Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint

Alpha-1 antitrypsin deficiencyDeficiencia de alfa-1 antitripsinaDeficiència d'alfa-1 antitripsinaAugmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress. Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient

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

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

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