COPD: systemic proteomic profiles in frequent and infrequent exacerbators.

Background: Some patients with COPD suffer frequent exacerbations (FE). We hypothesised that their systemic proteomic profile would be different from that of non-frequent exacerbators (NFE). The objective of the present study was to contrast the systemic proteomic profile in FE versus NFE. As a reference, we also determined the systemic proteomic profile of healthy controls (HC) and COPD patients during an actual episode of exacerbation (AE). Methods: In the analysis we included 40 clinically stable COPD patients (20 FE and 20 NFE), and 20 HC and 10 AE patients. Their plasma samples were analysed by combining two complementary proteomic approaches: label-free liquid chromatography-tandem mass spectrometry and multiplex immunoassays. Gene Ontology annotation, pathway enrichment and network analyses were used to investigate molecular pathways associated with differentially abundant proteins/peptides (DAPs). Results: Compared with HC, we identified 40 DAPs in FE, 10 in NFE and 63 in AE. Also compared to HC, pathway functional and protein-protein network analyses revealed dysregulation of inflammatory responses involving innate and antibody-mediated immunity in COPD, particularly in the FE group, as well as during an AE episode. Besides, we only identified alterations in the complement and coagulation cascades in AE. Conclusion: There are specific plasma proteome profiles associated with FE, which are partially shared with findings observed during AE, albeit others are uniquely present during the actual episode of AE.

Detection of Alpha-1 Antitrypsin Levels in Chronic Obstructive Pulmonary Disease in Respiratory Clinics in Spain: Results of the EPOCONSUL 2021 Audit.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021-2022, as well as to compare with a previous audit conducted in 2014-2015. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. RESULTS: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. CONCLUSIONS: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Measuring of Alpha-1 Antitrypsin Concentration by Nephelometry or Turbidimetry.

Most clinical laboratories quantify alpha-1 antitrypsin using either nephelometry or turbidimetry techniques because they are commercially available, amenable to automation, and precise. Both methods are based on light scatter. The foundation of both techniques is based on incubation of the specimen with anti-AAT polyclonal antibody solution, a polymer matrix between endogenous AAT and the reagent antibodies forms, leading to production of light-scattering large particles. Although these two terms are sometimes used synonymously, technically speaking they are not.Nephelometry measures the amount of turbidity or cloudiness of a solution by directly quantifying the intensity of the light scattered by insoluble particles in the sample. Therefore, this technique measures the light that passes through the sample, with the detector being placed at an angle from the sample. Turbidimetry is the process of measuring the loss of intensity of the light transmitted linearly through a sample caused by the scattering effect of insoluble particles. The decrease in light transmission is measured compared to a reference, and the absorbed light is quantified.Beyond specific technical differences between both techniques, there are two major differences between the two procedures that may influence the results. First, the concentration of the sample and the resulting intensity of scattered light relative to the intensity of the light source is one major factor. Second, the size of the scattering particles is also a key differentiating factor. This chapter describes the technical requirements, the different protocols, and the clinical applicability of these two techniques in the diagnosis of alpha-1 antitrypsin deficiency.

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit

Objective: The aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. Results: 4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], peripheral blood eosinophilia>300mm3 [OR: 2.16 (1.10–4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15–4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41–2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29–7.41), p<0.011]. Conclusions: Inhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy. (AU)

Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.

[Results of the Implementation of a Case-Finding Program for Alpha-1 Antitrypsin Deficiency in COPD Patients]. / Resultados de la implementación de un programa de detección de casos de déficit de alfa-1 antitripsina en pacientes con EPOC.

Objectives: Currently, the identification of new cases of alpha-1 antitrypsin deficiency (AATD) continues to be one of the great challenges facing the disease. The present study aims to perform an analysis of the results of the implementation of a systematic case detection program of AATD for patients with chronic obstructive pulmonary disease. Material and methods: Cross-sectional observational study in which the results of AAT screening until December 2022 were analyzed. The cases studied were divided into three periods: (1) no systematic case detection until 2013; (2) systematic case detection of S and Z alleles for cases with AAT < 90 mg/dL until 2018, and (3) systematic case detection of 14 mutations for cases with AAT < 120 mg/dL since 2018. Results: A total of 471 cases were studied, of which 306 (65.0%) were carriers of some mutation related to HAD. The number of detected cases of all mutations with their percentage against those studied in each period was respectively: 6 (100%), 48 (88.8%) and 253 (61.5%). If we limit to severe mutations (AAT < 57.2 mg/dL), the distribution by periods was respectively: 3 (50.0), 10 (18.5%) and 17 (4.1%). Conclusions: The present study describes the changes in the detection of patients carrying DAAT-related alleles with three different case identification policies. The data support the use of systematic case detection system in the COPD patient population.

Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis.

BACKGROUND: Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. METHODS: We first performed a systematic search of the different inhalation devices included on the July 2023 Spanish Ministry of Health Billing List. We then consulted the Spanish Agency for Medicines and Health Products to find the updated official label and to obtain the information on the exact composition. RESULTS: We identified 90 unique products, of which 22 were long-acting bronchodilators (and combinations thereof) and 68 were products containing inhaled corticosteroids (ICS). Overall, 10 products with bronchodilators and 40 with ICS were marketed with the metered dose, while 11 with bronchodilators and 28 with ICS were marketed with the delivered dose. In addition, in some bronchodilators, the drug was referred to as a type of salt, whereas in others the information referred to the drug itself. CONCLUSIONS: Our data show that for each inhaled drug there may be up to four different doses and that the marketed name may refer to any of these. Clinicians must be aware of these different dosages when prescribing inhaled medications.

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Exploring Current Concepts and Challenges in the Identification and Management of Early-Stage COPD.

The need to improve health outcomes, as well as disease prognosis, has led clinicians and researchers to propose new ways of identifying COPD in its earliest forms. This initiative is based on the hypothesis that an earlier intervention would have a greater prognostic impact. However, the operational definition of a patient in the initial stages of the disease is complex, and there is still no unanimously accepted definition. GOLD has recently proposed different concepts to identify COPD in its early stages, such as COPD in young people or COPD with mild functional impairment. In addition, GOLD proposes two other concepts, called pre-COPD (symptomatic non-obstructive patients) and PRISm (preserved ratio with impaired spirometry), which aim to identify the patient at risk of developing this chronic airflow obstruction. However, despite the attractiveness of these concepts, none have been taken up universally by the medical community. A universally accepted identification of how to define COPD in its early stages is necessary as a preliminary step in order to design clinical trials to find out the best way to treat these patients. This review deals with these concepts of COPD at the onset of the disease, highlighting their importance and the problems involved in identifying them as therapeutic targets in real clinical practice.

Recommendations for the Implementation of the Self-Administration of Alpha-1 Antitrypsin.

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT. Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3). Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support. Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit.

OBJECTIVE: The aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. RESULTS: 4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], peripheral blood eosinophilia>300mm3 [OR: 2.16 (1.10-4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15-4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41-2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29-7.41), p<0.011]. CONCLUSIONS: Inhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy.

Smoking and COPD Knowledge in the General Spanish Population: A CONOCEPOC Study.

BACKGROUND: The objective of this analysis is to evaluate tobacco use and the level of chronic obstructive pulmonary disease (COPD) knowledge among the general adult population in Spain and to compare these results to those obtained in the 2011 survey. METHODS: A cross-sectional, observational, epidemiological study was conducted by telephone interviews and stratified by sex, age, and setting. The study design was identical to that of the study conducted in 2011. RESULTS: Of a total of 89,601 phone contacts, there were 6534 respondents. The average age was 61.5 years. With respect to smoking, 30.9% reported being former smokers and 14.7% were current smokers, 63.6% of whom reported having attempted to quit. Among the current smokers, 19.7% claimed to use electronic cigarettes, although 88% believe these pose a health risk. No significant differences were found in smoking prevalence or frequency of attempts to quit according to residential setting (rural/urban). The highest prevalence of current smoking in men was recorded in the 55-64 years age range (31.6%), while in women it was from 45 to 54 years (34.6%). Smoking has decreased with respect to 2011, from 21.1% to 16.1% in men and from 17.9% to 13.2% in women, with a clear variability according to region. Of the population surveyed, 32.5% had spontaneous knowledge about COPD, with significant geographic variability. The most frequent sources of information about the disease were social media and the Internet (39.6%), followed by the media (35.2%). CONCLUSIONS: The prevalence of tobacco use in adults has considerably decreased and there is greater knowledge about COPD in Spain, although there is significant variability according to region, which could explain the geographic variability in the prevalence of COPD. Strategies are needed to increase COPD education and awareness and to reinforce smoking prevention measures among women.

Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network.

