Risk Factors for Airway Remodeling in Asthma Manifested by a Low Postbronchodilator FEV1/Vital Capacity Ratio

Abstract

Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to vital capacity (VC) at age 18 or 26 was used as a marker of airway remodeling. "Normal" study members with no history of asthma ever, no wheezing in the last year, and no smoking ever were used to determine sex- and age-specific reference values for this ratio. The lower limit of normal was defined as the mean ratio minus 1.96 standard deviation, delimiting the 2.5% of the normal population with the lowest FEV1/VC ratio. A low postbronchodilator FEV1/VC ratio was found in 7.4% and 6.4% of study members at ages 18 and age 26 and 4.6% at both assessments. Lung function was low throughout childhood in those with a consistently low postbronchodilator FEV1/VC ratio at both ages. Those with consistently low postbronchodilator ratios also showed a greater decline in the prebronchodilator FEV1/VC ratio from ages 9 to 26 compared with those with normal postbronchodilator ratios at both ages (males, -12% versus -6%, p < 0.0001; females, -10.5% versus -5.5%, p < 0.01). Asthma, male sex, airway hyperresponsiveness, and low lung function in childhood were each independently associated with a low postbronchodilator FEV1/VC ratio, which in turn was associated with an accelerated decline in lung function and decreased reversibility. These data suggest that airway remodeling in asthma, as manifested by impaired lung function, begins in childhood and continues into adult life.