Type Of Idiopathic Interstitial Pneumonia Research Articles

Multidisciplinary Approach to the Diagnosis of Idiopathic Interstitial Pneumonias: Focus on the Pathologist's Key Role.

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

Identifying potential biomarkers of idiopathic pulmonary fibrosis through machine learning analysis

Idiopathic pulmonary fibrosis (IPF) is the most common and serious type of idiopathic interstitial pneumonia, characterized by chronic, progressive, and low survival rates, while unknown disease etiology. Until recently, patients with idiopathic pulmonary fibrosis have a poor prognosis, high mortality, and limited treatment options, due to the lack of effective early diagnostic and prognostic tools. Therefore, we aimed to identify biomarkers for idiopathic pulmonary fibrosis based on multiple machine-learning approaches and to evaluate the role of immune infiltration in the disease. The gene expression profile and its corresponding clinical data of idiopathic pulmonary fibrosis patients were downloaded from Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) with the threshold of FDR < 0.05 and |log2 foldchange (FC)| > 0.585 were analyzed via R package “DESeq2” and GO enrichment and KEGG pathways were run in R software. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms were combined to screen the key potential biomarkers of idiopathic pulmonary fibrosis. The diagnostic performance of these biomarkers was evaluated through receiver operating characteristic (ROC) curves. Moreover, the CIBERSORT algorithm was employed to assess the infiltration of immune cells and the relationship between the infiltrating immune cells and the biomarkers. Finally, we sought to understand the potential pathogenic role of the biomarker (SLAIN1) in idiopathic pulmonary fibrosis using a mouse model and cellular model. A total of 3658 differentially expressed genes of idiopathic pulmonary fibrosis were identified, including 2359 upregulated genes and 1299 downregulated genes. FHL2, HPCAL1, RNF182, and SLAIN1 were identified as biomarkers of idiopathic pulmonary fibrosis using LASSO logistic regression, RF, and SVM-RFE algorithms. The ROC curves confirmed the predictive accuracy of these biomarkers both in the training set and test set. Immune cell infiltration analysis suggested that patients with idiopathic pulmonary fibrosis had a higher level of B cells memory, Plasma cells, T cells CD8, T cells follicular helper, T cells regulatory (Tregs), Macrophages M0, and Mast cells resting compared with the control group. Correlation analysis demonstrated that FHL2 was significantly associated with the infiltrating immune cells. qPCR and western blotting analysis suggested that SLAIN1 might be a signature for the diagnosis of idiopathic pulmonary fibrosis. In this study, we identified four potential biomarkers (FHL2, HPCAL1, RNF182, and SLAIN1) and evaluated the potential pathogenic role of SLAIN1 in idiopathic pulmonary fibrosis. These findings may have great significance in guiding the understanding of disease mechanisms and potential therapeutic targets in idiopathic pulmonary fibrosis.

What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update.

The most common type of idiopathic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF), an irreversible, progressive disorder that has lately come into question for possible associations with COVID-19. With few geographical exceptions, IPF is a rare disease but its prevalence has been increasing markedly since before the pandemic. Environmental exposures are frequently implicated in IPF although genetic factors play a role as well. In IPF, healthy lung tissue is progressively replaced with an abnormal extracellular matrix that impedes normal alveolar function while, at the same time, natural repair mechanisms become dysregulated. While chronic viral infections are known risk factors for IPF, acute infections are not and the link to COVID-19 has not been established. Macrophagy may be a frontline defense against any number of inflammatory pulmonary diseases, and the inflammatory cascade that may occur in patients with COVID-19 may disrupt the activity of monocytes and macrophages in clearing up fibrosis and remodeling lung tissue. It is unclear if COVID-19 infection is a risk factor for IPF, but the two can occur in the same patient with complicating effects. In light of its increasing prevalence, further study of IPF and its diagnosis and treatment is warranted.

Automated Classification of Idiopathic Pulmonary Fibrosis in Pathological Images Using Convolutional Neural Network and Generative Adversarial Networks.

