Publications by authors named "Fernanda Hernandez-Gonzalez"

17 Publications

  • Page 1 of 1

Cellular Senescence in Lung Fibrosis.

Int J Mol Sci 2021 Jun 29;22(13). Epub 2021 Jun 29.

Department of Pulmonology, ICR, Hospital Clinic, 08036 Barcelona, Spain.

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.
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http://dx.doi.org/10.3390/ijms22137012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267738PMC
June 2021

Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge.

Arch Bronconeumol 2021 Apr 24;57 Suppl 2:59-61. Epub 2021 Feb 24.

Respiratory Institute, Hospital Clinic, University of Barcelona, C/Villaroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Roselló 149, 08036 Barcelona, Spain.

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http://dx.doi.org/10.1016/j.arbres.2021.01.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903150PMC
April 2021

Improving home oxygen therapy in patients with interstitial lung diseases: application of a noninvasive ventilation device.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620963027

Servei de Pneumologia, Respiratory Institute, Hospital Clínic, C/Villarroel 170, Barcelona, 08036, Spain.

Background: Proper adjustment of arterial oxygen saturation (SaO) during daily activities in patients with interstitial lung disease (ILD) requiring long-term oxygen therapy is challenging. Given the multifactorial nature of the limited exercise tolerance in patients with ILDs, the isolated use of oxygen therapy may not be enough. As demonstrated previously in patients with chronic obstructive pulmonary disease, the use of a noninvasive ventilation (NIV) device combined with oxygen therapy may prevent the falling of oxygen saturation during exercise, due to an improvement of the ventilation-perfusion ratio and a reduction of the respiratory work, thus enhancing exercise tolerance. We sought to assess in patients diagnosed with ILD who are in need of oxygen therapy, the effect of associating an NIV to improve oxygen parameters and the distance covered during the 6 min walking test (6MWT).

Methods: We conducted a prospective observational study in patients with ILDs. After a clinical characterization, we performed a 6MWT in two different situations: using a portable oxygen concentrator with the regular flow used by the patient during their daily life activities and afterwards adding the additional support of a NIV. The oxygen saturation parameters were registered with a portable oximeter.

Results: We included 16 patients with different ILDs who have oxygen therapy prescribed. The use of NIV associated with oxygen therapy in comparison with the use of oxygen therapy alone showed an increase of the average SaO [91% (88-93) 88% (86-90%);  = 0.0005] and a decrease in the percentage of time with oxygen saturation <90%: 36% (6-56%) 58% (36-77%);  < 0.0001. There were no changes in the 6MWT distance: 307 m (222-419 m) 316 m (228-425 m);  = 0.10.

Conclusions: In our study the use of a NIV system associated with long-term oxygen therapy during exercise showed beneficial effects, especially improvement of oxygen saturation.The reviews of this paper are available via the supplemental material section.
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http://dx.doi.org/10.1177/1753466620963027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586034PMC
September 2021

ERS International Congress, Madrid, 2019: highlights from the Interstitial Lung Diseases Assembly.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

Dept of Diseases of the Thorax, Ospedale GB Morgagni, Forli, Italy.

This article discusses a selection of the scientific presentations in the field of interstitial lung diseases (ILDs) that took place at the 2019 European Respiratory Society International Congress in Madrid, Spain. There were sessions from all four groups within Assembly 12: group 12.01 "Idiopathic interstitial pneumonias", group 12.02 "ILDs/diffuse parenchymal lung diseases (DPLDs) of known origin", group 12.03 "Sarcoidosis and other granulomatous ILDs/DPLDs" and group 12.04 "Rare ILDs/DPLDs". The presented studies brought cutting-edge developments on several aspects of these conditions, including pathogenesis, diagnosis and treatment. As many of the ILDs are individually rare, the sharing of experiences and new data that occur during the Congress are very important for physicians interested in ILDs and ILD patients alike.
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http://dx.doi.org/10.1183/23120541.00143-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533302PMC
October 2020

Current treatment of sarcoidosis.

