ABSTRACT
Nonspecific interstitial pneumonia (NSIP) represents a subset of idiopathic interstitial pneumonias (IIPs) which has only recently been categorized (1). Since the initial description of NSIP in 1994 (1), several investigators have confirmed that NSIP has an improved prognosis and responsiveness to therapy compared to usual interstitial pneumonia (UIP) (2-9). In addition, virtually all series of idiopathic pulmonary fibrosis (IPF) or cryptogenic fibrosing alveolitis (CFA) included a mix of histological entities, including NSIP (2,10). Classification schema utilizing pathological criteria were developed more than 25 years ago (11) and continue to be refined (12). The first pathological schema, developed by the eminent pathologist Liebow, recognized five distinct histological categories among IIPs including UIP, bronchiolitis obliterans with interstitial pneumonia (BIP), desquamative insterstitial pneumonia (DIP), giant cell interstitial pneumonia (GIP), and lymphocytic interstitial pneumonia (LIP) (11). Subsequent investigators affirmed that GIP was the pathological hallmark of hard metal pneumoconiosis (13) and should not be included as an IIP. Further, BIP, now considered to be synonymous with bronchiolitis obliterans organizing pneumonia (BOOP) (14) or cryptogenic organizing pneumonia (COP) (15,16), is an intraluminal disease rather than an interstitial disorder and has been dropped from the IIP classification schema (2). LIP, a
lymphoproliferative disorder often associated with immunodeficiencies (particularly human immunodeficiency virus [HIV] infections) (5,17,18), was dropped from the IIP classification schema of Katzenstein and Myers (2) but was retained in the most recent consensus statement of IIPs endorsed by the American Thoracic Society (ATS) and European Respiratory Society (ERS) (12). Acute interstitial pneumonia (AIP), a rapidly progressive form of IIP which exhibits histopathological features of diffuse alveolar damage (DAD), is indistinguishable from the acute respiratory distress syndrome (ARDS) (19-22). Although a subset of patients with IPF/UIP develop an accelerated course, often as a terminal event, with features of DAD on lung biopsy or necropsy (23,24), clinical and radiographic features of AIP differ sharply from other IIPs (2). Another variant of IIP, termed respiratory bronchiolitis interstitial lung disease (RB-ILD), was described in the 1980s (25,26), principally in smokers, characterized by pigmented alveolar macrophages within respiratory bronchioles, and with histological features which overlap with desquamative interstitial pneumonia (DIP) (27,28). In 1998, Katzenstein and Myers published a classic article recognizing four distinct forms of IIPs (i.e., UIP, NSIP, DIP/RB-ILD, and AIP) (2). In that article, they emphasized ‘‘. . . the term ‘idiopathic pulmonary fibrosis’ should be reserved for cases of UIP, the most common idiopathic interstitial pneumonia’’ (2). In 2000, an international consensus statement produced by a collaborative effort from the ATS, ERS, and the American College of Chest Physicians (ACCP) stated that ‘‘. . . usual interstitial pneumonia (UIP) is the histopathological pattern that identified patients with IPF’’ and that other histopathological patterns should be considered distinct from IPF (29). More recently, a joint consensus statement from the ATS and ERS classified IIP into seven clinical-radiological-pathological entities: IPF, NSIP, COP, AIP, RB-ILD, DIP, and LIP (12). These experts reaffirmed that UIP is the histological pattern observed in IPF. They also recognized that the histological pattern NSIP may be observed in response to occupational exposures or in the context of collagen vascular disorders (CVDs) as well as a form of IIP. They stated ‘‘. . . after considerable debate, . . . use of the term NSIP was acceptable as a provisional measure until there is further clarity on the nature of the corresponding clinical condition’’ (12). They also pointed out that information was lacking in several important aspects of NSIP, including incidence or prevalence, whether clinical features can distinguish NSIP from other IIPs, whether further subclassification of NSIP is warranted or possible, and what relationship exists (if any) between NSIP and UIP.
