Cases Of Usual Interstitial Pneumonia Research Articles

Differential TH1/TH2 Chemokine Expression in Interstitial Pneumonia

T-helper (Th)-2 background in the lungs may favor the development of pulmonary fibrosis. We hypothesized that usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), major pathologic patterns of chronic interstitial pneumonia, would have different expression profiles of TH1 and TH2 chemokines. MethodsTotal RNA was isolated from lung tissues obtained by surgical biopsy (18 cases of UIP and 29 cases of NSIP). The expression of ligands for CXCR3 [TH1 cells chemoattractant: monokine induced by interferon (IFN)-γ (MIG), IFN-γ-inducible protein of 10 kD, and IFN-inducible T cell α chemoattractant] and ligands for CCR4 [TH2 cells chemoattractant: thymus- and activation-regulated chemokine and macrophage-derived chemokine (MDC)] were analyzed by real-time reverse transcriptase polymerase chain reaction. ResultsMIG and IFNy-inducible protein of 10 kD expression were significantly higher in NSIP compared with UIP. MDC expression was increased in UIP compared with NSIP, although the difference was not significant. MIG/MDC is significantly elevated in NSIP but not UIP. Interestingly, MIG/MDC was significantly higher in NSIP group 3 (NSIP with extensive fibrosis) compared with UIP. ConclusionsThese results may indicate that these 2 diseases have a different pathophysiology. MIG/ MDC may be a useful marker to distinguish these 2 diseases.

Systemic sclerosis and idiopathic interstitial pneumonia: histomorphometric differences in lung biopsies

The aim of this study was to examine the parenchymal and extracellular matrix remodeling process in two histologic patterns-nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP)-in cases of idiopathic and sclerosis/systemic sclerosis (SSc)-associated interstitial pneumonia. We examined 15 cases of idiopathic NSIP, 10 cases of idiopathic UIP, 5 cases of SSc-UIP and 9 cases of SSc-NSIP. In the lung parenchyma, epithelial cells, endothelial cells and myofibroblasts were evaluated by immunohistochemical staining, whereas histochemical staining was used in order to evaluate collagen/elastic fibers in the extracellular matrix. The percentage of surfactant protein A-positive epithelial cells was significantly greater in idiopathic NSIP than in SSc-NSIP, as well as being greater in idiopathic UIP than in SSc-UIP. Idiopathic NSIP and idiopathic UIP presented significantly higher immunoexpression of alpha smooth muscle actin in myofibroblasts than did SSc-NSIP and SSc-UIP. The percentage of CD34 endothelial cells in the pulmonary microvasculature was significant lower in idiopathic UIP than in SSc-UIP. The density of collagen fibers was significantly greater in idiopathic NSIP and idiopathic UIP than in SSc-NSIP and UIP. In contrast, the elastic fiber density was significantly lower in idiopathic UIP than in SSc-UIP. Increased collagen synthesis, destruction of elastic fibers, high myofibroblast proliferation and poor microvascularization might represent a remodeling process found in idiopathic interstitial pneumonia, whereas the reverse might represent a repair process in SSc-associated interstitial pneumonia.

Probable relationship between increased number of birefringent particles and diffuse interstitial lung diseases

ABSTRACT Background and aim: Although there is increasing evidence that inhaled birefringent particles (BPs) cause pulmonary fibrotic reaction, the relationship between BPs and diffuse interstitial lung diseases (DILDs) remains unclear. Methods: We assessed 85 cases of interstitial lung diseases including 50 cases of usual interstitial pneumonia (UIP), 22 cases of nonspecific interstitial pneumonia (NSIP) and 13 cases of bronchiolitis obliterans‐organizing pneumonia (BOOP) and 55 cases of normal lung tissue from control group. BPs were measured and counted by image analyzer under polarizing microscope. Results: The average BP count in all types of interstitial lung disease was 223.60/10 high power fields (HPF), significantly higher than the average of 116.80/10HPFs found in the control group (P= 0.01). Among individual disease entities, UIP showed significantly higher BP count than control (232.80/10HPFs, P= 0.01). Although statistically insignificant, NSIP and BOOP also revealed higher BP counts than the control (192.09/10HPFs and 241.54/10HPFs, respectively). Conclusions: Increased BPs in the lung might be related to the fibrogenic process of interstitial lung diseases.

