Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review.

INTRODUCTION: New tools such as cryobiopsy of mediastinal lymph nodes (cryoEBUS) have been described to improve the diagnostic usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The literature suggests that this novel procedure could be associated with greater diagnostic usefulness than conventional EBUS-TBNA. METHODS: To develop a systematic analysis and meta-analysis on the diagnostic diagnostic yield and safety of cryobiopsy of hilar and mediastinal adenopathies compared to EBUS-TBNA. RESULTS: Seven studies that had included a total of 555 patients were considered in this review, with 365 (65.7%) of these patients having an etiology of malignant lymph node involvement. The overall diagnostic usefulness of cryoEBUS was higher compared to EBUS-TBNA (92% vs. 80%). However, when the results were analysed according to the specific aetiologies of the adenopathies, cryoEBUS was especially useful in cases of lymphomas or non-pulmonary carcinomas (83% vs. 42%) and in cases that were benign (87% vs. 60.1%), with no significant differences being found in specific cases of lung cancer. For lymphoma, cryoEBUS was diagnostic in 87% of cases compared to 12% for EBUS-TBNA and in addition, also allowed the characterisation of every lymphoma subtype. Genetic studies and immunohistochemical determination of PD-L1 was possible in almost all (97%) of the samples obtained by cryoEBUS, while this was only possible in 79% of those obtained by EBUS-TBNA. The most frequent complication was light bleeding, which was described in up to 85% of cases in some series. CONCLUSION: CryoEBUS could represent a promising technique in the diagnostic algorithm used for mediastinal and hilar involvement. Although cryoEBUS did not significantly improve the diagnosis of lung cancer compared to EBUS-TBNA, the results were significantly better in patients with benign pathologies and other tumour types, including lymphomas. In addition, it seems that the samples obtained by cryoEBUS better defined the histological subtypes of lymphoma and allowed complete molecular characterisation in cases of lung cancer. The technique has proven to be safe and no serious complications were described after the procedure.

Tobacco Patterns and Risk of Chronic Obstructive Pulmonary Disease: Results From a Cross-Sectional Study.

INTRODUCTION: There is still uncertainty about which aspects of cigarette smoking influence the risk of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to estimate the COPD risk as related to duration of use, intensity of use, lifetime tobacco consumption, age of smoking initiation and years of abstinence. METHODS: We conducted an analytical cross-sectional study based on data from the EPISCAN-II study (n=9092). All participants underwent a face-to-face interview and post-bronchodilator spirometry was performed. COPD was defined as post-bronchodilator FEV1/FVC<70%. Parametric and nonparametric logistic regression models with generalized additive models were used. RESULTS: 8819 persons were included; 858 with COPD and 7961 without COPD. The COPD risk increased with smoking duration up to ≥50 years [OR 3.5 (95% CI: 2.3-5.4)], with smoking intensity up to ≥39cig/day [OR 10.1 (95% CI: 5.3-18.4)] and with lifetime tobacco consumption up to >29 pack-years [OR 3.8 (95% CI: 3.1-4.8)]. The COPD risk for those who started smoking at 22 or later was 0.9 (95% CI: 0.6-1.4). The risk of COPD decreased with increasing years of cessation. In comparison with both never smokers and current smokers, the lowest risk of COPD was found after 15-25 years of abstinence. CONCLUSION: COPD risk increases with duration, intensity, and lifetime tobacco consumption and decreases importantly with years of abstinence. Age at smoking initiation shows no effect. After 15-25 years of cessation, COPD risk could be equal to that of a never smoker. This work suggests that the time it takes to develop COPD in a smoker is about 30 years.

Occupation as a risk factor of small cell lung cancer.

Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present.

[Effectiveness of nebulized hypertonic saline in patients with bronchial hypersecretion]. / Efectividad del suero salino hipertónico nebulizado en pacientes con hipersecreción bronquial.

INTRODUCTION: Nebulized hypertonic saline (HS) improves quality of life and reduces exacerbations in patients with cystic fibrosis. It is unknown if it would offer the same benefits in other hypersecretory pathologies. METHODS: Retrospective observational study. Patients who passed the tolerance test and started HS 5.8% with one year of follow-up were included. Clinical and healthcare parameters were quantified in the year before and after the start of treatment. RESULTS: 101 patients, 60.4% women, 65years (95%CI: 62.4-67.9): 82 (81.2%) bronchiectasis, 6 (5.9%) COPD, 2 (2%) asthma, 1 (1%) ILD, and 10 (9.9%) other causes. There was a reduction in bronchorrhea (91.1% vs 75.2%), recurrent infections (57.4% vs 22.8%) and cycles of antibiotic therapy (1.54 vs 0.55), as well as an increase in FEV1 (1881ml vs. 1942ml) and a decrease in visits to primary care (2.94 vs. 1.1), emergencies (0.36 vs. 0.17) and hospitalizations (0.17 vs. 0.17). 06). 73 patients (72.3%) presented an adequate tolerance. CONCLUSION: Nebulization of HS 5.8% in patients with bronchial hypersecretion is safe and has a remarkable clinical and healthcare impact.

