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Jose Luis López-Campos,1,2 María Abad Arranz,1 Carmen Calero Acuña,1,2 Fernando Romero Valero,3 Ruth Ayerbe García,4 Antonio Hidalgo Molina,3 Ricardo I Aguilar Perez-Grovas,4 Francisco García Gil,5 Francisco Casas Maldonado,6 Laura Caballero Ballesteros,5 María Sánchez Palop,6 Dolores Pérez-Tejero,7 Alejandro Segado,7 Jose Calvo Bonachera,8 Bárbara Hernández Sierra,8 Adolfo Doménech,9 Macarena Arroyo Varela,9 Francisco González Vargas,10 Juan J Cruz Rueda10 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, 3Hospital Universitario Puerta del Mar, Cádiz, 4Hospital Juan Ramón Jiménez, Huelva, 5Hospital Universitario Reina Sofía, Córdoba, 6Hospital Universitario San Cecilio, Granada, 7Hospital Infanta Margarita, Cabra, Córdoba, 8Hospital Torrecárdenas, Almería, 9Hospital Regional Universitario de Málaga, 10Hospital Universitario Virgen de las Nieves, Granada, Spain Introduction: This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment.Methods: This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate. Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change. Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation.Results: The present analysis evaluated 565 clinical records (91%) of the complete audit. Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme. Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves. In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment.Conclusion: The majority of doctors did not change the prescription. When changes were made, a number of related factors were noted. Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up. Keywords: quality of care, outpatient care, treatment strategies, follow-up, respiratory diseases, airway diseases

The objectives of this work were to assess the diagnostic sensitivity and specificity of nasopharyngeal (NP) swabs for viral community-acquired pneumonia (CAP) and the performance of pneumonia severity index (PSI) and CURB-65 severity scores in the viral CAP in adults. A prospective observational cohort study of consecutive 341 hospitalized adults with CAP was performed between January 2018 and March 2020. Demographics, comorbidities, symptoms/signs, analytical data, severity scores, antimicrobials, and outcomes were recorded. Blood, NP swabs, sputum, and urine samples were collected at admission and assayed by multiplex real time-PCR, bacterial cultures, and Streptococcus pneumoniae and Legionella pneumophila antigens detection, to determine the etiologies and quantify the viral load. The etiology was identified in 174 (51.0%) patients, and in 85 (24.9%) it was viral, the most frequent rhinovirus and influenza virus. The sensitivity of viral detection in sputum (50.7%) was higher than in NP swabs (20.9%). Compared with sputum, the positive predictive value and specificity of NP swabs for viral diagnosis were 95.8% and 96.9%, respectively. Performance of PSI and CURB-65 scores in all CAP with etiologic diagnosis were as expected, with mortality associated with higher values, but they were not associated with mortality in patients with viral pneumonia. NP swabs have lower sensitivity but high specificity for the diagnosis of viral CAP in adults compared with sputum, reinforcing the use NP swabs for the diagnostic etiology work-up. The PSI and CURB-65 scores did not predict mortality in the viral CAP, suggesting that they need to be updated scores based on the identification of the etiological agent., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response., Methods: We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA., Results: Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts., Conclusions: Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype., (©Copyright: the Author(s).)

Objectives: In a clinical phenotype-based management strategy for COPD, it would be preferable to at least assign all patients to a phenotype, but to a single phenotype only. The aim of this study was to evaluate whether all patients are assigned to one and only one phenotype using the Spanish COPD guidelines (GesEPOC) and to evaluate the criteria that define these categories., Method: The Time-based Register and Analysis of COPD Endpoints study (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients attending annual visits since 2012, which collects GesEPOC phenotypes. Although the GesEPOC recommends that patients considered to be at low risk are not phenotyped, an analysis of the criteria for identifying high- and low-risk phenotypes was performed, comparing the distribution of phenotypes and the criteria applied between these 2 groups., Results: The cohort included 970 patients with a confirmed diagnosis of COPD, divided into 427 (44.02%) low-risk and 543 (55.9%) high-risk patients. The most frequent phenotype was the non-exacerbator (44.9% of high-risk patients). Overall, 20.6% of low-risk patients met criteria for asthma-COPD overlap syndrome, while 9.2% of the cohort did not meet the diagnostic criteria for any phenotype, and 19.1% met the criteria for 2 phenotypes, with no differences between risk groups., Conclusions: Our data highlight some of the weaknesses of the current clinical phenotype strategy, revealing overlapping categories in some cases, and patients to whom no phenotype was assigned., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