Interstitial pneumonia of uncertain cause is referred to as idiopathic interstitial pneumonia (IIP). Among the various types of IIPs, the prognosis of cases of idiopathic pulmonary fibrosis (IPF) is extremely poor, and accurate differentiation between IPF and non-IPF pneumonia is critical. In this study, we consider deep learning (DL) methods owing to their excellent image classification capabilities. Although DL models require large quantities of training data, collecting a large number of pathological specimens is difficult for rare diseases. In this study, we propose an end-to-end scheme to automatically classify IIPs using a convolutional neural network (CNN) model. To compensate for the lack of data on rare diseases, we introduce a two-step training method to generate pathological images of IIPs using a generative adversarial network (GAN). Tissue specimens from 24 patients with IIPs were scanned using a whole slide scanner, and the resulting images were divided into patch images with a size of 224 × 224 pixels. A progressive growth GAN (PGGAN) model was trained using 23,142 IPF images and 7817 non-IPF images to generate 10,000 images for each of the two categories. The images generated by the PGGAN were used along with real images to train the CNN model. An evaluation of the images generated by the PGGAN showed that cells and their locations were well-expressed. We also obtained the best classification performance with a detection sensitivity of 97.2% and a specificity of 69.4% for IPF using DenseNet. The classification performance was also improved by using PGGAN-generated images. These results indicate that the proposed method may be considered effective for the diagnosis of IPF.

Mannan-Binding Lectin Reduces Epithelial-Mesenchymal Transition in Pulmonary Fibrosis via Inactivating the Store-Operated Calcium Entry Machinery

Idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia with a poor clinical prognosis. Increasing evidence has demonstrated that epithelial-mesenchymal transition (EMT) contributes to the production of pathogenic myofibroblasts and plays a pivotal role in the development of pulmonary fibrosis. Mannan-binding lectin (MBL) is a soluble calcium-dependent complement molecule. Several studies have reported associations between serum MBL levels and lung diseases; however, the effect of MBL on IPF remains unknown. The present study observed aggravated pulmonary fibrosis in bleomycin-treated MBL−/− mice compared with their wild-type counterparts. Lung tissues from bleomycin-treated MBL−/− mice displayed a more severe EMT phenotype. In vitro studies determined that MBL inhibited the EMT process through attenuating store-operated calcium entry (SOCE) signaling. It was further demonstrated that MBL promoted the ubiquitination of Orai1, an essential component of SOCE, via pyruvate dehydrogenase kinase 1 (PDK1)-serum glucocorticoid-regulated kinase 1 signaling. PDK1 inhibition abolished the MBL-mediated regulation of SOCE activity and the EMT process. Notably, biochemical analysis showed that MBL interacted with PDK1 and contributed to PDK1 ubiquitination. In summary, the present findings suggested that MBL limited the EMT phenotype in human alveolar epithelial cells through regulation of SOCE, and MBL could be recognized as a potential therapeutic target for IPF.

Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation.

