Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4.

Pulmonary fibrosis is a progressive, dysregulated response to injury culminating in compromised lung function due to excess extracellular matrix production. The heparan sulfate proteoglycan syndecan-4 is important in mediating fibroblast-matrix interactions, but its role in pulmonary fibrosis has not been explored. To investigate this issue, we used intratracheal instillation of bleomycin as a model of acute lung injury and fibrosis. We found that bleomycin treatment increased syndecan-4 expression. Moreover, we observed a marked decrease in neutrophil recruitment and an increase in both myofibroblast recruitment and interstitial fibrosis in bleomycin-treated syndecan-4-null (Sdc4-/-) mice. Subsequently, we identified a direct interaction between CXCL10, an antifibrotic chemokine, and syndecan-4 that inhibited primary lung fibroblast migration during fibrosis; mutation of the heparin-binding domain, but not the CXCR3 domain, of CXCL10 diminished this effect. Similarly, migration of fibroblasts from patients with pulmonary fibrosis was inhibited in the presence of CXCL10 protein defective in CXCR3 binding. Furthermore, administration of recombinant CXCL10 protein inhibited fibrosis in WT mice, but not in Sdc4-/- mice. Collectively, these data suggest that the direct interaction of syndecan-4 and CXCL10 in the lung interstitial compartment serves to inhibit fibroblast recruitment and subsequent fibrosis. Thus, administration of CXCL10 protein defective in CXCR3 binding may represent a novel therapy for pulmonary fibrosis.

Destaques das diretrizes de doenças pulmonares intersticiais da Sociedade Brasileira de Pneumologia e Tisiologia

As doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.

Classification of interstitial lung disease patterns using local DCT features and random forest.

Over the last decade, a plethora of computer-aided diagnosis (CAD) systems have been proposed aiming to improve the accuracy of the physicians in the diagnosis of interstitial lung diseases (ILD). In this study, we propose a scheme for the classification of HRCT image patches with ILD abnormalities as a basic component towards the quantification of the various ILD patterns in the lung. The feature extraction method relies on local spectral analysis using a DCT-based filter bank. After convolving the image with the filter bank, q-quantiles are computed for describing the distribution of local frequencies that characterize image texture. Then, the gray-level histogram values of the original image are added forming the final feature vector. The classification of the already described patches is done by a random forest (RF) classifier. The experimental results prove the superior performance and efficiency of the proposed approach compared against the state-of-the-art.

Sputum cytology in the diagnosis of pulmonary paracoccidioidomycosis

The presence of Paracoccidioides brasiliensis was determined in sputum samples from 50 patients with paracoccidioidomycosis using four different techniques: (a) cell-block preparations stained with silver methenamine, (b) direct microbiologie examination, (c) smears stained with Shorr, and (d) smears stained with silver methenamine. Overall, cell-block preparations and smears stained with silver methenamine proved to be the most sensitive techniques, followed by smears stained with Shorr and direct microbiologic examination in decreasing order of sensitivity. Sputum cytology tended to be less positive in patients with interstitial pulmonary lesions as determined by chest X-ray than in patients with alveolar lesions. In addition to its high sensitivity, cell-block preparation technique allows storage of blocks and slides for further studies. © 1991 Kluwer Academic Publishers.

When and how to treat pulmonary non-tuberculous mycobacterial diseases

Nontuberculous mycobacteria are ubiquitous environmental organisms that have been recognised as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12-24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side effects. Published success rates range from 30-82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomised controlled trials in well described patients would provide stronger evidence-based data to guide therapy of NTM lung diseases, and thus are much needed.

Lung health care for Aboriginal and Torres Strait Islander Queenslanders : breathing easy is not so easy

Objectives In Aboriginal and Torres Strait Islander peoples in Queensland, to (a) determine the disease burden of common chronic lung diseases and (b) identify areas of need with respect to lung health services. Methods Literature reviews and analyses of hospitalisation and mortality data were used to describe disease epidemiology and available programs and services. Key stakeholder interviews and an online survey of health professionals were used to evaluate lung health services across the state and to identify services, needs and gaps. Results Morbidity and mortality from respiratory diseases in the Indigenous population is substantially higher than the non-Indigenous population across all age groups and regions. There are inadequate clinical services and resources to address disease prevention, detection, intervention and management in an evidence-based and culturally acceptable fashion. There is a lack of culturally appropriate educational resources and management programs, insufficient access to appropriately engaged Indigenous health professionals, a lack of multi-disciplinary specialist outreach teams, fragmented information systems and inadequate coordination of care. Conclusions Major initiatives are required at all levels of the healthcare system to adequately address service provision for Indigenous Queenslanders with lung diseases, including high quality research to investigate the causes for poor lung health, which are likely to be multifactorial.

