Prevalence of α1-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review.

The percentage of α1-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country.A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD. We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio. Finally, results were presented using an Inverse Distance Weighted Interpolation map.We found 36 298 (95% CI 23 643-56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293-40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08-0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe.These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.

Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide.

The alpha-1 antitrypsin (AAT) haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established. Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects worldwide, based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW) interpolation method, to provide numerical and geographical information of the Pi*SZ distribution worldwide. A total of 262 cohorts from 71 countries were included in the analysis. With the data provided by these cohorts, a total of 1,490,816 Pi*SZ were estimated: 708,792 in Europe; 582,984 in America and Caribbean; 85,925 in Africa; 77,940 in Asia; and 35,176 in Australia and New Zealand. Remarkably, the IDW interpolation maps predicted the Pi*SZ prevalence throughout the entire world even in areas lacking real data. These results may be useful to plan strategies for future research, diagnosis, and management of affected individuals.

Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update.

In alpha-1 antitrypsin deficiency (AATD), the Z allele is present in 98% of cases with severe disease, and knowledge of the frequency of this allele is essential from a public health perspective. However, there is a remarkable lack of epidemiological data on AATD worldwide, and many of the data currently used are outdated. Therefore, the objective of this study was to update the knowledge of the frequency of the Z allele to achieve accurate estimates of the prevalence and number of Pi*ZZ genotypes worldwide based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) measurements performed using a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop maps with an inverse distance weighted (IDW)-interpolation method, providing numerical and graphical information of Pi*Z distribution worldwide. A total of 224 cohorts from 65 countries were included in the study. With the data provided by these cohorts, a total of 253,404 Pi*ZZ were estimated worldwide: 119,594 in Europe, 91,490 in America and Caribbean, 3,824 in Africa, 32,154 in Asia, 4,126 in Australia, and 2,216 in New Zealand. In addition, the IDW-interpolation maps predicted Pi*Z frequencies throughout the world even in some areas that lack real data. In conclusion, the inclusion of new well-designed studies and the exclusion of the low-quality ones have significantly improved the reliability of results, which may be useful to plan strategies for future research and diagnosis and to rationalize the therapeutic resources available.

Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls.

BACKGROUND: The association between alpha-1 antitrypsin (AAT) deficiency and colorectal cancer (CRC) is currently controversial. The present study compares AAT serum concentrations and gene frequencies between a group of CRC patients and a control group of healthy unrelated people (HUP). METHODS: 267 CRC subjects (63% males, 72 ± 10 years old) were enlisted from a Hospital Clinic setting in Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 ± 7.5 years old) from the same geographical region. Outcome measures were AAT serum concentrations measured by nephelometry, and AAT phenotyping characterization by isoelectric focusing. RESULTS: Significantly higher serum concentrations were found among CRC (208 ± 60) than in HUP individuals (144 ± 20.5) (p = 0.0001). No differences were found in the phenotypic distribution of the Pi*S and Pi*Z allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC (21%) than in HUP subjects (15%). CONCLUSIONS: The only statistically significant finding in this study was the markedly higher AAT serum concentrations found in CRC subjects compared with HUP controls, irrespective of whether their Pi* phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although there was a trend towards the more deficient Pi* phenotype the more advanced the tumor, the results were inconclusive due to the small sample size. Consequently, more powerful studies are needed to reach firmer conclusions on this matter.

Colonic perianastomotic carcinogenesis in an experimental model.

BACKGROUND: To examine the effect of anastomosis on experimental carcinogenesis in the colon of rats. METHODS: Forty-three 10-week-old male and female Sprague-Dawley rats were operated on by performing an end-to-side ileorectostomy. Group A:16 rats received no treatment. Group B: 27 rats received 18 subcutaneous injections weekly at a dose of 21 mg/kg wt of 1-2 dimethylhydrazine (DMH), from the eighth day after the intervention. Animals were sacrificed between 25-27 weeks. The number of tumours, their localization, size and microscopic characteristics were recorded. A paired chi-squared analysis was performed comparing tumoral induction in the perianastomotic zone with the rest of colon with faeces. RESULTS: No tumours appeared in the dimethylhydrazine-free group. The percentage tumoral area was greater in the perianastomotic zone compared to tumours which had developed in the rest of colon with faeces (p = 0.014). CONCLUSION: We found a cocarcinogenic effect due to the creation of an anastomosis, when using an experimental model of colonic carcinogenesis induced by DMH in rats.