Anna Annunziata1, Ilaria Ferrarotti2, Antonietta Coppola1, Maurizia Lanza1, Pasquale Imitazione1, Sara Spinelli1, Pierpaolo Di Micco3, Giuseppe Fiorentino1. 1. Unit of Respiratory Physiopathology, Department of Critic Area, Monaldi Hospital, 80131 Naples, Italy. 2. Center for Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Pneumology Unit, Department of Internal Medicine and Therapeutics, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy. 3. Department of Medicine, Buon Consiglio Fatebenefratelli Hospital of Naples, 80128 Naples, Italy.
Abstract
INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years' duration. The purpose of this study was to evaluate the incidence of alpha-1 antitrypsin deficiency in patients with the chronic pulmonary disease after a thorough screening in the city of Naples in southern Italy. MATERIALS AND METHODS: Two hundred patients suffering from respiratory pathology (chronic obstructive pulmonary disease (COPD), emphysema, asthma, or bronchiectasis) were examined and evaluated in our outpatients' clinic and tested for serum levels of AAT. Patients who had a respiratory disease suspected of AATD and/or serum AAT < 120 mg/dL underwent genetic testing. Genetic screening was performed on samples from 141 patients. RESULTS: A total of 36 patients had an intermediate deficiency of AAT levels. Among them, 8 were PI*MZ, 6 were PI*MS and 22 had rare pathological mutations. Five patients had a severe AATD, all were composite heterozygous with S or Z allele, while the other allele had a rare pathological mutation. CONCLUSIONS: The incidence of genetic defects as AATD in the population of patients affected by chronic respiratory disorders is always a matter of discussion because of the frequent interaction between genes and environmental causes. In our series, numerous rare variants and compound heterozygosity have been described. No homozygous patients have been described. The present is one of few studies available on the incidence of rare variants in the geographic area of the city of Naples. So, our results could be considered interesting not only to know the incidence of AATD and its related rare mutations but also to support early diagnosis and treatments for patients with chronic pulmonary disease and frequent exacerbation and to fight the association with environmental causes of pulmonary damages as smoking.
INTRODUCTION:Alpha-1 antitrypsindeficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years' duration. The purpose of this study was to evaluate the incidence of alpha-1 antitrypsindeficiency in patients with the chronic pulmonary disease after a thorough screening in the city of Naples in southern Italy. MATERIALS AND METHODS: Two hundred patients suffering from respiratory pathology (chronic obstructive pulmonary disease (COPD), emphysema, asthma, or bronchiectasis) were examined and evaluated in our outpatients' clinic and tested for serum levels of AAT. Patients who had a respiratory disease suspected of AATD and/or serum AAT < 120 mg/dL underwent genetic testing. Genetic screening was performed on samples from 141 patients. RESULTS: A total of 36 patients had an intermediate deficiency of AAT levels. Among them, 8 were PI*MZ, 6 were PI*MS and 22 had rare pathological mutations. Five patients had a severe AATD, all were composite heterozygous with S or Z allele, while the other allele had a rare pathological mutation. CONCLUSIONS: The incidence of genetic defects as AATD in the population of patients affected by chronic respiratory disorders is always a matter of discussion because of the frequent interaction between genes and environmental causes. In our series, numerous rare variants and compound heterozygosity have been described. No homozygous patients have been described. The present is one of few studies available on the incidence of rare variants in the geographic area of the city of Naples. So, our results could be considered interesting not only to know the incidence of AATD and its related rare mutations but also to support early diagnosis and treatments for patients with chronic pulmonary disease and frequent exacerbation and to fight the association with environmental causes of pulmonary damages as smoking.