Publications by authors named "Marc Miravitlles"

433 Publications

Economic Impact of Low Adherence to COPD Management Guidelines in Spain.

Authors:
Marc Miravitlles Alexandra Solé Helena Aguilar Ana Ampudia Jaume Costa-Samarra Maria Mallén-Alberdi Diana Nieves

Int J Chron Obstruct Pulmon Dis 2021 16;16:3131-3143. Epub 2021 Nov 16.

Oblikue Consulting SL, Barcelona, Spain.

Objective: The objective of this study was to assess the non-adherence level of Spanish clinical practice to guideline recommendations for the treatment of chronic obstructive pulmonary disease (COPD) and to estimate the potential impact on pharmaceutical expenditure resulting from transitioning current treatment patterns according to guidelines.

Methods: A model was developed to compare current prescribing patterns with two alternative scenarios: the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2020) recommendations, and the second with the Spanish Guidelines for COPD (GesEPOC 2017). Current treatment practice was obtained from publications that describe treatment patterns by pulmonology departments in Spain. The economic impact between patterns was calculated from the perspective of the Spanish National Health System (NHS), considering the annual pharmacological costs of COPD inhaled maintenance therapy. Two additional analyses were performed: one that included current prescribing patterns of patients managed by pulmonology and primary care centers in Spain (published aggregated data); and another that only considered the appropriate use of inhaled corticosteroids (ICS) treatment according to guidelines.

Results: It was estimated that 54% and 38% of patients were not treated in line with GOLD and GesEPOC recommendations, respectively, mainly due to a broader use of ICS-based therapies. Adapting treatment to recommendations could provide a potential annual cost-saving of €17,792,022 (according to GOLD) and €5,881,785 (according to GesEPOC). In scenario analysis 1, a 26% of non-adherence to GesEPOC guideline was observed with a potential annual pharmacological cost-saving of €2,707,554. In scenario analysis 2, considering only inappropriate use of ICS treatment, an annual cost-saving of €17,863,750 (according to GOLD) and €9,904,409 (according to GesEPOC) was calculated.

Conclusion: More than a third of treatments for COPD patients in Spain are not prescribed in accordance with guideline recommendations. The adaptation of clinical practice to guideline recommendations could provide important cost-savings for the Spanish NHS.
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http://dx.doi.org/10.2147/COPD.S322793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611727PMC
November 2021

ROSE: radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group.

Authors:
Letizia Traversi Marc Miravitlles Miguel Angel Martinez-Garcia Michal Shteinberg Apostolos Bossios Katerina Dimakou Joseph Jacob John R Hurst Pier Luigi Paggiaro Sebastian Ferri Georgios Hillas Jens Vogel-Claussen Sabine Dettmer Stefano Aliberti James D Chalmers Eva Polverino

ERJ Open Res 2021 Oct 22;7(4). Epub 2021 Nov 22.

Pneumology Dept, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Barcelona, Spain.

Introduction: The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians.

Methods: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the "COPD- [bronchiectasis] BE association".A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds.

Results: 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of "COPD-BE association" was: "The coexistence of (1) specific radiological findings ( in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV/[forced vital capacity] FVC <0.7), (3) at least two characteristic symptoms () and (4) current or past exposure to smoke ≥) or other toxic agents (bi)". These criteria form the acronym "ROSE" (Radiology, Obstruction, Symptoms, Exposure).

Conclusions: The Delphi process formulated a European consensus definition of "COPD-BE association". We hope this definition will have broad applicability across clinical practice and research in the future.
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http://dx.doi.org/10.1183/23120541.00399-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607072PMC
October 2021

Respiratory symptoms (COPD Assessment Test and modified Medical Research Council dyspnea scores) and GOLD-ABCD COPD classification: the LASSYC study.

Authors:
Maria Montes de Oca Maria Victorina Lopez Varela Ana Maria B Menezes Fernando C Wehrmeister Larissa Ramirez Marc Miravitlles

J Bras Pneumol 2021 12;47(5):e20210156. Epub 2021 Nov 12.

Department of Pneumology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, CIBER de Enfermedades Respiratorias, Barcelona, Spain.

Objective: To assess the frequency and severity of 24-hour respiratory symptoms according to COPD GOLD-ABCD classification (2017-version), the distribution of the patients with COPD into GOLD categories using mMRC (≥2) or CAT (≥10) scores, and agreement between these cut-off points.

Methods: In this cross-sectional study (LASSYC study), 24-hour day respiratory symptoms were assessed by the Evaluating Respiratory Symptoms in COPD (E-RS) questionnaire, Nighttime Symptoms of COPD Instrument (NiSCI), Early Morning Symptoms of COPD Instrument (EMSCI), CAT and mMRC scores.