AKR1B10 in usual interstitial pneumonia: Expression in squamous metaplasia in association with smoking and lung cancer

The incidence of lung cancer (LC) is markedly increased among patients with usual interstitial pneumonia (UIP), and tobacco smoking is its superimposed risk factor. AKR1B10 (aldo-keto reductase 1B10) is frequently overexpressed in pulmonary squamous cell carcinoma and adenocarcinoma in smokers. To investigate the role of AKR1B10 in the pulmonary carcinogenesis in UIP with correlation to tobacco smoking, we examined 13 UIP cases with LC, 13 UIP cases without LC, and 30 cases of non-UIP LC using AKR1B10 immunohistochemistry. AKR1B10 immunoreactivity was confined to squamous metaplasia in honeycomb lesions of UIP and neoplastic cells of LC. Squamous metaplastic foci showed AKR1B10 immunoreactivity more frequently in UIP with LC (24/36 foci, 67%) than in UIP without LC (16/44 foci, 37%) ( P<0.01). AKR1B10 expression in UIP was also more frequent in squamous metaplastic foci in smokers (38/67 foci, 57%) than in non-smokers (2/13 foci, 15%) ( P<0.01). AKR1B10 expression was frequently observed in both UIP-associated LC (10/13 foci, 77%) and non-UIP LC (18/30 foci, 60%). Ki-67 labeling index was significantly higher in AKR1B10-positive squamous metaplasia of UIP than in AKR1B10-negative squamous metaplasia of UIP. Our results demonstrate that AKR1B10 is involved in the development of LC in UIP in association with smoking. AKR1B10 might be useful as a new marker for identification of high LC risk patients in UIP.

Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia

To clarify the localization of KL-6 and epithelial membrane antigen (EMA) in human lungs, immune reactions to antibodies to these factors were examined in detail at light and electron microscopic levels. Immunohistochemical investigation was performed in 17 cases of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), collagen vascular disease-associated interstitial pneumonias (CVD-IP), viral pneumonia, and bronchobronchioloectasis, as well as in 10 cases of presumably normal pulmonary tissue resected as a result of spontaneous pneumothorax. Immunohistochemical study revealed similar discontinuous linear or dome-shaped positive patterns restricted to type II alveolar cells in presumably normal tissue and only some regions of interstitial pneumonia. In sharp contrast, immune reactions with each of the two antibodies yielded a continuous linear pattern surrounding damaged areas in most regions of interstitial pneumonias and some normal areas as well. Staining for EMA antibody was negative in some regenerating alveolar and bronchial cells in regenerating foci in interstitial pneumonias, although staining for KL-6 antibody was always positive in these cells. Immunoelectron microscopic studies demonstrated similar positive reactions with both antibodies on the surface of alveolar epithelial cells in three of the cases examined, with surface positive granules 100-200 nm in diameter. Thus, although staining for both KL-6 and EMA antibodies exhibited discontinuous positivity restricted to type II alveolar cells in nondamaged regions, immune reactions were continuous and linear in pattern in or around damaged areas of the lungs at both light and electron microscopic levels, probably as a consequence of cell-surface barrier function. These findings in pulmonary tissue might be evidence of defense functions.

Response

I believe that Drs. Shorr, Lettieri, and Helman misinterpreted the message of our article (May 2006). 1 Berbescu E Katzenstein AL Snow J et al. Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar This work generated a hypothesis that will require further testing. It was not intended to produce a clinical recommendation to use transbronchial lung biopsies (TBBs) to diagnose usual interstitial pneumonia (UIP). In our article, we clearly state that TBBs should be tested in a blinded fashion and in a cohort of diffuse lung diseases including UIP and non-UIP cases.1 However, it is undeniable, as we show in several of our figures, that features specific for UIP, such as patchwork pattern of interstitial fibrosis, fibroblastic foci, and honeycomb change, 2 Katzenstein A-LA Myers JL Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 PubMed Google Scholar , 3 Katzenstein A-LA Zisman DA Litzky LA Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 PubMed Google Scholar are readily recognizable in many TBB specimens. 1 Berbescu E Katzenstein AL Snow J et al. Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar We did not report findings of nonspecific interstitial pneumonia in 9 of 21 patients, as Drs. Shorr, Lettieri, and Helman state. We make clear in the “Materials and Methods” section that findings were “nonspecific” if there was only interstitial fibrosis on TBB specimens. 1 Berbescu E Katzenstein AL Snow J et al. Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar Unfortunately, it has become accepted, despite lack of convincing data, that TBBs are not useful in diagnosing idiopathic interstitial pneumonias. However, if in the future TBBs are found useful in diagnosing UIP from a pool of patients with diverse idiopathic interstitial pneumonias, many unnecessary surgical lung biopsies with associated morbidity and mortality could be prevented. 4 Utz JP Transbronchial biopsy in usual interstitial pneumonia. Chest. 2006; : 1126-1131 PubMed Google Scholar Role for Transbronchial Biopsy in the Diagnosis of Usual Interstitial PneumoniaChestVol. 131Issue 1PreviewWe read with interest the article by Berbescu et al1regarding the role for transbronchial biopsy (TBB) in the diagnosis of usual interstitial pneumonia (UIP). The authors conclude that TBB may be more useful than previously appreciated in the diagnosis of UIP. We do not believe their data support this conclusion. Full-Text PDF

