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Am. J. Respir. Crit. Care Med., Volume 157, Number 4, April 1998, 1063-1072

Idiopathic Pulmonary Fibrosis
Predicting Response to Therapy and Survival

STEVEN E. GAY, ELLA A. KAZEROONI, GALEN B. TOEWS, JOSEPH P. LYNCH III, BARRY H. GROSS, PHILLIP N. CASCADE, DAVID L. SPIZARNY, ANDREW FLINT, M. ANTHONY SCHORK, RICHARD I. WHYTE, JOHN POPOVICH, ROBERT HYZY, and FERNANDO J. MARTINEZ

Divisions of Pulmonary and Critical Care Medicine, Department of Radiology, Department of Pathology, and Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor; Division of Pulmonary and Critical Care Medicine and Department of Radiology, Henry Ford Hospital, Detroit; and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan

Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity 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 function and improved longer term survival. In all patients, a pretreatment clinical (dyspnea), radiographic (chest radiograph), and physiologic (pulmonary function including exercise saturation) score was generated (CRP). A high-resolution CT scan (HRCT) was independently scored by four radiologists for ground glass (CT-alv) and linear opacity (CT-fib) on a scale of 0-4. Open lung biopsy samples were scored for cellular infiltration, interstitial fibrosis, desquamation, and granulation by an experienced pulmonary pathologist. All patients were treated with 3 mo of high-dose steroids and the CRP scoring repeated. Patients were divided into three groups: responders with a greater than 10-point drop 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) than 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 biopsies 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 scores were lower in responders than nonresponders. Receiver operating curve (ROC) analysis was employed to identify pretreatment features of longer term survival (follow-up of 29.1 ± 2.3 mo). Only CT-fib (p = 0.009) and pathology fibrosis score (p = 0.03) were able to predict mortality. A pretreatment CT-fib score >=  2.0 demonstrated 80% sensitivity and 85% specificity in predicting survival. Those patients who did not respond to initial steroid therapy demonstrated a worse long-term survival and greater likelihood of decreased pulmonary function. We demonstrate that pretherapy pulmonary function, pathologic and radiographic parameters are different in individuals who respond to initial prednisone therapy. Only HRCT imaging and pathologic fibrosis were able to reliably predict long-term survival in patients with biopsy-proven IPF.




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