Results: Among the 734 patients with COPD, 61% were male, age 69.6±8.7 years, FEV1% post-BD 49.1±17.5%, mMRC 1.8±1.0 and CAT 15.3±.8.1. By mMRC 33.7% were group-A, 29.2% group-B, 10.2% group-C and 26.9% group-D. By CAT 22.3% were group-A, 41% group-B, 4.8% group-C and 31.9% group-D. Using the mMRC the severity of E-RS, NiSCI and EMSCI scores increased from group A to D. Using the CAT, the groups B and D had the higher scores. Agreement between mMRC and CAT was 89.5% (Kappa statistics=75.7%). For mMRC score of 2, CAT score of ≥11 showed the maximum Youden's index (1.34). For mMRC score of 1, CAT score of ≥9 and ≥10 showed the maximum Youden's index (1.48).

Conclusion: GOLD COPD classification by CAT seems to better discriminate 24-hour symptoms. Results do not support the equivalent use of CAT≥10 and mMRC≥2 for assessing symptoms.
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http://dx.doi.org/10.36416/1806-3756/e20210156DOI Listing
November 2021

Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade.

Authors:
Davies Adeloye Dhiraj Agarwal Peter J Barnes Marcel Bonay Job F van Boven Jamie Bryant Gaetano Caramori David Dockrell Anthony D'Urzo Magnus Ekström Gregory Erhabor Cristóbal Esteban Catherine M Greene John Hurst Sanjay Juvekar Ee Ming Khoo Fanny W Ko Brian Lipworth Jose L López-Campos Matthew Maddocks David M Mannino Fernando J Martinez Miguel A Martinez-Garcia Renae J McNamara Marc Miravitlles Hilary Pinnock Alison Pooler Jennifer K Quint Peter Schwarz George M Slavich

J Glob Health 2021 9;11:15003. Epub 2021 Oct 9.

Cousins Center for Psychoneuroimmunology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USA.

Background: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD.

Methods: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.

Results: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity.

Conclusions: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
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http://dx.doi.org/10.7189/jogh.11.15003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542376PMC
November 2021

Correction to: Association between circulating alpha-1 antitrypsin polymers and lung and liver disease.

Authors:
Alexa Núñez Irene Belmonte Elena Miranda Miriam Barrecheguren Georgina Farago Eduardo Loeb Mònica Pons Francisco Rodríguez-Frías Pablo Gabriel-Medina Esther Rodríguez Joan Genescà Marc Miravitlles Cristina Esquinas

Respir Res 2021 Nov 1;22(1):283. Epub 2021 Nov 1.

Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain.

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http://dx.doi.org/10.1186/s12931-021-01874-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559341PMC
November 2021

Estimated Prevalence and Number of PiMZ Genotypes of Alpha-1 Antitrypsin in Seventy-Four Countries Worldwide.

Authors:
Cristina Martinez-González Ignacio Blanco Isidro Diego Patricia Bueno Marc Miravitlles

Int J Chron Obstruct Pulmon Dis 2021;16:2617-2630. Epub 2021 Sep 17.

Pneumology Department, Hospital Universitari Vall d'Hebron/Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Background: The α-1 antitrypsin (AAT) protease inhibitor PiMZ is a moderately deficient genotype, until recently considered of little or negligible risk. However, a growing number of studies show that MZ carriers have an increased risk of developing lung and liver diseases, if exposed to smoking or other airborne or industrial pollutants, and hepatotoxic substances.

Methods: We used the epidemiological studies performed to determine the frequencies of PiM and PiZ worldwide, based on the following criteria: 1) samples representative of the general population; 2) AAT phenotyping or genotyping characterized by adequate methods, including isoelectric focusing and polymerase chain reaction; and 3) studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals, to measure the precision of the results in terms of dispersion of the data around the mean.

Results: The present review reveals an impressive number of MZs of more than 35 million in 74 countries of the world with available data. Seventy-five percent of them are people of Caucasian European heritage, mostly living in Europe, America, Australia and New Zealand. Twenty percent of the remaining MZs live in Asia, with the highest concentrations in the Middle East, Eastern¸ Southern, and South-eastern regions of the Asian continent. The remaining five percent are Africans residing in Western and Eastern Africa.

Conclusion: Considering the high rate of smoking, the outdoor and the indoor air pollution from solid fuels used in cooking and heating, and the exposure to industrial dusts and chemicals in many of these countries, these figures are very worrying, and hence the importance of adequately assessing MZ subjects, recommending them rigorous preventive measures based on the adoption of healthy lifestyles, including avoidance of smoking and alcohol.
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http://dx.doi.org/10.2147/COPD.S327803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455519PMC
October 2021

Association between circulating alpha-1 antitrypsin polymers and lung and liver disease.

Authors:
Alexa Núñez Irene Belmonte Elena Miranda Miriam Barrecheguren Georgina Farago Eduardo Loeb Mònica Pons Francisco Rodríguez-Frías Pablo Gabriel-Medina Esther Rodríguez Joan Genescà Marc Miravitlles Cristina Esquinas

Respir Res 2021 Sep 15;22(1):244. Epub 2021 Sep 15.

Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Background: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease.

Method: This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected.

Results: A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004).

Conclusions: Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.
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http://dx.doi.org/10.1186/s12931-021-01842-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442448PMC
September 2021

Long-term effect of α-antitrypsin augmentation therapy on the decline of FEV in deficient patients: an analysis of the AIR database.

