Subtypes Of Idiopathic Interstitial Pneumonias Research Articles

The pathogenesis and pathology of idiopathic pleuroparenchymal fibroelastosis.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonias that consists of elastofibrosis involving the lung parenchyma and pleural collagenous fibrosis predominantly located in the upper lobes. IPPFE has various distinct clinical and physiological characteristics, including platythorax and a marked decrease of forced vital capacity with an increased residual volume on a respiratory function test. The concept of IPPFE is now widely recognized and some diagnostic criteria have been proposed. In addition, the accumulation of cases has revealed the pathological features of IPPFE. However, little is known about the pathogenesis or the process of disease formation in IPPFE. This review article will provide a summary of the pathological features and previously reported hypotheses on disease formation in IPPFE, to discuss the potential etiologies and pathogenesis of IPPFE.

Clinical, radiological, and pathological evaluation of “NSIP with OP overlap” pattern compared with NSIP in patients with idiopathic interstitial pneumonias

BackgroundNonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP) are major subtypes of idiopathic interstitial pneumonias (IIPs) and closely related to connective tissue diseases (CTDs). “NSIP with OP overlap” is a controversial finding that has recently appeared in the criteria of interstitial pneumonia with autoimmune features (IPAF). However, details of this controversial entity are not well known. ObjectiveTo determine the frequency of “NSIP with OP overlap” pattern in IIPs and to identify differences from idiopathic NSIP (iNSIP). MethodsIn 524 patients with interstitial pneumonia from 39 institutes who underwent surgical lung biopsy, 444 were diagnosed as IIPs by a multidisciplinary discussion meeting via a cloud-based integrated database. Among these patients, 44 (9.9%) who had iNSIP and 21 (4.7%) with histopathologically-defined “NSIP with OP overlap” pattern (a pathological NSIP and OP pattern, but without a UIP pattern) were retrospectively studied. ResultsPatients with “NSIP with OP overlap” pattern showed a significantly greater extent of consolidation (p < 0.001), more subpleural ground glass attenuation (p = 0.036), and more peripheral + bronchovascular distribution (p = 0.009) on high-resolution computed tomography than those with iNSIP. The incidences of newly-developed CTDs during follow-up was similar between the groups and polymyositis/dermatomyositis was the most frequent CTD in both groups. Nearly half of the patients fulfilled IPAF criteria, but no significant difference was found between iNSIP and “NSIP with OP overlap” pattern (47.7% vs. 42.9, p = 0.712). The incidence of acute exacerbation and the survival rates were similar between the groups. ConclusionsThe incidence of “NSIP with OP overlap” pattern is 4.7% in IIPs. The frequency of newly-developed CTDs during follow-up, mainly polymyositis/dermatomyositis, the frequency of acute exacerbation, and the survival rate in “NSIP with OP overlap” pattern are similar to those of iNSIP.

Remodeling of the pulmonary artery in idiopathic pleuroparenchymal fibroelastosis

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonia that consists of alveolar septal elastosis and intra-alveolar collagenosis, which is predominantly located in the upper lobes. The aim of this study was to examine the remodeling of the pulmonary arteries in patients with IPPFE. This study included 18 patients with IPPFE, 24 patients with idiopathic pulmonary fibrosis (IPF), and 5 patients without pulmonary disease as controls. We selected muscular pulmonary arteries and calculated the percentage of the thickness of each layer of the wall (intima, media, and adventitia) in relation to the external diameter. We also quantified the percentage of areas of elastic fiber in the media divided by the whole area of the media (medial elastic fiber score). The percentage of adventitial thickness in IPPFE was significantly higher than that in IPF and in control lungs. The percentage of medial thickness did not differ statistically between IPPFE and IPF. However, the medial elastic fiber score in IPPFE was also significantly larger than that in IPF and control lungs. These results suggest that collagenous thickening of the adventitia and medial elastosis are distinct histological features in the muscular pulmonary arteries of patients with IPPFE.

Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

Background The types of cells most significantly linked to individual subtypes of idiopathic interstitial pneumonias (IIPs) remain unclear. Few studies have examined CD163+ macrophages in IIPs. Objective We retrospectively aimed to immunohistochemically characterize the CD163+ macrophages in IIPs. Methods Paraffin-embedded lung tissue samples were obtained from 47 patients with IIPs, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (NSIP), and cryptogenic organizing pneumonia (COP), and 12 normal controls were immunohistochemically analyzed, using primary antibodies against CD68 and CD163 as indicators of pan and M2 macrophages, respectively. Results CD68+ macrophage density was significantly increased in the 3 subtypes of IIPs relative to that in the control group, although no difference was detected within the different IIPs. CD163+ macrophage density was significantly increased in NSIP and COP samples relative to that in IPF samples. The density ratio of CD163+ macrophages to CD68+ macrophages was significantly decreased in IPF/UIP samples relative to that in the others, while the densities in NSIP and COP were significantly higher than those in control cases. Conclusion CD163+ macrophages show distinct profiles among IIPs, and the standardized numerical density is decreased in IPF cases that have poor prognoses.