Curr Opin Pulm Med 2020 09;26(5):591-597

University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Purpose Of Review: Sarcoidosis is a granulomatous systemic disease of unknown cause where the lung is the most frequently affected organ. Therapeutic management of the disease is challenging as clinical presentation and prognosis are very heterogeneous. In the present review, we will summarize the main advances in sarcoidosis therapy.

Recent Findings: Current sarcoidosis therapies are categorized in three lines: glucocorticoids (first line), immunosuppressants (second line), and biologics (third line). Recent glucocorticoid studies have reported that efficacy could be similar with high and low doses, but with an increase in side effects with higher doses. In immunosuppressants, recent publications in mycophenolate and repository corticotropin injection (RCI) have added more information in their use and efficacy. Finally, new evidence has been published in the use of antitumor necrosis factor (anti-TNFα) agents in refractory cardiac sarcoidosis and neurosarcoidosis.

Summary: Sarcoidosis therapy is constantly evolving, and new drugs have been added to the recommended treatments. However, extensive clinical trials are still necessary to optimize the current recommendations.
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http://dx.doi.org/10.1097/MCP.0000000000000720DOI Listing
September 2020

Influence of MUC5B gene on antisynthetase syndrome.

Sci Rep 2020 Jan 29;10(1):1415. Epub 2020 Jan 29.

Rheumatology Department, Hospital Universitario de Bellvitge, Barcelona, Spain.

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.
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http://dx.doi.org/10.1038/s41598-020-58400-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989632PMC
January 2020

Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases.

Medicine (Baltimore) 2020 Jan;99(4):e18589

Servei de Pneumologia, Hospital Clínic, IDIBAPS, Universitat de Barcelona.

To date, there is no clear agreement regarding which is the best method to detect a connective tissue disease (CTD) during the initial diagnosis of interstitial lung diseases (ILD). The aim of our study was to explore the impact of a systematic diagnostic strategy to detect CTD-associated ILD (CTD-ILD) in clinical practice, and to clarify the significance of interstitial pneumonia with autoimmune features (IPAF) diagnosis in ILD patients.Consecutive patients evaluated in an ILD Diagnostic Program were divided in 3 groups: IPAF, CTD-ILD, and other ILD forms. Clinical characteristics, exhaustive serologic testing, high resolution computed tomography (HRCT) images, lung biopsy specimens, and follow-up were prospectively collected and analyzed.Among 139 patients with ILD, CTD was present in 21 (15.1%), 24 (17.3%) fulfilled IPAF criteria, and 94 (67.6%) were classified as other ILD forms. Specific systemic autoimmune symptoms such as Raynaud phenomenon (19%), inflammatory arthropathy (66.7%), and skin manifestations (38.1%) were more frequent in CTD-ILD patients than in the other groups (all P < .001). Among autoantibodies, antinuclear antibody was the most frequently found in IPAF (42%), and CTD-ILD (40%) (P = .04). Nonspecific interstitial pneumonia, detected by HRCT scan, was the most frequently seen pattern in patients with IPAF (63.5%), or CTD-ILD (57.1%) (P < .001). In multivariate analysis, a suggestive radiological pattern by HRCT scan (odds ratio [OR] 15.1, 95% confidence interval [CI] 4.7-48.3, P < .001) was the strongest independent predictor of CTD-ILD or IPAF, followed by the presence of clinical features (OR 14.6, 95% CI 4.3-49.5, P < .001), and serological features (OR 12.4, 95% CI 3.5-44.0, P < .001).This systematic diagnostic strategy was useful in discriminating an underlying CTD in patients with ILD. The defined criteria for IPAF are fulfilled by a considerable proportion of patients referred for ILD.
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http://dx.doi.org/10.1097/MD.0000000000018589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004576PMC
January 2020

Identification and characterization of Cardiac Glycosides as senolytic compounds.

Nat Commun 2019 10 21;10(1):4731. Epub 2019 Oct 21.

Laboratory of Stem Cells in Cancer and Aging, Health Research Institute of Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706, Santiago de Compostela, Spain.

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.
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http://dx.doi.org/10.1038/s41467-019-12888-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803708PMC
October 2019

Acute exacerbations of idiopathic pulmonary fibrosis: Does clinical stratification or steroid treatment matter?