Authors:
Iris G M Schouten Marise J Kasteleyn Roula Tsonaka Robert Bals Alice C Turner Ilaria Ferrarotti Angelo G Corsico Beatriz Lara Marc Miravitlles Robert A Stockley Jan Stolk

ERJ Open Res 2021 Jul 23;7(3). Epub 2021 Aug 23.

Dept of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.

Background: Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2-3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV).

Methods: To compare the trajectory of FEV change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models.

Results: Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV decline of -0.931% predicted per year (95% CI -1.144 to -0.718) in the untreated group and a decline of -1.016% predicted per year (95% CI -1.319 to -0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71).

Conclusion: In our study population, we could not detect a significant difference in the annual decline of FEV by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.
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http://dx.doi.org/10.1183/23120541.00194-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381156PMC
July 2021

CONQUEST Quality Standards: For the Collaboration on Quality Improvement Initiative for Achieving Excellence in Standards of COPD Care.

Authors:
Rachel Pullen Marc Miravitlles Anita Sharma Dave Singh Fernando Martinez John R Hurst Luis Alves Mark Dransfield Rongchang Chen Shigeo Muro Tonya Winders Christopher Blango Hana Muellerova Frank Trudo Paul Dorinsky Marianna Alacqua Tamsin Morris Victoria Carter Amy Couper Rupert Jones Konstantinos Kostikas Ruth Murray David B Price

Int J Chron Obstruct Pulmon Dis 2021 12;16:2301-2322. Epub 2021 Aug 12.

Observational and Pragmatic Research Institute, Singapore, Singapore.

Background: Chronic obstructive pulmonary disease (COPD) are managed predominantly in primary care. However, key opportunities to optimize treatment are often not realized due to unrecognized disease and delayed implementation of appropriate interventions for both diagnosed and undiagnosed individuals. The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) is the first-of-its-kind, collaborative, interventional COPD registry. It comprises an integrated quality improvement program focusing on patients (diagnosed and undiagnosed) at a modifiable and higher risk of COPD exacerbations. The first step in CONQUEST was the development of quality standards (QS). The QS will be imbedded in routine primary and secondary care, and are designed to drive patient-centered, targeted, risk-based assessment and management optimization. Our aim is to provide an overview of the CONQUEST QS, including how they were developed, as well as the rationale for, and evidence to support, their inclusion in healthcare systems.

Methods: The QS were developed (between November 2019 and December 2020) by the CONQUEST Global Steering Committee, including 11 internationally recognized experts with a specialty and research focus in COPD. The process included an extensive literature review, generation of QS draft wording, three iterative rounds of review, and consensus.

Results: Four QS were developed: 1) identification of COPD target population, 2) assessment of disease and quantification of future risk, 3) non-pharmacological and pharmacological intervention, and 4) appropriate follow-up. Each QS is followed by a rationale statement and a summary of current guidelines and research evidence relating to the standard and its components.

Conclusion: The CONQUEST QS represent an important step in our aim to improve care for patients with COPD in primary and secondary care. They will help to transform the patient journey, by encouraging early intervention to identify, assess, optimally manage and followup COPD patients with modifiable high risk of future exacerbations.
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http://dx.doi.org/10.2147/COPD.S313498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370848PMC
September 2021

Efficacy and safety of discontinuing antibiotic treatment for uncomplicated respiratory tract infections when deemed unnecessary. A multicentre, randomized clinical trial in primary care.

Authors:
Carl Llor Ana Moragas Carolina Bayona Josep M Cots Silvia Hernández Olga Calviño Migdalia Rodríguez Marc Miravitlles

Clin Microbiol Infect 2021 Aug 4. Epub 2021 Aug 4.

Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Objectives: To determine the benefits and harms of discontinuing unnecessary antibiotic therapy for uncomplicated respiratory tract infections (RTI) when antibiotics are considered no longer necessary.

Methods: Multicentre, open-label, randomized controlled clinical trial in primary care centres from 2017 to 2020 (ClinicalTrials.gov, NCT02900820). Adults with RTIs-acute rhinosinusitis, sore throat, influenza or acute bronchitis-who had previously taken any dose of antibiotic for less than 3 days, which physicians no longer deemed necessary were recruited. The patients were randomly assigned in a 1:1 ratio to discontinuing antibiotic therapy or the usual strategy of continuing antibiotic treatment. The primary outcome was the duration of severe symptoms (number of days scoring 5 or 6 on a six-item Likert scale). Secondary outcomes included days with symptoms, moderate symptoms (scores of 3 or 4), antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.

Results: A total of 467 patients were randomized, out of which 409 were considered valid for the analysis. The mean (SD) duration of severe symptoms was 3.0 (1.5) days for the patients assigned to discontinuation and 2.8 (1.3) days for those allocated to the control group (mean difference 0.2 days; 95% CI -0.1 to 0.4 days). Patients randomized to the discontinuation group used fewer antibiotics after the baseline visit (52/207 (25.1%) versus 182/202 (90.1%); p 0.001). Patients assigned to antibiotic continuation presented a relative risk of adverse events of 1.47 (95% CI 0.80-2.71), but the need for further health-care contact in the following 3 months was slightly lower (RR 0.61; 95% CI 0.28-1.37).

