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BACKGROUND: The role of radiology in the diagnosis of interstitial lung diseases (ILDs) has evolved over time, in part replacing histology. Radiology now represents a pillar of diagnostics and monitoring in ILDs. OBJECTIVE: To what extent does radiology influence diagnostics and treatment in ILDs? MATERIALS AND METHODS: A literature review was conducted, and current findings were discussed in the context of clinical data. RESULTS: Radiology plays a crucial role in the diagnosis of ILDs. Within the framework of the multidisciplinary conference, it provides specific CT patterns such as usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and organizing pneumonia (OP), or helps in identifying cystic lung diseases. Multicompartment diseases can be detected, and pulmonary hypertension or extrapulmonary involvement of the respective diseases can be suspected. Progressive pulmonary fibrosis requires radiologic assessment as one of the required criteria. Interstitial lung abnormalities are usually detected by radiological studies performed for an unrelated indication. CONCLUSION: Radiology plays an important role within the multidisciplinary conference to determine both diagnosis and treatment with antifibrotic or anti-inflammatory drugs, or a combination of both.
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Enfermedades Pulmonares Intersticiales , Tomografía Computarizada por Rayos X , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Pulmonares Intersticiales/diagnóstico , Humanos , Tomografía Computarizada por Rayos X/métodos , Diagnóstico DiferencialRESUMEN
High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.
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The fibrotic fibroblasts derived from idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are surrounded by specific environments, characterized by increased stiffness, aberrant extracellular matrix (ECM) composition, and altered lung architecture. The presented research was aimed at investigating the effect of biological, physical, and topographical modification of the substrate on the properties of IPF- and NSIP-derived fibroblasts, and searching for the parameters enabling their identification. Soft and stiff polydimethylsiloxane (PDMS) was chosen for the basic substrates, the properties of which were subsequently tuned. To obtain the biological modification of the substrates, they were covered with ECM proteins, laminin, fibronectin, and collagen. The substrates that mimicked the 3D structure of the lungs were prepared using two approaches, resulting in porous structures that resemble natural lung architecture and honeycomb patterns, typical of IPF tissue. The growth of cells on soft and stiff PDMS covered with proteins, traced using fluorescence microscopy, confirmed an altered behavior of healthy and IPF- and NSIP-derived fibroblasts in response to the modified substrate properties, enabling their identification. In turn, differences in the mechanical properties of healthy and fibrotic fibroblasts, determined using atomic force microscopy working in force spectroscopy mode, as well as their growth on 3D-patterned substrates were not sufficient to discriminate between cell lines.
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Neumonías Intersticiales Idiopáticas , Fibrosis Pulmonar Idiopática , Humanos , Neumonías Intersticiales Idiopáticas/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Fibroblastos/metabolismoRESUMEN
BACKGROUND: The aim of the research presented here was to find a set of parameters enabling discrimination between three types of fibroblasts, i.e., healthy ones and those derived from two disorders mimicking each other: idiopathic pulmonary fibrosis (IPF), and nonspecific interstitial pneumonia (NSIP). METHODS: The morphology and growth of cells were traced using fluorescence microscopy and analyzed quantitatively using cell proliferation and substrate cytotoxicity indices. The viability of cells was recorded using MTS assays, and their stiffness was examined using atomic force microscopy (AFM) working in force spectroscopy (FS) mode. To enhance any possible difference in the examined parameters, experiments were performed with cells cultured on substrates of different elasticities. Moreover, the chemical composition of cells was determined using time-of-flight secondary ion mass spectrometry (ToF-SIMS), combined with sophisticated analytical tools, i.e., Multivariate Curve Resolution (MCR) and Principal Component Analysis (PCA). RESULTS: The obtained results demonstrate that discrimination between cell lines derived from healthy and diseased patients is possible based on the analysis of the growth of cells, as well as their physical and chemical properties. In turn, the comparative analysis of the cellular response to altered stiffness of the substrates enables the identification of each cell line, including distinguishing between IPF- and NSIP-derived fibroblasts.
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Proliferación Celular/fisiología , Fibroblastos/patología , Neumonías Intersticiales Idiopáticas/patología , Fibrosis Pulmonar Idiopática/patología , Anciano , Línea Celular , Elasticidad/fisiología , Femenino , Humanos , Pulmón/patologíaRESUMEN
This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.
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BACKGROUND: There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD). METHODS: Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated. RESULTS: A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012). CONCLUSIONS: These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy.
