European screening for alpha1 -antitrypsin deficiency in subjects with lung disease.

BACKGROUND AND AIMS: Alpha1 -antitrypsin deficiency (AATD) predisposes individuals to early-onset emphysema. Despite its prevalence, especially among patients with chronic obstructive pulmonary disease, AATD is still underdiagnosed. The aim of this study is to identify individuals with lung disease and severe AATD in central-eastern Europe. METHODS: Subjects with respiratory symptoms that could be indicative of AATD provided blood samples as dried blood spot. The alpha1 -antitrypsin (AAT) concentration was determined by nephelometry and, if lower than 1.70 mg/dL in dried blood spot (equivalent to 1.04 g/L in serum), polymerase chain reaction was used to detect the PiS and PiZ alleles. Isoelectric focusing was used for confirmation of doubtful genotype results. RESULTS: From 13 countries, 11 648 subjects were included. Genotyping of 1404 samples with AAT levels <1.70 mg/dL revealed 71 (5.06%) PiS, 151 (10.8%) PiZ, 1 (0.071%) PiSS, 8 (0.57%) PiSZ and 32 (2.28%) PiZZ. Phenotyping of 1363 samples negative for the S and Z alleles or with PiS and PiZ genotype showed two (0.147%) PiZ(rare) and two (0.147%) Pi(null)(null). The countries with the highest rate of severe AATD were Croatia, Russia and Slovakia. By regions, the Baltic countries area showed the highest rate of both PiZ and severe AATD (2.45% and 1.20%, respectively) while the lowest rates were observed in the Balkan Peninsula (0.48% and 0.31%, respectively). CONCLUSION: This study confirms the need for targeted testing of symptomatic patients and provides AATD genotype data from countries for which only some estimates of prevalence were available until now.

Alpha-1 antitrypsin deficiency and spontaneous pneumothorax: possible causal relationship.

BACKGROUND: An increased incidence of serum alpha-1 antitrypsin deficiency has been reported in patients with chronic obstructive pulmonary disease, but has not been well proven in association with spontaneous pneumothorax. The aim of our study was to evaluate frequency of alpha-1 antitrypsin deficiency in subjects with spontaneous pneumothorax. METHODS: 39 patients with the diagnosis of spontaneous pneumothorax and 100 age- and sex-matched control subjects were included in the study. Alpha-1 antitrypsin concentrations were determined by nephelometry, Serum qualitative Z antitrypsin variant was analyzed using commercial ELISA kits and alpha-1 antitrypsin phenotyping was carried out by means of isoelectric focusing. RESULTS: AAT deficiency phenotypes were detected in 3 (7.7%) patients with spontaneous pneumothorax, and only in 1 (1%) case in the control group. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. The mean serum alpha-1 antitrypsin level was significantly higher in patients with spontaneous pneumothorax (1.53 +/- 0.23 g/l) than controls (1.34 +/- 0.37 g/l) (p = 0.03). CONCLUSIONS: Preliminary data confirm the clinical importance of alpha-1 antitrypsin deficiency phenotypes in patients with spontaneous pneumothorax and the need to screen them for alpha1-antitrypsin deficiency.