PULMONARY FIBROSIS IN SEVERE ACUTE RESPIRATORY-FAILURE

Abstract

Diffuse interstitial fibrosis often follows severe acute lung injury of diverse causes. Total lung collagen (g/m2 of body surface area) was determined in 12 patients who died at various times after severe acute respiratory failure (ARF). The total collagen content of each lung was calculated from the mean concentration of collagen (hydroxyproline .times. 7.23) in numerous tissue samples taken from 1-3 lobes and the total wt of the lung. These results were compared to those obtained with 9 normal lungs. In 2 patients who succumbed during the 1st 10 days of ARF, total lung collagen was within the normal range; it was abnormally high in patients who survived for longer periods (12-29 days). Morphologic evidence of fibrosis correlated with chemical results in the patients with ARF. After 3-4 wk of ARF, the lungs of all patients had severe and diffuse interstitial fibrosis as evidenced by histologic assessment; in these lungs, the total collagen content was increased 2- to 3-fold. During ARF, the addition to the lung of large amounts of inflammatory proteins and blood-borne cells increased the dry wt, protein and DNA content of tissue samples and prevented accurate calculation of the collagen concentration. As a result, the values for collagen concentration appear within or below the normal range; the concentration increased significantly when a correction was made by subtracting Hb, a major contaminant of the lungs of patients with ARF. The contradictory findings of morphologic evidence of severe pulmonary fibrosis in lungs that have a chemically normal or low collagen concentration are explained. Determining the mean collagen concentration is further complicated by intralobar and interlobar variation of collagen concentration. Regional heterogeneity in ARF requires the analysis of large samples from as many lobes as possible. Chemical analysis of a lung biopsy specimen for collagen will not provide a reliable chemical estimate of fibrosis.