Background In the general population without COPD, indoor air pollution from biomass is a causal factor of cognitive impairment (CI). CI is also common in patients with tobacco smoke COPD and has been associated with hypoxemia and cardiovascular comorbidities. CI and its risk factors have not been evaluated in COPD patients living at high altitude, who experience greater hypoxemia and frequent exposure to wood smoke. Methods Patients with COPD residing at high altitude with FEV1/FVC <0,70 and COPD risk factors (wood smoke, Tobacco smoke or combined exposure). Measurement of the Mini-Mental State Examination to assess CI, educational level, comorbidities, exacerbations, arterial blood gases, diffusion (DLCO), and 6-min walk test (6MWT). Comparisons between groups with and without CI using the X2 test and unpaired t-test. Logistic regression with odds ratio (OR) calculation was used to evaluate the association of CI with the variables of interest. Results In the 199 patients included, 16.1% had CI, the majority with mild involvement (68.8%). Those with CI had more frequent exposure to wood smoke (p<0.001), older age (p=0.017), lower educational level, PaO2 (p=0.032), DLCO (p=0.036), and fewer meters in the 6MWT (p=0.007), with no differences in sex, severity of obstruction or comorbidities. Adjusting for the other variables, exposure to wood smoke was associated with CI [OR and 95% CI: 4.82 (1.62-14.33). Conclusions In patients with mild to moderate COPD living at high altitude, regardless of hypoxemia, age, educational level, comorbidities, and lung function, exposure to wood smoke was associated with CI.

OBJECTIVE:Uncontrolled asthma is common among Latin American patients. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, drivers of type 2 inflammation. METHODS:This post hoc analysis of 48-96 week open-label extension TRAVERSE (NCT0213402) study assessed dupilumab 300 mg every 2 wk up to 148 wk (parent study plus extension) in patients with moderate-to-severe asthma enrolled from Latin American centers who previously completed a dupilumab asthma study (phase 2b or phase 3 QUEST). Endpoints included treatment-emergent adverse events, severe asthma exacerbations, pre-bronchodilator forced expiratory volume in 1 s (FEV1), 5-Item Asthma Control Questionnaire (ACQ-5), Asthma Quality of Life Questionnaire (AQLQ), and type 2 biomarkers. RESULTS:A total of 596 (28.9%) patients were enrolled from Latin American centers. Safety was consistent with the known dupilumab safety profile. Annualized rate of severe exacerbations remained low across patients (0.115-0.459). Improvements in pre-bronchodilator FEV1 were sustained to Week 96 (mean change from parent study baseline of 0.28-0.35 L) and in ACQ-5 and AQLQ scores to Week 48 (last assessed time-point). Patients receiving placebo during parent studies demonstrated improvements once switched to dupilumab in TRAVERSE. Patients receiving dupilumab during parent studies demonstrated further improvements in exacerbations, ACQ-5, and AQLQ. Type 2 biomarkers decreased over time. CONCLUSIONS:Consistent with results in the overall population, long-term efficacy and safety of dupilumab was observed in patients with moderate-to-severe asthma with a treatment duration of up to 148 wk, supporting the long-term benefits of dupilumab use in Latin American patients.

BACKGROUND AND OBJECTIVES:Triple therapy (TT) is effective for asthma patients whose disease remains uncontrolled with dual therapy. However, relevant questions remain unanswered. Objectives: To evaluate the long-term effectiveness of TT in a real-world setting; to determine the extent to which it prevents escalation to oral corticosteroids (OCS), azithromycin, or biologics; and to identify factors related to failure. METHODS:Retrospective multicenter cohort study. Data were collected at baseline, 16-24 weeks, 52 weeks, and at the last visit. Follow-up extended to treatment escalation or the last visit. Effectiveness of TT was defined as no treatment escalation plus asthma control (Asthma Control Test [ACT] ≥20 and no severe exacerbations in the preceding 12 months). RESULTS:A total of 390 patients were analyzed (median follow-up 40.0 months). Of these, 83 (22.5%) escalated treatment; TT was effective in 54% at the last visit. Complete remission (control plus FEV1 ≥80%) was achieved in 20.6%. Severe exacerbations, OCS load, symptoms, and FEV1 improved significantly. The factors associated with failure of TT in the previous year were smoking history (HR 1.84), lack of asthma control at 16-24 weeks (HR 3.41), bronchiectasis (HR 1.91), baseline ACT ≤15 (HR 1.81), ≥2 severe exacerbations in the previous year (HR 2.01), and low eosinophil count (HR 2.58). FEV1 declined >30 mL/year in 25.3% of patients in whom TT was effective. CONCLUSIONS:TT achieved sustained control in a significant proportion of patients whose disease was not controlled with dual therapy. Bronchiectasis, smoking history, greater clinical severity at initiation of TT, and lack of control at 16-24 weeks predicted poorer outcome.