Management of a Pregnant Woman with Idiopathic Interstitial Pneumonia Accompanied by Secondary Pulmonary Hypertension: Case Report and Literature Review

Idiopathic interstitial pneumonias (IIPs) typically occur in the fifth and sixth decades, and thus are uncommon in the child-bearing age group. We herein report an extremely rare case of a pregnant woman with IIP accompanied by secondary pulmonary hypertension that had a successful cesarean delivery. A 36-year-old primigravida woman was referred to our Obstetrics department at 6 weeks of gestation. Seven years ago, she had a dry cough and moderate dyspnea, and was diagnosed with non-specific interstitial pneumonia (NSIP), a subtype of IIP. At 11 weeks of gestation, spirometry showed a vital capacity of 1.89 L (60% of predicted). An arterial blood gas analysis showed PaO2 of 77.2 mmHg and oxygen saturation of 95% in breathing room air at rest. An echocardiogram revealed mild pulmonary hypertension; systolic pulmonary artery blood pressure (PABP) of 44 mmHg. Fetal growth and amniotic fluid volume were normal. Our management plan was to maintain oxygen saturation at more than 95% of oxygen saturation and systolic PABP at less than 50 mmHg. Oxygen therapy was initiated at 13 weeks of gestation because of dyspnea at rest. At 28 weeks of gestation, an echocardiogram showed severe pulmonary hypertension with systolic PABP of 64 mmHg. Therefore, we performed cesarean section at 30 weeks of gestation. The newborn was a male weighing 1.452 g with Apgar scores of 6 and 7 at 1 min and 5 min, respectively. Although the patient’s post-operative course was uneventful, she was discharged on a regimen of oxygen therapy. The effects of pregnancy on IIPs remain unclear because of its extreme rarity. In the management of pregnant women with IIPs accompanied by secondary pulmonary hypertension, the maintenance of systolic PABP of less than 50 mmHg on an echocardiogram may be effective.

Relationship between gene expression and lung function in Idiopathic Interstitial Pneumonias.

BackgroundIdiopathic interstitial pneumonias (IIPs) are a group of heterogeneous, somewhat unpredictable diseases characterized by progressive scarring of the interstitium. Since lung function is a key determinant of survival, we reasoned that the transcriptional profile in IIP lung tissue would be associated with measures of lung function, and could enhance prognostic approaches to IIPs.ResultsUsing gene expression profiling of 167 lung tissue specimens with IIP diagnosis and 50 control lungs, we identified genes whose expression is associated with changes in lung function (% predicted FVC and % predicted DLCO) modeled as categorical (severe vs mild disease) or continuous variables while adjusting for smoking status and IIP subtype; false discovery rate (FDR) approach was used to correct for multiple comparisons. This analysis identified 58 transcripts that are associated with mild vs severe disease (categorical analysis), including those with established role in fibrosis (ADAMTS4, ADAMTS9, AGER, HIF-1α, SERPINA3, SERPINE2, and SELE) as well as novel IIP candidate genes such as rhotekin 2 (RTKN2) and peptidase inhibitor 15 (PI15). Protein-protein interactome analysis of 553 genes whose expression is significantly associated with lung function when modeled as continuous variables demonstrates that more severe presentation of IIPs is characterized by an increase in cell cycle progression and apoptosis, increased hypoxia, and dampened innate immune response. Our findings were validated in an independent cohort of 131 IIPs and 40 controls at the mRNA level and for one gene (RTKN2) at the protein level by immunohistochemistry in a subset of samples.ConclusionsWe identified commonalities and differences in gene expression among different subtypes of IIPs. Disease progression, as characterized by lower measures of FVC and DLCO, results in marked changes in expression of novel and established genes and pathways involved in IIPs. These genes and pathways represent strong candidates for biomarker studies and potential therapeutic targets for IIP severity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2102-3) contains supplementary material, which is available to authorized users.

