Alpha‐1 antitrypsin (AAT) deficiency is an under‐recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000–1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000–10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad‐spectrum anti‐inflammatory, immunomodulatory, anti‐infective and tissue‐repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

The current study focuses on developing estimates of the numbers of individuals carrying the two most common deficiency alleles, PI*S and PI*Z, for a 1 -antitrypsin deficiency (AT-D) in Europe.Criteria for selection of epidemiological studies were: 1) AT phenotyping performed by isoelectrofocusing or antigen-antibody crossed electrophoresis; 2) rejection of ''screening studies''; 3) statistical precision factor score of o5 for Southwest, Western and Northern Europe, o4 for Central Europe, o3 for Eastern Europe; and 4) samples representative of the general population.A total of 75,390 individuals were selected from 21 European countries (one each from Austria, Belgium, Latvia, Hungary, Serbia-Montenegro, Sweden and Switzerland; two each from Denmark, Estonia and Lithuania; three each from Portugal and the UK; four each from Finland, the Netherlands, Norway and Spain; five each from Russia and Germany; six from Poland; eight from Italy; and nine from France). The total AT-D populations of a particular phenotype in the countries selected were: 124,594 ZZ; 560,515 SZ;16,323,226 MZ; 630,401 SS;and 36,716,819 MS. The largest number of ZZ (5,000-15,000) were in

Genetic epidemiological studies on the prevalence and numbers of individuals with α1-antitrypsin deficiency in each of 97 countries worldwide were used to estimate the numbers in each of the five following phenotypic classes: PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ. These 97 countries were then grouped into 10 major geographic regions to make it possible to compare the numbers in each of these five phenotypic classes in immediately adjacent countries. Such groupings also make it possible to review the spread of the PI*S and PI*Z alleles from one major geographic grouping to another in the world as well as the spread of these two deficiency alleles within a major geographic region. The data in the 10 tables on the numbers in each of the five phenotypic classes in the countries in the same geographic region as well as the prevalence of the PI*S and PI*Z alleles in countries in the same geographic region provide a novel database for the identification of large numbers of individuals in a given phenotypic class. The database also provides useful information for the identification of countries with high numbers of PI*ZZ individuals for augmentation therapy within a given geographic region.

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.

Alpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world, as its affects all major racial subgroups worldwide, and there are an estimated 120.5 million carriers and deficient subjects worldwide. This genetic disease is related to susceptibility for development of jaundice in infants, liver disease in children and adults and pulmonary emphysema in adults. Moreover, AAT deficiency carrier phenotypes (PiMS and PiMZ) and deficiency allele phenotypes (PiSS, PiSZ and PiZZ) are suspected to predispose subjects to a variety of other adverse health effects. Because there is a limited database on the number of individuals affected by this disease worldwide, we have collected data on control cohorts in genetic epidemiological studies published on case-control studies in the peer-reviewed literature worldwide. Based on these data, we estimated the numbers of carriers and deficiency allele combinations for the two most common defective alleles, namely PiS and PiZ in 58 countries worldwide. The present paper focuses on the distribution of the PiS and PiZ deficiency alleles in Australia, Canada, New Zealand and the United States of America. A total of 31,042,232 individuals at risk for adverse health effects have been calculated in these four countries: 2,144,158 in Australia, 3,258,564 in Canada, 430,922 in New Zealand and 24,909,548 in the United States of America. The prevalences for all five phenotypic classes of AAT deficiency in each of these countries is as follows: Australia 1 out of 8.9, Canada 1 out of 9.8, New Zealand 1 out of 8.5 and the United States of America 1 out of 11.3. The geographical distribution of individual control cohorts and estimates of the numbers of carriers and deficiency allele phenotypes in each of these four countries are given in individual tables.

Existing data on chronic obstructive pulmonary disease (COPD) prevalence are irregularly distributed around the world, and in many geographic regions data are scarce or even nonexistent. This fact hinders the implementation of adequate preventive and therapeutic interventions to reduce the high burden and costs of COPD [1]. In the current study, we have used the Geographic Information System (GIS) inverse distance weighted (IDW) interpolation technique with the objective of visualising spatial data of COPD prevalence in the world and obtaining a visual impression of the magnitude of this global health problem. GIS has been recognised as an effective tool to display the geographical distribution of data, even when they are few and widely separated, as is the case with the prevalence of COPD [2-4].

The objective of the present study was to review published surveys on allelic frequencies S and Z in European populations to evaluate the validity of the reported data. More than a hundred studies on the topic, published since 1965 until 2000, were retrieved by Medline, Index Medicus and bibliographic references consultation. The criteria for studies selection were: 1) sample size> or =250 individuals; 2) alpha-1-antitrypsin phenotype determination performed by means of crossed antigen-antibody or isoelectric focusing in polyacrylamide gels; 3) PI type determination performed without any previous screening procedure; 4) S and Z 95% confidence interval (CI) of the reported outcomes with a calculated coefficient of variation <42.3 for S and <95.8 for Z; 5) S and Z 95% CI of the reported outcomes comprised within 95% CI limits of comparative hypothetical surveys designed with the same sample size of the questioned surveys and the highest/lowest frequencies accepted for a specific area, according to the figures of isogen boundary maps. Seventy studies comply with the five established criteria for analysis. According to the data of the selected studies, a geographical distribution on S and Z gene frequencies in Europe is proposed.

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.