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

Abstract

With the aim of providing better clinical characterisation of patients with a 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 (n5547), the PI*SZ (n5124) 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. @ERSpublications New characterisation of clinical phenotypes in patients with alpha-1 antitrypsin deficiency

The Impact of Smoke Exposure on the Clinical Phenotype of Alpha-1 Antitrypsin Deficiency in Ireland: Exploiting a National Registry to Understand a Rare Disease

“…Our data would contradict these findings, demonstrating that radiologically detected bronchiectasis is both common in AATD and that there is no dependent relationship to emphysema or indeed a history of smoking. This is supported by similar studies on bronchiectasis and emphysema in AATD and also by registry data showing a high prevalence of bronchiectasis in the AATD population in Spain and Italy (14,23). Most people in our study had evidence of mild radiological bronchiectasis with minimal associated clinical symptoms such as increased frequency of cough or pulmonary exacerbation compared to those with emphysema, however those with more severe bronchiectasis did report significantly poorer health status outcomes.…”

“…A significant proportion of the severely deficient AATD population in the Irish registry are compound heterozygote PiSZ individuals, a finding reflected in reports from other national registries (14). Despite a growing number of known PiSZ individuals there is a paucity of data in relation to outcomes of this AAT--deficient phenotype (4).…”

“…The detection of asymptomatic individuals (non--index) through the family screening of probands is an opportunity to better understand the natural history of AATD (13,14).…”

Targeted screening programmes in COPD: how to identify individuals with α1-antitrypsin deficiency

“…In terms of clinical presentation, the average age of our patients (49.9 years) was similar to that reported in studies from Italy, Germany and Spain (45-49 years) and COPD was the most frequent diagnosis ( fig. 3) [19,20].…”

Recent advances in α-1-antitrypsin deficiency-related lung disease

“…Holme and Stockley confirmed this in a prospective study of individuals identified with physiological discordance (normal FEV 1 and low diffusing capacity and vice versa) [65]. An observational study of 745 patients with severe A1ATD compared subjects with emphysema, chronic bronchitis and asthma overlap [66]. This study found chronic bronchitis patients were younger with a lower number of pack years and had better preserved lung function.…”