TOM5 regulates the mitochondrial membrane potential of alveolar epithelial cells in organizing pneumonia.

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Properties of Pleural Mesothelial Cells in Idiopathic Pulmonary Fibrosis and Cryptogenic Organizing Pneumonia.

BACKGROUND: Profibrotic properties of pleural mesothelial cells may play an important role in the fibrosis activity in idiopathic pulmonary fibrosis (IPF). The purpose of this study was to compare the expression of pleural mesothelial cell markers in IPF and cryptogenic organizing pneumonia (COP), with an assumption that increased expression implies increase in fibrosis. METHODS: Twenty IPF lung samples were stained by immunohistochemistry for the pleural mesothelial cell markers: leucine rich repeat neuronal 4 (LRRN4), uroplakin 3B, CC-chemokine ligand 18, and laminin-5. Nine COP lung samples were used as controls. A semi-quantitative analysis was performed to compare markers expression in IPF and COP. RESULTS: LRRN4 expression was found in epithelial lining cells along the honeycombing and fibroblastic foci in IPF, but not in the fibrotic interstitial lesion and airspace filling fibrous tufts in COP. We found a significant decrease in baseline forced vital capacity when LRRN4 expression was increased in honeycombing epithelial cells and fibroblastic foci. CONCLUSION: LRRN4 expression patterns in IPF are distinct from those in COP. Our findings suggest that mesothelial cell profibrotic property may be an important player in IPF pathogenesis and may be a clue in the irreversibility of fibrosis in IPF.

[The role of histone deacetylases in the pathogenesis of idiopathic pulmonary fibrosis and cryptogenic organizing pneumonia].

Objective: To explore the role of histone deacetylases(HDAC) in the pathogenesis of idiopathic pulmonary fibrosis(IPF) and cryptogenic organizing pneumonia(COP). Methods: Fifteen IPF patients [14 males and 1female, age 40-73 years, mean age (59±8) years] and 15 COP patients [5 males and 10 females, age 41-71 years, mean age (59±8) years] from Peking Union Medical College Hospital were recruited from March 2018 to October 2018. Fifteen healthy donors[4 males and 11females, age 43-70 years, mean age (58±6) years] were enrolled as controls. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The nuclear and cytoplasmic proteins were extracted by Nuclear Extraction Kit. HDAC activity was measured by fluorimetric method. The relations between HDAC activity and clinical parameters were analyzed with SPSS. Results: The HDAC activity of cytoplasmic protein and nuclear protein from patients with IPF were (724±216) nmol/L and (2 309±708) nmol/L, which were higher than that of health controls (409±105) nmol/L and (1 572±611) nmol/L (P<0.01 for both). So as to the HDAC activity of cytoplasmic protein and nuclear protein from patients with COP which were (718±245) nmol/L and (3 310±1 005) nmol/L (P<0.01 for both).The HDAC activity of nuclear protein from COP patients was higher than that from IPF patients (Z=-2.840, P=0.005). The HDAC activity of nuclear protein was negatively correlated with FEV(1) and D(L)CO in IPF patients (r=-0.574, P=0.025; r=-0.583, P=0.029), and negatively correlated with FVC and TLC in COP patients(r=-0.846, P=0.016; r=-0.900, P=0.015). Conclusion: HDAC may be involved in the pathogenesis of COP and IPF.

Cicatricial variant of cryptogenic organizing pneumonia.

This study of 12 patients focused on a variant of cryptogenic organizing pneumonia (COP) labeled the cicatricial form in which the airspaces of the lung are filled with and consolidated by dense collagenized scar tissue associated with preservation of underlying lung architecture. Patients were predominantly middle-aged men and presented with bilateral lung disease in the majority of cases, often with nodular or reticulonodular disease (10/12; 83%). Patients were usually symptomatic with shortness of breath, cough, and dyspnea on exertion. Fifty-five percent of patients (6/11) had persistent or progressive disease at follow-up (mean, 68.5 months; median, 110 months). The cicatricial variant of cryptogenic organizing pneumonia may be predictive of a more recalcitrant form of COP that needs to be morphologically separated from classical COP, usual interstitial pneumonia, and nonspecific interstitial pneumonia.