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

GOOD COP OR BAD COP: USE OF MACROLIDES TO ARREST THE INFLAMMATORY TURMOIL OF CRYPTOGENIC ORGANIZING PNEUMONIA

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cryptogenic organizing pneumonia (COP) represents a rare type of idiopathic interstitial pneumonia that is characterized by the recruitment of inflammatory cells and deposition of fibrinous material in the form of intraluminal plugs within alveolar ducts and surrounding alveoli. Clinical symptoms include subacute shortness of breath, cough, and fever, and radiological findings include peripheral, patchy, and peribronchovascular regions of ground-glass opacities (GGOs), consolidation on chest CT. CASE PRESENTATION: A 67-year-old man presented to the Pulmonology clinic with 3 months history of worsening shortness of breath(SOB) associated with a cough with white sputum. CT chest revealed widespread GGOs suspicious for a diffuse interstitial lung process. The physical exam was unremarkable except for some dry inspiratory crackles with no wheezing. Serum studies, including inflammatory markers such as sedimentation rate and C-reactive protein, were normal. Autoimmune assays and the Quantiferon Gold test for tuberculosis were negative. Pulmonary function testing was consistent with a restrictive pattern. Bronchoscopy with transbronchial biopsies was performed for further evaluation and negative for any malignant process or infectious etiologies. The patient was started empirically on prednisone with little symptomatic and radiologic improvement at a 2-month interval. Hypersensitivity pneumonitis or a nonspecific interstitial pneumonitis variant of interstitial lung disease were considered and, hence, mycophenolate was added to the patient's steroid regimen. Despite this intensive immunosuppressive therapy, the patient returned to the clinic with a worsening SOB and cough with yellowish, mucopurulent sputum. His immunosuppressive agents were stopped and a repeat bronchoscopy with transbronchial biopsies was obtained that was, again, inconclusive. A multidisciplinary discussion with Infectious Disease and Thoracic Surgery ensued and a surgical biopsy was obtained that revealed findings suggestive of chronic COP. Considering the patient's poor clinical response to steroid therapy alone, a trial of azithromycin was initiated following consultation with Pulmonologists at other US facilities. Patient-reported a remarkable improvement in symptoms at 3 months follow-up with a near resolution of GGOs on chest CT. DISCUSSION: COP is remarkably responsive to steroid therapy, but relapse is common. Steroid-sparing agents such as cyclophosphamide and azathioprine have been used as alternatives with inconsistent benefits and poor tolerability. The anti-inflammatory properties of macrolide antibiotics are well known and have been explored in recent times with few case reports showing promising results. CONCLUSIONS: This case report demonstrates the clinical utility of macrolide antibiotics in the management of COP and conveys the importance of exploring this approach further to improve clinical outcomes in COP. REFERENCE #1: Pathak V, Kuhn JM, Durham C, Funkhouser WK, Henke DC. Macrolide use leads to clinical and radiological improvement in patients with cryptogenic organizing pneumonia. Ann Am Thorac Soc. 2014 Jan;11(1):87-91. doi: 10.1513/AnnalsATS.201308-261CR. PMID: 24460438. REFERENCE #2: Stover DE, Mangino D. Macrolides: a treatment alternative for bronchiolitis obliterans organizing pneumonia? Chest. 2005 Nov;128(5):3611-7. doi: 10.1378/chest.128.5.3611. PMID: 16304320. DISCLOSURES: No relevant relationships by Tania Dhawan, source=Web Response No relevant relationships by Faisal Siddiqui, source=Web Response No relevant relationships by Naresh Veerabattini, source=Web Response

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 4. Cryptogenic Organizing Pneumonia.

Cryptogenic organizing pneumonia (COP) is a type of idiopathic interstitial pneumonia with an acute or subacute clinical course. Bilateral lung consolidations located in the subpleural area and bronchovascular bundle are the most common findings on chest high-resolution computed tomography. The pathologic manifestations include granulation tissue in the alveoli, alveolar ducts, and bronchioles. COP responds fairly well to glucocorticoid monotherapy with rapid clinical improvement, but recurrence is common. However, treatment with combined immunosuppressant agents is not recommended, even if the COP patient does not respond to glucocorticoid monotherapy with expert opinion.

Interstitial Score and Concentrations of IL-4Rα, PAR-2, and MMP-7 in Bronchoalveolar Lavage Fluid Could Be Useful Markers for Distinguishing Idiopathic Interstitial Pneumonias.

Idiopathic interstitial pneumonia (IIP) entails a variable group of lung diseases of unknown etiology. Idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, interstitial lung diseases related to connective tissue disease (CTD-ILD), and hypersensitivity pneumonitis (HP) can manifest with similar clinical, radiological, and histopathological features. In a differential diagnosis, biomarkers can play a significant role. We assume that levels of specific cyto- or chemokines or their receptors can signal pathogenetic processes in the lungs. Eighty patients with different types of idiopathic interstitial pneumonia were enrolled in this study. Cell counts and concentrations of tumor necrosis factor (TNF)-α, interleukin-4 receptor α, proteinase-activated receptor (PAR)-2, matrix metalloproteinase (MMP)-7, and B cell-activating factor were measured in bronchoalveolar lavage fluid using commercial ELISA kits. High resolution computer tomography results were evaluated using alveolar and interstitial (IS) score scales. Levels of TNF-α were significantly higher in HP compared to fibrosing IIP (p < 0.0001) and CTD-ILD (p = 0.0381). Concentrations of IL-4Rα, PAR-2, and MMP-7 were positively correlated with IS (p = 0.0009; p = 0.0256; p = 0.0015, respectively). Since TNF-α plays a major role in inflammation, our results suggest that HP is predominantly an inflammatory disease. From the positive correlation with IS we believe that IL-4Rα, PAR-2, and MMP-7 could serve as fibroproliferative biomarkers in differential diagnosis of IIP.

Prognosis after acute exacerbation in patients with interstitial lung disease other than idiopathic pulmonary fibrosis.