BACKGROUND: Knowledge of the frequency of rare SERPINA1 mutations could help in the management of alpha1 antitrypsin deficiency (AATD). The present study aims to assess the frequencies of rare and null alleles and their respiratory and hepatic pathogenicity. METHODS: This is a secondary analysis of a study that evaluated the viability of the Progenika diagnostic genotyping system in six different countries by analyzing 30,827 samples from cases of suspected AATD. Allele-specific genotyping was carried out with the Progenika A1AT Genotyping Test which analyses 14 mutations in buccal swabs or dried blood spots samples. SERPINA1 gene sequencing was performed for serum AAT-genotype discrepancies or by request of the clinician. Only cases with rare mutations were included in this analysis. RESULTS: There were 818 cases (2.6%) carrying a rare allele, excluding newly identified mutations. All were heterozygous except for 20 that were homozygous. The most frequent alleles were the M-like alleles, PI*Mmalton and PI*Mheerlen. Of the 14 mutations included in the Progenika panel, there were no cases detected of PI*Siiyama, PI*Q0granite falls and PI*Q0west. Other alleles not included in the 14-mutation panel and identified by gene sequencing included PI*Mwürzburg, PI*Zbristol, and PI*Zwrexham, and the null alleles PI*Q0porto, PI*Q0madrid, PI*Q0brescia, and PI*Q0kayseri. CONCLUSIONS: The Progenika diagnostic network has allowed the identification of several rare alleles, some unexpected and not included in the initial diagnostic panel. This establishes a new perspective on the distribution of these alleles in different countries. These findings may help prioritize allele selection for routine testing and highlights the need for further research into their pathogenetic role.

Prevalence of genetic mutations in alpha-1 antitrypsin deficiency (aatd) in patients with chronic obstructive pulmonary disease in Colombia.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.

Age-period-cohort effect on lung cancer mortality in Spain, 1982-2021.

BACKGROUND: The aim of the study is to provide up-to-date information and evaluate the age-period-cohort effects of age-period cohorts on lung cancer (LC) mortality in Spain for the period 1982 to 2021. METHODS: We analysed deaths by LC and population for the period 1982-2021, available from the Spanish National Institute of Statistics. The LC corresponds to code 162 and codes C33 and C34 of the 9th and 10th editions of the International Classification of Diseases, respectively. Age-period-cohort (A-P-C) modelling was applied to compute the net drift, local drift, longitudinal age curve, and rate ratios (RR) of each period and cohort. A-P-C analysis was performed using the A-P-C Web Tool provided by the National Cancer Institute of the United States. RESULTS: Estimated relative risk in the male birth cohorts has followed a steady downward trend in all cohorts born since 1922, showing an initial period (1922-1947) of slight decline, followed by a more marked decrease in the cohorts born during the period 1947-1977. In the younger cohorts (1977-1997), the decline appears to have stabilised. In women, a strong cohort effect is observed. In those born after the Spanish Civil War (1936 to 1939), the risk increased until it peaked in the 1960s, after which it started to decrease with the same intensity. Period RR in men decreased from 1987 to 1991 (1.1) to 2017-2021 (0.6), while period RR in women increased during this time (from 0.8 to 1.6). CONCLUSIONS: The cohort effect observed in women born after the Civil War suggests that the onset of the LC epidemic may have been due to a higher prevalence of women smokers in these cohorts. However, the trend observed in the younger cohorts suggests a possible slowing-down in the increase in mortality risk in the following years.

Chronic obstructive pulmonary disease mortality trends in Spain, 1980-2020.

OBJECTIVES: In Spain, there has been a recent increase in the mortality rate for chronic obstructive pulmonary disease (COPD) in younger women. This study aimed to analyze trends in the COPD mortality rate in Spain from 1980 to 2020, evaluating any differences between genders and age groups. METHODS: Death certificates and mid-year population data were obtained from the Spanish National Institute of Statistics. For both genders, age group-specific and standardized (overall and truncated) rates were calculated by the direct method using the world standard population. The data were analyzed using the joinpoint regression method. RESULTS: In both men and women, the number of COPD deaths increased from 1980 to 1999 (average annual increase of 7% in men and 4% in women), while from 1999 onwards, deaths decreased by -1.0% per year in both genders. In women, there was a significant final period of increase in the 55-59 to 70-74 age groups and a slowing of the decline in the over 75 age group. Additionally, an increase in mortality for the truncated rates was observed for women between 2006 and 2020. In men under 70 years of age, there was an initial period in which death rates remained stable or significantly increased, followed by a period in which they decreased significantly. CONCLUSIONS: Our study shows age and gender differences in COPD mortality trends in Spain. Although the data show a downward trend, we have identified a worrying increase in the truncated rates in women for the last few years.