Pathologic Subgroups of Nonspecific Interstitial Pneumonia

To determine whether the subtypes of nonspecific interstitial pneumonia (NSIP) could be differentiated from other idiopathic interstitial pneumonias (IIPs) on the basis of findings on high-resolution computed tomography (CT). Two observers evaluated the high-resolution CT findings in 90 patients with IIPs. The patients included 36 with NSIP, 11 with usual interstitial pneumonia (UIP), 8 with cryptogenic organizing pneumonia (COP), 10 with acute interstitial pneumonia (AIP), 14 with desquamative interstitial pneumonia (DIP) or respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and 11 with lymphoid interstitial pneumonia (LIP). The NSIP cases were subdivided into group 1 NSIP (n = 6), group 2 NSIP (n = 15), and group 3 NSIP (n = 15). Observers made a correct diagnosis with a high level of confidence in 65% of NSIP cases, 91% of UIP cases, 44% of COP cases, 40% of AIP cases, 32% of DIP or RB-ILD cases, and 82% of LIP cases. Group 1 NSIP was misdiagnosed as AIP, DIP or RB-ILD, and LIP in 8.3% of patients, respectively. Group 2 NSIP was misdiagnosed as COP in 10% of patients, LIP in 6.7%, AIP in 3.3%, and DIP or RB-ILD in 3.3%. Group 3 NSIP was misdiagnosed as UIP in 6.7% of patients, COP in 6.7%, and DIP or RB-ILD in 3.3%. In most patients, NSIP can be distinguished from other IIPs based on the findings on high-resolution CT. Only a small percentage of patients with predominantly fibrotic NSIP (group 3 NSIP) show overlap with the high-resolution CT findings of UIP.

Collagen and elastic system in the remodelling process of major types of idiopathic interstitial pneumonias (IIP)

Structural remodelling in acute and chronic idiopathic interstitial pneumonia (IIP) has been extensively investigated, but little attention has been directed to the elastic tissue in these situations. The aim of this study was to determine whether elastic deposition accompanies collagen deposition in the four major histological patterns of IIP: diffuse alveolar damage (DAD), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides of open lung biopsies, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: 10 cases of DAD; nine cases of OP; nine cases of NSIP; and 10 cases of UIP. Four normal lungs were used for comparison. The content of collagen fibres was significantly higher in UIP when compared to DAD, NSIP, OP and normal lung. The content of elastic fibres was increased in comparison with normal lungs but this was not significantly different among the histological patterns. Acute and chronic IIP cause a similar increase in the collagen and elastic contents of the lungs, representing a process of 'fibroelastosis' rather than an exclusive process of fibrosis. A profibrogenic mechanism is responsible for the unparallelled collagen augmentation observed in UIP subjects, the nature of which is yet to be determined.

Histologic features and pathologic diagnosis in usual interstitial pneumonia

To study the pathologic features, differential diagnosis and role of open lung biopsies (OLB) in usual interstitial pneumonia (UIP). The authors reviewed the pathologic, clinical and radiologic features of five cases of UIP (one autopsy case and four OLB cases), with follow-up information. The typical histologic features were a non-uniform distribution of alveolar inflammation, fibroblastic foci, interstitial fibrosis and honeycomb change. There also was associated metaplasia of bronchiolar epithelium, type II pneumocyte hyperplasia and accumulation of alveolar macrophages. Characteristically, UIP exhibits temporal heterogeneity under low-power light microscopy, which includes changes in both the early and end stages. Open lung biopsy is an important diagnostic adjunct for suitable patients with atypical radiologic features on computerized tomography. Correlation between clinical, radiologic and pathologic findings is also essential for a correct diagnosis.

Usual interstitial pneumonia: histologic study of biopsy and explant specimens.