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Artritis Reumatoide/complicaciones , Artritis Reumatoide/terapia , Bronquiolitis/diagnóstico por imagen , Bronquiolitis/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Pulmón/diagnóstico por imagen , Intensificación de Imagen Radiográfica , Radiografía Torácica , Tomografía Computarizada por Rayos X , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Sedimentación Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies. However, recent animal model data are incongruous with established paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development of effective interventions for RA-ILD.
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Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/etiología , Animales , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/epidemiología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Interstitial lung diseases are heterogeneous, and patients with chronic fibrosing interstitial pneumonia (CFIP) often have clinical, serologic, and morphologic features suggestive but not diagnostic of connective tissue disease. Recently, the concept of interstitial pneumonia with autoimmune features (IPAF) has been proposed as a platform for such patients. However, the prognostic role of IPAF, including the cumulative incidence of acute exacerbations (AEs), is not fully clear. The aim of this study was to elucidate the clinical features and prognostic significance of IPAF. METHODS: The clinical characteristics and prognostic relevance of a diagnosis of IPAF were retrospectively explored in 194 patients with CFIP, including 163 with idiopathic pulmonary fibrosis (IPF) and 31 with nonspecific interstitial pneumonia (NSIP), in our interstitial lung disease database. RESULTS: Sixteen percent of patients with CFIP (8% of IPF, 61% of NSIP) met the criteria for IPAF. Patients with IPAF were significantly younger and included a higher proportion of women, never-smokers, and patients with NSIP than those without IPAF. The morphologic domain was the most common in patients with IPAF (97%), followed by the serologic domain (72%) and clinical domain (53%). CFIP patients with IPAF had a more favorable prognosis with regard to overall survival (OS; Pâ¯<â¯0.001, log-rank test) and incidence of AEs (Pâ¯=â¯0.029, Gray's test) than those without IPAF. In the subgroup analysis, NSIP patients with IPAF had significantly better survival than those without IPAF (Pâ¯=â¯0.031, log-rank test), and IPF patients with IPAF tended to have better OS than those without IPAF (Pâ¯=â¯0.092, log-rank test). However, there were no significant differences in the incidence of AEs between patients with IPAF and those without IPAF in the IPF and NSIP subgroups. Furthermore, fulfilment of the IPAF criteria was an independent predictor of OS (hazard ratio (HR) 0.127; 95% confidence interval (CI) 0.017-0.952; Pâ¯=â¯0.045) and incidence of AEs (HR 0.225: 95% CI 0.054-0.937; Pâ¯=â¯0.040). CONCLUSIONS: A diagnosis of IPAF might predict a favorable prognosis and less risk of AEs in patients with CFIP.
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Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Anciano , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades del Tejido Conjuntivo/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/inmunología , Fibrosis Pulmonar Idiopática/patología , Incidencia , Pulmón/inmunología , Pulmón/patología , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: The aim of this study was to evaluate the incidence and clinical features of patients who developed collagen vascular disease (CVD) after an initial diagnosis of idiopathic nonspecific interstitial pneumonia (NSIP). METHODS: We conducted a retrospective review of 72 consecutive patients with NSIP who were diagnosed by surgical lung biopsy in our institution (idiopathic NSIP, n = 35; CVD-NSIP, n = 37 at initial diagnosis). No patients fulfilled the American College of Rheumatology criteria for a diagnosis with CVD within six months after the diagnosis of idiopathic NSIP. RESULTS: Of 35 patients initially diagnosed with idiopathic NSIP, six patients (17.1%) developed CVD during the follow-up period (5.5 ± 5.0 years); three patients were diagnosed with dermatomyositis (DM), two patients with overlap syndrome (DM and Sjogren's syndrome), and one patient with rheumatoid arthritis. The mean time until CVD diagnosis was 2.0 years (six months - 3.5 years), and the one-, two- and three-year incidences of CVD development were 3.6%, 15.2% and 20.0%, respectively. There was no significant difference in clinical characteristics and survival among patients with NSIP preceding CVD diagnosis, those with idiopathic NSIP, or those with CVD-NSIP. In addition, at the time of initial diagnosis, there was no significant difference for the fulfillment of previous criteria such as interstitial pneumonia with autoimmune feature (IPAF) between patients with NSIP preceding CVD diagnosis and those with idiopathic NSIP. CONCLUSIONS: It is difficult to predict CVD occurrence and careful attention is needed to detect the development of CVD in patients with idiopathic NSIP.
