Usual interstitial pneumonia end-stage features from explants with radiologic and pathological correlations.

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.

Rabeyrin M ，Thivolet F ，Ferretti GR ，Chalabreysse L ，Jankowski A ，Cottin V ，Pison C ，Cordier JF ，Lantuejoul S ... -  《-》

A comparative study of honeycombing on high resolution computed tomography with histologic lung remodeling in explants with usual interstitial pneumonia.

There is little information comparing high-resolution computed tomography (HRCT) findings in UIP with different components that make up remodeling histologically. We compared histologic features with HRCT scans from 69 explants with UIP. The extent of 7 histologic features were semi-quantitated: respiratory-lined cysts, bronchiolectasis, pulmonary interstitial emphysema (PIE), lobular remodeling, areas resembling non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP)-like pattern, and mucus pooling within cysts extending into surrounding parenchyma. Subpleural cystic spaces and areas of lobular remodeling were measured morphometrically. Histologic features were compared to three findings on HRCT: diagnostic pattern (UIP, probable UIP, or inconsistent with UIP pattern), degree of honeycombing, and degree of ground-glass opacities. Histologically, respiratory-lined cysts were observed in 78%, bronchiolectasis in 83%, interstitial emphysema in 22%, lobular remodeling in 96%, NSIP-like areas in 87%, DIP-like reaction in 10%, and mucin extravasation in 78%. Morphometrically, cysts of PIE measured 6.2±2.9 mm, respiratory-lined cysts 3.5±2.4 mm, and bronchiolectatic cysts 3.3±1.5 mm. Remodeled lobules measured 3.6±1.1 mm. UIP pattern on CT correlated strongly with histologic extent of bronchiolectasis (p=0.001). HRCT honeycombing showed a positive correlation with histologic bronchiolectasis (p=0.001) and respiratory-lined cysts (p=0.001). GGO was positively associated with NSIP-like areas (p=0.02) and extravasated mucus (p=0.05). HRCT findings typical of UIP and HRCT honeycombing correlate best with bronchiolectasis histologically. NSIP pattern is common, and is associated with CT finding of GGO.

Staats P ，Kligerman S ，Todd N ，Tavora F ，Xu L ，Burke A ... -  《-》

The histopathology of idiopathic pulmonary fibrosis in West Highland white terriers shares features of both non-specific interstitial pneumonia and usual interstitial pneumonia in man.

Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) is a breed-related, spontaneously arising disease that is a potential animal model for IPF in man. Histopathological similarity between IPF in WHWTs and usual interstitial pneumonia (UIP), the histopathological correlate for IPF in man, has not been confirmed and histological features of non-specific interstitial pneumonia (NSIP), another form of human idiopathic interstitial pneumonia, have been reported in WHWTs with IPF. This study describes the pulmonary histopathological findings in 18 WHWTs with IPF, including lobe-specific samples in nine of the dogs. The canine lesions and their distribution pattern are compared with histopathological characteristics in samples of human UIP and NSIP. Underlying diffuse mature fibrosis, resembling human NSIP more than UIP, was seen in the lungs of all dogs with IPF. Additionally, the majority of dogs with IPF showed multifocal areas of accentuated subpleural and peribronchiolar fibrosis with occasional 'honeycombing' and profound alveolar epithelial changes, reminiscent of human UIP and not commonly seen in NSIP. Interstitial fibroblastic foci, characteristic of UIP, were not seen in WHWTs with IPF. Progressive fibrosis, with intra-alveolar organizing fibrosis alongside interstitial mature collagen deposition, was present within the more severely affected areas of lung in WHWTs with IPF. Severe pulmonary lesions were seen more commonly in the caudal than in the cranial lung lobes.

Syrjä P ，Heikkilä HP ，Lilja-Maula L ，Krafft E ，Clercx C ，Day MJ ，Rönty M ，Myllärniemi M ，Rajamäki MM ... -  《-》

[Acute exacerbation of usual interstitial pneumonia and nonspecific interstitial pneumonia: analysis of 6 cases].

Tian XL ，Xu WB ，Shi JH ，Feng RE ，Xu ZJ ，Liu HR ，Wang MZ ，Xu F ，Huang H ，Zhu YJ ... -  《-》

Idiopathic pulmonary fibrosis with emphysema: evidence of synergy among emphysema and idiopathic pulmonary fibrosis in smokers.

Emphysema and fibrosis, typically the idiopathic pulmonary fibrosis (IPF) form of usual interstitial pneumonia (UIP), can co-exist as combined pulmonary fibrosis emphysema (CPFE). It is unknown whether there is a pathobiologic basis for CPFE beyond the coexistence of fibrosis and emphysema. The aim of this study was to ascertain radiologic differences in severity of fibrosis and emphysema in smokers with IPF versus other forms of UIP. Computed tomography thorax images were prospectively rescored in retrospectively identified smokers (minimum 5-pack-year history) with radiologic UIP (any etiology). Radiologic severity (emphysema/fibrosis/reticulation) was scored in consensus by two radiologists, blinded to clinical details, across 5 lung regional levels, and then correlated with clinical data. For the whole cohort (IPF, n=102; non-IPF UIP [mainly rheumatoid arthritis/asbestosis/scleroderma], n=30), IPF and non-IPF UIP smokers were similar regarding pack-year, age, gender, and lung function (P>.1). IPF smokers had greater whole lung fibrosis and reticulation scores (P<.04 in all cases). CPFE was present in n=61 (IPF, n=49; non-IPF UIP, n=12). Compared with smokers with non-IPF CPFE, smokers with IPF and emphysema (IPFE) were similar regarding confounders (P>.1). There were significantly greater regional reticulation severity (P=.009), cumulative emphysema severity (P=.04), and cumulative reticulation severity (P<.001) scores in IPFE versus non-IPF CPFE. When controlled for confounders, smokers with IPFE have worse radiologic CPFE than other smokers with non-IPF UIP and emphysema, suggesting an interactive synergy among IPF, emphysema, and smoking, with more extensive emphysema due to either inherent susceptibility and/or traction effects. IPFE should be considered separately from other CPFE in future work. It is currently unknown whether CPFE is a distinct pathobiologic entity; therefore, we identified subjects with radiologic UIP (any etiology) who had been similarly exposed to smoke, and asked whether there are differences in the extent/severity of radiologic fibrosis and/or emphysema in those with IPF versus individuals with non-IPF UIP. Although relevant confounders were similar, IPF smokers had greater whole lung fibrosis and reticulation scores than smokers with secondary forms of UIP, and in the CPFE subgroup, smokers with IPF/emphysema had worse radiologic CPFE findings than smokers with non-IPF UIP/emphysema. It is shown for the first time that relevant confounding variables do not explain the observed excess radiologic severity of emphysema and fibrosis in smokers with IPF compared with smokers with non-IPF UIP, lending support to the hypothesis that there is a pathobiologic mechanism or synergy involved in IPF with emphysema that is distinct from the mere co-existence of UIP and emphysematous processes.

Mitchell PD ，Das JP ，Murphy DJ ，Keane MP ，Donnelly SC ，Dodd JD ，Butler MW ... -  《-》