Prevalence Of Alpha-1 Antitrypsin Deficiency Research Articles

Prevalence of alpha-1 antitrypsin deficiency in patients with acute exacerbation of chronic obstructive pulmonary disease: Insights from a prospective study.

Alpha-1 antitrypsin (AAT) deficiency is a genetic risk factor for chronic obstructive pulmonary disease (COPD) but prevalence data in acutely exacerbated Indian patients is limited. This study determined AAT deficiency rates and correlations with inflammation and lung function among hospitalized patients with COPD. A total of 106 patients hospitalized for acute COPD exacerbations were prospectively enrolled from June 2016 to February 2018 in Kerala, India, excluding any with known AAT deficiency. Serum AAT levels were quantified and correlated with C-reactive protein (CRP) levels as well as postbronchodilator spirometry. Mean serum AAT level was 1.48 ± 0.27 g/L. No AAT deficiency cases were identified, although AAT and CRP both significantly increased during flares. AAT levels positively correlated with FEV1, FVC, and FEV1/FVC ratios. Patients with lower AAT had worse pulmonary status. Despite finding no AAT deficiency in this regional Indian cohort, further studies across expanded, more diverse populations are warranted to definitively establish prevalence nationwide. Temporal monitoring of AAT kinetics could help gauge exacerbation trajectories.

Genetic Epidemiology of Alpha-1 Antitrypsin Deficiency in Macaronesia

Introduction: The prevalence of alpha-1 antitrypsin deficiency (AATD) in Macaronesia (i.e., Azores, Madeira, Canary Islands, and Cape Verde archipelagos) is poorly known. Our goal was to update it by selecting the most reliable available articles. Method: Literature search using MEDLINE, Embase (via Ovid), and Google Scholar, until December 2023, for studies on prevalence of AATD in the general population and in screenings, published in peer-reviewed journals. Results: Three studies carried out in the general population of Madeira, La Palma, and Cape Verde, and three screenings carried out in La Palma (2) and Gran Canaria (1) were selected. The frequencies of PI*S in the general population showed an ascending gradient, from South to North, with values (per thousand) of 35 in Cape Verde, 82 in La Palma, and 180 in Madeira. The PI*Z frequencies showed this same gradient, with values of 2 × 1,000 in Cape Verde, 21 in La Palma, and 25 in Madeira. Screenings detected high percentages of defective alleles, including several rare and null alleles, some unique to these islands. Conclusion: The frequencies of PI*S and PI*Z in Madeira are comparable to the highest in the world. Those of the Canary Islands are similar to those of the peninsular population of Spain, and contrast with the low rates of Cape Verde. Screenings detected high numbers of deficient alleles. These results support the systematic investigation of AATD in clinically suspected patients and in relatives of index cases, to reduce underdiagnosis and apply early preventive and therapeutic measures in those affected.

Prevalence of Alpha-1 Antitrypsin Deficiency, Self-Reported Behavior Change, and Health Care Engagement Among Direct-to-Consumer Recipients of a Personalized Genetic Risk Report

Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition that predisposes to emphysema, cirrhosis, panniculitis, and vasculitis. Underrecognition has prompted efforts to enhance early detection and testing of at-risk individuals. Direct-to-consumer (DTC) genetic testing represents an additional method of detection. The study addressed three questions: (1) Does a DTC testing service identify previously undetected individuals with AATD? (2) What was the interval between initial AATD-related symptoms and initial diagnosis of AATD in such individuals? and (3) What was the behavioral impact of learning about a new diagnosis of AATD through a DTC test? In this cross-sectional study, 195,014 individuals responded to a survey within the 23andMe, Inc. research platform. Among 195,014 study participants, the allele frequency for the PI∗S and PI∗Z AATD variants was 21.6%(6.5%for PI∗Z and 15.1%for PI∗S); 0.63%were PI∗ZZ, half of whom reported having a physician confirm the diagnosis. Approximately 27%of those with physician-diagnosed AATD reported first becoming aware of AATD through the DTC test. Among those newly aware participants, the diagnostic delay interval was 22.3 years. Participants frequently shared their DTC test results with health care providers (HCPs) and the reported impact of learning a diagnosis of AATD was high. For example, 51.1%of PI∗ZZ individuals shared their DTC result with an HCP. The OR for PI∗ZZ smokers to report smoking reduction as a result of receiving the DTC result was 1.7 (95% CI= 1.4-2.2) compared with those without a Z allele and for reduced alcohol consumption this was 4.0 (95% CI= 2.6-5.9). In this largest available report on DTC testing for AATD, this test, in combination with clinical follow-up, can help to identify previously undiagnosed AATD patients. Moreover, receipt of the DTC AATD report was associated with positive behavior change, especially among those with risk variants.

Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil.

ABSTRACTObjective:To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods:This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results:Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions:The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients.

Correction to: The Prevalence of Alpha-1 Antitrypsin Deficiency Among Patients Found to Have Airflow Obstruction

Correction to: The Prevalence of Alpha-1 Antitrypsin Deficiency Among Patients Found to Have Airflow Obstruction

The Prevalence of Alpha-1 Antitrypsin Deficiency Among Patients Found to Have Airflow Obstruction

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic disease that may be manifested by chronic obstructive pulmonary disease. Despite professional society guidelines that recommend broad testing of at-risk individuals, fewer than 10% of affected individuals have been identified. The goals of this study were to estimate the frequency of abnormal AAT genotypes among patients found to have fixed airflow obstruction and to assess the feasibility of having Pulmonary Function Laboratory personnel administer the study. Methods: Nineteen medical centers in the United States participated in the study. Eligible patients (> GOLD II, FEV1/FVC ratio < 0.7, with post-bronchodilator FEV1<80% predicted) were offered testing for AATD by the Pulmonary Function Laboratory personnel at the time of pulmonary function testing. Results: A total of 3,457 patients were tested, of whom 3152 were eligible. Deficient patients (ZZ, SZ) constituted 0.63% of subjects, while 10.88% were carriers (MS, MZ). Neither demographic (except African-American race) nor post-bronchodilator pulmonary function variables (FEV1, FVC, FEV1/FVC ratio, TLC, and FEV1/FVC) allowed us to predict AAT heterozygote or deficiency status. Conclusions: The prevalence of AATD among patients undergoing pulmonary function tests with fixed airflow obstruction was 0.63%. Pulmonary Function Laboratory personnel effectively conducted the study.

The prevalence of alpha 1-antitrypsin deficiency in a representative population sample from Poland

Severe alpha(1)-antitrypsin (AAT) deficiency is one of the most common genetic disorders in Caucasians. The aim of the present study was to assess an unbiased frequencies of PI*S and PI*Z alleles using genotyping of a representative sample from the general population of Poland. A random sample of age- and gender-stratified residents, aged 20 years or older, was drawn from the municipal directory of Kraków, Poland. The two most common deficiency alleles: PI*S and PI*Z were genotyped with qualitative real-time PCR using degenerative dual-labeled allele-specific fluorescent probes. In the total population of 859 adult subjects (mean age: 49.5 years; range: 20-90), 28 heterozygotes MS, 18 heterozygotes MZ and one homozygote S were diagnosed. The frequency of PI*S allele was 17.5 (95% CI: 11.6-23.9) per 1000; and that of PI*Z was 10.5 (95% CI: 5.8-15.7) per 1000. Therefore, the estimated prevalence of inherited severe AAT deficiency (homozygotes Z) in Poland is 1/9110 (95% CI: 1/4057-1/29,727). In the whole population of Poland comprising 38 millions, one may expect of about 4189 (95% CI: 1284-9406) subjects with severe AAT deficiency. These numbers are high enough to consider genetic testing being introduced into a common clinical practice.

Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed.