Residential Radon and Small Cell Lung Cancer. Final Results of the Small Cell Study.

INTRODUCTION: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study. METHODS: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. RESULTS: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. CONCLUSIONS: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure.

Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review.

INTRODUCTION: Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis. MATERIALS AND METHODS: We conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences. RESULTS: We included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times. CONCLUSIONS: All articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer.

Long COVID in hospitalized and non-hospitalized patients in a large cohort in Northwest Spain, a prospective cohort study.

Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.

Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review.

INTRODUCTION: Relatively little is known about the risk factors for chronic obstructive pulmonary disease (COPD) in never-smokers, and these factors have not yet been fully characterised. This study therefore sought to analyse COPD risk factors in never-smokers by conducting a systematic review of the literature on the topic. MATERIALS AND METHODS: We performed a search in PubMed (Medline) and Embase from 2000 onwards, to locate studies on COPD in never-smokers. For literature search and evidence synthesis purposes, we used the PRISMA guidelines and drew up a specific quality scale to quantify the evidence of each study included. RESULTS: The bibliographic search retrieved a total of 557 papers, 20 of which fulfilled the designated inclusion criteria (two case-control studies, four cohort studies and 14 cross-sectional studies). These studies were undertaken in Europe, the United States, Latin America, Asia and Africa. The risk factors for never-smokers were varied and ranged from exposure to biomass, occupational exposure and passive smoking to having a history of asthma, tuberculosis or respiratory infections during childhood. The effect of residential radon was unclear. The highest risk was obtained for previous respiratory diseases of any type, with a magnitude much higher than that observed for other risk factors. CONCLUSIONS: There are few studies on COPD risk factors in never-smokers. More purpose-designed studies in this subpopulation are thus called for, including well-designed studies to specifically assess if indoor radon has any role on COPD onset.

Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case-control study.

BACKGROUND: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk. This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. METHODS: A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were non-smokers diagnosed with LC, and controls were composed of never-smoking individuals undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. RESULTS: The study included 457 cases (42%) and 631 controls (58%), with a predominance of women (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. CONCLUSIONS: No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk.

Residential radon and characteristics of chronic obstructive pulmonary disease.

It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case-control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients' homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1% < 50 had radon concentrations below 100 Bq/m3, as compared to 35.6% with the same severity of obstruction who had over 300 Bq/m3. COPD cases with radon concentrations higher than > 600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPD.

Fruits and Vegetables and Lung Cancer Risk in Never Smokers. A Multicentric and Pooled Case-Control Study.

BACKGROUND: The etiology of lung cancer in never smokers is partly unknown. We aimed to assess the effect of fruits and vegetables consumption on lung cancer risk in never smokers. METHODS: We pooled five multicenter case-control studies performed in Northwestern Spain. Cases and controls were all never smokers. All lung cancer cases had anatomopathological confirmed diagnoses. We performed a multivariate logistic regression to analyze the effect of different types of fruits and vegetables consumption on lung cancer risk. RESULTS: A total of 438 cases and 781 controls were included. We observed that a consumption from one to six times per week shows a negative association with lung cancer risk for: kiwis (OR 0.67; 95%CI 0.46-0.95), oranges (OR 0.55; 95%CI 0.37-0.80), turnip tops (OR 0.48; 95%CI 0.34-0.66), "berza gallega" (OR 0.70; 95%CI 0.51-0.97) and broccoli (OR 0.55; 95%CI 0.35-0.83) compared to less than once a week consumption. On the other hand, we found an increased risk for lung cancer with a daily consumption of tomatoes, carrots and potatoes. CONCLUSIONS: Oranges, kiwis, turnip tops, berza gallega and broccoli may play a protective role on lung cancer development in never smokers while tomatoes, carrots and potatoes might have some association with this disease.

The Diagnostic Contribution of Systematic Lung Ultrasonography in Patients Admitted to a Conventional Pulmonology Hospitalization Unit.

OBJECTIVE: Although the evidence to date remains limited, we hypothesized that performing protocolized lung ultrasound (LUS) in patients, admitted to a conventional pulmonology hospitalization unit, could improve diagnostic precision. The main objectives of this study were to evaluate the diagnostic contribution and changes in the treatments administered after performing a protocolized LUS in patients hospitalized in a Pulmonology Department ward. METHODOLOGY: This was a prospective, observational study, which included patients admitted from the Emergency Department to a conventional Pulmonology Department hospitalization unit, after first being evaluated by a pulmonologist. LUS was performed within the first 48 hours of admission. The diagnosis at the time of discharge was used as the reference diagnosis. RESULTS: A total of 180 patients were included in this study. The admitting diagnoses were the decompensation of an underlying obstructive disease in 60 patients (33.3%), respiratory infection in 93 (51.7%), pulmonary thromboembolism (PE) in 9 (5%), exacerbation of an interstitial lung disease in 14 (7.8%), and other causes in 4 cases (2.2%). Ultrasonography provided new information, unsuspected at the patient's admission, in 117 (65%) of the patients by capturing images suggestive of infection in 63 patients (35%), 1 new case of ILD, 23 (12.7%) cases of cardiogenic edema, and pleural pathology in 19 (10.5%), as well as two tumors and indirect data related to a PE. The use of LUS resulted in the decision to change the already established treatment in 17.2% of the cases. CONCLUSIONS: LUS provided additive information in more than half of patients that ended up reclassifying or potentially changing diagnosis or treatment. Thus, including LUS in management algorithms could reduce the need for other complementary tests or unnecessary treatments.

