Respiratory symptoms in smokers with normal spirometry: clinical significance and management considerations

Current respiratory society guidelines recommend confirming the diagnosis of chronic obstructive pulmonary disease (COPD) with demonstration of airflow obstruction on spirometry. However, multiple recent studies have demonstrated that smokers without overt airflow obstruction on spirometry, termed symptomatic smokers, have evidence of structural lung disease on imaging, have a substantial symptom burden, and also suffer respiratory exacerbations. In this review, we provide an overview of the epidemiology of symptomatic smokers, and address issues of screening and diagnosis, evaluation, and management considerations.

Two large prospective cohorts of adults with and at risk for COPD quantified the respiratory morbidity of symptomatic smokers. These studies demonstrated that approximately half of smokers without spirometrically defined airflow obstruction have increased respiratory symptoms, poor quality of life, low functional capacity, and suffer from respiratory exacerbations. Symptomatic smokers also have evidence of structural lung disease on imaging, and are at risk for faster lung function decline compared with those without respiratory symptoms. Several methods have been proposed to detect smoking-related lung damage among symptomatic smokers with normal forced expired volume in 1 second (FEV1)/forced vital capacity (FVC) ratio. Novel spirometry measures have been reported to diagnose disease before detection using traditional spirometry thresholds. Small airway involvement can be detected earlier using impulse oscillometry and metrics on multiple breath nitrogen washout tests. Imaging biomarkers have been developed that are associated with respiratory morbidity and lung function decline in symptomatic smokers. The translation of novel methods for COPD disease detection into more timely introduction of therapeutics and a consequent reduction in long-term morbidity and mortality has not yet been observed.

A better understanding of the pathobiologic basis of disease in smokers without overt airflow limitation, and earlier recognition of lung disease, while also appropriately evaluating for comorbidities that may account for the symptoms, will enhance the management of symptomatic smokers with preserved lung function.