What is the histology of idiopathic pulmonary fibrosis? (hint, not usual interstitial pneumonia)

As I have indicated in a previous blog post, IPF has been historically considered as a chronic relentlessly progressive fibrotic lung disease.  Diagnostically, it has been characterized by a particular gross and microscopic appearance the latter of which is summarized as “usual interstitial pneumonia” (UIP).  At one point, the association between these two was sufficient that the ATS recognized UIP as the essential underlying substrate of the IPF. How did this association come about?

Universally, the phrase UIP is credited to the Yale pathologists Averill Leibow and Charles Carrington from a review article published in 1969. (Ironically, Leibow had already left Yale for UCSD when that article was published. He left after being passed over for Chairman at Yale. The history of Yale pathology is another story entirely and possibly a topic for another blog post.)

Like many classic papers, this is much more commonly cites than read. I have also been guilty of this same oversight. What did Leibow and Carrington actually describe?

They start by indicating that there were five types of interstitial lung diseases (1) . Their first is described as follows: 

“The classical undifferentiated or usual interstitial pneumonia (UIP). As described for example by Hamman and Rich, this is a highly variegated lesion with evidence of hyaline membrane formation and varying degrees of exudation. The exudate often includes protein and a great variety of cells and there is interstitial organization...The essential process appears to be diffuse alveolar damage of a type that leaves the basement membrane of the alveolus for the most part intact.  As a result, there is not only exudation, but often hyaline membrane formation.” 

A diagram from that paper makes this completely explicit.  Note the title. 



This description is then followed by mention of various experimental models of acute lung injury including hyperoxic and/or barotrauma injury. 

How is UIP described today?  The diagnostic criteria is that there is 1) established fibrosis that disrupts the lung architecture which includes areas of established fibrosis and areas of uninvolved lung 2) Fibrosis is subpleural / paraseptal 3) presence of fibroblast foci 4) there are no features of some other process (malignancy, aspirated or other foreign material).  Note that none of those were mentioned in the original description of UIP. Hence UIP as originally described is not the histology of IPF. So where did the current description arise?  That will have to wait for another blog post.


(1) Liebow, A. and Carrington, C.B. (1969) The Interstitial Pneumonias. In: Simon, M., Potchen, E.J. and LeMay, M., Eds., Frontiers of Pulmonary Radiology, Grune & Stratton, New York, 102-141.



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