course of childhood conditions such as asthma and rhinitis . However, adolescence is a period of dynamic physiological changes that may influence the development of atopic diseases , where the presence of sensitization could be less important .…”

Longitudinal Asthma Patterns in Italian Adult General Population Samples: Host and Environmental Risk Factors

“…This relationship emerged also in UK and US studies where active smoke was a risk factor for undiagnosed wheeze at 18 years old (OR 2.54 and OR 2.60, respectively) [ 39 , 41 ]. In a recent paper about the same UK sample, subjects identified as “undiagnosed-wheezers” phenotype had the highest prevalence of smoking habit (74.6%) with respect to the other “wheezers” phenotypes [ 42 ]. A possible explanation is that respiratory symptoms, such as wheeze or breathlessness, are misinterpreted as due to smoking, rather than referred to asthmatic condition and, thus, not reported to the physician.…”

Recent Insights into the Management of Inflammation in Asthma

“…Yet clinical studies show wide heterogeneity to asthma both across the life course and at different levels of asthma severity. 25,[80][81][82] It is also clear that a proportion of patients with asthma do not attain good asthma control with current treatments. This failure to deliver good asthma control with current approaches was the focus of a Lancet 2017 Commission "After asthma: redefining airways disease".…”