Factors associated with the relapse of cryptogenic and secondary organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) is a histopathological response pattern to lung inflammation. It is clinically classified into cryptogenic OP and secondary OP, which is associated with various clinical conditions. Rapid resolution with corticosteroids and frequent relapses are common in OP. However, few studies have investigated the factors associated with OP relapse. METHODS: The medical records of 75 patients with biopsy-proven OP, diagnosed between January 2010 and August 2015, who underwent corticosteroid therapy were retrospectively reviewed. Initially, the patients were all treated successfully; however, 31 patients experienced relapse thereafter (R group), whereas the others did not (NR group; 44 patients). The clinical, radiological, and pathological characteristics and administered corticosteroid doses were compared between the two groups. RESULTS: The neutrophil percentage in the bronchoalveolar lavage (BAL) fluid and the level of fibrin deposition in lung biopsy specimens were higher in the R group than in the NR group (P=0.01 and P=0.002, respectively). The multivariate analysis demonstrated that both factors were statistically significant predictors of OP relapse. CONCLUSIONS: A high neutrophil percentage in the BAL and the level of fibrin deposition in lung biopsy specimens are considered predictive factors of OP relapse during the tapering or after the cessation of steroid therapy. Patients without these findings may be treated with low-dose corticosteroids.

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. AIM OF THE STUDY: In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. MATERIALS AND METHODS: The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). RESULTS: In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. CONCLUSION: In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.

Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia.

PURPOSE: Galectin-9 (Gal-9) is a ß-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS: Gal-9, transforming growth factor-ß1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS: Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.

Increased expression of epidermal growth factor receptor (EGF-R) in patients with different forms of lung fibrosis.

INTRODUCTION: Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). PATIENTS AND METHODS: Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. RESULTS: A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. CONCLUSIONS: We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.

Prognostic value of clinical, morphologic, and immunohistochemical factors in patients with bronchiolitis obliterans-organizing pneumonia.

Bronchiolitis obliterans-organizing pneumonia (BOOP) is an inflammatory and fibrosing disease involving the distal bronchioles, bronchiolar ducts, and alveoli. We studied 91 patients with BOOP. Univariate analysis was used to relate age, sex, smoking, morphology, and expression of immunohistochemical markers CD68, D2-40, CD31, CD34, collagen IV, collagen III, platelet-derived growth factor receptor, and vascular endothelial growth factor (VEGF) with the response to corticosteroid therapy. Seventy-two patients had idiopathic BOOP and 19 secondary BOOP. The median age of the patients was 59.54 years. Most patients were current or former smokers. All cases had a patchy lesion consisting of small buds of fibromyxoid tissue in small bronchioles, bronchiolar ducts, and alveoli. The buds contained collagen and reticulin fibers, fibroblasts, macrophages, mononuclear inflammatory cells, and vessels in different proportions. We found no morphologic differences between primary and secondary BOOP. Patients younger than 38 years and nonsmokers had a significant good response to corticosteroid therapy. Favorable morphologic predictors were the presence of large bronchial plugs and mild inflammatory reaction (P = .093). By immunohistochemistry, the presence of collagen IV with the absence of collagen III, CD68-positive cells and positive VEGF were associated with a good response to corticosteroid therapy. We conclude that age, smoking, localization, and extension of proliferative intrabronchiolar plugs and positive immunostains for CD68, VEGF, and collagen IV with negative collagen III were useful to predict response to corticosteroid therapy and relapse.

Macrolides inhibit cytokine production by alveolar macrophages in bronchiolitis obliterans organizing pneumonia.

BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans organizing pneumonia (BOOP) is a distinct clinicopathological entity histologically characterized by intra-alveolar granulation tissue and absence of extensive fibrotic lesions. Effective macrolide treatment of BOOP has been reported anecdotally. This study aimed to investigate whether alveolar macrophages (AMs) produce aberrant proinflammatory cytokines in BOOP and whether this can be inhibited by clarithromycin (CAM) or azithromycin (AZM). METHODS: AMs collected by bronchoalveolar lavage (BAL) from 6 BOOP patients and 8 non-ILD controls were cultured for 24h in the presence or absence of CAM, AZM, lipopolysaccharide (LPS), or dexamethasone (DEX). Tumor necrosis factor alpha (TNF-α), soluble TNF receptor 1 (sTNFR1), sTNFR2, interleukin 1beta (IL-1ß), IL-6, IL-8, IL-10, interferon gamma inducible protein 10 (IP-10) and CC chemokine ligand 18 (CCL18) were measured in the culture supernatant by ELISA. RESULTS: The spontaneous and LPS-stimulated production of all investigated cytokines by AMs was significantly increased in BOOP compared to controls. CAM and AZM induced a dose-dependent suppression of spontaneous TNF-α, sTNFR2, IL-6, IL-8 and CCL18 production (p<0.05). CAM also inhibited the IL-1ß production. CAM and AZM significantly and dose-dependently attenuated the LPS-stimulated production of sTNFR1, sTNFR2, IL-8 and CCL18 (p<0.05). CAM also inhibited the LPS-stimulated TNF-α, IL-1ß, IL-6 and IL-10 production. CONCLUSIONS: AMs from BOOP patients produce abundant proinflammatory cytokines which may be pivotal in the disease pathogenesis. Macrolides inhibit this cytokine production, CAM more efficiently than AZM.

