Breathlessness Predicts Mortality in Adults: A Systematic Review and Meta-Analysis

Breathlessness is a commonly encountered symptom, and although its relationship with mortality is well established for many conditions, less clear is this relationship in healthy adults. This systematic review and meta-analysis examines whether breathlessness is associated with mortality in a general population. This is important in understanding the impact of this common symptom on a patient's prognosis. This review was registered with PROSPERO (CRD42023394104). Medline, EMBASE, CINAHL and EMCARE were searched for the terms 'breathlessness' and 'survival' or 'mortality' on January 24, 2023. Longitudinal studies of >1,000 healthy adults comparing mortality between breathless and non-breathless controls were eligible for inclusion. If an estimate of effect size was provided, studies were included in the meta-analysis. Eligible studies underwent critical appraisal, data extraction and risk of bias assessment. A pooled effect size was estimated for the relationship between the presence of breathlessness and mortality and levels of severity of breathlessness and mortality. Of 1,993 studies identified, 21 were eligible for inclusion in the systematic review and 19 for the meta-analysis. Studies were of good quality with a low risk of bias, and the majority controlled for important confounders. Most studies identified a significant relationship between the presence of breathlessness and increased mortality. A pooled effect size was estimated, with the presence of breathlessness increasing the risk of mortality by 43% (risk ratio (RR): 1.43, 95% confidence interval (CI): 1.28-1.61). As breathlessness severity increased from mild to severe, mortality increased by 30% (RR: 1.30, 95% CI: 1.21-1.38) and 103%, respectively (RR: 2.03, 95% CI: 1.75-2.35). The same trend was seen when breathlessness was measured using the modified Medical Research Council (mMRC) Dyspnoea Scale: mMRC grade 1 conferred a 26% increased mortality risk (RR: 1.26, 95% CI: 1.16-1.37) compared with 155% for grade 4 (RR: 2.55, 95% CI: 1.86-3.50). We conclude that mortality is associated with the presence of breathlessness and its severity. The mechanism underlying this is unclear and may reflect the ubiquity of breathlessness as a symptom of many diseases.