Invited Commentary

Invited Commentary

Pulmonary Resection for Lung Cancer in Patients With Idiopathic Interstitial Pneumonia

After pulmonary resection, patients with lung cancer who have idiopathic pulmonary fibrosis (IPF) have been reported to have higher pulmonary morbidity and mortality and poorer outcomes than patients without IPF. However, whether morbidity, mortality, and outcomes differ according to the subtype of idiopathic interstitial pneumonia (IIP) remains unclear. The clinical records of 678 patients with non-small cell lung cancer who underwent pulmonary resection were reviewed retrospectively. A total of 103 patients had IIP and were classified into an IPF group and a non-IPF group in accordance with the 2011 statement. The IPF group comprised 46 patients, and the non-IPF group comprised 57. The 5-year survival rate was significantly higher in the non-IPF group (53.2%) than in the IPF group (22.1%; p= 0.0093). Cause of death was IIP-related respiratory failure in 26.1% (12 of 46) of the patients in the IPF group as compared with 7.0% (4 of 57) of patients in the non-IPF group (p= 0.008). Multivariate Cox analysis indicated that IPF was a significant predictor of long-term survival (hazard ratio 1.910, 95% confidence interval: 1.102 to 3.313; p= 0.021). Idiopathic pulmonary fibrosis is independently associated with poorer overall survival in patients with lung cancer who undergo pulmonary resection. The decision whether to perform surgery in patients who have lung cancer with IIP should therefore take into account the subtype of IIP and the poorer outcomes associated with IPF.

Gene expression profile analysis for different idiopathic interstitial pneumonias subtypes

ABSTRACTObjective: Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unknown etiology characterized by the presence of various degrees of inflammation and fibrosis. We aimed to screen the differences among IIPs subtypes in the gene level by using the microarray expression profiles of normal lung tissue and IIPs tissue for the key genes associated with early diagnosis and treatment of IIPs. Methods: The gene expression profile of six kinds of IIPs (GSE 32537) subtypes tissue and normal lung tissues were downloaded. The differentially expressed genes (DEGs) in different IIPs subtypes were selected by using the expression profiling. In addition, the screened DEGs were further analyzed by function annotation, pathway analysis, and interaction network analysis to reveal the differences among these subtypes. Results: The gene expression analysis showed that nine genes including SERPINA3, IL1R2, CBS, MGAM, SLCO4A1, S100A12, FPR1, SDR16C5, and MT1X in six subtypes of IIPs were significantly increased. There were significant differences in DEGs among six subtypes of IIPs, and the DEGs of some IIPs subtypes involved in immune, inflammatory response and cell adhesion processes. Moreover, the PPI network analysis indicated that SERPINA3 played an important role in the molecular mechanisms of IIPs. Conclusion: This comprehensive description of altered gene expression in different subtypes of IIPs underscores the complex biological processes characteristic of different subtypes of IIPs and may provide a foundation for future research into this devastating disease.

Quantitative comparison of idiopathic interstitial pneumonias on high-resolution computed tomographic findings

To analyze the high-resolution computed tomographic (HRCT) findings of IPF (interstitial pulmonary fibrosis), NSIP (nonspecific interstitial pneumonia) and COP (cryptogenic organizing pneumonia) retrospectively through quantification methods and to explore their distinguishing features. Observers with no prior knowledge of the diagnosis evaluated the frequency, extent and distribution of various thin-section CT findings in 29 males and 17 females. The mean age was 50 ± 10 years old (range: 25 - 76). They had a histological diagnosis of IPF (n = 19), nonspecific interstitial pneumonia (NSIP) (n = 14) and cryptogenic organizing pneumonia (COP) (n = 13). Ground-glass opacity, thickening of bronchovascular bundles and interlobular septal thickening were frequent features of IPF and NSIP. The frequency and extent of honeycombing and bronchiolectasis were more found in IPF than in NSIP and COP (P < 0.05). The frequency and extent of air space consolidation were more found in COP than IPF (P < 0.05). There were more number of segments with traction bronchiectasis and less extent of air space consolidation in IPF than NSIP and COP. The number of segments with traction bronchiectasis was less in NSIP than that of IPF and COP. The various subtypes of idiopathic interstitial pneumonias often have the distinguishing characteristics easily identified on HRCT. Bronchiolectasis and honeycombing are valuable features for IPF; air space consolidation is a valuable feature for COP. The features of NSIP are also found in both IPF and COP so that additional features are required for both.

Idiopathic airway-centered interstitial fibrosis: report of two cases

Idiopathic airway-centered interstitial fibrosis: report of two cases

Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia

Background: Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks...