Conclusions: Discontinuing antibiotic treatment for uncomplicated RTIs when clinicians consider it unnecessary is safe and notably reduces antibiotic consumption.
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http://dx.doi.org/10.1016/j.cmi.2021.07.035DOI Listing
August 2021

Reduction in hospitalised COPD exacerbations during COVID-19: A systematic review and meta-analysis.

Authors:
Jaber S Alqahtani Tope Oyelade Abdulelah M Aldhahir Renata Gonçalves Mendes Saeed M Alghamdi Marc Miravitlles Swapna Mandal John R Hurst

PLoS One 2021 3;16(8):e0255659. Epub 2021 Aug 3.

UCL Respiratory, University College London, London, United Kingdom.

Background: Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations. However, the magnitude of this reduction varies between studies.

Method: Electronic databases were searched from January 2020 to May 2021. Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions. Exacerbation reduction was compared against the COVID-19 Containment and Health Index.

Results: A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries. Nine studies could be included in the meta-analysis. The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57). Findings on the rate of community-treated exacerbations were inconclusive. Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period. There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).

Conclusion: There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations. Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255659PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330941PMC
August 2021

Burden of Disease Among Exacerbating Patients with COPD Treated with Triple Therapy in Spain.

Authors:
Bernardino Alcázar-Navarrete Francisco García-Rio Guadalupe Sánchez Esther Mariscal Andrea García Maribel Cuesta Estefany Uría Marc Miravitlles

Int J Chron Obstruct Pulmon Dis 2021 21;16:2149-2161. Epub 2021 Jul 21.

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.

Background: The cost of chronic obstructive pulmonary disease (COPD) in Spain has been studied from different perspectives, but parameters such as the patient's phenotype have seldom been considered. Our aim was to describe the disease burden of COPD patients with frequent exacerbator phenotype, treated with triple therapy.

Methods: An observational, multicenter study was carried out from December 2017 to November 2018 in pulmonology services among patients ≥40 years with COPD confirmed diagnosis receiving triple therapy (ICS/LAMA/LABA) and history of ≥2 moderate or ≥1 severe exacerbation in the 12 months prior to the inclusion visit. COPD-related healthcare resources were collected over a 12-months period prior to the inclusion visit: pharmacological and non-pharmacological treatments, medical and ER visits, hospitalizations, tests and productivity loss. Costs were updated to €2019. Patients were classified according to blood eosinophil levels: <150 cells/µL and ≥150 cells/µL.

Results: A total of 306 patients were included (77.1% men), with mean age of 69.9 years. Mean COPD exacerbation rate was 2.5/patient/year and 51.3% of patients had ≥150 cells/µL eosinophil level. On average, for the total population, COPD-related visits/patients/year were 6.2. Resource use in moderate exacerbation was higher in patients with eosinophils ≥150 cells/µL, whereas in severe exacerbation was higher in patients with eosinophils <150cells/µL. According to eosinophil levels, total annual mean (SD) costs/patient accounted for €8382 (9863) and €5144 (5444) for patients with eosinophils <150 cells/µL and ≥150 cells/µL, respectively.

Conclusion: The impact of exacerbating COPD patients treated with triple therapy in Spain is large, especially among those with eosinophils <150 cells/µL.
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http://dx.doi.org/10.2147/COPD.S310319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312318PMC
August 2021

How to get the most out of the ERS International Congress 2021 and an overview of the Early Career Member session.

Authors:
Amy Farr Niki Ubags Christopher Brightling Marc Miravitlles Miriam Barrecheguren Pierantonio Laveneziana Reinoud Gosens Richard Costello Joana Cruz

Breathe (Sheff) 2021 Jun;17(2):210057

Center for Innovative Care and Health Technology (ciTechCare), School of Health Sciences (ESSLei), Polytechnic of Leiria, Leiria, Portugal.

https://bit.ly/3dBNrYC.
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http://dx.doi.org/10.1183/20734735.0057-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291941PMC
June 2021

Physical Activity Levels and Associated Factors in a Latin American COPD Population of Patients. The LASSYC Study.

Authors:
Laura Mendoza María Montes de Oca María Victorina López Varela Alejandro Casas Alejandra Ramírez-Venegas Ana López Luis Ugalde Fernando C Wehrmeister Filip Surmonti Ana M B Menezes Marc Miravitlles

COPD 2021 08 28;18(4):393-400. Epub 2021 Jun 28.