Acute exacerbation (AE) is recognized as a life-threatening condition with acute respiratory worsening in idiopathic pulmonary fibrosis (IPF). AE also occurs in fibrotic interstitial lung disease (ILD) other than IPF, including other types of idiopathic interstitial pneumonias (IIPs), ILD associated with collagen vascular disease (CVD-ILD), and chronic hypersensitivity pneumonia (CHP). However, the clinical impact after AE in those patients is still unclear. A retrospective review of 174 consecutive first-episodes with AE of ILD in our institution from 2002 to 2016 was performed. AE was defined according to the revised definition and diagnostic criteria proposed by an international working group in 2016. Clinical characteristics, 90-day survival, and the requirement of long-term oxygen therapy (LTOT) after AE were evaluated in each underlying ILD. There were 102 patients with AE of IPF (AE-IPF) and 72 with AE of ILD other than IPF, including non-IPF IIPs (n=29) and secondary ILD (n=43) [CVD-ILD (n=39), CHP (n=4)]. In CVD-ILD, rheumatoid arthritis (n=17) was most common. The 90-day mortality after AE was 57% in IPF, 29% in non-IPF IIPs, and 33% in secondary ILD. After AE, ILD other than IPF had a significantly better survival rate than IPF (P<0.001). Among survivors, the rates of patients requiring LTOT after AE were 63% in IPF, 35% in non-IPF IIPs, and 46% in secondary ILD, respectively. AE of ILD other than IPF might have a better prognosis than AE-IPF, but both are fatal conditions that cause chronic respiratory failure.

IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages.

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has one of the poorest prognosis. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined that IL-24, an IL-20 subfamily cytokine member, was increased both in the serum of IPF patients and the bronchoalveolar lavage fluid (BALF) of mice following bleomycin (BLM)-induced pulmonary fibrosis. As a result, IL-24 deficiency protected mice from BLM-induced lung injury and fibrosis. Specifically, loss of IL-24 significantly attenuated transforming growth factor β1 (TGF-β1) production and reduced M2 macrophage infiltration in the lung of BLM-induced mice. Mechanistically, IL-24 alone did not show a perceptible impact on the induction of M2 macrophages, but it synergized with IL-4 to promote M2 program in macrophages. IL-24 suppressed IL-4-induced expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, through which it enhanced signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma (STAT6/PPARγ) signaling, thereby promoting IL-4-induced production of M2 macrophages. Collectively, our data support that IL-24 synergizes with IL-4 to promote macrophage M2 program contributing to the development of pulmonary fibrosis.

Interstitial lung disease and diabetes.

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has been steadily increasing all over the world. DM and its associated micro and macrovascular complications result in significant morbidity and mortality. The microvascular complications are usually manifested as retinopathy, neuropathy, nephropathy and macrovascular complications generally affect the cardiovascular system. In addition to these complications, DM also affects the lungs because of its rich vascularity and abundance in connective tissue (collagen and elastin). DM has been found to cause microvascular complications and proliferation of extracellular connective tissue in the lungs, leading to decline in lung function in a restrictive pattern. Interstitial lung disease (ILD) includes a diverse group of disease conditions characterized by different degrees of inflammation and fibrosis in the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of the common type of idiopathic interstitial pneumonia with a high mortality rate. IPF is characterized by chronic progressive fibrosis leading to progressive respiratory failure. In this review we focus on lung as the target organ in DM and the association of DM and ILD with special emphasis on IPF.

Evaluation of the Diagnostic Efficacies of Serological Markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in Idiopathic Interstitial Pneumonia

