Maximal mid-expiratory flow detects early lung disease in α1-antitrypsin deficiency

Pathological studies suggest that loss of small airways precedes airflow obstruction and emphysema in chronic obstructive pulmonary disease (COPD). Not all alpha 1-antitrypsin deficiency (AATD) patients develop COPD, and measures of small airways function might be able to detect those at risk. Maximal mid-expiratory flow (MMEF), forced expiratory volume in 1 s (FEV1), ratio of FEV1/forced vital capacity (FVC), health status, presence of emphysema (computed tomography (CT) densitometry) and subsequent decline in FEV1 were assessed in 196 AATD patients. FEV1/FVC, FEV1 % predicted and lung densitometry related to MMEF % pred (r(2)= 0.778, p< 0.0001; r(2)= 0.787, p< 0.0001; r(2)= 0.594, p< 0.0001, respectively) in a curvilinear fashion. Patients could be divided into those with normal FEV1/ FVC and MMEF (group 1), normal FEV1/ FVC and reduced MMEF (group 2) and those with spirometrically defined COPD (group 3). Patients in group 2 had worse health status than group 1 (median total St George's Respiratory Questionnaire (SGRQ) 23.15 (interquartile range (IQR) 7.09- 39.63) versus 9.67 (IQR 1.83- 22.35); p= 0.006) and had a greater subsequent decline in FEV1 (median change in FEV1 - 1.09% pred per year (IQR - 1.91- 0.04% pred per year) versus - 0.04% pred per year (IQR - 0.67- 0.03% pred per year); p= 0.007). A reduction in MMEF is an early feature of lung disease in AATD and is associated with impaired health status and a faster decline in FEV1.