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The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias
G. Raghu,A. G. Nicholson,D. Lynch
European Respiratory Review , 2008,
Abstract: The idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of rare interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases, which, as their name implies, are of unknown aetiology. The past 10 yrs have seen important advances in the classification of the IIPs into idiopathic pulmonary fibrosis (IPF) and its corresponding histopathological pattern of usual interstitial pneumonia (UIP), plus six non-IPF IIP subtypes. The present article will look at the current classification of IIPs, arising from the Consensus Statement of the American Thoracic Society and European Respiratory Society, and discusses the importance of differential diagnosis of IPF from the non-IPF IIP subtypes, especially nonspecific interstitial pneumonia. Diagnosis of IIPs is a dynamic process involving close collaboration between pulmonologists, radiologists and pathologists. Increasingly accurate diagnosis of IPF has been made possible by the use of high-resolution computed tomography (HRCT) and refinements in surgical lung biopsy. In IPF, a lung HRCT will typically reveal irregular reticular opacities, traction bronchiestasis and, most importantly, peripheral honeycombing. In contrast, histological examination shows evidence of UIP manifesting as typically subpleural and paraseptal established fibrosis, often with honeycomb changes, associated with mild chronic inflammation and varying numbers of fibroblastic foci in continuity with the edges of areas of established fibrosis. Despite these advances, obtaining a consistent and uniform diagnosis of idiopathic interstitial pneumonias is difficult, with studies showing significant disagreement in the diagnosis of interstitial lung diseases between academic centres of expertise and community-based clinicians. Greater interaction between academic and community clinicians, together with improved education, is needed to bridge this gap.
Idiopathic interstitial pneumonias: Classification revision  [cached]
Demosthenes Bouros MD, PhD, FCCP
Pneumon , 2010,
Abstract: The American Thoracic Society (ATS), the European Respiratory Society (ERS) and the Japan Respiratory Society (JRS) are planning a revision of the 2002 ATS/ERS International Multidisciplinary Classification of Idiopathic Interstitial Pneumonias (IIPs)1. In two years’ time it will be 10 years since its publication and with a view to publishing the revision after 10 years (i.e., in 2012), a steering committee has been established, which met in New Orleans during ATS congress in May 2010 and more recently in Barcelona during the ERS congress (Photo). The committee will meet again during the ATS and the ERS congresses that will be held in the next two years, with an additional meeting in Modena, Italy, in Αpril 2011.
High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis
Tomoyuki Kakugawa, Shin-ichi Yokota, Hiroshi Mukae, Hiroshi Kubota, Noriho Sakamoto, Syunji Mizunoe, Yasuhiro Matsuoka, Jun-ichi Kadota, Nobuhiro Fujii, Kazuhiro Nagata, Shigeru Kohno
BMC Pulmonary Medicine , 2008, DOI: 10.1186/1471-2466-8-23
Abstract: We measured the serum levels of the autoantibodies to HSP47 in 38 patients with various forms of IIP [16 with idiopathic pulmonary fibrosis (IPF), 15 with idiopathic NSIP, 7 with cryptogenic organizing pneumonia (COP)] and 18 healthy volunteers.The serum levels of autoantibodies to HSP47 in patients with idiopathic NSIP were significantly higher than in patients with IPF (P < 0.01), COP (P < 0.05), and healthy volunteers (P < 0.05). In addition, those in fibrosing NSIP were significantly higher than those of cellular and fibrosing NSIP (p < 0.05).We found high levels of anti-HSP47 autoantibody titers in sera of patients with idiopathic fibrosing NSIP compared with other IIPs and healthy volunteers.The classification of idiopathic interstitial pneumonias (IIP) includes seven clinico-radiologic-pathological entities. Usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) are the two largest subsets of IIP [1,2]. The distinction between NSIP and UIP is important for clinical decision-making because the prognosis is generally better and the response to corticosteroids and immunosuppressants is also better in patients with NSIP compared with UIP [3-7]. In addition, patients with cellular NSIP are reported to have excellent long-term prognosis, while the majority of patients with fibrotic NSIP die mostly within 5 to 10 years of diagnosis [6]. Because of these reasons, the distinction between cellular NSIP and fibrotic NSIP is also important.Clinicians often speculate on the presence of such pathological changes based on noninvasive imaging studies such as high-resolution computed tomography (HRCT) scans. However, the discrimination between NSIP and UIP cannot always be predicted accurately by HRCT. Although surgical (open or thoracoscopic) lung biopsy has been traditionally the ''gold standard'' for the diagnosis of interstitial lung diseases (ILD) and is clinically relevant for selection of appropriate therapy [8], it seems to be relatively inva
