ABSTRACT
BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM). METHODS: We considered a total of 613 patients: 330 with the PI*ZZ genotype, 183 with the PI*MZ genotype and 100 with the PI*MM genotype. Radiological exams, pulmonary function test, and measurement of quality of life have been performed on all cohorts of patients. RESULTS: The three populations differ significantly in terms of age at COPD/AATD diagnosis (P=0.00001), respiratory function (FEV1, FVC, DLCO P<0.001), quality of life (P=0.0001) and smoking history (P<0.0001). PI*ZZ genotype had 24.9 times a higher likelihood of developing airflow obstruction. The MZ genotype is not associated with a significant early risk of airflow obstruction. CONCLUSIONS: The comparison of populations with PI*ZZ, MZ and MM genotypes allows to delineate the role of alpha1-antitrypsin deficiency on respiratory function and on the impact on quality of life, in relation to other risk factors. These results highlight the crucial role of primary and secondary prevention on smoking habits in PI*MZ subjects and the importance of an early diagnosis.
Subject(s)
Pulmonary Disease, Chronic Obstructive , alpha 1-Antitrypsin Deficiency , alpha 1-Antitrypsin , Humans , alpha 1-Antitrypsin Deficiency/complications , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/diagnosis , Genotype , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/etiology , Quality of Life , Risk Factors , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin/metabolismABSTRACT
Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996-2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.
Subject(s)
Quality of Life , Registries , alpha 1-Antitrypsin Deficiency , Adolescent , Adult , Aged , Early Diagnosis , Female , Humans , Italy , Male , Middle Aged , Phenotype , Severity of Illness Index , Young Adult , alpha 1-Antitrypsin Deficiency/complications , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/therapyABSTRACT
The aim of this study was: (1) to compare the new pathological findings as detected by the IASLC/ATS/ERS classification with the traditional radiological features in pulmonary pN0 adenocarcinomas, (2) to evaluate their prognostic significance on overall survival (OS). A total of 42 surgically resected pN0 pulmonary adenocarcinomas were analyzed. On CT scans, the following radiological data were recorded: sphericity, predominant margins, cavitation and bronchogram, attenuation and percentage of ground glass opacity (GGO). On pathological examination, tumors were categorized according to the IASLC/ATS/ERS classification; Sica score and grade, pathological stage, tumor major axis, pleural invasion, vascular and lymphatic invasion, peritumoral lymphoid infiltration, and cytological features were also determined. Clinical follow up was available in 37 cases (range 1-117 months). Radiologically, 31 solid and 11 semisolid tumors were found. Morphologically, 2 minimally invasive and 40 invasive adenocarcinomas were diagnosed. In radiological-pathological comparisons, (1) the acinar pattern was higher in tumors with solid attenuation and low GGO (p=0.018); (2) the lepidic pattern was more elevated in tumors with high GGO (p=0.012). In multivariate survival analyses with stage, predominant margins on CT scans (p=0.036) and Sica score (p=0.028) significantly affected OS. This study confirms the validity of the new classification of pulmonary adenocarcinomas in radiological-pathological comparisons and underlines the importance of both radiological and pathological findings in correctly identifying their prognostic features.
Subject(s)
Adenocarcinoma/classification , Adenocarcinoma/diagnostic imaging , Lung Neoplasms/classification , Lung Neoplasms/diagnostic imaging , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Proportional Hazards Models , Survival Analysis , Tomography, X-Ray ComputedABSTRACT
A 39-y-old male had a diagnosis of sarcoidosis and corticosteroid therapy was started. Surprisingly, following his discharge from hospital, Mycobacterium marinum was isolated in 1 of 3 sputum samples taken 7 weeks earlier on admission. After this, Mycobacterium marinum-DNA was identified in the stored lung biopsies by the PCR-RFLP of the hsp65 gene.