The pathologic findings in biopsy and subsequent explant specimens from 20 patients with usual interstitial pneumonia (UIP) were reviewed to refine histologic criteria for diagnosis, to identify factors that may confound diagnosis, and to assess the relationship of UIP and nonspecific interstitial pneumonia (NSIP). One case of NSIP was also identified and included for comparison. Surgical biopsies from 15 of the 20 UIP cases were diagnosed as UIP, whereas 5 showed only nondiagnostic changes. An important new observation is that areas resembling nonspecific interstitial pneumonia (NSIP-like areas) are present in the majority of UIP cases in both biopsy and explant specimens, and they are extensive in some. Ten of the 15 UIP biopsies were considered straightforward, with typical patchy interstitial fibrosis, honeycomb change, and fibroblast foci. Five cases were considered difficult because of prominent NSIP-like areas in two, extensive honeycomb change in one, superimposed diffuse alveolar damage in one, and superimposed bronchiolitis obliterans-organizing pneumonia in one. The most helpful feature for diagnosing UIP in difficult cases was the presence of a distinct patchwork appearance to the characteristic uneven or variegated parenchymal involvement along with evidence of architectural derangement. No explant showing UIP was preceded by biopsy findings of NSIP, and the one NSIP case appeared similar at biopsy and explant. NSIP or NSIP-like areas and UIP may reflect different mechanisms of fibrosis related either to different severity of injury or to different injuries.

The appearance of S-100 protein-positive dendritic cells and the distribution of lymphocyte subsets in idiopathic nonspecific interstitial pneumonia

Idiopathic interstitial pneumonia (IIP) is a progressive interstitial lung disease of unknown etiology. We investigated dendritic cells in idiopathic nonspecific interstitial pneumonia (NSIP) immunohistochemically, using anti-S-100 protein antibody and anti-HLA-DR antibody and also evaluated the relationship between the distribution of S-100 protein-positive dendritic cells (S-100 DCs) and the lymphocytic subsets in the lung tissue of NSIP. Fifteen patients with the pathological diagnosis of idiopathic NSIP and six patients with usual interstitial pneumonia (UIP) were recruited into this study. Many S-100 DCs were observed in all the cases of idiopathic NSIP but S-100 DCs were not recognized in UIP cases invariably. In the mirror section method, most S-100 DCs showed a positive reaction of anti-HLA-DR antibody but a negative reaction for anti-CD1a antibody. CD8 and CD4 positive lymphocytes were infiltrated diffusely around S-100 DCs. It was demonstrated that the infiltration of CD8 positive lymphocytes predominated in the fibrosing areas and lymphoid follicles around S-100 DCs more so than CD4 positive lymphocytes. We speculate that the pathogenesis of NSIP is different from UIP and that DC and T cell-mediated immune mechanisms may play a role in the development and perpetuation of NSIP.

Eosinophilic Pneumonia-like Areas in Idiopathic Usual Interstitial Pneumonia

Usual interstitial pneumonia is the most common idiopathic chronic interstitial pneumonia, characterized by a temporally heterogenous pattern of interstitial injury with interstitial mononuclear infiltrates, septal fibromyxoid nodules, and parenchymal scarring. This report details the presence of focal eosinophilic pneumonia in six cases of usual interstitial pneumonia in the absence of known causes of this reaction. The relationship of eosinophilic infiltrates in usual interstitial pneumonia with regard to pathogenesis, differential diagnosis, and prognosis is discussed.

Increased levels of interleukin-6 are associated with lymphocytosis in bronchoalveolar lavage fluids of idiopathic nonspecific interstitial pneumonia.

Local overexpression of interleukin-6 (IL-6) experimentally induces lymphocytic infiltration in the bronchial tree of rat. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia/fibrosis (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid when compared with usual interstitial pneumonia (UIP). To reveal a relation of IL-6 with the lymphocyte infiltration of NSIP, IL-6 was measured in BAL fluids of idiopathic NSIP (n = 7), idiopathic UIP (n = 16), and normal control subjects (n = 45). IL-6-producing sites were assessed by IL-6 protein stain on biopsy specimens of NSIP, UIP, and normal lung of mediastinal tumors. Lymphocyte numbers and IL-6 levels in BAL fluids were higher in NSIP than those in UIP (p < 0.01, respectively), which were also higher when compared with those of normal control subjects (p < 0.01, respectively). In NSIP, the levels of IL-6 correlated with the number of lymphocytes (r = 0.93, p < 0.01). UIP cases were divided into two groups: high-UIP (n = 7) or low-UIP (n = 9) according to IL-6 levels greater than or within the 95 percentile of normal control subjects, respectively. The high-UIP group had BAL lymphocytosis when compared with the low-UIP group (p < 0.05). IL-6 stained on epithelial cells of the bronchial tree and on alveolar macrophages of NSIP and UIP. In conclusion, the lymphocytosis in BAL fluid of patients with NSIP and a subgroup of UIP is associated with the high levels of IL-6 and its sources are the epithelial cells of the small airway and the alveolar macrophages.