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 1 =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., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) patients constitute a heterogeneous population in terms of treatment response. Our objective was to identify possible predictive factors of response to treatment with single bronchodilation monotherapy in patients diagnosed with COPD. The Time-based Register and Analysis of COPD Endpoints (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients who have been attending annual visits since 2012. Patients who were kept on a single bronchodilator during the first year of follow-up were selected. The responders were defined according to all of the following variables: any improvement in morning post-dose forced expiratory volume in 1 s or deterioration <100 mL, no change or improvement in dyspnea score, and no occurrence of exacerbations. Significant and plausible variables were analyzed using a proportional hazard Cox regression for single bronchodilator responders. We analyzed 764 cases, of whom 128 (16.8%) were receiving monotherapy with one bronchodilator. Of these, 85 patients (66.4%) were responders. Factors affecting responder status were: female gender (hazard ratio (HR) 0.276; 95% confidence interval (CI) 0.089-0.858), dyslipidemia (HR 0.436; 95%CI 0.202-0.939), not performing regular exercise (HR 0.523; 95%CI 0.254-1.076), active smoking (HR 0.413; 95%CI 0.186-0.920), and treatment adherence (HR 2.527; 95%CI 1.271-5.027). The factors associated with a single bronchodilation response are mainly non-pharmacological interventions and comorbidities.

We systematically reviewed the current knowledge on fixed-dose triple therapies for the treatment of chronic obstructive pulmonary disease (COPD), with a specific focus on its efficacy versus single bronchodilation, double fixed dose combinations, and open triple therapies. Articles were retrieved from PubMed, Embase, and Scopus up to 3 August 2018. We selected articles with randomized controlled or crossover design conducted in patients with COPD and published as full-length articles or scientific letters, evaluating triple therapy combinations in a single or different inhaler, and with efficacy data versus monocomponents, double combinations, or open triple therapies. Our systematic search reported 108 articles, of which 24 trials were finally selected for the analysis. A total of 7 studies with fixed dose triple therapy combinations, and 17 studies with open triple therapies combinations. Triple therapy showed improvements in lung function [trough forced expiratory volume (FEV 1) ranging from not significant (NS) to 147 ml], health status using the St. George's Respiratory Questionnaire [(SGRQ) from NS to 8.8 points], and exacerbations [risk ratio (RR) from NS to 0.59 for all exacerbations] versus single or double therapies with a variability in the response, depending the specific combination, and the comparison group. The proportion of adverse effects was similar between study groups, the exception being the increase in pneumonia for some inhaled corticosteroid (ICS) containing groups. The reviews of this paper are available via the supplementary material section.

Introduction: Despite widespread recommendations to use standardized questionnaires and multidimensional indices for the assessment of patients with chronic obstructive pulmonary disease (COPD), few data are available on the application of these tools in clinical practice. This study evaluates the attitude of physicians participating in the On-Sint cohort toward the use of health status questionnaires and multidimensional indices, as well as toward the frequency of visits and spirometry in primary care and specialized care., Methods: During the constitution of the On-Sint cohort, the participating physicians were surveyed about their clinical practice. They were questioned on the frequency of spirometry and visits and on the use of various questionnaires and indices. The health status questionnaires assessed were St. George's respiratory questionnaire, chronic respiratory questionnaire, airways questionnaire 20 and COPD assessment test (CAT). Physicians were also asked about the use of the medical research council (MRC) dyspnea scale and multidimensional indices such as body mass index, airflow obstruction, dyspnea, exercise capacity (BODE)., Results: Of the 356 physicians who participated in the study, 258 (72.5 %) completed the investigator's questionnaire (185 primary care, 73 specialized care). Nonscheduled visits were inversely proportional to the severity of COPD. Overall, 34.1% reported using health status questionnaires, mainly CAT (20.9%). We found differences between primary and specialized care in the use of multidimensional indices (84.9% vs 47.6%; P < 0.001). Of all the participants, 33.3% reported using the MRC scale and 28.7% the BODE index., Conclusions: Multidimensional indices and questionnaires are not commonly used with some differences between primary care and specialized care physicians. There is a considerable variability in the frequency of follow-up visits and spirometry., (© 2015 John Wiley & Sons Ltd.)

Objectives. A detailed understanding of the intricate relationships between different acute phase reactants (APRs) in chronic obstructive pulmonary disease (COPD) can shed new light on its clinical course. In this case-control study, we sought to identify the interaction networks of a number of plasma APRs in COPD, with a special focus on their association with disease severity. Methods. COPD cases and healthy smoking controls (3:1 ratio) were recruited in our outpatient pulmonary clinic. Cardiopulmonary exercise testing was used to rule out the presence of ischemic heart disease. All subjects were males as per protocol. Multiple plasma APRs - including α-2-macroglobulin, C-reactive protein (CRP), ferritin, fibrinogen, haptoglobin, procalcitonin (PCT), serum amyloid A (SAA), serum amyloid P, and tissue plasminogen activator (tPA) - were measured using commercial Acute Phase Bio-Plex Pro Assays and analyzed on the Bio-Plex manager software. Correlations between different APRs were investigated using a heat map. Network visualization and analyses were performed with the Cytoscape software platform. Results. A total of 96 COPD cases and 33 controls were included in the study. Plasma A2M, CRP, and SAP levels were higher in COPD patients than in controls. Circulating concentrations of haptoglobin and tPA were found to increase in parallel with the severity of the disease. Increasing disease severity was associated with distinct intricate networks of APRs, which were especially evident in advanced stages. Conclusions. We identified different networks of APRs in COPD, which were significantly associated with disease severity., Competing Interests: The authors have declared that no competing interest exists.

