10779/rcsi.10785089.v1 M Emmett O'Brien M Emmett O'Brien Kevin Pennycooke Kevin Pennycooke Tomás P. Carroll Tomás P. Carroll Jonathan Shum Jonathan Shum Laura T. Fee Laura T. Fee Catherine O'Connor Catherine O'Connor P Mark Logan P Mark Logan Emer P. Reeves Emer P. Reeves Noel G. McElvaney Noel G. McElvaney 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. Royal College of Surgeons in Ireland 2019 Adult Aged 80 and over Bronchiectasis Cross-Sectional Studies Disease Progression Female Health Surveys Humans Ireland Male Middle Aged Phenotype Pulmonary Disease Chronic Obstructive Pulmonary Emphysema Rare Diseases Registries Risk Factors Severity of Illness Index Smoking Surveys and Questionnaires Tobacco Smoke Pollution Tomography X-Ray Computed alpha 1-Antitrypsin Deficiency Medicine 2019-11-22 16:33:25 Journal contribution https://repository.rcsi.com/articles/journal_contribution/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_/10785089 <p>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.</p>