34 research outputs found
Population-based study of LAMA monotherapy effectiveness compared with LABA/LAMA as initial treatment for COPD in primary care
This epidemiological study aimed to describe and compare the characteristics and outcomes of COPD patients starting treatment with a long-acting anti-muscarinic (LAMA) or a combination of a long-acting beta-2 agonist (LABA)/LAMA in primary care in Catalonia (Spain) over a one-year period. Data were obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database containing information of 5.8 million inhabitants (80% of the population of Catalonia). Patients initiating treatment with a LAMA or LABA/LAMA in 2015 were identified, and information about demographic and clinical characteristics was collected. Then, patients were matched 1:1 for age, sex, FEV1%, history of exacerbations, history of asthma and duration of treatment, and the outcomes between the two groups were compared. During 2015, 5729 individuals with COPD started treatment with a LAMA (69.8%) or LAMA/LABA (30.2%). There were no remarkable differences between groups except for a lower FEV1 and more previous hospital admissions in individuals on LABA/LAMA. The number of tests and referrals was low and decreased in both groups during follow-up. For the same severity status, the evolution was similar with a reduction in exacerbations in both groups. Treatment was changed during follow-up in up to 34.2% of patients in the LABA/LAMA and 26.3% in the LAMA group, but adherence was equally good for both. Our results suggest that initial therapy with LAMA in monotherapy may be adequate in a significant group of mild to moderate patients with COPD and a low risk of exacerbations managed in primary care. A single rather than combined long-acting inhaler therapy may be adequate for most patients when treating mild to moderate chronic lung disease. Marc Miravitlles at the Hospital Universitari Vall d'Hebron, Barcelona, Spain, and co-workers have shown that, in the initial stages of chronic obstructive pulmonary disease (COPD), treatment with an inhaled drug called a long-acting anti-muscarinic agent (LAMA) is as effective as an alternative inhaler that combines LAMA with another drug (LABA). The researchers identified 5729 COPD patients from Catalonia starting on inhaled treatment in 2015 and followed up on their progress after 1 year. Patients starting on LAMA monotherapy were matched closely in terms of demographics and previous medical history to those starting on LAMA/LABA treatment. The team found no remarkable differences in clinical characteristics between the groups over the year
How to get the most out of the ERS International Congress 2021 and an overview of the Early Career Member session
Sociedad Respiratoria Europea (ERS); Ayudar a los asistentesSocietat Respiratòria Europea (ERS); Ajudar els assistentsEuropean Respiratory Society (ERS); Help attendeesThis article provides a brief description of the Early Career Member session and guidance on how to get the most out of the European Respiratory Society (ERS) International Congress 2021, to help attendees plan their Congress in advance
Diagnosis of alpha1-antitrypsin deficiency not just in severe COPD
Alpha1-antitrypsin deficiency (AATD) is a well known genetic risk factor for pulmonary disease and is the most frequent hereditary disease diagnosed in adults. Despite being one of the most common hereditary diseases, AATD remains under-diagnosed because of its variable clinical presentation and the poor knowledge of this disease by physicians. With the aim of identifying clinical differences that could influence early diagnosis, we compared two groups of six AATD Pi*ZZ patients with different lung function severity and clinical expression at diagnosis. On comparing the two groups, we observed a younger mean age at diagnosis and more exacerbations in the severe group, but the percentage of smokers did not statistically differ between the two groups. Our results suggest that AATD continues being a disease suspected on younger patients with a worse lung function. In addition these findings confirm the clinical variability of the disease and that there are still unknown factors that contribute to its development. Therefore, early diagnosis may modify the prognosis of this disease
Practice and knowledge about diagnosis and treatment of alpha-1 antitrypsin deficiency in Spain and Portugal
Background: determining physicians' awareness about alpha-1 antitrypsin (AAT) deficiency (AATD) may help to explain the discrepancy between the observed and expected number of patients diagnosed with this disease. This study was designed to assess the opinions on knowledge, practice pattern and attitude regarding AATD among physicians in Spain and Portugal. Methods: as online anonymous survey was performed on pulmonologists (n = 100), internal medicine specialists (IMS) (n = 100) and primary care physicians (PCP) (n = 176). Of the total number of physicians, 221 were from Spain, and 155 were from Portugal. Physicians answered 21 questions related to their personal and professional profile, knowledge regarding AATD and chronic obstructive pulmonary disease (COPD), performance and attitude about AATD, and use of augmentation therapy. Responses were ranked on a 4-point scale indicating the level of agreement. In addition, some of the responses were rated as either "low" or "high" indicating the level of knowledge the respondent felt he/she possessed. Results: only 14 % of physicians reported to "know very well" about AATD (3.3 [SD 0.6] for pulmonologists vs. 2.64 [SD 0.60] for IMS and 2.48 [SD 0.71] for PCP; p < 0.001). Only 45.2 % of physicians correctly answered "<50 mg/dL" as the threshold value of serum AAT to be considered severe AATD (55.0 % of pulmonologists vs. 47.0 % of IMS and 38.6 % of PCP; p = 0.001). Choice of the correct answer did not agree with those physicians self-declaring a high level of AATD knowledge (51.2 %). A total of 43.9 % of physicians correctly identified all diseases or conditions in a list associated or not with AATD. A similar trend was detected when identifying which conditions would be responsive to augmentation therapy (<50 %). Only 15.8 % of specialists performed AATD testing in all patients with COPD (27.0 % pulmonologists, 12.6 % PCP; p = 0.001). Conclusion: the results suggest that a knowledge gap may be contributing to the underdiagnosis of AATD. Physicians in Spain and Portugal showed a marked lack of awareness of their shortcomings in knowledge about AATD, and in general did not follow guidelines and recommendations for AATD testing