Alpha-1 antitrypsin (AAT) is a medium-sized globular glycoprotein distributed in serum and tissues. In the lungs, it inhibits serine proteases and has anti-inflammatory properties in different types of cells, protecting lung tissue from damage. Mutations in the SERPINA1 gene that codes for AAT are related to asthma and chronic obstructive pulmonary disease. In Colombia, there are no published data on the prevalence of alpha-1 antitrypsin deficiency (AATD) in adult patients with difficult-to-manage asthma. ​This study aims to determine the prevalence of genetic mutations related to AAT in adult patients with difficult-to-treat asthma in Colombia. This prospective, multicenter, cross-sectional study included adult patients with difficult-to-treat asthma in five asthma care centers in Colombia. Informed consent was obtained, and gingival mucosa was sampled for genetic diagnosis of AATD using the A1AT Genotyping Test. Data analysis was performed using the Chi2 test, Student's t-test, and Mann-Whitney test for group comparison. A total of 449 adult patients with difficult-to-treat asthma were included with a mean age of 56.1 ± 14.9 years; 73.1% (N = 328) were women; and 89.1% were using high-dose inhaled corticosteroid / long-acting B2 agonists. Mutations in the AAT gene were found in 12.5% (N = 56) of patients. Of these, 85.7% had the M/S genotype, 10.7% the M/Z genotype, 1.8% the M/I genotype, and 1.8% the S/S genotype. The study identified a prevalence of AAT mutations in 12.5% of adult patients with difficult-to-treat asthma in Colombia made up of four genotypes: M/S, M/Z, M/I and S/S.

Background:Real-world effectiveness and safety of dupilumab for asthma treatment have been evaluated in USA and Europe, but research from Latin America is lacking. We aimed to describe the effectiveness of dupilumab in terms of changes in the annual rate of asthma exacerbations (AER) and their impact on lung function in Colombian patients. Methods:Real-world, descriptive, and multi-centric (five clinical centers located in four different cities in Colombia) retrospective study that included patients aged ≥18 years with severe asthma, as defined by the GINA criteria. Data were collected from medical records of medical centers specialized in pulmonology or allergy care) spanning from 12 months before the prescription of dupilumab (baseline) to 25 months later. Follow-up data were categorized at various time points (2-4, 5-7, 8-10, 11-13, 14-18, and 19-25 months). Main outcomes were annual rates of asthma exacerbations (emergency visits or hospitalizations due to asthma), lung function measured through FEV1 and percent predicted FEV1 (FEV1pp), and Asthma Control Test (ACT) scores. Outcome rates were compared between baseline and follow-up data points. FeNO and absolute eosinophil counts throughout the observed period was also explored. Results:A total of 98 patients were included. At baseline, the mean AER was 0.61 ± 1.45 per adult. Lower AER were observed after one (0.11 ± 0.54) or two-years (0.08 ± 0.20) of dupilumab treatment (p = 0.03). FEV1 measurements after one or two years of dupilumab treatment were significantly lower than baseline (p = 0.03). Mean change from baseline in FEV1 was 302.1 ± 481.97 ml (n = 19), 282.00 ± 231.99 ml (n = 10), and 248.18 ± 281.21 ml (n = 11) in the 2-4-, 11-13-, and 19-25-month follow-up periods, respectively. FEV1pp showed higher but not significant values from the 2-4-month period, with a median change of 12.5% (IQR: 0.3, 21.5). The proportion of patients with uncontrolled asthma (ACT ≤15) decreased from 68% at baseline to 19% and 20% at year-one and second year of treatment, respectively (p = 0.003). The proportion of patients reaching FeNO values below 25 ppb was lower after dupilumab treatment than in baseline (p < 0.0001). Of the total cohort (n = 99), 15 (15.2%) experienced an adverse event (AE). Three patients discontinued dupilumab permanently, and two discontinued dupilumab due to AEs. Conclusions:Dupilumab is an effective and well-tolerated treatment for severe asthma in Colombia, resulting in reduced exacerbations and improved asthma control, lung function, and FeNO levels.

