Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1805-1809

Longitudinal Changes in Physiological, Radiological, and Health Status Measurements in ₁-Antitrypsin Deficiency and Factors Associated with Decline

LEE J. DOWSON, PETER J. GUEST, and ROBERT A. STOCKLEY

Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom

The FEV₁ declines rapidly in ₁-antitrypsin deficiency (₁-ATD) but less is known about other measures of disease severity and the factors, other than smoking, that are associated with progression of emphysema. The natural history of ₁-ATD was studied prospectively in 43 patients with the PiZ phenotype and emphysema at a single center over 2 yr. The mean ± SE change in FEV₁ was 67 ± 14 ml/yr, accompanied by a reduction in transfer factor (mean change in diffusing capacity of the lung for CO [DL_CO] -1.07 ± 0.21 ml/min/mm Hg/yr; p < 0.001) and lung density in the upper zones as assessed by quantitative high-resolution computed tomography (HRCT) (mean change in voxel index 2.8 ± 0.6%/yr; p < 0.001). The decline in FEV₁ related to baseline FEV₁ (r = 0.56, p < 0.001), bronchodilator reversibility (r = 0.52, p < 0.001), and (for patients with FEV₁ > 35% predicted) exacerbation frequency (r = 0.38, p = 0.02). There was also a decline in the St. George's Respiratory Questionnaire (SGRQ) Activity score (mean change 4.3 ± 1.2 units/yr, p < 0.001) that correlated with FEV₁ decline (r = 0.45, p = 0.002). Progression of emphysema in ₁-ATD is dependent on baseline physiology and exacerbation frequency and may be detected by several different measurements of which HRCT density mask analysis and DL_CO appear most sensitive.

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