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Research Project

Characteristics and risk factors for lung disease in never smokers with alpha1-antitrypsin deficiency and Pi*ZZ genotype

Principal Investigator:
Chiara Premuda / Miriam Barrecheguren
Università degli Studi di Milano, Milano, Italy / Vall d’Hebron Research Institute (VHIR), Barcelona, Spain.
Milano (Italy) / Barcellona (Spain)
Start date:
January 2024
Contact E-mail:
chiara.premuda@gmail.com / miriam.barrecheguren@vallhebron.cat
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In alpha1-antitrypsin (AAT) deficiency the role of cigarette smoking as a risk factor for the development of emphysema is well known. It has been demonstrated that smoking patients with severe AAT deficiency  (AATD) develop chronic obstructive pulmonary disease (COPD) earlier than non-smokers. Previous studies have focused on the differences between smoking and non-smoking individuals with severe AATD, finding that those who never smoked had better lung function with lower lung function decline, less respiratory symptoms and higher life expectancy and quality. Nonetheless, also never smokers patients with AATD can experience lung disease.

However, the population of Pi*ZZ non smoking patients is highly heterogeneous, ranging from healthy individuals found through family screening to severely ill patients with serious lung or liver impairment. Moreover, as of today studies involving large international cohorts are missing.


  1. What are the characteristics of lung disease in Pi*ZZ never smokers patients in terms of clinical management (time to diagnosis, diagnostic workup, decision to undergo medications) and clinical features (past medical history, symptoms, exacerbations, lung function, blood and gas analysis, radiology, sputum characteristics, other AATD-related diseases)?
  2. Are there any differences in Pi*ZZ non smoking patients diagnosed through family screening (non-index cases) and Pi*ZZ non smoking patients diagnosed as index cases?
  3. Are there risk factors, in terms of exposure, alcohol intake or past medical history, associated with low pulmonary function, higher pulmonary symptoms burden or worse quality of life questionnaires scores?

Inclusion criteria

Individuals with PI*ZZ genotype registered in EARCO who have never smoked

Brief summary

  • Retrospective study using data from the EARCO International registry, including never smokers Pi*ZZ patients.
  • Sociodemographic and clinical data will be collected: risk factors exposure, medical history and medications, exacerbations, AATD-related diseases, data from CT scan (presence and characteristics of emphysema and bronchiectasis), data from lung function tests (spirometry and diffusion lung capacity), liver elastography and physical examination data.
  • Moreover, routine serum biomarkers will be collected: haemoglobin, platelets, leucocytes, neutrophils, lymphocytes, eosinophils, monocytes, basophils, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alkaline transaminase (ALT), aspartate transaminase (AST), C-reactive protein and fibrinogen. 
  • A descriptive analysis will be performed of Pi*ZZ never-smoking patients. Next, comparisons of clinical, analytical and radiological characteristics between index and non index cases will be conducted.
  • Finally, we will perform an analysis of risk factors for lung disease.