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Abstract 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.

Abstract Introduction Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey. Methods This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was

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.

Resumen: La imposición del estado de alarma por el Gobierno Español como principal medida para evitar el contagio ha supuesto un cambio en la aproximación clínica al paciente crónico. Aunque las nuevas tecnologías de la comunicación nos ofrecen numerosas formas de establecer un contacto directo, pero en la distancia, las peculiaridades del paciente con EPOC hacen que con frecuencia esta atención sanitaria se vea reducida al teléfono. El reto de atender a los pacientes con EPOC por teléfono supone una complejidad añadida a la atención sanitaria. La entrevista se realizará sin la exploración del paciente, sin nuevas pruebas complementarias y sin poder verificar la técnica inhalatoria. Por tanto, los sanitarios que realicen estas entrevistas deben estar entrenados para conseguir realizarla adecuadamente para permitir la toma de decisiones. Este documento va dirigido a profesionales sanitarios que tengan que realizar algún tipo de atención telefónica a pacientes con EPOC durante la pandemia de SARS-CoV-2 y se basa en la experiencia de sus autores en entrevistas telefónicas mantenidas durante esta pandemia. En él se resumen aspectos esenciales sobre cómo debe afrontar esta entrevista, cómo llevarla a cabo, qué aspectos se deben tener presentes, cómo organizarla y cómo informar a los pacientes. Es muy probable que a partir de ahora este tipo de entrevista tenga que generalizarse para la atención de nuestros pacientes, por lo que necesitamos aprender a estructurar muchas de las visitas clínicas que hasta ahora se hacían presenciales en un nuevo modelo de atención sanitaria. Abstract: The state of alarm declared by the Spanish government as the main measure for preventing contagion has involved a change in the clinical management of chronic patients. Although new communication technologies offer us many ways to establish direct but remote contact, the peculiarities of the COPD patient often mean that their healthcare is reduced to telephone calls. The challenge of caring for COPD patients is made even more complex when it has to be delivered over the phone. The interview must be conducted without examining the patient, without performing additional tests, and without checking their inhalation technique. Therefore, healthcare providers who conduct these interviews must be trained to perform them properly in order to make the right decisions. This document is aimed at healthcare professionals who need to provide some form of telephone care to COPD patients during the SARS-CoV-2 pandemic and is based on the authors’ experience in telephone interviews conducted during this period. It summarizes essential aspects of how this interview should be approached, how to conduct it, what factors should be kept in mind, how to organize the interview, and how to keep patients informed. It is very likely that from now on this type of interview will be common practice in the care of our patients, so we need to learn how to structure a new model of healthcare for many of the clinical visits that have until now been conducted face-to-face.

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. Methods In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. Results 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. Conclusions 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.

José Luis Lopez-Campos, Pilar Cejudo, Eduardo Marquez, Francisco Ortega, Esther Quintana, Carmen Carmona, Emilia BarrotUnidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospitales Universitarios Virgen del Rocío, Seville, SpainAim: It has been recently shown that the original BODE index has a high degree of correlation with two modified BODE indexes using maximal oxygen uptake expressed either as mL/min/kg (mBODE) or as the percentage predicted (mBODE%). In this study we investigated the agreement between the two modified BODE indexes (mBODE and mBODE%) in patients with stable chronic obstructive pulmonary disease (COPD).Methods: A total of 169 patients with stable COPD were enrolled in this cross-sectional study. Differences between the two mBODE indexes were assessed using kappa coefficients and Bland-Altman plots. One out of every three patients underwent the six-minute walking test to investigate the agreement with the original BODE index.Results: Correlations between the two mBODE indexes with each other (r = 0.96, P < 0.001) and with the original BODE index (mBODE r = 0.88, P < 0.001; mBODE% r = 0.93, P < 0.001) were excellent. However, the two mBODE indexes were significantly different from each other (mBODE 5.27 ± 2.3 versus mBODE% 4.31 ± 2.5; P < 0.001). The kappa coefficients were significantly lower (entire study group k = 0.5, P < 0.001) for every GOLD stage. The mean difference between the two mBODE indexes was 0.8 ± 0.6 units. Differences with the original BODE were higher for the mBODE (1.8 ± 0.9) than for the mBODE% (0.6 ± 0.8).Conclusions: The new mBODE indexes are highly correlated but significantly different from each other. The differences between the novel indexes deserve further scrutiny.Keywords: BODE index, chronic obstructive pulmonary disease, exercise testing, multidimensional evaluation, oxygen uptake