Effects of red cell distribution width on prognosis of inpatients with idiopathic interstitial pneumonias

ZOU Xiao
, NI Ying-meng, CHEN Wei

- , 2015, DOI: 11.3969/j.issn.1674-8115.2015.08.019
Abstract: 目的 探讨红细胞分布宽度(RDW)与特发性间质性肺炎(IIPs)预后的相关性。方法 经诊断明确的IIPs患者61例,以死亡/生存作为观察终点对患者进行分组,记录两组患者的临床资料,分析IIPs的危险因素,探讨RDW与IIPs预后的相关性。结果 61例患者男33例,女28例,男女比例为1.2∶1,平均年龄(64.60±16.33)岁,死亡组35例,生存组26例。与生存组相比,死亡组平均年龄更高(P=0.004)、出现呼吸衰竭更明显(P=0.002)。所有患者的RDW基线值为(15.12±1.71)%,RDW末次值为(16.30±2.54)%。死亡组RDW基线值和末次值分别为(15.95±1.50)%和(17.84±2.26)%,均明显高于生存组(P=0.000)。Logistic多变量分析显示,在控制性别及年龄因素的基础上,RDW是IIPs预后的独立预测因素。RDW判断IIPs预后的界值为15.70%,受试者工作特征曲线(ROC曲线)下面积为0.94(95%CI:1.61~1.95),判断IIPs预后的敏感度为88.60%,特异度为96.20%;RDW≥15.70%组死亡率明显高于RDW<15.70%组(P=0.000)。结论 RDW与IIPs病变的严重程度独立相关,是IIPs预后的独立预测因素。
: Objective To explore the correlation between red cell distribution width (RDW) and prognosis of idiopathic interstitial pneumonias (IIPs). Methods A total of 61 patients with confirmed diagnosis of IIPs were divided into the survival group and death group by using death/survival as end point of observation. Their clinical data were recorded. The risk factors of IIPs were analyzed and the correlation between RDW and prognosis of IIPs was explored. Results Among 61 patients, 33 were males and 28 were females, the ratio of male and female was 1.2∶1, and the average age was 64.60±16.33. Compared with the survival group (n=26), the average age of death group (n=35) was higher (P=0.004) and respiratory failure was severer (P=0.002). The baseline value of RDW of all patients was (15.12±1.71)% and last value of RDW was (16.30±2.54)%. The baseline value and last value of RDW of the death group were (15.95 ± 1.50)% and (17.84±2.26)% and significantly higher than those of the survival group (P=0.000). Logistic multivariate analysis showed that RDW was an independent factor for predicting the prognosis of IIPs based on gender and age being controlled. The threshold value for predicting the prognosis of IIPs by RDW was 15.70% and the area under receiver operating characteristic (ROC) curve was 0.94 (95%CI 1.61-1.95) with the sensitivity of 88.60% and specificity of 96.20%. The mortality of patients with RDW≥ 15.70% was significantly higher than that of patients with RDW<15.70% (P=0.000). Conclusion RDW independently correlates with severity of IIPs and is an independent factor for predicting the prognosis of IIPs
Diagnostic approach to interstitial pneumonias in a single centre: report on 88 cases
Dirk Theegarten, Heike Müller, Francesco Bonella, Jeremias Wohlschlaeger, Ulrich Costabel
Diagnostic Pathology , 2012, DOI: 10.1186/1746-1596-7-160
Abstract: 88 patients with interstitial pneumonia that underwent open lung biopsies were investigated. Histology and clinical records were available for review. Diagnosis was made in three steps: first on the sole basis of histology, second with clinical information given initially and third, on the basis of an interdisciplinary case evaluation.63 patients (72%) were diagnosed as idiopathic interstitial pneumonias according to ATS/ERS criteria. Further 10 (11%) cases of hypersensitivity pneumonitis, 7 (8%) Langerhans cell histiocytosis and 8 (9%) interstitial pneumonias of other known causes or associations were detected. Histological patterns alone agreed with the final diagnosis in 67%. In 82% histology and clinical information given to the pathologist could provide correct diagnosis. In the rest of cases, especially in non idiopathic interstitial pneumonias, an interdisciplinary case evaluation was needed.Diagnosis of interstitial pneumonias by open lung biopsies needs sufficient clinical information. Because of the overlap of histological patterns, an interdisciplinary case evaluation that includes at least one clinical expert and one pathologist with excellent expertise and the follow-up of the patients is necessary to find correct diagnosis in all cases.The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5031706258025129 webciteDiffuse interstitial lung diseases (ILD) are disorders with a large spectrum of possible underlying causes. Most of ILD belong to the group of idiopathic interstitial pneumonias (IIP). But these diagnoses can only be made after exclusion of known etiological factors or associations.Pulmonary fibrosis was first described by VON BüHL in 1872 [1]. The first generally accepted classification of idiopathic interstitial pneumonia was introduced by LIEBOW in 1975 [2]. He distinguished usual interstitial pneumonia (UIP), bronchiolitis obliterans with interstitial pneumonia (BIP), desquamative interstitial