Background: The objective of this study was to evaluate the diagnostic value of serological markers Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), SP-D, chemokine ligand 2 (CCL2), and chemokine 13 (CXCL13) in idiopathic interstitial pneumonia (IIP). Methods: Patients with IIP aged 18–80 years from the First Affiliated Hospital of Guangzhou Medical University were enrolled in this retrospective case-control study. Data on the general patient characteristics, laboratory test results, chest high-resolution CT, and pulmonary function test results were collected. The diagnosis of idiopathic pulmonary fibrosis (IPF) was based on the international practice guidelines for the diagnosis and treatment of IPF, a collaborative effort published by the American Thoracic Society (ATS)/European Respiratory Association (ERS), Japanese Respiratory Society, and Latin American Thoracic Society. The diagnostic criteria of non-IPF (N-IPF) followed the consensus classification of the IIPs, which was jointly issued by the ATS and ERS in 2002. The diagnosis of interstitial pneumonia with autoimmune features (IPAF) was based on the official research statement on IPAF, which was jointly issued by the ATS and ERS in 2015. Serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were measured. The differences in the expression of these biomarkers and their correlation with the severity of the disease were analyzed. The sensitivity, specificity, cutoff value, and area under the curve (AUC) value for each of the indices were determined using the receiver operating characteristic (ROC) curve analysis. Findings: Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, ­SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. The detection of these markers was found to have better diagnostic efficacy in patients with IIP than in those with pneumonia. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide (DLCO; r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Although their expression levels along with that of SP-D were elevated in patients with IPF, N-IPF, and IPAF, it was difficult to distinguish between these 3 conditions by detecting the 5 serum biomarkers together. Our findings indicate that the serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enriched the study on serum markers for IIPs. Between September 2015 and October 2017, 69 patients with IIP. Of these patients, 19 had IPF, 23 had N-IPF, and 27 had IPAF. We also enrolled 20 age- and gender-matched patients with pneumonia and 15 uninfected individuals as normal control. The serum levels of KL-6, SP-A, SP-D, CCL2, and CXCL13 were significantly higher in patients with IIP than in patients with pneumonia and the normal controls. Of these markers above, KL-6 had the highest diagnostic value (AUC 0.96, 95% CI 0.93–0.99). Based on a logistics regression analysis, the combination of KL-6, CCL2, and CXCL13 had an improved diagnostic efficacy for IIP. In patients with IIP, the serum levels of KL-6, SP-A, CCL2, and CXCL13 all showed a significant negative correlation with the DLCO (r = –0.36, –0.37, –0.36, –0.30, respectively; all p < 0.05). Our findings indicate that the serum levels of KL-6, ­SP-A, SP-D, CCL2, and CXCL13 are notably elevated in patients with IIP and show significant correlation with the severity of interstitial lung lesions. Additionally, we further explore the diagnostic efficacy of 5 biomarkers in different types of IIP. It is the first time that the level of serum marker CXCL13 of N-IPF and IPAF patients was higher than IPF patients, which further enrich the study on serum markers in IIPs. Interpretation: Although the combined detection of KL-6, CCL3, and CXCL13 significantly improves the diagnosis of IIP, detection of all the 5 markers together is unable to distinguish between IPF, N-IPF, and IPAF.

Differences in small airway lesions in patients with different types of idiopathic interstitial pneumonia

Objective: To investigate the differences in small airway lesions in patients with different types of idiopathic interstitial pneumonia (IIPs). Methods: A total of 46 patients with IIPs confirmed by video assisted thoracoscopic or open lung biopsy, hospitalized in the Respiratory and Critical Care Medicine of Beijing Chao-Yang Hospital, from Dec. 1998 through Nov. 2007 were studied, including 19 patients with idiopathic pulmonary fibrosis (IPF group), 14 with nonspecific interstitial pneumonia (NSIP group), and 13 cryptogenic organizing pneumonia (COP group). Pulmonary function and high resolution CT (HRCT) of the patients were examined before lung biopsy, and lung biopsy tissue were stained with hematoxylin-eosin. The abnormality of small airways in pathology, pulmonary function and HRCT were compared among these patients with IIPs. Results: Small airway inflammatory cell infiltration score (53.8±17.7) was significantly higher in the COP group than in the IPF group (38.8±9.7) (P<0.01). The fibrous tissue proliferation score in small airways (42.9±12.1) in the IPF group was significantly higher than that in the NSIP group (31.4±10.5) and the COP group (26.7±16.3) (both P<0.05). In the IPF group, NSIP group and COP group, the small airway function index was significantly reduced, and the maximum expiratory flow rate (V(25%), V(50%)) at 25% and 50% of the lung capacity was<80% predicted, the incidences of small airway dysfunction in the three groups were 63.2%, 69.2%, and 63.6%, respectively. There was no significant difference among the groups (P>0.05). Small airway inflammatory cell infiltration was negatively correlated with V(50%) of small airway function (r=-0.305, P=0.049). The bronchodilation rate in the HRCT of the IPF group (100%) was significantly higher than that of the NSIP group (50.0%) and the COP group (53.8%) (both P<0.01). Conclusion: The patients with IPF, NSIP and COP have abnormal pathologic, physiological and imaging changes of small airways, moreover have different characteristics.

