Rationale: Acute airway response, measured as cross-shift change in forced expiratory volume in one second (FEV₁), to cotton dust may lead to subsequent chronic loss of lung function in exposed workers. Objectives: To explore the association between the magnitude and frequency of cross-shift change and chronic loss of FEV₁. Methods: Four-hundred-eight cotton workers and 417 silk workers from Shanghai textile mills were observed prospectively for 20 years, with cross-shift measurements at baseline and followup surveys at approximately 5-year intervals. To account for repeated measures of 5-year change, Generalized Estimating Equations (GEE) were used to estimate the relationship between the magnitude of cross-shift change in FEV₁ (FEV₁) and subsequent 5-year annualized change. Linear regression models were used to examine the association between the number of drops in cross-shift FEV₁ (FEV₁<0) and annualized change over the entire study period. Main Results: Exposure to cotton dust was associated with a 10 ml/yr decrement in 5-year annualized FEV₁ decline. In addition, every 10 ml in FEV₁ drop was associated with an additional 1.5 ml/yr loss in annualized FEV₁ decline. The association between the frequency of drops and annualized decline was stronger for cotton workers than for silk workers over the entire study period. Conclusions: Cotton workers had larger and more frequent drops, as well as excessive chronic declines in FEV₁, than did silk workers. The magnitude and frequency of cross-shift drops were associated with chronic loss in FEV₁ over the entire 20-year period.