Clinical features and prognosis of life time non-smokers with severe alpha 1-antitrypsin deficiency

Abstract

Background-The hereditary disorder 1 -antitrypsin deficiency is characterised by development of severe emphysema at an early age with smoking being the most significant additional risk factor. The purpose of the present paper was to analyse potential risk factors other than smoking for emphysema and to estimate the prognosis of life time non-smokers. Methods-Patientswere identified through the files of the Danish 1 -antitrypsin deficiency register which contains information on more than 700 persons with the condition. Many of the patients, the non-index cases, were identified from family studies. Results-There were 75 life time nonsmokers with PiZ (27 index cases and 48 non-index cases) aged 20 years or more at entry. Twenty one subjects died during the follow up period. The Standardised Mortality Ratio (SMR) was 3.0 (95% confidence intervals (CI) 1.9 to 4.6). There was no significant diVerence in SMR between males and females. The SMR was 8.8 (95% CI 5.0 to 14) for the index cases and 0.96 (95% CI 0.3 to 2.3) for the non-index cases based on five deaths. The overall mean % predicted forced expiratory volume in one second (FEV 1 ) at entry was 83% with a significant diVerence between index cases (54%) and non-index cases (100%) (p<0.001). The diVerence in the ratio of FEV 1 to forced vital capacity (FVC) was also highly significant with values of 0.57 and 0.79 for index and non-index cases, respectively (p<0.001). In the non-index group only three had an FEV 1 % predicted of less than 70%. Conclusions-Occupational exposure to airway irritants did not have any significant influence on the development of emphysema. Only a few life time nonsmokers develop severe emphysema; most never develop pulmonary symptoms and thus remain undetected unless family members of index cases are screened. (Thorax 1998;53:265-268)

An Investigation into Causative Factors in Patients with Bronchiectasis

“…Case reports have shown that bronchiectasis occurs in some persons with the Pi-ZZ phenotype (severe deficiency), but there were alternative causes for bronchiectasis in many of these cases, and thorough exclusion of other causes was not always performed (33). Our findings of no Pi-ZZ persons and no significant increase in the frequency of partial deficiency phenotypes (Pi-MS and Pi-MZ) fail to support any role for ␣ 1 -antitrypsin deficiency in the etiology of bronchiectasis and is in keeping with some previous studies (31,34).…”

Canadian Guidelines for the Management of Acute Exacerbations of Chronic Bronchitis

“…Some alpha-1 antitrypsin-deficient smokers never develop obstruction (25). Some families appear to have an increased risk of COPD and it is probable that other genetic factors may increase susceptibility to COPD (26).…”

Different Training-Induced Skeletal Muscle Adaptations in COPD Patients with and without Alpha-1 Antitrypsin Deficiency

“…A subgroup of COPD patients has an inherited PiZZ (Glu342Lys) alpha-1 antitrypsin deficiency (A1ATD), which is a genetic risk factor for early-onset emphysematous COPD [10]. In the recent literature, solely the Canadian Thoracic Society recommends PR particularly for patients with A1ATD-related COPD [11].…”