Observer agreement in the diagnosis of interstitial lung diseases based on HRCT scans
Antunes, Viviane Baptista;Meirelles, Gustavo de Souza Portes;Jasinowodolinski, Dany;Pereira, Carlos Alberto de Castro;Verrastro, Carlos Gustavo Yuji;Torlai, Fabíola Goda;D'Ippolito, Giuseppe;
Jornal Brasileiro de Pneumologia , 2010, DOI: 10.1590/S1806-37132010000100007
Abstract: objective: to determine the interobserver and intraobserver agreement in the diagnosis of interstitial lung diseases (ilds) based on hrct scans and the impact of observer expertise, clinical data and confidence level on such agreement. methods: two thoracic radiologists and two general radiologists independently reviewed the hrct images of 58 patients with ilds on two distinct occasions: prior to and after the clinical anamnesis. the radiologists selected up to three diagnostic hypotheses for each patient and defined the confidence level for these hypotheses. one of the thoracic and one of the general radiologists re-evaluated the same images up to three months after the first readings. in the coefficient analyses, the kappa statistic was used. results: the thoracic and general radiologists, respectively, agreed on at least one diagnosis for each patient in 91.4% and 82.8% of the patients. the thoracic radiologists agreed on the most likely diagnosis in 48.3% (κ = 0.42) and 62.1% (κ = 0.58) of the cases, respectively, prior to and after the clinical anamnesis; likewise, the general radiologists agreed on the most likely diagnosis in 37.9% (κ = 0.32) and 36.2% (κ = 0.30) of the cases. for the thoracic radiologist, the intraobserver agreement on the most likely diagnosis was 0.73 and 0.63 prior to and after the clinical anamnesis, respectively. that for the general radiologist was 0.38 and 0.42.the thoracic radiologists presented almost perfect agreement for the diagnostic hypotheses defined with the high confidence level. conclusions: interobserver and intraobserver agreement in the diagnosis of ilds based on hrct scans ranged from fair to almost perfect and was influenced by radiologist expertise, clinical history and confidence level.
Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis
Parra, E.R.;Araujo, C.A.L.;Lombardi, J.G.;Ab’Saber, A.M.;Carvalho, C.R.R.;Kairalla, R.A.;Capelozzi, V.L.;
Brazilian Journal of Medical and Biological Research , 2012, DOI: 10.1590/S0100-879X2012007500066
Abstract: because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (iips) and increase their severity. we investigated the distribution of lymphatics in different remodeling stages of iips by immunohistochemistry using the d2-40 antibody. pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (aip/dad, n = 24), cryptogenic organizing pneumonia/organizing pneumonia (cop/op, n = 6), nonspecific interstitial pneumonia (nsip/nsip, n = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (ipf/uip, n = 19). d2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. we observed an increase in the d2-40+ percent from dad (6.66 ± 1.11) to uip (23.45 ± 5.24, p = 0.008) with the advanced process of remodeling stage of the lesions. kaplan-meier survival curves showed a better survival for patients with higher lymphatic d2-40+ expression than 9.3%. lymphatic impairment occurs in the lungs of iips and its severity increases according to remodeling stage. the results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with aip/dad. therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to iips.
Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias
Nobuhiko Nagata, Yasuhiko Kitasato, Kentaro Wakamatsu, Masaharu Kawabata, Kazuo Fukushima, Akira Kajiki, Yoshinari Kitahara, Kentaro Watanabe
Diagnostic Pathology , 2011, DOI: 10.1186/1746-1596-6-25
Abstract: This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs.We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK), and epithelial membrane antigen (EMA) in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells.In patients with usual interstitial pneumonia (UIP), the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio) in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP), many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis.The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative/hyperplastic alveolar epithelial cells) may predict a worse prognosis for patients with IIPs, especially patients with UIP. A prospective study is needed to confirm these results.Idiopathic pulmonary fibrosis (IPF) is a form of idiopathic interstitial pneumonia (IIP) characterized by progressive lung fibrosis and a poor prognosis. It is difficult to predict survival in patients with IPF. Longer survival has been associated with younger age, female gender, a shorter symptomatic period prior to diagnosis, less dyspnea, preserved pulmonary function,
Angiogenesis in Interstitial Lung Diseases: a pathogenetic hallmark or a bystander?