Chron Respir Dis 2019 Jan-Dec;16:1479973119869334

1 Servei de Pneumologia, Respiratory Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is defined as a sudden acceleration of the disease with the appearance of pulmonary infiltrates superimposed on the characteristic pattern of IPF that leads to a significant decline in lung function. It has high in-hospital mortality rates, despite medical treatment with systematic steroids. We sought to investigate whether there were in-hospital mortality differences according to clinical stratification (AE, suspected AE, or AE of known cause) and/or treatment with systemic steroids. We reviewed the clinical characteristics and outcomes of patients with IPF admitted to our hospital during the years 2003-2014 due to a worsening of their clinical status. We identified 50 IPF patients, 9 with AE (18%), 12 with suspected exacerbation (24%), and 29 with AE of known cause (58%), mostly respiratory infections. In-hospital mortality was similar in the three groups (33% vs. 17% vs. 34%, respectively). Likewise, we did not find differences between them with respect to the use of systemic steroids (length of treatment duration or total dose). Nevertheless, there was an independent association between in-hospital mortality and high average daily steroid dose. We did not observe significant differences in prognosis or use of systemic steroids according to current diagnostic stratification groups in patients hospitalized because of an exacerbation of IPF.
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http://dx.doi.org/10.1177/1479973119869334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704413PMC
April 2020

Comorbidities and Complications in Idiopathic Pulmonary Fibrosis.

Med Sci (Basel) 2018 Aug 30;6(3). Epub 2018 Aug 30.

Hospital Clínic, Respiratory Department, 08036 Barcelona, Spain.

Though idiopathic pulmonary fibrosis (IPF) is characterized by single-organ involvement, many comorbid conditions occur within other organ systems. Patients with IPF may present during evolution different complications and comorbidities that influence the prognosis and modify the natural course of their disease. In this chapter, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current treatment data for several key comorbidities. The diagnosis and treatment of these comorbidities is a challenge for the pulmonologist specialized in interstitial lung diseases (ILDs). We will focus on pulmonary emphysema, lung cancer, gastroesophageal reflux, pulmonary hypertension, obstructive sleep apnea (sleep disorders), and acute exacerbation of IPF.
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http://dx.doi.org/10.3390/medsci6030071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163702PMC
August 2018

Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis.

Chest 2016 09 25;150(3):533-43. Epub 2016 Mar 25.

Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF.

Methods: We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated.

Results: No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent.

Conclusions: Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.
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http://dx.doi.org/10.1016/j.chest.2016.03.021DOI Listing
September 2016

Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.

Medicine (Baltimore) 2016 Feb;95(5):e2573

From the Servei de Pneumologia, Hospital Clínic, IDIBAPS, Universitat de Barcelona, (JS, FH-G, CMªL, SC, AX); Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028) (JS, CMªL); Servei de Cirurgia Toràcica, Hospital Clínic, IDIBAPS, Universitat de Barcelona (MP); Servei de Malalties Autoimmunes (PB-Z, SP-G, GE); Servicio de Radiodiagnóstico (MB, MS); and Servicio de Anatomía Patológica, Hospital Clínic, Barcelona, Spain (JR).

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 (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). 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.
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http://dx.doi.org/10.1097/MD.0000000000002573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748881PMC
February 2016

Keratinolytic Fungi in the Feather Stuffing of a Sofa: A Rare Cause of Hypersensitive Pneumonitis.

Arch Bronconeumol 2015 Sep 20;51(9):474-5. Epub 2015 Jan 20.

Servicio de Neumología, Institut del Tórax, Hospital Clínic, Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2014.11.015DOI Listing
September 2015

Cryobiopsy in the diagnosis of diffuse interstitial lung disease: yield and cost-effectiveness analysis.

Arch Bronconeumol 2015 Jun 3;51(6):261-7. Epub 2014 Nov 3.

Servicio de Neumología y Alergia Respiratoria, Institut del Tòrax, Hospital Clínic, Barcelona, España.

Background: Assessment 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.

Methods: This 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.

Results: Criobiopsy 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.

Conclusion: Cryobiopsy 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.
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http://dx.doi.org/10.1016/j.arbres.2014.09.009DOI Listing
June 2015
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