Severe asthma causes a high burden of morbidity and costs for healthcare systems, especially in low- and middle-income countries, where patients continue to be treated exclusively in primary care settings and face many barriers to accessing high-quality healthcare. Evidence has shown that managing patients with severe asthma in specialized clinics with an interdisciplinary team and continuous and systematic evaluation improves cost-effectively disease outcomes. In this article, we will delve into the main challenges faced and the valuable lessons learned throughout the building and implementation of a severe asthma clinic, in a tertiary respiratory care institution located in Colombia, a middle-income country, and using this documented experience we pose how to build severe asthma clinics/programs applicable to low- and middle-income countries. It has been documented that patients with severe asthma in low- and middle-income countries experience multiple barriers in having a proper diagnosis, timely periodic medical and test follow-up appointments, proper educational support, and opportune delivery of medications, perpetuating asthma exacerbations and poor control. Multidisciplinary clinics have been shown to be useful in improving clinical outcomes and reducing costs of severe asthma care in high-income developed countries, but there is very little information on the feasibility of implementing these types of clinics in low- and middle-income countries. Three years ago, with the cumulative experience of our general asthma program, we decided to organize and implement the institutional severe asthma clinic (Asmaire ReXpira) the which, with just this short time of operation, has successfully demonstrated improvement in quality of life, exacerbation rates, and disease control of the patients, with education being the most important tool for achieving these results. We have confirmed the feasibility of establishing and the importance of developing an interdisciplinary SAC in a middle-income country, and using this experience we pose that it is also necessary and feasible to build non-complex, lower sophisticated successful SACs in LMICs, despite the challenges that may arise during this process. These SACs, adopting a systematic and multidimensional evaluation of the patients, have shown to decrease rates of clinically relevant asthma exacerbations and systemic steroid use while improving symptom control, lung function, and overall quality of life. We suggest that education stands as the cornerstone of successful SACs, enabling the patients with essential skills for self-managing their disease effectively in both the short and long term.

Objective:Severe asthma burdens patients and presents clinical management challenges for healthcare professionals. Biologics are crucial interventions for severe type two (T2) patients with high eosinophil counts. We conducted a Delphi consensus in seven developing or typically underrepresented countries to understand expert agreement on managing severe asthma with type two (T2) inflammation. Methods:The study comprised two online survey rounds and a participant meeting, involving 21 and 20 respiratory experts in the first and second survey, respectively. We developed a 70-statement questionnaire after literature review. Responses were recorded on a Likert scale (0-9) with 75% consensus threshold. Results:Consensus was reached on 37/60 closed-ended questions, including subtypes, in survey-1 and 20/47 closed-ended questions in survey-2. 95% of participants agreed on biomarker use for biologic treatment selection. 100% agreed timely biologic treatment leads to improvement in patients with severe asthma and an eosinophilic phenotype. 90% agreed to avoid maintenance oral corticosteroids (OCS) and start biologic therapy directly. Experts defined clinical remission on treatment as no exacerbations, no OCS use, Asthma Control Questionnaire (ACQ)-5 score < 1.5, and lung function optimization (forced expiratory volume in one second [FEV1] ≥ 80% of predicted or pre-bronchodilator FEV1 increase ≥ 100 mL from baseline). In survey-1, 81% agreed these outcomes are achievable in practice. All referral statements achieved consensus. Conclusions:This Delphi study focused on understanding patients with severe asthma and T2 inflammation in developing/underrepresented countries. Appropriately utilizing biomarkers, timely treatment interventions for best outcomes, expert consensus on clinical remission, and referral are crucial for improving patient management.