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Colágeno/metabolismo , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/epidemiología , Neumonías Intersticiales Idiopáticas/complicaciones , Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/epidemiología , Adulto , Anciano , Artritis Reumatoide/patología , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/patología , Enfermedades del Tejido Conjuntivo/patología , Dermatomiositis/patología , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/patología , Incidencia , Pulmón/patología , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Sjögren/patología , Fumar/epidemiología , Tomógrafos Computarizados por Rayos X , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/patologíaRESUMEN
BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has recently been proposed as a histologic type of idiopathic interstitial pneumonia (IIP), but its broad spectrum of clinicopathologic findings and variable prognosis are poorly understood. It is particularly unclear how NSIP and usual interstitial pneumonia (UIP) are related. The present study investigated the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP. METHODS: The clinicopathologic findings and prognosis in 21 NSIP and 18 UIP patients who underwent surgical or video-assisted thoracoscopic lung biopsy were reviewed. RESULTS: NSIP was more frequent in women and showed nonspecific clinical manifestations. High-resolution computed tomography (HRCT) demonstrated ground-glass, net-like, and patchy attenuation in both lungs. Semiquantitative HRCT showed a median fibrosis score of 3 (range, 0 to 7) in NSIP patients and 5 (range, 2 to 7) in UIP patients (P<0.01). On histopathologic examination, NSIP cases were heterogeneous and the findings could be categorized into cellular and fibrosing patterns. The mean age of the NSIP and UIP patients was 48 and 60 years, respectively. The frequencies of fibroblast foci, myogelosis, honeycomb lesions, and pulmonary structural destruction in NSIP and UIP patients were 16.7% and 100% (P<0.001), 22.2% and 85.7% (P<0.05), 16.7% and 92.9% (P<0.001), and 27.8% and 100% (P<0.05), respectively. The responses to glucocorticoid treatment and the prognosis were significantly greater in NSIP than those in UIP. CONCLUSIONS: NSIP was difficult to be differentiated from UIP by general clinical manifestations, but HRCT can be helpful for this purpose. Definitive diagnosis depends on the results of surgical lung biopsy.
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Idiopathic pulmonary fibrosis is a difficult disease to diagnose. Idiopathic pulmonary fibrosis is a member of a class of diseases known as idiopathic interstitial pneumonias. Other members include nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and lymphocytic interstitial pneumonia. Usual interstitial pneumonia (UIP) is the pathological equivalent of idiopathic pulmonary fibrosis. Prior to 2011, the diagnosis was based on major and minor criteria, but because these criteria were not evidence based, the criteria were modified by consensus from the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. These new criteria now include satisfying three core requirements, including exclusion of other possible cause of interstitial lung disease, specific findings of usual interstitial pneumonia on high resolution computed tomography, and a combination of "possible UIP" findings on high resolution computed tomography and UIP findings on lung biopsy. Idiopathic pulmonary fibrosis is a severe, progressive disease with limited treatment options, and exacerbations are associated with a high degree of morbidity and mortality.
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Fibrosis Pulmonar Idiopática/diagnóstico , Animales , Biopsia , Diagnóstico Diferencial , Humanos , Fibrosis Pulmonar Idiopática/etiología , Fibrosis Pulmonar Idiopática/terapia , Enfermedades Pulmonares Intersticiales/diagnóstico , Guías de Práctica Clínica como Asunto , Tomografía Computarizada por Rayos X/métodosRESUMEN
Interstitial pneumonia is a heterogenous group of inflammatory and fibrosing lesions that manifest themselves as infiltrative lung disease. Of these, nonspecific interstitial pneumonia is characterized as a variable degree of interstitial inflammation with or without fibrosis and is distinguished from usual interstitial pneumonia and desquamative interstitial pneumonia, histologically. The influx of inflammatory cells and the responses of immune effector cells injury to the alveolar wall and these initial injuries results in alveolitis and fibrosis. Consequently, the gas exchange throughout the alveolar wall is impaired and the patients suffer from lung diseases of a restrictive pattern. The chief complaints represented are dyspnea and dry cough. We experienced a case of nonspecific interstitial pneumonia in a 10-year old girl. The patient had been healthy and had not been exposed to organic dusts or other toxic materials. The pathology of lung biopsy tissue showed that the alveoli were thickened by a mixture of chronic inflammatory cells and collagen type fibrosis. High resolution computed tomography(HRCT) found the patchy areas of ground-glass opacity with patchy consolidation and irregular reticular opacity, and diffuse distribution without zonal predominance. The forced vital capicity(FVC) was 31%, forced expiratory volume in one second (FEV1) 29% and FEV1/FVC 90%, so a restrictive pulmonary insufficiency was found.