Immunohistochemical localization of surfactant apoproteins in usual interstitial pneumonia associated with pulmonary carcinoma.

Surfactant apoproteins A and B (SP-A and SP-B) are antigenic determinants of pulmonary surfactant complexes. The role and functional significance of these proteins are largely unknown and the pattern of expression is probably related to the functional maturation of type II pneumocytes. Differential expression of SP-A and SP-B was reported in the developing human lung but little is known of their expression in the chronic injury. We studied 5 surgical cases of usual interstitial pneumonia (UIP) associated with carcinoma to evaluate the expression of pulmonary surfactant apoproteins. These cases were immunohistochemically examined by the streptavidin-biotin complex method using monoclonal antibodies HS-1 and HS-2 against pulmonary surfactant apoprotein A (SP-A) and B (SP-B), respectively. In UIP, SP-B was expressed strongly in type II pneumocytes and Clara cells but bronchiolar epithelium and metaplastic squamous cell lines in the honeycomb lesion were non-reactive. SP-A showed a similar pattern but much weaker reactivity when compared to that of SP-B. Type II pneumocytes in normal lung tissue exhibited weak immunoreactivity and no difference in the intensity of staining between SP-A and SP-B. Neither carcinomatous area nor metaplastic lining cells at honeycomb lesion show immunoreactivity to SP-A and SP-B. These results suggest that type II pneumocytes in the UIP are functionally immature in their expression of the apoprotein types and the metaplastic squamous cells or neoplastic transformed cells do not have molecular characteristics of type II pneumocytes.

Lung cancer associated with usual interstitial pneumonia.

There were 83 cases of usual interstitial pneumonia (UIP) in 3712 consecutive autopsy cases during 1972 to 1992 in Toranomon Hospital. Primary lung cancer had arisen in 40 cases of UIP in that period. The prevalence of lung cancer (48.2%) in UIP was significantly higher than that of lung cancers (9.1%) in the age-matched general population without UIP (P < 0.001). The prevalence of association of multiple lung cancer in UIP (20.0%) was also significantly increased. Thus, UIP showed a remarkable potency to develop lung cancers. The lung cancer cases in UIP had obvious smoking habits. Both the rates of smokers and the quantity of smoking were significantly increased in the lung cancer cases in UIP (P < 0.05). There was a distinct anatomical distribution of lung cancer in UIP. Most cancers in UIP (98%) arose in the peripheral area of the lung (P < 0.001, compared to lung cancer cases without UIP) with close relation to the honeycombing lesion. Studies on surgical specimens with small cancers showed that most tumors in UIP arose in the border area between honeycombing and the non-fibrotic area. Thus, the front of the remodeling of the lung is suspected to be a potential field of developing lung cancer. The chronic inflammatory process resulting in the remodeling of the lung may play an important part in the development of lung cancer in UIP under the circumstance of heavy smoking.

Bronchiolitis obliterans and usual interstitial pneumonia. A comparative clinicopathologic study.

The clinical, radiographic, and pathologic features were studied in 24 cases of bronchiolitis obliterans and 16 cases of usual interstitial pneumonia, to define better their distinguishing characteristics. Bronchiolitis obliterans had a more acute onset often associated with fever, while the presentation of usual interstitial pneumonia was insidious with dyspnea and cough. The radiographs in usual interstitial pneumonia uniformly showed bilateral interstitial opacities, while they were more variable in bronchiolitis obliterans, with air space densities in 15 and interstitial opacities in nine. Prognosis was considerably better for bronchiolitis obliterans patients. Resolution of disease occurred in nearly half, while no patient with usual interstitial pneumonia recovered. Three individuals with bronchiolitis obliterans (12.5%) died of progressive disease, compared to 10 with usual interstitial pneumonia (62.5%). Pathologically, the lesion in bronchiolitis obliterans affected mainly air spaces in a peribronchiolar distribution, while the changes in usual interstitial pneumonia were mainly interstitial and randomly distributed. The fibrosis in bronchiolitis obliterans was composed of proliferating fibroblasts, compared to collagen deposition in usual interstitial pneumonia. These findings emphasize that bronchiolitis obliterans and usual interstitial pneumonia represent separate and distinct clinicopathologic entities.