Department of Pneumology. Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus; CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Reduced physical activity (PA) is an independent risk factor for lung function decline, hospitalization and mortality in chronic obstructive pulmonary disease (COPD) and affects a large proportion of patients from Europe and the United States. However, little is known of the level of PA of COPD patients in Latin America. The aim of this study was to provide information of the level of PA and its determinants in COPD patients in Latin America. This is an observational, cross-sectional study on patients with COPD in seven Latin American countries. PA level was evaluated with the short version of the International Physical Activity Questionnaire (IPAQ) and the association between PA and other variables was investigated. Complete information of PA level was obtained in 734 COPD patients consecutively recruited from specialized outpatient clinics; 448 (61%) were men, with a mean age of 69.6 years (standard deviation [SD] = 8.7) and a mean FEV (% predicted) = 49.1% (17.5%). In 37.9% the level of PA was low, and the average sitting time was 36.1 h per week. Patients with low levels of PA were older, with higher levels of dyspnea and higher CAT scores. Additionally, we found that patients with low level of PA presented more symptoms during the day. Low levels of PA have been observed in a large proportion of COPD patients of Latin America, which is higher in women and older patients and it is related with worse functional and clinical characteristics.
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http://dx.doi.org/10.1080/15412555.2021.1937090DOI Listing
August 2021

Spanish COPD Guidelines (GesEPOC) 2021 Update Diagnosis and Treatment af COPD Exacerbation Syndrome.

Authors:
Juan José Soler-Cataluña Pascual Piñera Juan Antonio Trigueros Myriam Calle Ciro Casanova Borja G Cosío José Luis López-Campos Jesús Molina Pere Almagro José-Tomás Gómez Juan Antonio Riesco Pere Simonet David Rigau Joan B Soriano Julio Ancochea Marc Miravitlles

Arch Bronconeumol (Engl Ed) 2021 May 26. Epub 2021 May 26.

CIBER de Enfermedades Respiratorias (CIBERES), Madrid, España; Servicio de Neumología, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, España.

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.
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http://dx.doi.org/10.1016/j.arbres.2021.05.011DOI Listing
May 2021

Update on Asthma-COPD Overlap (ACO): A Narrative Review.

Authors:
Evgeni Mekov Alexa Nuñez Don D Sin Masakazu Ichinose Chin Kook Rhee Diego Jose Maselli Andréanne Coté Charlotte Suppli Ulrik François Maltais Antonio Anzueto Marc Miravitlles

Int J Chron Obstruct Pulmon Dis 2021 17;16:1783-1799. Epub 2021 Jun 17.

Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma-COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.
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http://dx.doi.org/10.2147/COPD.S312560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216660PMC
August 2021

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.

Authors:
Marc Miravitlles Ariadna Auladell-Rispau Mònica Monteagudo Juan Carlos Vázquez-Niebla Jibril Mohammed Alexa Nuñez Gerard Urrútia

Eur Respir Rev 2021 Jun 23;30(160). Epub 2021 Jun 23.

Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.
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http://dx.doi.org/10.1183/16000617.0075-2021DOI Listing
June 2021

Severe loss of mechanical efficiency in COVID-19 patients.

Authors:
Eulogio Pleguezuelos Amin Del Carmen Gemma Llorensi Jessica Carcole Paula Casarramona Eva Moreno Pilar Ortega Mateo Serra-Prat Elisabet Palomera Marc M Miravitlles Joan Carles Yebenes Ramón Boixeda Lluis Campins Koldo Villelabeitia-Jaureguizar Manuel Vicente Garnacho-Castaño

J Cachexia Sarcopenia Muscle 2021 08 8;12(4):1056-1063. Epub 2021 Jun 8.

GRI-AFIRS, School of Health Sciences, TecnoCampus, Universitat Pompeu Fabra, Mataró, Spain.

Background: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG).

Methods: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1.

Results: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO peak and DE and between the peak power output and DE (P < 0.001).

Conclusions: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO at each intensity. Resistance training should be considered during the early phase of rehabilitation.
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http://dx.doi.org/10.1002/jcsm.12739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242734PMC
August 2021

Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil.

Authors:
José R Jardim Francisco Casas-Maldonado Frederico Leon Arrabal Fernandes Maria Vera Cruz de O Castellano María Torres-Durán Marc Miravitlles

J Bras Pneumol 2021;47(3):e20200380. Epub 2021 May 31.

. Departamento de Neumología, Hospital Universitario Vall d'Hebron, Barcelona, España.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by a mutation in the SERPINA1 gene, which encodes the protease inhibitor alpha-1 antitrypsin (AAT). Severe AATD predisposes individuals to COPD and liver disease. Early diagnosis is essential for implementing preventive measures and limiting the disease burden. Although national and international guidelines for the diagnosis and management of AATD have been available for 20 years, more than 85% of cases go undiagnosed and therefore untreated. In Brazil, reasons for the underdiagnosis of AATD include a lack of awareness of the condition among physicians, a racially diverse population, serum AAT levels being assessed in a limited number of individuals, and lack of convenient diagnostic tools. The diagnosis of AATD is based on laboratory test results. The standard diagnostic approach involves the assessment of serum AAT levels, followed by phenotyping, genotyping, gene sequencing, or combinations of those, to detect the specific mutation. Over the past 10 years, new techniques have been developed, offering a rapid, minimally invasive, reliable alternative to traditional testing methods. One such test available in Brazil is the A1AT Genotyping Test, which simultaneously analyzes the 14 most prevalent AATD mutations, using DNA extracted from a buccal swab or dried blood spot. Such advances may contribute to overcoming the problem of underdiagnosis in Brazil and elsewhere, as well as being likely to increase the rate detection of AATD and therefore mitigate the harmful effects of delayed diagnosis.
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http://dx.doi.org/10.36416/1806-3756/e20200380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8332724PMC
June 2021

GesEPOC 2021 and GOLD 2021. Closer Together or Further Apart?