Genetic diagnosis of α1-antitrypsin deficiency using DNA from buccal swab and serum samples
Background: α1-Antitrypsin deficiency (AATD) is associated with a high risk of developing lung and liver disease. Despite being one of the most common hereditary disorders worldwide, AATD remains under-diagnosed and prolonged delays in diagnosis are usual. The aim of this study was to validate the use of buccal swab samples and serum circulating DNA for the complete laboratory study of AATD. Methods: Sixteen buccal swab samples from previously characterized AATD patients were analyzed using an allele-specific genotyping assay and sequencing method. In addition, 19 patients were characterized by quantification, phenotyping and genotyping using only serum samples. Results: the 16 buccal swab samples were correctly characterized by genotyping. Definitive results were obtained in the 19 serum samples analyzed by quantification, phenotyping and genotyping, thereby performing the complete AATD diagnostic algorithm. Conclusions: Buccal swab samples may be useful to expand AATD screening programs and family studies. Genotyping using DNA from serum samples permits the application of the complete diagnostic algorithm without delay. These two methods will be useful for obtaining more in depth knowledge of the real prevalence of patients with AATD
Longitudinal study on the diagnosis and treatment of COPD and alpha-one antitrypsin deficiency in Catalonia
El tratamiento de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) se adapta según las características clínicas y la gravedad del paciente. Sin embargo, las pautas de prescripción en los pacientes con nuevo diagnóstico de EPOC en Atención Primaria (AP) pueden diferir de las recomendaciones de las guías. Por otra parte, el deficit de alfa-1 antitripsina (D17T) sigue siendo una entidad infradiagnosticada a pesar de las recomendaciones de descartar la enfermedad en todos los pacientes con EPOC y las iniciativas llevadas a cabo para mejorar el conocimiento de la enfermedad. El objetivo principal de este estudio fue investigar las actitudes diagnósticas y de tratamiento de la EPOC en AP en Cataluña mediante el análisis de la base de datos Sistema de Información para el desarrollo de la Investigación en Atención Primaria (SIDIAP). SIDIAP es una base de datos poblacional que contiene información de 5.8 millones de habitantes (aproximadamente el 80% de la población de Cataluña). La primera fase del proyecto identificó 41592 pacientes con nuevo diagnóstico de EPOC en AP entre 2007 y 2012 y observamos que las pautas de tratamiento inicial con frecuencia no siguen las recomendaciones de las guías. El studio mostró un elevado infratratamiento; la pauta de tratamiento más frecuente fue el uso de un broncodilatador de acción corta (SABD) en monoterapia y hasta un 21,2% de pacientes no recibió tratamiento tras el diagnóstico. Además, algunos de los pacientes en estadíos más graves también recibían únicamente SABD o no eran tratados. El uso de corticoides inhalados (CI) era excesivo pero disminuyó durante el periodo del estudio, principalmente entre los pacientes no agudizadores. En una segunda fase, utilizamos la misma base de datos para cuantificar el número de determinaciones de alfa-1 antitripsina (17T) en la población general durante dos periodos (2007-2008/2010-2011) y describimos las características de los individuos a los que se les realizó la determinación. Durante esos cuatro años, se realizaron 12409 determinaciones, un número bajo en relación a la prevalencia de la EPOC, pero que se incrementó ligeramente durante el periodo a estudio. Observamos que la indicación para solicitar la prueba no siempre estaba clara y que los pacientes que presentaban un déficit grave no siempre eran remitidos al especialista. Por tanto, los resultados de esta tesis doctoral destacan el infratratamiento de la EPOC en los pacientes de Nuevo diagnóstico, el uso excesivo de CI y el infradiagnóstico del D17T. Estos resultados podrían ayudar a diseñar intervenciones para aumentar el conocimiento y el diagnóstico del D17T y para remarcar la importancia de personalizar el tratamiento de la EPOC.The treatment of chonic obstructive pulmonary disease (COPD) is tailored based on the clinical characteristics and the severity of the disease. However, prescription patterns in COPD patients newly diagnosed in primary care (PC) may differ from guideline recommendations. Moreover, alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite the recommendations of testing all COPD individuals and the initiatives developed to increase awareness. The main objective of the present study was to investigate the diagnosis of and treatment attitudes to COPD in PC in Catalonia through the analysis of the System for the Development of Research in Primary Care (SIDIAP) database. SIDIAP is a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). The first phase of the project identified 41,492 newly diagnosed COPD patients in PC from 2007 to 2012. We found that the initial treatment patterns often did not follow guideline recommendations. There was a marked undertreatment, as the most frequent treatment pattern was the use of a short-acting bronchodilator (SABD). Undertreatment of patients was marked, with the most frequent treatment pattern being the use of a short-acting bronchodilator (SABD) in monotherapy and as many as 21.2% COPD patients still remained untreated after diagnosis. Furthermore, some