Argyris Tzouvelekis, Stavros Anevlavis, Demosthenes Bouros
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-82
Abstract: The interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung diseases comprising different clinical and histopathological entities that have been broadly classified into several categories [1,2] including sarcoidosis and idiopathic interstitial pneumonias (IIPs). The latter have been recently classified into seven different disease-members [3-8]. The most important and frequent of these conditions are idiopathic pulmonary fibrosis (IPF) with the histopathologic pattern of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP). Their aetiology has remained elusive and the molecular mechanisms driving their pathogenesis are poorly understood. Recent theories implicate recurrent injurious exposure, imbalance that shifts Th1/Th2 equilibrium towards Th2 immunity and angiogenesis in the pathogenesis of pulmonary fibrosis, both in human and experimental studies [9]. The Th1/Th2 pathway and angiogenesis have been recently suggested to play pivotal role in the immunopathogenesis of sarcoidosis contributing to the formation of granuloma, the main histopathologic feature of the disease [10].The scope of this review article is to summarize the current state of knowledge regarding angiogenic and angiostatic activity in the most important and prevalent members of ILD disease-group such as IIPs and sarcoidosis, discuss its pathogenetic role and present some of the future perspectives and limitations based on authors' assessment or originated from the statements of original authors.Angiogenesis is the process of new capillary blood vessels growth and is instrumental under both physiologic and pathologic conditions. Physiologic conditions include embryogenesis, growth, tissue repair after injury and the female reproductive cycle whereas pathologic angiogenesis can occur in chronic inflammatory and fibroproliferative disorders and tumorigenesis of cancer. Angiogenesis is similar to but d
Do We Need Exercise Tests to Detect Gas Exchange Impairment in Fibrotic Idiopathic Interstitial Pneumonias?  [PDF]
Benoit Wallaert,Lidwine Wemeau-Stervinou,Julia Salleron,Isabelle Tillie-Leblond,Thierry Perez
Pulmonary Medicine , 2012, DOI: 10.1155/2012/657180
Abstract: In patients with fibrotic idiopathic interstitial pneumonia (f-IIP), the diffusing capacity for carbon monoxide (DLCO) has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. The aim of this study was to compare DLCO, resting PaO2, P(A-a)O2 at cardiopulmonary exercise testing peak, and oxygen desaturation during a 6-min walk test (6MWT). Results were obtained in 121 patients with idiopathic pulmonary fibrosis (IPF, ) and fibrotic nonspecific interstitial pneumonias (NSIP, ). All but 3 patients (97.5%) had low DLCO values (35?mmHg) and 100 (83%) demonstrated significant oxygen desaturation during 6MWT (>4%). Interestingly 27 patients had low DLCO and normal P(A-a)O2, peak and/or no desaturation during the 6MWT. The 3 patients with normal DLCO also had normal PaO2, normal P(A-a)O2, peak, and normal oxygen saturation during 6MWT. Our results demonstrate that in fibrotic IIP, DLCO better defines impairment of pulmonary gas exchange than resting PaO2, exercise P(A-a)O2, peak, or 6MWT SpO2. 1. Introduction According to the ATS/ERS statement, fibrotic interstitial idiopathic pneumonia (f-IIP) includes idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonia (f-NSIP) [1–4]. Although pathological abnormalities are quite different between these two diseases [5], alteration of gas exchange is a major abnormality which is thought to reflect the severity of fibrotic process [6]. Given the simplicity of pulmonary function testing, many investigators have examined the potential for simple resting physiologic measurements to stratify disease severity. The classic physiologic findings in the fibrotic IIP include a reduction in lung volumes (vital capacity; total lung capacity), a reduction in carbon monoxide diffusing capacity (DLCO), and hypoxemia that worsens with exercise [2]. Evaluation of gas exchange impairment can be performed in clinical practice by simple tests like DLCO, resting PaO2, and P(A-a)O2, measurement of SpO2 during a 6-min walk test (6MWT) or PaO2 and alveolar-arterial oxygen pressure difference P(A-a)O2 during cardiopulmonary exercise testing (CPET). Whereas DLCO is a valuable tool in the assessment of the efficiency of pulmonary gas exchange, the P(A-a)O2, especially during exercise, is thought to better reflect the normality of
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