Authors:
Marc Miravitlles

Arch Bronconeumol (Engl Ed) 2021 Apr 20. Epub 2021 Apr 20.

Servicio de Neumología, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2021.04.009DOI Listing
April 2021

Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency.

Authors:
Mònica Pons Alexa Núñez Cristina Esquinas María Torres-Durán Juan Luis Rodríguez-Hermosa Myriam Calle Ramón Tubio-Pérez Irene Belmonte Francisco Rodríguez-Frías Esther Rodríguez Joan Genescà Marc Miravitlles Miriam Barrecheguren

J Clin Med 2021 04 16;10(8). Epub 2021 Apr 16.

Pneumology Department, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.
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http://dx.doi.org/10.3390/jcm10081724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073267PMC
April 2021

Effectiveness and Safety of Inhaled Antibiotics in Patients With Chronic Obstructive Pulmonary Disease. A Multicentre Observational Study.

Authors:
David De la Rosa Carrillo Miguel-Ángel Martínez-García Esther Barreiro Eva Tabernero Huguet Roser Costa Sola Marta-María García-Clemente Nuria Celorrio Jiménez Laura Rodríguez Pons Carmen Calero Acuña Juan Luís Rodríguez Hermosa Rafael Golpe Raquel Dacal Quintas Silvia Sánchez-Cuéllar Irene Torres Arroyo Marina Blanco Aparicio Virginia Almadana Pacheco Marc Miravitlles

Arch Bronconeumol (Engl Ed) 2021 Mar 19. Epub 2021 Mar 19.

Pneumology Service, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorios (CIBERES), Passeig de la Vall d'Hebron 119, 08035, Barcelona, Spain.

Background: We aimed to describe the effectiveness and safety of inhaled antibiotics in chronic obstructive pulmonary disease (COPD) patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment.

Methods: Multicentre retrospective observational cohort study in COPD patients who had received ≥1 dose of inhaled antibiotics in the last 5 years. Clinical data from the two years prior to and subsequent to the start of the treatment were compared.

Primary Outcome: COPD exacerbations.

Secondary Outcomes: side effects, symptomatology (sputum purulence, dyspnoea), microbiological profile and pathogen eradication.

Results: Of 693 COPD patients analyzed (aged 74.1; 86.3% men; mean FEV=43.7%), 71.7% had bronchiectasis and 46.6% presented chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). After 1 year of treatment with inhaled antibiotics, there was a significant decrease in the number of exacerbations (-33.3%; P<.001), hospital admissions (-33.3%; P<.001) and hospitalization days (-26.2%; P=.003). We found no difference in effectiveness between patients with or without associated bronchiectasis. Positive patient outcomes were more pronounced in PA-eradicated patients. We found a significant reduction in daily expectoration (-33.1%; P=.024), mucopurulent/purulent sputum (-53.9%; P<.001), isolation of any potentially pathogenic microorganisms (PPM) (-16.7%; P<.001), CBI by any PPM (-37.4%; P<.001) and CBI by PA (-49.8%; P<.001). CBI by any PPM and ≥three previous exacerbations were associated with a better treatment response. 25.4% of patients presented non-severe side-effects, the most frequent of these being bronchospasm (10.5%), dyspnoea (8.8%) and cough (1.7%).

Conclusions: In COPD patients with multiple exacerbations and/or CBI by any PPM (especially PA), inhaled antibiotics appear to be an effective and safe treatment, regardless of the presence of bronchiectasis.
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http://dx.doi.org/10.1016/j.arbres.2021.03.009DOI Listing
March 2021

Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD.

Authors:
Marc Miravitlles Myriam Calle Jesús Molina Pere Almagro José-Tomás Gómez Juan Antonio Trigueros Borja G Cosío Ciro Casanova José Luis López-Campos Juan Antonio Riesco Pere Simonet David Rigau Joan B Soriano Julio Ancochea Juan José Soler-Cataluña

Arch Bronconeumol (Engl Ed) 2021 Mar 17. Epub 2021 Mar 17.

CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España; Servicio de Neumología, Hospital Arnau de Vilanova-Lliria, Valencia, España.

