Lung Function Decline in Asthma: Mechanisms, Risk Factors, and Clinical Implications for Personalized Management

Lung function evaluation is a cornerstone in the clinical assessment of patients with asthma. Monitoring lung function decline provides valuable insights into disease progression, the impact of risk factors, and the efficacy of treatments. Accelerated lung function decline often results from the interplay between modifiable risk factors and innate predispositions. Modifiable exposures such as early life respiratory infections, air pollutants, or tobacco smoke can negatively affect lung development and increase the risk of future decline. On the other hand, nonmodifiable factors, including genetic polymorphisms, epigenetic alterations, and congenital conditions such as pulmonary dysplasia or prematurity may determine lower baseline lung function and greater susceptibility to decline. Moreover, in adulthood, persistent airway inflammation, recurrent asthma exacerbations, and progressive airway remodeling further contribute to functional deterioration, particularly in patients with severe asthma. These interacting factors give rise to heterogeneous clinical trajectories of lung function over time, underscoring the need for individualized assessment and management. Clinically, lung function deterioration should be suspected in patients with frequent asthma exacerbations, persistent symptoms, and unsuppressed inflammatory biomarkers despite optimized therapy, or progressive loss of bronchodilator response. The presence of risk factors associated with poor lung function development from childhood may also help identify those at higher risk. In some cases, symptoms alone may not correlate with objective lung function impairment, highlighting the need for serial spirometric assessments during follow-up visits. The challenges for clinicians lie in identifying early functional deterioration, recognizing treatable traits, and implementing tailored therapies within a personalized management approach. In this review we explore the pathophysiologic mechanisms underlying accelerated lung function decline and discuss diagnostic strategies and therapeutic implications aimed at optimizing care for patients with asthma.