BackgroundCost-effectiveness studies evaluate health technologies and help choose treatments. The current study compared dupilumab to omalizumab, mepolizumab, and benralizumab in Colombian adults with severe uncontrolled type 2 asthma.MethodsOver a 5-year period, a Markov model was utilized to assess the costs of biological treatments and management of exacerbations, comparing various doses of exacerbations, comparing various doses of dupilumab, omalizumab, mepolizumab, and benralizumab as add-on treatments. It included a 5% annual discount rate per local HTA, and set willingness-to-pay at three times GDP per capita per quality-adjusted life year (QALY) in Colombia.ResultsDupilumab (200 mg) exhibited greater QALYs and reduced overall costs compared to mepolizumab (100 mg), benralizumab (30 mg), and omalizumab (450 mg and 600 mg), with the incremental cost-effectiveness ratio (ICER) per QALYgained being -$5.429, -$6.269, -$196.567 and -$991.007, respectively. Dupilumab had greater QALYs and costs versus omalizumab 300 mg (ICERof $200.653 per QALY, above the willingness-to-pay threshold of 3 x GDP per capita). Sensitivity analyses were consistent with base case results.ConclusionsDupilumab 200 mg was strongly dominant versus omalizumab 450 mg and 600 mg, mepolizumab 100 mg, and benralizumab 30 mg; however, cost-effectiveness was not demonstrated versus omalizumab 300 mg. These results could assist healthcare professionals in choosing an appropriate biologic for treating severe type 2 asthma.

There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.

Background: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. Objective: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogota, Colombia. Material and Methods: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundacion Neumologica Colombiana in Bogota (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE =100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils =300 cells/mu L; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/ non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/mu L). Results: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. Conclusions: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) constituye un importante desafío tanto en el ámbito económico como en el de la salud pública, tanto a nivel mundial como en el contexto colombiano. Esta condición no solo repercute en los pacientes que la padecen, sino que también afecta a sus cuidadores y al sistema de salud en su conjunto. Se ha observado un incremento en el ausentismo laboral tanto por parte de los pacientes como de sus familiares, lo que resulta en pérdidas económicas y oportunidades laborales, agravando aún más el impacto adverso en el individuo y su entorno familiar. El propósito de esta guía clínica es establecer pautas basadas en la evidencia científica disponible para mejorar la atención médica y la gestión de recursos en el tratamiento de la EPOC en la población colombiana. Objetivo: Esta guía de práctica clínica (GPC) informada en evidencia de la Asociación Colombiana de Neumología y Cirugía de Tórax (Asoneumocito), Asociación Colombiana de Medicina Interna (ACMI) y Asociación colombiana de medicina familiar (SOCMEF) y Asociación Colombiana de Fisioterapia (ASCOFI), pretende apoyar a los pacientes, profesionales de la salud, y otros actores en la toma de decisiones sobre el diagnostico, enfoque, pronóstico y manejo de adultos con la EPOC en el contexto colombiano. Materiales y métodos: El Comité de la EPOC de Asoneumocito por delegación de la presidencia de esta, conformó un panel de expertos multidisciplinario para balancear y minimizar el potencial sesgo proveniente de los conflictos de intereses e invitó a las demás asociaciones que hicieron parte de esta guía. La Universidad de los Andes coordinó y desarrolló la actualización o realización de novo de revisiones sistemáticas de la literatura acorde a la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation). El comité de EPOC planteó una serie de preguntas que el panel de expertos priorizó, así como los desenlaces según su importancia para los profesionales de la salud y los pacientes. Se utilizaron los marcos de la Evidencia a la Decisión (EtD) desarrollados por el grupo de trabajo GRADE, los cuales estuvieron sujetos a comentarios públicos. Resultados: El panel elaboró 10 recomendaciones basadas en evidencia para el manejo de pacientes con la EPOC que recibieron alguna de las siguientes intervenciones: oxigenoterapia a largo plazo, vacunación contra virus de influenza, rehabilitación pulmonar, inhaloterapia con anticolinérgicos de acción prolongada, inhaloterapia con terapia triple, suplementos nutricionales, terapia complementaria con azitromicina, cesación tabáquica con vareniclina y reemplazo de alfa-1 antitripsina. Conclusiones: Las recomendaciones incluidas en esta guía se desarrollaron para el contexto colombiano. El panel consideró que hacen falta por desarrollar estudios de evaluaciones económicas, así como el impacto de las intervenciones evaluadas en áreas como la equidad, aceptabilidad y factibilidad de implementación en Colombia.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an uncommon antineutrophil cytoplasmatic antibody (ANCA) associated vasculitis involving small and medium size blood vessels. It has a variable clinical presentation depending on the main organ involved, making it difficult to diagnose. Treatment is mainly based on high-dose steroids and other immunosuppressants like cyclophosphamide, which may prevent end-organ damage and induce remission at the expense of having important adverse effects. However, new therapeutic agents had been shown to provide better results with favorable safety profiles. Biologic therapy with monoclonal antibodies such as Rituximab and Mepolizumab has been approved for its use in ANCA vasculitis including eosinophilic granulomatosis with polyangiitis. These cases describe two patients with EGPA whose initial presentation was severe asthma and who appeared to have extrapulmonary end-organ damage. Mepolizumab was used in both cases with a successful response.

