Ana Bustamante

Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency

With the aim of providing better clinical characterisation of patients with &agr;1-antitrypsin deficiency (AATD), we analysed the data of adult patients with severe AATD enrolled in the Spanish and Italian national registries. We assessed 745 subjects, 416 of whom were enrolled in the Spanish registry and 329 in the Italian registry. 57.2% were male and 64.9% were smokers or former smokers with a mean±sd age of 49.9±13.8 years. Most (81.2%) were index cases, mainly having the PI*ZZ genotype (73.4%), and the mean±sd diagnostic delay was 9.0±12.1 years. Patients with chronic bronchitis were younger, had better preserved lung function and lower tobacco consumption. Overlap patients (chronic obstructive pulmonary disease with asthma) were mainly females, more frequently never-smokers and received respiratory medications more often. 48% of emphysema, 27.5% of chronic bronchitis and 44.8% of overlap subjects were receiving augmentation therapy. Compared with PI*ZZ patients (n=547), the PI*SZ (n=124) subjects were older at diagnosis and had more preserved lung function, despite a higher mean smoking consumption. Early diagnosis of AATD is still an unmet need. Augmentation therapy is administered to similar proportions of patients with different clinical phenotypes. PI*ZZ patients in both registries had more severe respiratory disease than those with PI*SZ, despite lower smoking levels.

Actualización sobre indicaciones de búsqueda activa de casos y tratamiento con alfa-1 antitripsina por vía intravenosa en pacientes con enfermedad pulmonar obstructiva crónica asociada a déficit de alfa-1 antitripsina

The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form of chronic obstructive pulmonary disease (COPD). AAT deficiency (AATD) is defined as a serum concentration lower than 35% of the expected mean value or 50 mg/dl (determined by nephelometry). It is associated in over 95% of cases with Pi*ZZ genotypes, and much less frequently with other genotypes resulting from combinations of Z, S, rare and null alleles. A systematic qualitative review was made of 107 articles, focusing mainly on an active search for AATD in COPD patients and intravenous (iv) treatment with AAT. On the basis of this review, the consultant committee of the Spanish Registry of Patients with AATD recommends that all COPD patients be screened for AATD with the determination of AAT serum concentrations, and when these are low, the evaluation must be completed with phenotyping and, on occasions, genotyping. Patients with severe AATD COPD should receive the pharmacological and non-pharmacological treatment recommended in the COPD guidelines. There is enough evidence from large observational studies and randomized placebo-controlled clinical trials to show that the administration of iv AAT reduces mortality and slows the progression of emphysema, hence its indication in selected cases that meet the inclusion criteria stipulated in international guidelines. The administration of periodic infusions of AAT is the only specific treatment for delaying the progression of emphysema associated with AATD.

Registro español de pacientes con déficit de alfa-1 antitripsina: evaluación de la base de datos y análisis de la población incluida

INTRODUCTION AND OBJECTIVE REDAAT, the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency, was set up in order to improve knowledge of this disease. This study is an evaluation of the registry and an analysis of its patient population. METHODS The registry has a database hosted on the website www.redaat.es. It collects clinical and functional data on patients with PiSZ, ZZ phenotypes and other rare variants. RESULTS Thanks to the collaboration of 124 physicians, the registry currently contains information on 511 individuals from 103 healthcare centers. Of these 511, 348 (74.2%) are Pi*ZZ homozygotes, and 100 (19.5%) are Pi*SZ heterozygotes. More cases are seen in tertiary level hospitals. A total of 81% of the cases have respiratory disease, and a lower proportion of AATD cases were detected by family screening or liver disease. Follow-up data are available for 45% of the cases, and 35% received alpha-1 antitripsin replacement therapy. CONCLUSIONS The REDAAT registry is a useful tool for obtaining quality information about this minority disease in routine clinical practice conditions, although it is difficult to obtain follow-up data, and the representativeness of the sample included cannot be determined.

Déficit de alfa-1-antitripsina asociado a la variante Matawa

The most common deficiency alleles for alpha-1-antitrypsin deficiency (AATD) are Pi*S and Pi*S, but there are also other deficiency variants. This case report describes the first two cases of AATD detected in Spain resulting from the combination of a null Mattawa allele with a normal PI*M, and a rare Mmalton. Both cases were initially diagnosed as Pi*MM by isoelectric focusing (IEF), but the low serum AAT values led us to suspect the existence of rare deficiency alleles that were undetectable using this technique, and to performing molecular analysis of the gene, which provided the correct diagnosis. Inconsistencies between serum AAT values and the phenotype should make one suspect the existence of one of these rare alleles.

Costes de la tuberculosis en España: factores relacionados

OBJECTIVE To analyze the direct and indirect costs of diagnosis and management of tuberculosis (TB) and associated factors. PATIENTS AND METHODS Prospective study of patients diagnosed with TB between September 2014 and September 2015. We calculated direct (hospital stays, visits, diagnostic tests, and treatment) and indirect (sick leave and loss of productivity, contact tracing, and rehabilitation) costs. The following cost-related variables were compared: age, gender, country of origin, hospital stays, diagnostic testing, sensitivity testing, treatment, resistance, directed observed therapy (DOT), and days of sick leave. Proportions were compared using the chi-squared test and significant variables were included in a logistic regression analysis to calculate odds ratio (OR) and corresponding 95% confidence intervals. RESULTS 319 patients were included with a mean age of 56.72±20.79 years. The average cost was €10,262.62±14,961.66, which increased significantly when associated with hospital admission, polymerase chain reaction, sputum smears and cultures, sensitvity testing, chest computed tomography, pleural biopsy, drug treatment longer than nine months, DOT and sick leave. In the multivariate analysis, hospitalization (OR=96.8; CI 29-472), sensitivity testing (OR=4.34; CI 1.71-12.1), chest CT (OR= 2.25; CI 1.08-4.77), DOT (OR=20.76; CI 4.11-148) and sick leave (OR=26,9; CI 8,51-122) showed an independent association with cost. CONCLUSION Tuberculosis gives rise to significant health spending. In order to reduce these costs, more control of transmission, and fewer hospital admissions would be required.