Jacobo Sellarés

Utilidad de la criobiopsia en el diagnóstico de la enfermedad pulmonar intersticial difusa : análisis de rentabilidad y coste

BACKGROUNDnAssessment of patients with suspected interstitial lung disease (ILD) includes surgical lung biopsy (SLB) when clinical and radiological data are inconclusive. However, cryobiopsy is acquiring an important role in the ILD diagnostic process. The objective of this study was to evaluate the diagnostic yield, safety and economic costs of the systematic use of cryobiopsy in the assessment of patients with suspected ILD.nnnMETHODSnThis was a retrospective observational study of patients who had undergone transbronchial cryobiopsy for evaluation of ILD from January 2011 to January 2014. The procedures were performed with a video bronchoscope using a cryoprobe for the collection of lung parenchyma specimens, which were analyzed by pathologists. Diagnostic yield, complications and economic costs of this technique were analyzed.nnnRESULTSnCriobiopsy specimens from a total of 33 patients were included. A specific diagnosis was obtained in 26, producing a diagnostic yield of 79%. In 5 patients, SLB was required for a histopathological confirmation of disease, but the procedure could not be performed in 4, due to severe comorbidities. The most frequent complications were pneumothorax (12%) and gradei (9%) or gradeii (21%) bleeding. There were no life-threatening complications. The systematic use of cryobiopsy saved up to €59,846.nnnCONCLUSIONnCryobiopsy is a safe and potentially useful technique in the diagnostic assessment of patients with ILD. Furthermore, the systematic use of cryobiopsy has an important economic impact.

Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia

Abstract Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables. We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: “presence” or “nonpresence” of bilateral Velcro crackles. Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (Pu200a=u200a0.002) and lung diffusion capacity for carbon monoxide (Pu200a=u200a0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (Pu200a=u200a0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern. In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.

Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model

Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14 Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis.

Towards a global initiative for fibrosis treatment (GIFT)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterised by increased scarring of lung tissue. Despite the recent introduction of novel drugs that slow disease progression, IPF remains a deadly disease, and the benefits of these new drugs differ markedly between patients. Human diseases arise due to alterations in an almost limitless network of interconnected genes, proteins, metabolites, cells and tissues, in direct relationship with a continuously changing macro- or microenvironment. Systems biology is a novel research strategy that seeks to understand the structure and behaviour of the so-called “emergent properties” of complex systems, such as those involved in disease pathogenesis, which are most often overlooked when just one element of disease pathogenesis is observed in isolation. This article summarises the debate that took place during a European Respiratory Society research seminar in Barcelona, Spain on December 15–16, 2016, which focused on how systems biology could generate new data by integrating the different IPF pathogenic levels of complexity. The main conclusion of the seminar was to create a global initiative to improve IPF outcomes by integrating cutting-edge international research that leverages systems biology to develop a precision medicine approach to tackle this devastating disease. A novel call to action for implementing systems biology in IPF research http://ow.ly/Is0A30gpnVb

Corticosteroids in acute exacerbations of idiopathic interstitial pneumonias: Time to debate: Correspondence

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The Burden of Comorbidity and Complexity in Sarcoidosis: Impact of Associated Chronic Diseases

PurposeTo evaluate comorbidity, complexity and poor outcomes in patients with sarcoidosis and to compare those scores with a control group.Methods218 consecutive patients were diagnosed with sarcoidosis according to the ATS/ERS/WASOG criteria; extrathoracic involvement was evaluated using the 2014 WASOG organ assessment instrument. Sarcoidosis patients were compared with an age- and gender-matched control group of primary care outpatients without sarcoidosis. Comorbidities were assessed retrospectively using the Charlson Comorbidity Index (CCI); complexity was evaluated according to the classification into Clinical Risk Groups (CRG) and severity levels.ResultsThe cohort included 142 women and 76 men; the mean age was 47.1xa0years at diagnosis of sarcoidosis and 55.9xa0years at the last visit. Patients with a CCIu2009>u20091 had a higher frequency of calcium/vitamin D abnormalities (pu2009<u20090.001), kidney involvement (pu2009=u20090.005) and a higher mortality rate (pu2009<u20090.001) compared with patients with a CCIu2009≤u20091. Patients with a CRGu2009≥u20096 had a higher frequency of extrathoracic involvement (pu2009=u20090.039), calcium/vitamin D abnormalities (pu2009=u20090.019) and treatment with glucocorticoids (pu2009=u20090.032) compared with patients with a CRGu2009<u20096. 11% patients died after a mean follow-up of 102.3xa0months. Country of birth, kidney involvement and extrathoracic disease were significantly associated with death. Patients with sarcoidosis had a higher frequency of liver (pu2009<u20090.001), pulmonary (pu2009=u20090.002) and autoimmune disease (pu2009=u20090.011) and cancer (pu2009=u20090.007) compared with the control group.ConclusionWe found higher rates of comorbidity and complexity in patients with sarcoidosis compared with a control group. Liver, pulmonary, autoimmune and neoplastic diseases were the main comorbidities found in patients with sarcoidosis.

Pirfenidone in Lung Interstitial Diseases: Indications and How to Evaluate its Effects

Idiopathic pulmonary fibrosis (IPF) is one of the most severe forms of interstitial pneumonia with a progressive and irreversible course and a mean survival of approximately 3 to 5 years from the time of diagnosis. Previous treatments with combinations of corticosteroids and immunosuppressive drugs did not demonstrate their effectiveness in reducing mortality in IPF. Pirfenidone is one of the newly implemented antifibrotic treatments whose effectiveness has been assessed by recent clinical trials, demonstrating its ability to slow down the progression of the disease, improve exercise tolerance, and reduce mortality. Because of these encouraging results, the Food and Drug Administration and the European Medicine Agency have recently approved its use in the treatment of IPF. Its distribution has been initiated not only in United States of America but also in several other countries. This article aims to review some of the most relevant articles concerning pirfenidone, with a summary of its indications, previous studies that support its use, possible adverse effects, and the clinical monitoring of patients. We also have hypothesized the potential use of pirfenidone in other interstitial lung diseases.