The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then have undergone a series of updates incorporating new evidence on the diagnosis and treatment of COPD. GesEPOC was drawn up in partnership with scientific societies involved in the treatment of COPD and the Spanish Patients' Forum. Their recommendations are based on an evaluation of the evidence using GRADE methodology, and a narrative description of the evidence in areas in which GRADE cannot be applied. In this article, we summarize the recommendations on the pharmacological treatment of stable COPD based on 9 PICO questions. COPD treatment is a 4-step process: 1) diagnosis, 2) determination of the risk level, 3) initial and subsequent inhaled therapy, and 4) identification and management of treatable traits. For the selection of inhaled therapy, high-risk patients are divided into 3 phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Some treatable traits are general and should be investigated in all patients, such as smoking or inhalation technique, while others affect severe patients in particular, such as chronic hypoxemia and chronic bronchial infection. COPD treatment is based on long-acting bronchodilators with single agents or in combination, depending on the patient's risk level. Eosinophilic exacerbators must receive inhaled corticosteroids, while non-eosinophilic exacerbators require a more detailed evaluation to choose the best therapeutic option. The new GesEPOC also includes recommendations on the withdrawal of inhaled corticosteroids and on indications for alpha-1 antitrypsin treatment. GesEPOC offers a more individualized approach to COPD treatment tailored according to the clinical characteristics of patients and their level of complexity.
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http://dx.doi.org/10.1016/j.arbres.2021.03.005DOI Listing
March 2021

Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: a pro/con debate on a working hypothesis.

Authors:
Igor Barjaktarevic Marc Miravitlles

BMC Pulm Med 2021 Mar 23;21(1):99. Epub 2021 Mar 23.

Pneumology Department, Hospital Universitari Vall D'Hebron, Vall D'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Alpha-1 antitrypsin deficiency (AATD) is a significantly under-diagnosed genetic condition caused by reduced levels and/or functionality of alpha-1 antitrypsin (AAT), predisposing individuals to lung, liver or other systemic diseases. The management of individuals with the PI*MZ genotype, characterized by mild or moderate AAT deficiency, is less clear than of those with the most common severe deficiency genotype (PI*ZZ). Recent genetic data suggest that the PI*MZ genotype may be significantly more prevalent than currently thought. The only specific treatment for lung disease associated with severe AATD is the intravenous infusion of AAT augmentation therapy, which has been shown to slow disease progression in PI*ZZ individuals. There is no specific evidence for the clinical benefit of AAT therapy in PI*MZ individuals, and the risk of emphysema development in this group remains controversial. As such, current guidelines do not support the use of AAT augmentation in PI*MZ individuals. Here, we discuss the limited data on the PI*MZ genotype and offer pro and con perspectives on pursuing an AAT-specific therapeutic strategy in PI*MZ individuals with lung disease. Ultimately, further research to demonstrate the safety, risk/benefit balance and efficacy of AAT therapy in PI*MZ individuals is needed.
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http://dx.doi.org/10.1186/s12890-021-01466-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989144PMC
March 2021

Clinical characteristics and factors associated with triple therapy use in newly diagnosed patients with COPD.

Authors:
Mònica Monteagudo Miriam Barrecheguren Iryna Solntseva Nafeesa Dhalwani Alison Booth Alexa Nuñez Dimitra Lambrelli Marc Miravitlles

NPJ Prim Care Respir Med 2021 03 22;31(1):16. Epub 2021 Mar 22.

Medicine Department, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care. This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD. A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis. Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO). Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer. A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis.
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http://dx.doi.org/10.1038/s41533-021-00227-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985144PMC
March 2021

Evolution and Comparative Analysis of Hospitalizations in Spain Due to COPD and Bronchiectasis between 2004 and 2015.

Authors:
Annie Navarro-Rolon David de la Rosa-Carrillo Cristina Esquinas Marc Miravitlles Miguel Angel Martinez-García Pedro Almagro

COPD 2021 04 17;18(2):210-218. Epub 2021 Mar 17.

Multimorbidity Patients Unit, Internal Medicine Deparment, Hospital Universitario Mutua de Terrassa, Terrassa, Spain.

Chronic obstructive pulmonary disease (COPD) is the leading cause of hospitalization for chronic respiratory illness in Spain. In recent years hospital admissions due to bronchiectasis have been increasing, although it is not known whether this is in proportion to COPD hospitalizations. Our main objective was to analyze the temporal evolution of discharges due to COPD, bronchiectasis, and their combination, and secondly, to assess their impact on in-hospital mortality and healthcare costs. We performed a retrospective study, based on the analysis of the Minimum Basic Data Set (MBDS) of hospital discharges using data from Spanish Ministry of Health with diagnostic codes of COPD or bronchiectasis between 2004 and 2015. We found 3 356 186 discharges with a diagnosis of COPD or bronchiectasis. After exclusions, 1 386 430 episodes were analyzed: 85.2% with COPD, 8.4% bronchiectasis, and 6.4% with both pathologies. Mean age of patients was 74.8 (10.9) years and with a male predominance of 80.1%. The increase in the annual number of discharges was greater in the two groups with bronchiectasis: 48.8% in the bronchiectasis group and 55.4% in the mixed group, compared to 6.6% in the COPD group. The mean length of stay was greater in both groups with bronchiectasis ( < 0.001), while in-hospital mortality was higher in the COPD group ( < 0.001). Similarly, the annual increase of costs was more evident in the two groups with bronchiectasis. Conclusions: Hospitalizations and health costs for bronchiectasis have increased in recent years significantly more than for COPD.Supplemental data for this aricle can be accessed here.
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http://dx.doi.org/10.1080/15412555.2021.1896692DOI Listing
April 2021

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database.