Results from a Spanish national survey on the application of ultrasound in pulmonology services.

BACKGROUND: This was an observational, cross-sectional, and multicentre study carried out from October to December 2020, through a survey sent to Spanish Society of Pulmonology and Thoracic Surgery members in public hospitals with different levels of complexity. Our objective was to complete a national analysis of clinical practice, organisation, infrastructure, the services portfolio, teaching, and research activity related to ultrasound. RESULTS: Data from 104 hospitals were analysed. Ultrasound was used in 56.7% of cases, both in the area of bronchopleural techniques and on conventional wards, with no differences between centres. Lung ultrasound (LUS) was performed more often in the procedures area in intermediate-complexity centres compared to high- and low-complexity centres (36% vs. 31% and 6.25%, respectively). More high-complexity centres had three or more ultrasound scanners than intermediate-complexity centres (38% vs. 16%); 43% of low-complexity centres shared their ultrasound equipment with other specialties. Fewer than 6% of centres did not have an ultrasound machine. LUS was most often used during the treatment of pleural effusion (91.3%), in the differential diagnosis of dyspnoea (51.9%), and to rule out iatrogenic pneumothorax (50.9%). Only 5.7% of the centres had a pulmonologist specialised in LUS. Finally, fewer than 35% of the hospitals were teaching centres and fewer than 18% participated in research projects. CONCLUSIONS: The use and availability of LUS has grown in pulmonology services, however, still relatively few pulmonologists are specialised in its use. Moreover, teaching and research activity in this field is scarce. Strategies are necessary to improve physicians' skill at using LUS and to promote its use, with the ultimate goal of improving healthcare activity.

Serum levels of inflammatory mediators as prognostic biomarker in silica exposed workers.

Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed: interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-ß1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.

A rapid calprotectin test for the diagnosis of pleural effusion.

In previous studies, measuring the levels of calprotectin in patients with pleural effusion (PE) was an exceptionally accurate way to predict malignancy. Here, we evaluated a rapid method for the measurement of calprotectin levels as a useful parameter in the diagnosis of malignant pleural effusion (MPE) in order to minimise invasive diagnostic tests. Calprotectin levels were measured with Quantum Blue® sCAL (QB®sCAL) and compared with the gold standard reference ELISA method. Calprotectin levels in patients with benign pleural effusion (BPE) were significantly higher (p < 0.0001) than for MPE patients. We measured the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LRs) for a cut-off value of ≤ 14,150 ng/mL; the diagnostic accuracy was 64%. The odds ratio for PE calprotectin levels was 10.938 (95% CI [4.133 - 28.947]). The diagnostic performance of calprotectin concentration was better for predicting MPE compared to other individual parameters. Comparison of two assays showed a slope of 1.084, an intercept of 329.7, and a Pearson correlation coefficient of 0.798. The Bland-Altman test showed a positive bias for the QB®sCAL method compared to ELISA fCAL®. Clinical concordance between both these methods was 88.5% with a Cohen kappa index of 0.76 (95% CI [0.68 - 0.84]). We concluded that QB®sCAL is a fast, reliable, and non-invasive diagnostic tool for diagnosing MPE and represents an alternative to ELISA that could be implemented in medical emergencies.

Residential radon and lung cancer characteristics at diagnosis.

PURPOSE: This study sought to ascertain whether there might be an association between radon concentrations and age, gender, histologic type, and tumor stage at diagnosis. MATERIALS AND METHODS: Lung cancer cases from different multicenter case-control studies were analyzed, and clinical data were retrieved from electronic health records and personal interviews. A radon device was placed in all dwellings of participants, and we then tested the existence of an association between residential radon and lung cancer characteristics at diagnosis. RESULTS: Of the total of 829 lung cancer cases included, 56.7% were smokers or ex-smokers. There was no association between indoor radon concentrations and age, gender, histologic type or tumor stage at diagnosis. Median indoor radon concentrations increased with age at diagnosis for men, but not for women. When analyzing participants exposed to more than 1000 Bq/m3, a predominance of small cell lung cancer and a higher presence of advanced stages (IIIB and IV) were observed. CONCLUSIONS: There seems to be no association between radon and age, gender, histologic type or tumor stage at diagnosis. Higher radon exposure is more frequent in the case of small-cell lung cancer.