José Antonio Rodríguez Portal

Coronavirus disease 2019 (COVID‐19) global pandemic has affected more than 600 million people up to date. The symptomatology and severity of COVID‐19 are very broad, and there are still concerns about the long‐term sequelae that it can have on discharged patients. The development of pulmonary fibrotic sequelae after this infection is especially worrying. Our aim was to determine if there was a metabolomic signature that could predict the development of pulmonary fibrotic sequelae. It is a multicenter prospective observation subcohort based on the COVID‐FIBROTIC study. A metabolomic analysis was performed by nuclear magnetic resonance (NMR) on serum samples from patients admitted with bilateral COVID‐19 pneumonia collected 2 months after hospital discharge. One year after admission, clinical, functional and radiological data were collected from these same patients. Finally, 109 patients (mean age 57.68 [DS14.03], 65.13% male) were available. Fibrotic sequelae 1 year after COVID‐19 disease were found in 33% of them. Based on the NMR analysis of the serum samples, it was possible to distinguish with 80.82% of sensitivity, 72.22% of specificity and 0.83 of an area under the curve (AUC) value which patients would have radiological signs of pulmonary fibrotic pattern 1 year after sample collection. According to the metabolites participating in the discriminative model and the univariate statistics, glucose, valine, and fatty acids (═CH–CH2–CH═) were suggested as potential biomarkers of the development of pulmonary fibrotic sequelae after COVID‐19. Trial Registration Number: clinicaltrials.gov NCT04409275 (June 1, 2020).

Little is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR). This is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries. Upon inclusion, mean ± SD predicted forced vital capacity was 77.6% ± 19.4, diffusing capacity for carbon monoxide was 48.5% ± 17.7, and the 6-min walk distance was 423.5 m ± 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile. The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts.

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.

Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable tolerability profile. This article reviews new available evidence on the long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis. Data from extension trials indicate that nintedanib continues to slow disease progression for up to 3 years and is similarly effective in patients with mild and severe impairment of lung function. Treatment with nintedanib reduces the risk of acute exacerbations, and a combined analysis of data from clinical trials of nintedanib shows a trend towards a reduction in mortality. Nintedanib is well tolerated and has been shown to be safe for up to 51 months. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Currently available data confirm its safety profile in real-life clinical settings, with no new safety concerns identified in patients with comorbidities.

Malignant pleural mesothelioma (MPM) is an extremely aggressive tumor which develops in the epithelial lining of the lungs. Exposure to asbestos is the most influential risk factor for developing this disease. Despite recent advances in the treatment of other types of cancer, patients with mesothelioma currently face a poor prognosis. Therefore, it is highly important to develop an early diagnostic method with the greatest challenge on screening techniques to detect the disease at a subclinical stage. Early detection is critical for the development of more effective therapies in these patients. Unfortunately, radiologic studies have not proven effective. Biomarkers might be a useful adjunct tool among populations previously exposed to asbestos. This review will provide an update of recent progress in serum biomarkers (osteopontin (OPN), soluble mesothelin (SM), and megakaryocyte potentiating factor (MPF)) to diagnose, detect, and monitor MPM. Of these, SM has demonstrated the greatest diagnostic potential although MPF may serve as an equal alternative. Despite recent studies, it is apparent that long-term large-cohort research is required to conclusively demonstrate the usefulness of these markers in this disease.

Background: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease. Patients: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA. Results: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM. Conclusions: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure. (Cancer Epidemiol Biomarkers Prev 2009;18(2):646–50)