Pathobiology of frailty in lung disease

Frailty is a clinical state of vulnerability to stressors resulting from cumulative alterations in multiple physiological and molecular systems. Frailty assessment in patients with chronic disease is useful for identifying those who are at increased risk for poor clinical and patient reported outcomes. Due to biobehavioral changes purported to cause both frailty and certain chronic lung diseases, patients with lung disease appear susceptible to frailty and prone to developing it decades earlier than community dwelling healthy populations. Herein, we review the literature and potential pathobiological mechanisms underpinning associations between frailty in lung disease and age, sex, comorbidity and symptom burden, severity of lung disease, inflammatory biomarkers, various clinical parameters, body composition measures, and physical activity levels. We also propose a multipronged program of future research focused on improving the accuracy and precision of frailty measurement in lung disease, identifying blood-based biomarkers and measures of body composition for frailty, determining whether subphenotypes of frailty with distinct pathobiology exist, and developing personalized interventions that target the specific underlying mechanisms causing frailty.