Differences Between Patients With Idiopathic Pleuroparenchymal Fibroelastosis and Those With Other Types of Idiopathic Interstitial Pneumonia in Candidates for Lung Transplants

IntroductionThe prognostic implications of having patients with idiopathic pleuroparenchymal fibroelastosis (IPPFE) on lung transplantation waiting lists have been unclear. In Japan, where a severe shortage of brain-dead donors remains a major limitation for organ transplantation, it is particularly important to predict the prognoses of patients when they are listed for transplantation. The purpose of this study was to investigate the characteristics of lung transplantation candidates with IPPFE and the influence of those characteristics on prognosis. MethodsThis was a retrospective review of 29 consecutive adult lung transplant candidates with idiopathic interstitial pneumonia between January 2014 and April 2018. ResultsEight patients with IPPFE and 21 with other types of idiopathic interstitial pneumonia were included. Body mass index (median 17.1 kg/m2 vs 23.5 kg/m2, P < .01) and ratio of anteroposterior to transverse diameter of the thoracic cage were significantly lower (0.530 vs 0.583, P = .02) in the IPPFE group. Patients with a body mass index <20.0 kg/m2 (P = .02), 6-minute walk distance <250.0 m (P < .01), ratio of PaO2 to fraction of inspiratory oxygen <300.0 mm Hg (P < .01), and an inability to perform the diffusing capacity of carbon monoxide test (P < .01) had significantly shorter survival times in the other idiopathic interstitial pneumonia, but not in the IPPFE, group. Some patients with IPPFE survived for long enough to undergo transplantation. ConclusionsPatients with IPPFE waiting for transplantation have some distinctive characteristics and should be retained on waiting lists to receive transplants.

Causes of Pulmonary Fibrosis in the Elderly.

Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown, several pathogenic pathways have been described that could explain this process, involving aging, environmental factors, genomic instability, loss of proteostasis, telomere attrition, epigenetic changes, mitochondrial dysfunction, cell senescence, and altered intercellular communication. One of the main prognostic factors for the development of IPF in broad epidemiological studies is age. The incidence increases with age, making this a disease that predominantly affects the elderly population, being exceptional under 45 years of age. However, the degree to which each of these mechanisms is involved in the etiology of the uncontrolled fibrogenesis that defines IPF is still unknown. Clarifying these questions is crucial to the development of points of intervention in the pathogenesis of the disease. This review briefly summarizes what is known about each possible etiological factor, and the questions that most urgently need to be addressed.

Lung transplantation in IIP: A review.

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long-term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post-transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long-term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.

Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanib

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and is characterized by a poor prognosis, with an estimated 5-year survival of approximately 20%. Progressive and irreversible lung functional impairment leads to chronic respiratory insufficiency with a severely impaired quality of life. In the last 2 decades, novel treatments for IPF have been developed as a consequence of an increasing understanding of disease pathogenesis and pathobiology. In IPF, injured dysfunctional alveolar epithelial cells promote fibroblast recruitment and proliferation, resulting in scarring of the lung tissue. Recently, pirfenidone and nintedanib have been approved for the treatment of IPF, having shown efficacy to slow functional decline and disease progression. This article focuses on the pharmacologic characteristics and clinical evidence supporting the use of nintedanib, a potent small-molecule tyrosine kinase inhibitor, as therapy for IPF. After introducing the mechanism of action and pharmacokinetics, an overview of the safety and efficacy results from the most recent clinical trials of nintedanib in IPF is presented.

特発性器質化肺炎患者に対して積極的呼吸理学療法を実施した一症例

〔目的〕特発性器質化肺炎（COP）に対する呼吸理学療法の有効性を検討することとした．〔対象〕COP患者一症例とした．〔方法〕症例研究法を用いて，初期（1週），最終（7週）の肺機能検査，心肺運動負荷試験，長崎大学呼吸器疾患日常生活活動評価表（NRADL）の評価結果を比較した．〔結果〕症例の運動耐容能，NRADLが改善した．〔結語〕Idiopathic Interstitial Pneumonias（以下，IIPs）の病型分類に基づく呼吸理学療法はCOP患者に対して有効であることが示唆される．

Diagnosis of idiopathic pulmonary fibrosis: Current issues.

Idiopathic pulmonary fibrosis (IPF) accounts for the majority of lung diseases classified as idiopathic interstitial pneumonia (IIP). It is considered to be lethal because prognosis is very poor and far worse than other types of IIP. An early and accurate diagnosis of IPF is critical. The diagnostic process is complex and requires a multidisciplinary approach involving a pulmonologist, radiologist and pathologist.