Molecular basis for the development of diagnostic methods and specific treatment modalities for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unknown aetiology and poor prognosis. IPF is characterized by alveolar epithelial damage that leads tissue remodelling and ultimately to the loss of normal lung architecture and function. Treatment has been focused on anti-inflammatory therapies, but due to their poor efficacy new therapeutic modalities are being sought. There is a need for early diagnosis and also for differential diagnostic markers for IPF and other interstitial lung diseases. The study utilized patient material obtained from bronchoalveolar lavage (BAL), diagnostic biopsies or lung transplantation. Human pulmonary fibroblast cell cultures were propagated and asbestos-induced pulmonary fibrosis in mice was used as an experimental animal model of IPF. The possible markers for IPF were scanned by immunohistochemistry, RT-PCR, ELISA and western blot. Matrix metalloproteinases (MMPs) are proteolytic enzymes that participate in tissue remodelling. Microarray studies have introduced potential markers that could serve as additional tools for the assessment of IPF and one of the most promising was MMP 7. MMP-7 protein levels were measured in the BAL fluid of patients with idiopathic interstitial lung diseases or idiopathic cough. MMP-7 was however similarly elevated in the BAL fluid of all these disorders and thus cannot be used as a differential diagnostic marker for IPF. Activation of transforming growth factor (TGF)-ß is considered to be a key element in the progression of IPF. Bone morphogenetic proteins (BMP) are negative regulators of intracellular TGF-ß signalling and BMP-4 signalling is in turn negatively regulated by gremlin. Gremlin was found to be highly upregulated in the IPF lungs and IPF fibroblasts. Gremlin was detected in the thickened IPF parenchyma and endothelium of small capillaries, whereas in non-specific interstitial pneumonia it localized predominantly in the alveolar epithelium. Parenchymal gremlin immunoreactivity might indicate IPF-type interstitial pneumonia. Gremlin mRNA levels were higher in patients with end-stage fibrosis suggesting that gremlin might be a marker for more advanced disease. Characterization of the fibroblastic foci in the IPF lungs showed that immunoreactivity to platelet-derived growth factor (PDGF) receptor-α and PDGF receptor-β was elevated in IPF parenchyma, but the fibroblastic foci showed only minor immunoreactivity to the PDGF receptors or the antioxidant peroxiredoxin II. Ki67 positive cells were also observed predominantly outside the fibroblastic foci, suggesting that the fibroblastic foci may not be composed of actively proliferating cells. When inhibition of profibrotic PDGF-signalling by imatinib mesylate was assessed, imatinib mesylate reduced asbestos-induced pulmonary fibrosis in mice as well as human pulmonary fibroblast migration in vitro but it had no effect on the lung inflammation.

Pneumopathies interstitielles diffuses idiopathiques [Idiopathic interstitial pneumonias].

Idiopathic interstitial pneumonias represent approximately 30% of all interstitial lung diseases. The new classification of idiopathic interstitial pneumonias published in 2013 distinguishes 6 major entities, including chronic fibrosing forms (idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia), acute/subacute forms (cryptogenic organizing pneumonia and acute interstitial pneumonia) and smoking-related disorders (respiratory bronchiolitis interstitial lung disease and desquamative interstitial pneumonia). Pleuroparenchymal fibroelastosis is individualized as a new rare clinco-pathologic entity. For cases not fitting any specific clinic- pathological category, a pragmatic classification based on disease behavior is proposed.

Hallazgos radiológicos de la enfermedad pulmonar en pacientes Colombianos con esclerodermia

La esclerosis sistémica (ES) es una enfermedad autoinmune multisistémica que afecta principalmente la piel, los pulmones, el tracto gastrointestinal, el corazón y los riñones. La enfermedad pulmonar, presente en casi el 100% de los casos, es el factor con mayor influencia en la mortalidad. El propósito de este estudio es realizar un análisis detallado de la enfermedad pulmonar por tomografía computarizada de alta resolución(TCAR) en pacientes Colombianos con ES, para lo cual se realizó un estudio de prevalencia analítica en 44 pacientes con ES valorados en el Hospital Universitario Mayor Méderi en los últimos 7 años. Los resultados mostraron características demográficas y clínicas similares a las previamente descritas. La prevalencia de enfermedad pulmonar intersticial fue alta, y los hallazgos de fibrosis pulmonar como vidrio esmerilado y panal de abejas se asociaron con la presencia del autoanticuerpo antiSCL70. La medida del diámetro esofágico por TCAR fue mayor en los pacientes con disfagia, antiSCL 70 y linfopenia, los cuales son marcadores de mal pronóstico.

