Relationship between past airway pathology and current lung function in preschool wheezers

The functional outcome in preschool severe wheezers with eosinophilic airway inflammation and increased reticular basement membrane (RBM) thickness is unknown. We investigated the relationship between airway pathology at age 2 yrs and lung function at age 4-6 yrs in previous severe wheezers. Severe wheezers previously investigated by endobronchial biopsy and healthy children aged 4-6 yrs were recruited. Lung clearance index (LCI), conducting zone ventilation inhomogeneity (S(cond)), acinar ventilation inhomogeneity by multiple-breath washout, plethysmographic-specific airway resistance and exhaled nitric oxide fraction (F(eNO)) were measured. Lung function was compared between wheezers and healthy controls, and in wheezers correlated with past RBM thickness and mucosal eosinophilia (EG2+ cells). 72 healthy controls and 28 previous severe wheezers were tested. Wheezers had significantly higher median LCI (6.8 versus 6.6; p=0.001) and S(cond) (0.046 versus 0.016; p<0.0005) than healthy controls. Past RBM thickness (r=0.474, p=0.047) and EG2+ cells (r=0.552, p=0.041) showed significant correlations with current F(eNO), but no correlations were seen between past RBM thickness and current lung function. RBM thickness and EG2+ cells at age 2 yrs show a significant positive association with F(eNO) at age 5 yrs. Although lung function was abnormal at age 5 yrs in severe wheezers, this did not correlate with past RBM thickness.