AIMS: Although histological non-specific interstitial pneumonia (NSIP) is concisely defined, overlap with other patterns is described. While most frequently idiopathic, NSIP is seen in various clinical contexts such as connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). This study was designed to determine if NSIP could be separated into subgroups based on minor histological features and to correlate these subgroups with clinical associations and survival. METHODS AND RESULTS: One hundred and thirty-six patients with biopsy-proven NSIP were included [clinical diagnosis: CTDs (23%), cHP (12%), idiopathic (65%)]. In addition to the agreed NSIP criteria, seven subgroups were identified: essential NSIP and six overlap subgroups according to superimposed minor histological features. Interobserver concordance resulted in the following consensus: essential NSIP (36%), usual interstitial pneumonia (UIP) overlap (26%), cHP overlap (10%), organizing pneumonia (OP) overlap (6%), organizing diffuse alveolar damage (DAD) overlap (10%), desquamative interstitial pneumonia overlap (7%) and lymphoid interstitial pneumonia overlap (2%). OP overlap was associated with CTDs (P = 0.04) and cHP overlap with a cHP clinical diagnosis (P = 0.02). Survival was different between subgroups (P = 0.0002). Organizing DAD overlap exhibited poorer survival at 5 years (32%), followed by UIP overlap (57%). Independent predictors of mortality were organizing DAD overlap (HR = 4.99, 95% CI = 2.15-11.58, P = 0.0002), UIP overlap (HR = 2.11, 95% CI = 1.12-3.99, P = 0.02) and a clinical diagnosis of cHP (HR = 2.17, 95% CI = 1.05-4.47, P = 0.035). CONCLUSIONS: Non-specific interstitial pneumonia subdivision into pathological subgroups is clinically relevant from a prognostic and causal perspective.
AIMS: Although histological non-specific interstitial pneumonia (NSIP) is concisely defined, overlap with other patterns is described. While most frequently idiopathic, NSIP is seen in various clinical contexts such as connective tissue diseases (CTDs) and chronic hypersensitivitypneumonitis (cHP). This study was designed to determine if NSIP could be separated into subgroups based on minor histological features and to correlate these subgroups with clinical associations and survival. METHODS AND RESULTS: One hundred and thirty-six patients with biopsy-proven NSIP were included [clinical diagnosis: CTDs (23%), cHP (12%), idiopathic (65%)]. In addition to the agreed NSIP criteria, seven subgroups were identified: essential NSIP and six overlap subgroups according to superimposed minor histological features. Interobserver concordance resulted in the following consensus: essential NSIP (36%), usual interstitial pneumonia (UIP) overlap (26%), cHP overlap (10%), organizing pneumonia (OP) overlap (6%), organizing diffuse alveolar damage (DAD) overlap (10%), desquamative interstitial pneumonia overlap (7%) and lymphoid interstitial pneumonia overlap (2%). OP overlap was associated with CTDs (P = 0.04) and cHP overlap with a cHP clinical diagnosis (P = 0.02). Survival was different between subgroups (P = 0.0002). Organizing DAD overlap exhibited poorer survival at 5 years (32%), followed by UIP overlap (57%). Independent predictors of mortality were organizing DAD overlap (HR = 4.99, 95% CI = 2.15-11.58, P = 0.0002), UIP overlap (HR = 2.11, 95% CI = 1.12-3.99, P = 0.02) and a clinical diagnosis of cHP (HR = 2.17, 95% CI = 1.05-4.47, P = 0.035). CONCLUSIONS: Non-specific interstitial pneumonia subdivision into pathological subgroups is clinically relevant from a prognostic and causal perspective.