Increased expression of tumor necrosis factor receptors in cryptogenic organizing pneumonia.

BACKGROUND: TNF receptors (TNFR1 and TNFR2) and Fas belong to the system of apoptosis-signalling receptor molecules and may play a role in the pathogenesis of interstitial lung disease. Patients with cryptogenic organizing pneumonia (COP) usually respond well to corticosteroids, in contrast to those with idiopathic pulmonary fibrosis (IPF). This may be due to the different pathogenesis. METHODS: The expression of TNFR1, TNFR2 and Fas on bronchoalveolar lavage (BAL) macrophages and lymphocytes was analysed in 9 patients with COP, 10 with IPF and 12 controls. The production of soluble TNFR1, 2 and TNF-α by alveolar macrophages was measured by ELISA. RESULTS: TNFR1 and Fas expression on alveolar macrophages was significantly higher in COP than in controls and IPF. The expression of TNFR2 on alveolar macrophages was also increased in COP compared to controls. The expression of TNFR2 and Fas on lymphocytes was significantly higher in COP than in IPF and controls. In addition, the expression of TNFR1, TNFR2 and Fas on BAL cells correlated positively with BAL lymphocytes (p < 0.05 or p < 0.01). The production of sTNFR1 and 2 and TNF-α by macrophages in vitro was significantly increased in patients with COP compared to IPF and controls, spontaneously or with LPS stimulation (p < 0.05 or p < 0.01).There was a positive correlation between the spontaneous production of sTNFR2 and TNF-α (r = 0.494, p < 0.01). CONCLUSIONS: This study showed an increased expression of TNF receptors and Fas on BAL cells in COP that may be indicative of the local inflammatory activity in the lung. The biologic effects of this expression needs further investigation.

Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia and cryptogenic organizing pneumonia.

OBJECTIVE: Oxidant stress is thought to be involved in the establishment of idiopathic interstitial pneumonia (IIP). Thioredoxin 1 (TRX1) plays a role as a strong antioxidant in vivo, suggesting that TRX1 may be involved in the pathogenesis of IIPs. However, there is no report on TRX1 levels in the sera of IIPs. In addition, TRX1 expression in the lungs of non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP) patients also has not been reported. Here, we investigated whether or not TRX1 levels are altered in the lungs and sera of patients with idiopathic pulmonary fibrosis (IPF), NSIP, and COP. METHODS: Immunohistochemical analysis was performed to examine the expression of TRX1. TRX1 levels in sera were measured using an ELISA kit. RESULTS: TRX1 was expressed in the bronchiole-alveolar epithelium, especially with regenerative or metaplastic feature, and in alveolar macrophages in usual interstitial pneumonia (UIP) and fibrotic NSIP. TRX1 was weakly expressed in the lungs of cellular NSIP and COP. TRX1 producing cells in UIP (n=16), fibrotic NSIP (n=15), cellular NSIP (n=4), and COP (n=5) were significantly increased when compared to nonsmokers (n=7). TRX1 producing cells in UIP and fibrotic NSIP were significantly increased when compared to cellular NSIP and COP. TRX1 levels in the sera of the patients with IPF (n=32; 74.2 ± 7.5 ng/mL), fibrotic NSIP (n=7; 82.5 ± 18.4 ng/mL), cellular NSIP (n=3; 62.2 ± 3.2 ng/mL) and COP (n=17; 88.8 ± 19.7 ng/mL) were significantly higher than those of control subjects (n=74; 35.3 ± 2.7 ng/mL). Furthermore, TRX1 levels in the sera of IPF patients who later showed acute exacerbation (n=7; 106.6 ± 16.3 ng/mL) were significantly higher than those of IPF patients without acute exacerbation (n=25; 65.1 ± 7.6 ng/mL). CONCLUSION: Overproduction of TRX1 in the lungs and sera may play an important role in the pathogenesis of IIPs.

Proliferative activity in fibrosing lung diseases: a comparative study of Ki-67 immunoreactivity in diffuse alveolar damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia.