A robust approach for automated lung segmentation in thoracic CT

Lung segmentation in thoracic computed tomography (CT) scans is an important preprocessing step for computer-aided diagnosis (CAD) of lung diseases. This paper focuses on the segmentation of the lung field in thoracic CT images. Traditional lung segmentation is based on Gray level thresholding techniques, which often requires setting a threshold and is sensitive to image contrasts. In this paper, we present a fully automated method for robust and accurate lung segmentation, which includes a enhanced thresholding algorithm and a refinement scheme based on a texture-aware active contour model. In our thresholding algorithm, a histogram based image stretch technique is performed in advance to uniformly increase contrasts between areas with low Hounsfield unit (HU) values and areas with high HU in all CT images. This stretch step enables the following threshold-free segmentation, which is the Otsu algorithm with contour analysis. However, as a threshold based segmentation, it has common issues such as holes, noises and inaccurate segmentation boundaries that will cause problems in future CAD for lung disease detection. To solve these problems, a refinement technique is proposed that captures vessel structures and lung boundaries and then smooths variations via texture-aware active contour model. Experiments on 2,342 diagnosis CT images demonstrate the effectiveness of the proposed method. Performance comparison with existing methods shows the advantages of our method.

Linfonodo pulmonar na paracoccidioidomicose aguda infantil (relato de um caso).

The primary complex like Ghon was observed in a child's clinical roentgenographic study. C.S., white, male, 6 years old, was born in Curitiba (PR), Brazil and living in Guaratingueta (SP), Brazil, developed common cold, bimodal diary fever, chills, shake and sweats. Dyspnea, cough with general lymphadenopathy. Foot and right shoulder arthralgias. Six months ago visited a cave, equitation practice, dog and cat contacts and no transfusion, frontal sweats, fever (38.4 degrees C). T.A. was 8/6, tachycardia in generalized lymphadenopathy. Cardiopulmonary system was normal, mesogastric tumoral mass, hepatosplenomegaly and no ascites. Bone marrow with eosinophilia; nodule demonstrated presence of P. brasiliensis, hypoalbuminemia; hyperglobulinemia; anemia; leukocytosis with eosinophilia. Immunodiffusion with exoantigen 43 kd of P. brasiliensis was 1/32. Primary complex like Ghon was observed in interstitial pneumonia followed by mediastinal and mesogastric mass (35 to 40 days). Clavicular osteolytic lesions (45 to 60 days) appeared during paracoccidioidomycosis therapy. Recovery was observed 2 months after treatment of acute infantile paracoccidioidomycosis.

Preliminary diagnosis of ophtalmological diseases through machine learning techniques

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute respiratory distress syndrome secondary to antisynthetase syndrome is reversible with tacrolimus

Polymyositis and interstitial lung diseases, predominantly nonspecific interstitial pneumonia (NSIP), are known to be frequent in antisynthetase syndrome, where anti-aminoacyl-tRNA synthetase antibodies are often identified. An unusual case of acute respiratory distress syndrome, secondary to such proven NSIP of cellular type with predominant CD8 lymphocytes, is described herein. The patient described in the present case study initially had a poor recovery with high dose of steroids, but this was followed by a good improvement after the prescription of tacrolimus and a low dose of prednisone. A precise diagnosis in similar circumstances may be life-saving, allowing the successful application of new immunosuppressants.

Bacchus Neumonitis

Objective: Interstitial lung diseases (ILD) are a group of pathologies of undetermined frequency that require a broad differential diagnosis and continue to pose a challenge for clinicians. Observations: We present a clinical case of a 17-year-old male with acute interstitial pneumonitis, lung aspergillosis and foreign body lung granulomatosis after carbon monoxide (CO) intoxication. As far as we know, no similar cases have been reported in the literature. Conclusions: ILD require a broad differential diagnosis, which is of great importance to prognosis.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.