Authors:
Jennifer K Quint Jukka Montonen Daina B Esposito Xintong He Leslie Koerner Laura Wallace Alberto de la Hoz Marc Miravitlles

Adv Ther 2021 05 15;38(5):2249-2270. Epub 2021 Mar 15.

Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute de Recerca (VHIR), Barcelona, Spain.

Introduction: In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination.

Methods: Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Database were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history.

Results: The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history.

Conclusions: In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history.

Trial Registration: ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).
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http://dx.doi.org/10.1007/s12325-021-01646-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107175PMC
May 2021

Blood eosinophil count predicts treatment failure and hospital readmission for COPD.

Authors:
Marjan Kerkhof Isha Chaudhry Ian D Pavord Marc Miravitlles Chin Kook Rhee David M G Halpin Omar S Usmani Rupert Jones Janwillem Kocks Marianna Alacqua Tamsin Morris Alan Kaplan David B Price

ERJ Open Res 2020 Oct 10;6(4). Epub 2020 Nov 10.

Observational and Pragmatic Research Institute, Singapore, Singapore.

We examined associations between blood eosinophil counts (BEC) and risk of treatment failure or hospital readmission following acute oral corticosteroid (OCS)-treated COPD exacerbations. We conducted studies from the Optimum Patient Care Research Database (OPCRD) (www.optimumpatientcare.org/opcrd) and Clinical Practice Research Datalink (CPRD) (www.cprd.com/home/), validated databases for medical research, with linked Hospital Episode Statistics (HES) data for ∼20 000 COPD patients aged ≥40 years. For patients with OCS-treated COPD exacerbations treated in primary care, with BECs recorded on first day of OCS treatment (Cohort 1), we assessed treatment failure (COPD-related hospitalisations and OCS prescriptions beyond index OCS course). For patients hospitalised for COPD exacerbations, with BEC measured over an exacerbation-free period during the year prior to admission (Cohort 2), we assessed readmission rate. Cox proportional hazards regression analysis was adjusted for confounders to estimate the association between BEC and treatment outcomes. Of patients treated with OCS for COPD exacerbations in primary care (Cohort 1), 44% experienced treatment failure following single OCS courses, and 10% (255/2482) were hospitalised for ≤6 weeks. Greater BEC was associated with reduced hospital-admission risk (hazard ratio [HR]=0.26; 95% CI: 0.12-0.56, per 100 cells·µL increase). BEC increases of ≥200 cells·µL from exacerbation-free periods to exacerbations were associated with least hospitalisation risk (HR=0.32; 95% CI: 0.15-0.71) no BEC change. For patients hospitalised for COPD exacerbations (Cohort 2), 4-week hospital readmission was 12% (1189/10 245). BEC increases during an exacerbation-free period within the past year were associated with reduced risk of short-term readmission (HR=0.78; 95% CI: 0.63-0.96). Greater BEC predicted better outcomes for patients with OCS-treated COPD exacerbations, whether community or hospital managed. Eosinopenia predicted worse outcomes.
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http://dx.doi.org/10.1183/23120541.00188-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927786PMC
October 2020

Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency.

Authors:
Malin Fromme Carolin V Schneider Vitor Pereira Karim Hamesch Monica Pons Matthias C Reichert Federica Benini Paul Ellis Katrine H Thorhauge Mattias Mandorfer Barbara Burbaum Vivien Woditsch Joanna Chorostowska-Wynimko Jef Verbeek Frederik Nevens Joan Genesca Marc Miravitlles Alexa Nuñez Benedikt Schaefer Heinz Zoller Sabina Janciauskiene Nélia Abreu Luís Jasmins Rui Gaspar Rodrigo Liberal Guilherme Macedo Ravi Mahadeva Catarina Gomes Kai Markus Schneider Michael Trauner

Gut 2021 Feb 25. Epub 2021 Feb 25.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Vienna, Austria.

Objective: Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.

Design: Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.

Results: Among UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.

Conclusion: Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.
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http://dx.doi.org/10.1136/gutjnl-2020-323729DOI Listing
February 2021

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study.

Authors:
Helgo Magnussen Sarah Lucas Therese Lapperre Jennifer K Quint Ronald J Dandurand Nicolas Roche Alberto Papi David Price Marc Miravitlles

Respir Res 2021 Jan 21;22(1):25. Epub 2021 Jan 21.

Pneumology Department, Hospital Universitari Vall D'Hebron, Vall D'Hebron Institut de Recerca (VHIR), CIBER de Enfermedades Respiratorias (CIBERES), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Background: Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated.

Method: Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK.

Results: A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10-1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03-2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/μL.

Conclusions: In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).
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http://dx.doi.org/10.1186/s12931-021-01615-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818945PMC
January 2021
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