Because diffuse alveolar damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia are all related to acute lung injury, we postulated that the proliferative activity of fibroblasts and epithelium would be similar in all 3, and that of fibroblasts would be similar to skin scars. Ki-67 staining was assessed in 16 usual interstitial pneumonia, 9 bronchiolitis obliterans-organizing pneumonia, and 8 diffuse alveolar damage cases, 5 incidental fibroblast foci, 5 skin scars, and 5 keloids. The proliferative activity of alveolar macrophages was also measured and compared with that of 10 respiratory bronchiolitis cases. The greatest proliferative activity was found in fibroblasts and epithelium of diffuse alveolar damage (25.8% and 41.9%), and it was significantly greater (P = .000) than in usual interstitial pneumonia (1.88% and 2.6%), bronchiolitis obliterans-organizing pneumonia (4.07% and 1.55%), and incidental fibroblast foci (2.9% and 0.44%). The proliferative activity in fibroblasts of diffuse alveolar damage was significantly higher than that of fibroblasts in skin scars (P = .024). In contrast, the proliferative rate of fibroblasts in bronchiolitis obliterans-organizing pneumonia, usual interstitial pneumonia, and incidental fibroblast foci was significantly lower than that in skin scars (P = .000, P = .000, and P = .001) but similar to keloids (P = 1.000). Usual interstitial pneumonia macrophages showed an unexpectedly high proliferative rate (19.5%) that was significantly greater than that in bronchiolitis obliterans-organizing pneumonia (5.5%, P = .000), diffuse alveolar damage (9.01%, P = .007), incidental fibroblast foci (9.5%, P = .036), and respiratory bronchiolitis (11.45%, P = .031). Our results suggest different reactions to acute injury in usual interstitial pneumonia and bronchiolitis obliterans-organizing pneumonia compared with diffuse alveolar damage. The similar low proliferative activity of fibroblasts in usual interstitial pneumonia and keloids supports the hypothesis of abnormal wound healing in usual interstitial pneumonia. The high proliferative activity of macrophages in usual interstitial pneumonia suggests a role in the pathogenesis of usual interstitial pneumonia.

Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis.

BACKGROUND: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP). METHODS: Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects. RESULTS: A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients. CONCLUSION: Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.

Comparison of pulmonary CT findings and serum KL-6 levels in patients with cryptogenic organizing pneumonia.

The aim of this study was to retrospectively compare high-resolution CT findings among cryptogenic organizing pneumonia (COP) patients with normal and elevated serum KL-6 levels. Chest CT scans performed between April 1999 and April 2007 in 20 COP patients with a normal KL-6 level and 17 COP patients with an elevated KL-6 level were evaluated retrospectively by two chest radiologists. The CT findings in the COP patients with either a normal or an elevated KL-6 level mainly consisted of consolidation (n = 17 and n = 13, respectively) followed by ground-glass opacity (n = 11 and n = 13, respectively). Traction bronchiectasis and architectural distortion were significantly more frequent in patients with an elevated KL-6 level than in those with normal levels (n = 7 and n = 1, and n = 13 and n = 3, respectively) (p = 0.0077 and p = 0.00017, respectively). In follow-up CT scans, a relapse within 1 year after initial treatment with steroids, performed in 16 patients with a normal KL-6 level and 16 with an elevated KL-6 level, occurred in 2 (12.5%) patients with a normal KL-6 level and in 6 (37.5%) with an elevated KL-6 level. The frequency of relapse in patients with an elevated KL-6 level was higher than in those with a normal KL-6 level; however, no significant difference between the two groups was observed (p = 0.103). In conclusion, CT findings of traction bronchiectasis and architectural distortion in COP patients are associated with increased serum KL-6 levels, which might be related to a relapse after treatment.

Cryptogenic organising pneumonia.

Organising pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. Although nonspecific, this histopathological pattern, together with characteristic clinical and imaging features, defines cryptogenic organising pneumonia when no cause or peculiar underlying context is found. Rapid clinical and imaging improvement is obtained with corticosteroid treatment, but relapses are common after stopping treatment.

Elevated concentrations of soluble IL-2 receptor in both bronchoalveolar lavage fluid and serum in a patient with BOOP.

Activated soluble IL-2 receptor (sIL-2R) levels are elevated in a variety of diseases associated with T-cell activation. There are no reports of sIL-2R elevations in broncholitis obliterans organizing pneumonia/cryptogenic organizing pneumonia (BOOP/COP), although activated T cells are increased in BOOP/COP. We present a patient with BOOP/COP with an elevated concentration of soluble IL-2 receptors in both serum and bronchoalveolar lavage fluid. Concomitant resolution of the high serum sIL-2R and the roentogenographic findings after steroid treatment suggested that serum sIL-2R levels increase in response to a localized lymphocytic inflammatory reaction in the lung.