IDIOPATHIC PULMONARY FIBROSIS - PREDICTING RESPONSE TO THERAPY AND SURVIVAL

Idiopathic pulmonary fibrosis (IPF) is associated with significant mor bidity and mortality despite aggressive therapy. Thirty-eight patients with biopsy-proven IPF were studied to identify pretreatment features that could be used to predict short-term improvement in pulmonary fun ction and improved longer term survival. In all patients, a pretreatme nt clinical (dyspnea), radiographic (chest radiograph), and physiologi c (pulmonary function including exercise saturation) score was generat ed (CRP). A high-resolution CT scan (HRCT) was independently scored by four radiologists for ground glass (CT-alv) and linear opacity (CT-fi b) on a scale of 0-4. Open lung biopsy samples were scored for cellula r infiltration, interstitial fibrosis, desquamation, and granulation b y an experienced pulmonary pathologist. All patients were treated with 3 mo of high-dose steroids and the CRP scoring repeated. Patients wer e divided into three groups: responders with a greater than 10-point d rop in CRP (n = 10); stable with +/- 10 point change in CRP (n = 14); and nonresponders with > 10 point rise in CRP or death (n = 14). Those responding to steroids were treated for 18 mo in a tapering fashion. In all others, steroids were tapered quickly and oral cyclophosphamide prescribed. Responders (10 of 38) had a lower age (45.1 +/- 4.3 yr) t han nonresponders (61.4 +/- 3.5 yr) or those remaining stable (53.1 +/ - 3.3 yr) (p = 0.01). Pretreatment CRP was higher in responders (58.8 +/- 5.6) than nonresponders (40.5 +/- 4.7) or stable individuals (37.6 +/- 4.7) (p = 0.01). Cellular infiltration score of the open lung bio psies was higher in responders (7.6 +/- 0.6) than stable individuals ( 5.7 +/- 0.5) (p = 0.04). The CT-alv scores were higher and CT-fib scor es were lower in responders than nonresponders. Receiver operating cur ve (ROC) analysis was employed to identify pretreatment features of lo nger term survival (followup of 29.1 +/- 2.3 mo). Only CT-fib (p = 0.0 09) and pathology fibrosis score (p = 0.03) were able to predict morta lity. A pretreatment CT-fib score greater than or equal to 2.0 demonst rated 80% sensitivity and 85% specificity in predicting survival. Thos e patients who did not respond to initial steroid therapy demonstrated a worse long-term survival and greater likelihood of decreased pulmon ary function. We demonstrate that pretherapy pulmonary function, patho logic and radiographic parameters are different in individuals who res pond to initial prednisone therapy. Only HRCT imaging and pathologic f ibrosis were able to reliably predict long-term survival in patients w ith biopsy-proven IPF.