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

Abstract

Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland.

Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype.

Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV₁ and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV₁ decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age.

The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease.

Keywords:

• occupational exposure
• passive smoke
• phenotype
• questionnaire
• radiology
• SERPINA1

Funding

This work has been supported by funding from the Irish Government Department of Health and Children, Alpha One Foundation (Ireland), Alpha-1 Foundation (USA), and the Health Research Board (HRB) Ireland.

Declaration of Interest Statement

MEOB received the eALTA award 2013 from Grifols. The other authors declare they have no competing interests to disclose. The authors are responsible for the content and writing of this paper.

Supplemental Material

A supplementary table and figure can be found at http://www.dx.doi.org/10.3109/15412555.2015.1021913.

SUPPLEMENTARY MATERIALS FOR THIS PAPER ARE AVAILABLE ONLINE