severe GOLD patients were also receiving SABD or no treatment at all. The use of inhaled corticosteroids (ICS) was excessive but decreased over the study period mainly in non exacerbator patients. In the second phase, we used the same database to quantify the number of determinations of alpha-1 antitrypsin (AAT) in the general population in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. During these four years, 12,409 AAT determinations were performed. Although this number is low in relation to the prevalence of COPD, it increased slightly during the study period. We observed that the indication to perform the test was not always clear, and patients detected with the deficiency were not always referred to a specialist. Thus, the results of this doctoral thesis highlight the undertreatment of COPD in newly diagnosed COPD patients, as well as the excessive use of ICS and the underdiagnosis of AATD in PC. These results should help to design interven¬tions to increase the awareness and the diagnosis of AATS and to stress the importance of tailored treatment of COPD
El embarazo en la Fibrosis Quística
Las mejoras en la supervivencia y calidad de vida en pacientes con Fibrosis Quística han hecho que la maternidad no sea un fenómeno extraño hoy en día aunque actualmente no hay recomendaciones firmes al respecto. El objetivo del presente estudio es el seguimiento de pacientes con FQ embarazadas, comparando su evolución con un grupo control de características similares. Se observó que las pacientes embarazadas presentan caída significativa de la función pulmonar que se recupera 18 meses tras el parto sin aumentar la mortalidad respecto al grupo control. Factores como la insuficiencia pancreática, el tipo de mutación o colonizaciónes conllevan un peor pronóstico.Les millores en la supervivència i qualitat de vida en pacients amb fibrosi quística han fet que la maternitat no sigui un fenomen estrany avui en dia encara que actualment no hi ha recomanacions fermes sobre això. L'objectiu d'aquest estudi és el seguiment de pacients amb FQ embarassades, comparant la seva evolució amb un grup control de característiques similars. Es va observar que les pacients embarassades presenten caiguda significativa de la funció pulmonar que es recupera 18 mesos després del part sense augmentar la mortalitat respecte al grup control. Factors com la insuficiència pancreàtica, el tipus de mutació o colonitzacions comporten un pitjor pronòstic
Rapid detection of Mmalton α1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples
Background: α1-Antitrypsin deficiency (AATD) is an autosomal codominant disorder associated with a high risk of developing lung and liver disease. The most common deficient alleles are known as Z and S. However, another deficient variant, called Mmalton, which causes a deficiency similar to variant Z, is considered to be the second cause of severe AATD in Spain. Nevertheless, the Mmalton allele is not recognizable by usual diagnostic techniques and therefore, its real prevalence is underestimated. We describe a rapid real-time PCR and melting curves assay designed for the detection of Mmalton AATD. Methods: we tested the applicability of this new technique for the identification of the Mmalton allele in AATD screening using whole blood, dried blood spot (DBS) and serum samples. Mmalton heterozygote and homozygote samples and samples without this allele were included in the study. Results: this new assay is able to detect homozygous and heterozygous genotypes in the same reaction and in a single step, giving matching results with those obtained by SERPINA1 gene sequencing. Conclusions: this technology is optimal for working with small amounts of DNA, such as in DBS and even with residual DNA present in serum samples, allowing improvement in routine algorithms of AATD diagnosis or large-scale screening. This method will be useful for obtaining more in depth knowledge of the real incidence of the Mmalton variant
Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency: a new approach
Background and objectives: alpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a deficiency similar to that of the Z variant, but it is not easily recognizable and its detection seems to be underestimated. Therefore, we have included a rapid allele-specific genotyping assay for the detection of the Mmalton variant in the diagnostic algorithm of AATD used in our laboratory. The objective of this study was to test the usefulness of this new algorithm for Mmalton detection. Materials and methods: we performed a retrospective revision of all AATD determinations carried out in our laboratory over 2 years using the new diagnostic algorithm. Samples with a phenotype showing one or two M alleles and AAT levels discordant with that phenotype were analyzed using the Mmalton allele-specific genotyping assay. Results: we detected 49 samples with discordant AAT levels; 44 had the MM and five the MS phenotype. In nine of these samples, a single rare Mmalton variant was detected. During the study period, two family screenings were performed and four additional Mmalton variants were identified. Conclusion: the incorporation of the Mmalton allele-specific genotyping assay in the diagnostic algorithm of AATD resulted in a faster and cheaper method to detect this allele and avoided a significant delay in diagnosis when a sequencing assay was required. This methodology can be adapted to other rare variants. Standardized algorithms are required to obtain conclusive data of the real incidence of rare AAT alleles in each region
Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry
Alpha-1 antitrypsin; Phenotypes; RegistryAlfa-1 antitripsina; Fenotipos; RegistroAlfa-1 antitripsina; Fenotips; RegistreBackground
Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history.
Methods
The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022.
Results
A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%).
Conclusions
EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)