Efficacy of Interferon(IFN)-γ in Idiopathic Pulmonary Fibrosis

Background : Idiopathic pulmonary fibrosis(IPF), a subtype of IIP(idiopathic interstitial pneumonia), is a fatal disease with a 3-5 year median survival. Many attempts at treating this condition have failed to demonstrate a survival benefit in IPF. Recently Ziesche et al reported the efficacy of IFN-γ for treating IPF but there is still some controversy. The aim of this study was to determine the efficacy of IFN-γ in patients with advanced IPF who had not been responsive to steroid and cytotoxic agents. Method : Nine patients with advanced IPF(age: 55.4±15.3 years, Male: Female=8:1) were enrolled. One year treatment regime with 2 million IU of IFN-γ administered subcutaneously three times a week, and low dose prednisolone(10-30 mg/d) was also used. In the case of a definite aggravation and serious side effects, the IFN-γ was discontinued. During the IFN-γ trial, a pulmonary function test and chest radiography were checked every three month throughout the study. Result : 1) Among 9 patients, only 4 patients were able to complete the 12 month treatment with IFN-γ, and 5 patients died during the treatment period. 2) No improvement either in the respiratory symptoms or pulmonary functions were observed any of the patients, even in those who completed the 12 months trial of IFN-γ, 3) At the time of IFN-γ trial, the survivors who finished the IFN-γ treatment for 12 months had a higher oxygen level(81.3±2.8 vs. 67.4±8.4, P=0.024) and a better pulmonary function(FVC:

Video‐Assisted Thoracoscopic Lung Biopsy as a Possible Cause of Acute Interstitial Pneumonia in a Patient with Nonspecific Interstitial Pneumonia

The present case report describes a 44-year-old woman who presented with dyspnea due to diffuse interstitial lung disease. High-resolution computed tomography showed features of usual interstitial pneumonia, but the lung biopsy obtained by video-assisted thoracoscopy was consistent with a histological pattern of nonspecific interstitial pneumonia. Following the procedure, the patient developed progressive respiratory distress and died on postoperative day 13 with a clinical picture of acute interstitial pneumonia. The autopsy showed evidence of diffuse alveolar damage superimposed on the background pattern of nonspecific interstitial pneumonia. The present case report supports the notion that patients with a variety of subtypes of idiopathic interstitial pneumonias may be at risk of exacerbation of their underlying disease following thoracic procedures, including video-assisted thoracoscopic lung biopsy.

Nonspecific Interstitial Pneumonia (NSIP)

Nonspecific interstitial pneumonia (NSIP) represents one histologic subtype of idiopathic interstitial pneumonia (IIP). NSIP is typified by temporal homogeneity and less profusion of fibroblastic foci than is seen with usual interstitial pneumonia (UIP), the most common IIP. Clinically patients with NSIP present with similar symptoms (cough and dyspnea) when compared to patients with UIP. The duration of these symptoms prior to presentation is variable. The finding of fever may be more common in NSIP and clubbing may be more common in UIP; however, both findings can be seen in either UIP or NSIP. Physiological findings typically demonstrate a restrictive ventilatory defect with decreased gas transfer; little difference exists between UIP and NSIP. High resolution computed tomography (HRCT) scans are more likely to show honeycombing with UIP and a ground-glass pattern with NSIP, however, either of these findings can be seen with UIP or NSIP. The most striking differential feature between NSIP and UIP is the markedly better prognosis for patients with NSIP, a finding that cannot be explained by baseline differences in physiology or radiographic features. In this article we explore the clinical, physiological, and radiographic features of NSIP. We also review available information regarding response to therapy and prognosis.

Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients.

To determine whether idiopathic interstitial pneumonias can be differentiated on the basis of the pattern and distribution of abnormalities at thin-section computed tomography (CT). Thin-section CT scans in 129 patients with histologically proved idiopathic interstitial pneumonia (35 with usual interstitial pneumonia [UIP], 24 with bronchiolitis obliterans organizing pneumonia [BOOP], 23 with desquamative interstitial pneumonia [DIP], 20 with acute interstitial pneumonia [AIP], and 27 with nonspecific interstitial pneumonia and fibrosis [NIPF]) were independently assessed by two observers without knowledge of clinical or histologic data. The observers recorded the abnormalities, diagnosis, and degree of confidence in their diagnosis. Differential diagnosis was limited to the five types of idiopathic interstitial pneumonia. The two observers made a correct diagnosis, on average, in 74 (57%) cases. On average, the correct diagnosis was made in 25 (71%) cases of UIP, 19 (79%) of BOOP, 14.5 (63%) of DIP, 13 (65%) of AIP, and 2.5 (9%) of NIPF. The two observers made a correct diagnosis with a high degree of confidence in 50 (39%) readings. There was moderate agreement between the observers for the correct diagnosis (k = 0.55) and for the correct diagnosis with a high degree of confidence (k = 0.65). Except for NIPF, the various subtypes of idiopathic interstitial pneumonias often have a characteristic appearance that allows differentiation at thin-section CT.