CORRELATION OF STRUCTURE AND FUNCTION IN IDIOPATHIC PULMONARY FIBROSIS

The early stage of idiopathic pulmonary fibrosis (IPF) is thought to i nvolve a smaller number of alveoli and to be characterized predominant ly by cellularity and minimal fibrosis, whereas advanced disease invol ves a large number of alveoli and is characterized predominantly by fi brosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in par t by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help disting uish between the cellular and fibrotic phases of this disorder, as det ermined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tiss ue, and desquamation. Ninety-six untreated patients with biopsy-confir med IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relation ship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The DL(CO) correlated wi th the ''desquamation'' and the total pathology scores, whereas the TL C and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, DL(CO)/VA and FEV(1)/ FVC ratio were significantly lower than in never smokers and ex-smoker s, and TLC and FVC were higher than in never smokers. Also, the mean c ellularity and granulation/connective tissue factor scores were signif icantly lower, and the desquamation factor score was significantly hig her than those in never smokers and ex-smokers. Both age and smoking s tatus were significant for the cellularity factor score, whereas for t he connective/granulation tissue factor score, age was not significant but smoking status was. For the desquamation factor score, age was si gnificant but smoking status was not. There were significant differenc es between never smokers and ever smokers in the relationship between the pathology factors and measurements of respiratory function, and th is may explain some of the difficulty in assessing structure-function correlation in patients with IPF. In the never smokers, the correlatio ns between structure and function were likely the direct result of IPF per se. In the current smokers, bronchiolar and/or emphysematous chan ges associated with cigarette smoking may have complicated the patholo gic alterations caused by IPF, as well as influencing the functional d erangements.