Purpose:To compare the level of knowledge in vaccination against influenza and pneumococcus of patients with chronic obstructive pulmonary disease (COPD) who are managed in an Integrated Care Program (ICP) with those who receive usual care (UC).Methods:A telephone survey of patients diagnosed with COPD registered in public care networks or private institutions was done. A descriptive and comparative analysis of the characteristics of the ICP and UC groups was carried out. The relationship between belonging to an ICP and the level of knowledge about vaccination was evaluated using Propensity Score Matching (PSM) and multivariate logistic and ordinal regression models.Results:Of 674 study participants, 27.2% were from the ICP group. ICP patients were older, more frequently men, from a higher socioeconomic stratum and a higher educational level (p<0.05). 75.5% of the patients in the ICP group had a high level of vaccination knowledge compared to 42.7% in the UC group (p<0.001). In the multivariate analysis, adjusting for sociodemographic variables, years of COPD diagnosis, and comorbidities, belonging to the ICP was associated with a higher probability of answering questions about vaccination correctly and having a high level of knowledge (OR 3.397, IC 95% 2.058-5.608, p<0.001).Conclusion:Patients with COPD managed in an ICP have a higher level of knowledge in vaccination against influenza and pneumococcus, compared to patients in usual care.

The stepwise treatment approach recommended by the Global Initiative for Asthma (GINA) includes systemic corticosteroids (SCS) suggested as a final step if asthma is severe and/or difficult to treat. Yet, despite the effectiveness of SCS, they are also associated with potentially irreversible adverse outcomes such as type 2 diabetes, adrenal suppression, and cardiovascular disease. Based on recent data indicating that the risk of developing these conditions can increase after as few as 4 short-term (burst) courses of SCS, even patients with mild asthma who receive SCS occasionally for exacerbations are also at risk of these events. As a result, recent updates by GINA and the Latin American Thoracic Society recommend decreasing SCS use by optimizing administration of non-SCS therapies and/or increasing the use of alternatives, such as biologic agents. Recent and ongoing studies characterizing treatment patterns among patients with asthma have revealed alarming trends suggesting the widespread overuse of SCS around the world. In Latin America, asthma prevalence is approximately 17%, and data suggest that the majority of patients have uncontrolled disease. In this review, we summarize currently available data on asthma treatment patterns in Latin America, which indicate that SCS are prescribed to 20-40% of patients with asthma considered to be well controlled and over 50% of patients with uncontrolled disease. We also offer potential strategies to help reduce SCS use for asthma in everyday clinical practice.

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 X 2 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.

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann–Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher’s test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

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.