Background: Although tobacco smoke is the main risk factor for chronic obstructive pulmonary disease (COPD), other inhaled toxics have also been associated with the disease. The present study analyzes data from exposure to these substances in a cohort of patients with COPD and assesses their impact on the clinical presentation of the disease., Methods: This is a cross-sectional analysis of the Clinical presentation, diagnosis and course of chronic obstructive pulmonary disease (On-Sint) study. All patients were smokers or ex-smokers as per protocol. In addition, during the inclusion visit patients were enquired about their occupational and biomass exposure history. The clinical features of patients with and without an added risk factor to tobacco were compared and those significant were entered in a multivariate logistic regression analysis, expressed as odds ratio (OR)., Results: The sample size was 1214 patients with COPD, of which 1012 (83.4%) had tobacco as the only risk factor and 202 (16.6%) had additional ones, mainly 174 (14.3%) with occupational gases and 32 (2.6%) with biomass exposure. The geographical distribution of this exposure showed a preference for the northern parts of the country and the East coast. The biomass exposure was rather low. Male gender (OR: 2.180), CAT score (OR: 1.036) and the use of long-term oxygen therapy (OR: 1.642) were associated with having an additional risk factor in the multivariate analysis., Conclusions: Occupational exposures are more common than biomass in Spain. COPD caused by tobacco plus other inhalants has some differential features and a more impaired quality of life., (Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Conflicting data exist on the role of pulmonary dendritic cells (DCs) and their maturation in patients with chronic obstructive pulmonary disease (COPD). Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer., Materials and Methods: A total of 75 consecutive patients were included. Spirometry testing was used to identify COPD. Lung parenchyma sections anatomically distant from the primary lesion were examined. We used flow cytometry to identify different DCs subtypes-including BDCA1-positive myeloid DCs (mDCs), BDCA3-positive mDCs, and plasmacytoid DCs (pDCs)-and determine their maturation markers (CD40, CD80, CD83, and CD86) in all participants. We also identified follicular DCs (fDCs), Langerhans DCs (LDCs), and pDCs in 42 patients by immunohistochemistry., Results: COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers), whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers). The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively). Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects., Conclusions: Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.

Objectives: Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions. The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit., Methods: This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit. The appropriateness of the performance was categorized as excellent (>80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (<20%)., Results: During the audit, 621 clinical records were audited. Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy. The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations., Conclusions: The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics. Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved.

Chronic obstructive pulmonary disease (COPD) is characterized by both local and systemic inflammation. Because inflammation plays a critical role in the development, course and severity of COPD, inflammatory markers have the potential to improve the current diagnostic and prognostic approaches. Local inflammation in COPD is characterized by an infiltration of inflammatory cells, with an increased expression of cytokines, chemokines, enzymes, growth factors and adhesion molecules. Systemic low-grade inflammation is another common but nonspecific finding in COPD. Exacerbations of COPD are acute clinical events accompanied by an exaggerated inflammatory response. Future investigations in the field of COPD biomarkers should take into account different study designs and biochemical assays, disease course and duration, variations in symptom severity and timing of measurement.

Objectives: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow., Methods: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints., Conclusions: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.

Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1,900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalised medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

With the publication of the new guidelines (The Global Initiative for Chronic Obstructive Lung Disease 2011 and Guía Española de la COPD) on chronic obstructive pulmonary disease (COPD), the pharmacological treatment of this disease has changed substantially. In this article, the evidence supporting the use of pharmacological groups in COPD is summarized and the place of each of these drugs among the new therapeutic strategies is established. Although short-acting bronchodilators have been used as maintenance therapy for COPD for many years, few clinical trials are available on the efficacy and safety of these agents, whose role was defined at the very early stages of treatment. The introduction of long-acting bronchodilators, administered every 12 or 24 h, led to an increase in therapeutic effects and an improvement in both treatment adherence and dosage; therefore, both guidelines consider these drugs as the standard therapy for all types of patients and clinical phenotypes. The combination of long-acting bronchodilators from different families has been established as a new therapeutic approach for patients with persistent symptoms despite an appropriate bronchodilator treatment. Anti-inflammatory therapy with inhaled corticosteroids has been discussed at length, and is considered in the current guidelines as the treatment of choice in patients with a high risk of exacerbations associated with an impaired lung function or previous exacerbations, or presenting with phenotypes that are susceptible to the effect of corticosteroids. Roflumilast is a novel drug with a clearly defined indication. Finally, further evidence about other therapies, such as antibiotics or mucolytics, is emerging that will help define their appropriate use in selected patients. At present, pharmacological management of COPD is being re-evaluated. As long as we are able to apply the new treatment approaches to the clinical reality of our patients we will achieve greater benefits in both the short and the long term with a reduction in potential complications.