Articles in the literature on alpha-1 antitrypsin (AAT) deficiency have been interpreted as indicating that AAT deficiency is a rare disease that affects mainly Caucasians (whites) from northern Europe. In a recent publication on the worldwide racial and ethnic distribution of AAT deficiency, new data were presented demonstrating that it is also found in various populations of African blacks; Arabs and Jews in the Middle East; and Central, Far East, and Southeast Asians, as well as whites in Australia, Europe, New Zealand, and North America. The new data on the prevalence of AAT deficiency in other major racial groups worldwide will affect the standards for the diagnosis of AAT deficiency by the medical community, with the realization that is not a rare disease of whites in northern Europe and immigrants from these countries in the New World. In a total population of 4.4 billion in the 58 countries surveyed, there are at least 116 million carriers (those with Pi phenotypes PiMS and PiMZ) and 3.4 million with deficiency allele combinations (phenotypes PiSS, PiSZ, and PiZZ) for the two most prevalent deficiency alleles PiS and PiZ; therefore, the new data suggest that AAT deficiency may be one of the most common serious single-locus genetic diseases in the world. Particularly important is the unique susceptibility of AAT-deficient individuals to exposure to chemical and particulate environmental agents. Such exposures are known to result in both lung and liver disease as well as other adverse health effects.

Alpha-1-antitrypsin phenotypes among patients with intracranial aneurysms.

A deficiency of alpha 1-antitrypsin has been implicated in the development of arterial aneurysms, including intracranial aneurysms. The authors determined the prevalence of alpha 1-antitrypsin deficiency of different phenotypes in 100 consecutive patients with intracranial aneurysms and compared the distribution of alpha 1-antitrypsin phenotypes to that in the general population (904 people). The study population consisted of 44 men and 56 women with a mean age of 52 years (range 15-81 years). The heterozygous alpha 1-antitrypsin deficiency states (PiMS and PiMZ) were more common in patients (16%) than in the general population (7%), providing an odds ratio of 2.56 (95% confidence interval (CI) 1.32-4.75; p = 0.005). In addition, one patient (1%) was homozygous for the deficient allele (PiZZ) compared to an expected number of 0.015, providing an odds ratio of 67.0 (95% CI 2.0-363.3; p = 0.015). These findings lead the authors to suggest that the heterozygous and homozygous alpha 1-antitrypsin deficiency states are genetic risk factors for the development of intracranial aneurysms.

Alpha1-Antitrypsin Pi-Types in 965 COPD Patients

To study further the role of intermediate alpha 1-antitrypsin (AAT) deficiency in chronic obstructive pulmonary disease (COPD), AAT Pi-types and serum-trypsin-inhibitory-capacity (STIC) were measured in 965 patients with COPD. Heterozygosity of the Z variant was the major cause of intermediate AAT deficiency (primarily the MZ phenotype), accounting for 8.0 percent of the patients compared to 2.9 percent of control subjects (p less than .0005). ZZ homozygosity was detected in 1.9 percent of the patients, compared to 0.04 percent of control studies performed by others (none was present in our own control group of 1,380 subjects). The mean age for MS or MZ patients did not differ from that of the COPD patients as a whole, whereas the ZZ homozygotes were younger (55.9 +/- 9.8 vs 65.3 +/- 7.5 years). These results resemble those of a previous study in 66 male veterans with pulmonary emphysema suggesting that the MZ phenotype, or intermediate AAT deficiency in general, probably does predispose to the development of COPD. However, the prevalence of AAT deficiency in COPD patients is small (approximately 10 percent). The number with an MS phenotype was not increased in this group of COPD patients.

Heterozygous MZ alpha 1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis.

To determine the prevalence of alpha 1-antitrypsin deficiency in patients with cirrhosis or chronic active hepatitis, we performed a five-year prospective study of liver-biopsy specimens from 1055 adults. Thirty-four patients whose specimens contained hepatocyte inclusions characteristic of the deficiency were phenotyped, and 25 had phenotype MZ (2.4 per cent). The distribution of patients with this phenotype among the 185 patients with cirrhosis diagnosed histologically was three of 84 patients with alcoholic cirrhosis (3.5 per cent), seven of 34 with non-B chronic active hepatitis (20.5 per cent), six of 28 with cryptogenic cirrhosis (21 per cent), and one of 39 with other kinds of cirrhosis (2.6 per cent). The increased prevalence of MZ in patients with cryptogenic cirrhosis and with chronic active hepatitis is highly significant (P < 0.001). Because serum levels of alpha 1-antitrypsin may be unreliable for identification of the subgroup of patients with chronic active hepatitis or cryptogenic cirrhosis, analysis of serum for the MZ phenotype and meticulous examination of biopsy specimens may be necessary.