Ventilatory Long-Term Facilitation in Humans
Authors: Nicole J. Tester, David D. Fuller, Jason H. Mateika
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

pneumonias (1) takes us a long way from Liebow's (2) original five histological patterns, in both content and purpose.Liebow advocated splitting idiopathic pulmonary fibrosis (IPF) according to its histological pattern, in the hope that this would permit its cause(s) to be identified.This hope was partly realized when hard metal was recognized to be the cause of giant cell interstitial pneumonia, which was accordingly eliminated.However, with the exception of smoking as the cause of desquamative interstitial pneumonia, no further causes have been identified.Instead, new patterns have been described, and the purpose of the classification has switched from identifying causes to differential diagnosis and prognosis.This has undoubtedly facilitated management, but the joint committee might have taken a different approach, one that considers the target tissue and thereby provides insight into pathogenesis.In two of the American Thoracic Society/ European Respiratory Society major diagnoses, and probably three, the type 1 pneumocyte is targeted.The evidence that acute interstitial pneumonia (AIP) and usual interstitial pneumonia (UIP) represent attacks on the type 1 pneumocyte is ultrastructural.The epithelial basement membrane is denuded on a wide front in AIP and focally so in UIP (3).No such gaps in the alveolar epithelium are described in nonspecific interstitial pneumonia (NSIP), but a frequent finding is hyperplasia of the alveolar stem cell, the type 2 pneumocyte, without its differentiation into type 1 cells.This suggests that there is ongoing injury to the type 1 cells.Recognition that AIP, UIP, and NSIP have the same target cell suggests that they constitute one disease, IPF, representing the acute, progressive, and chronic forms of this disease, respectively.Further evidence includes the following: different lobes of the lungs may show different patterns (UIP and NSIP) at the same time (4); one lobe may show different patterns (UIP and NSIP again) at different times (5); and one pattern may be superimposed on another, as in acute exacerbations of IPF, when the features of AIP are superimposed on those of UIP (6).This leaves three other major patterns-cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and respiratory bronchiolitis interstitial lung disease-which, I submit, are not idiopathic interstitial pneumonias.They all predominantly affect the air space rather than the interstitium, whereas two are not idiopathic but related to smoking.These three conditions are important in differential diagnosis and prognosis but cannot be regarded as idiopathic interstitial pneumonias.I further submit that until we know the cause of IPF, it is premature to abandon Scadding's simple division of cryptogenic fibrosing alveolitis into lone (IPF) and systemic, relating the former to the collagen vascular diseases (but not categorizing it as such) (7).Also, the term fibrosing alveolitis neatly combines the inflammation intimated by the pathologists' UIP with the fibrosis of IPF and so avoids the confusing dual nomenclature favored by the joint committee.