Genotype is associated with smoking and other key health behaviors among individuals with alpha-1 antitrypsin deficiency-associated lung disease.

OBJECTIVE: To examine the association of genotype with smoking and other key health behaviors among individuals with alpha-1 antitrypsin deficiency (AATD) associated lung disease. METHODS: Self-reported data were analyzed from 3506 individuals with AATD-associated lung disease. All data were collected upon enrollment in a disease management program designed for individuals who have been prescribed augmentation therapy. Multivariate logistic regression was utilized to examine the extent to which genotype was associated with smoking and other key health behaviors (i.e., getting a pneumonia vaccine, getting a flu vaccine, exercising, and maintaining a healthy weight). We hypothesized that MZs and SZs are more likely than ZZs to be current smokers, and that genotype is associated with additional health behaviors. RESULTS: MZs and SZs had higher odds of being a current smoker than ZZs (MZ versus ZZ OR = 2.73, p < .001; SZ versus ZZ OR = 4.34, p < .001). For every additional health behavior examined, MZs had higher odds of unhealthy behavior than ZZs (ORs ranged from 1.35 to 1.98, p < .05). SZs had higher odds of unhealthy behavior than ZZs with regard to lack of exercise (OR = 1.52, p = .003) and failure to maintain a healthy weight (underweight OR = 1.93, p = .028; overweight OR = 1.43, p = .015). CONCLUSIONS: Among individuals who have been prescribed augmentation therapy for lung disease due to AATD, genotype is associated with smoking and additional health behaviors that are central to managing lung disease.

[Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. / Langzeit-Augmentationstherapie von Patienten mit Alpha-1-Antitrypsin-Mangel in der häuslichen Pflege.

BACKGROUND: Augmentation with human alpha-1 proteinase inhibitor is the only specific treatment for Alpha-1-Antitrypsin Deficiency (AATD), a rare genetic disease with symptoms of progressive COPD. OBJECTIVES: A prospective long-term exploration of outcomes during the "Alpha-1-Mobile" home care AAT augmentation program in seven advanced-stage patients. METHODS: Patients received weekly i. v. AAT augmentation and COPD therapy. Symptoms, lung function, health status, quality-of-life aspects, and safety were documented continuously. Outcomes during six years of home care augmentation therapy were observed and evaluated on an inter- and intraindividual basis. FEV1 profiles were compared to pre-program data. RESULTS: The seven patients had a mean age of 56.7 (40-68) years and had previously received augmentation for 8.8 (1-19) years. Compared to the three-year preprogram period, functional decline of FEV1 (ΔFEV1 0.47 L vs 0.17 L) slowed. Mean QoL scores showed seasonal fluctuations in the first three years of observation, and then stabilized. All blood samples tested exceeded the protective threshold of 50 mg/dL with a dose of 60 mg AAT/kg/week. Less than one exacerbation-related hospitalization occurred per patient-year. No adverse events of related to augmentation therapy were observed. CONCLUSIONS: Home care with i. v. augmentation therapy by medical professionals contributes to optimum care through consistent treatment and close health-status monitoring in our collective. Exacerbation-related hospitalizations were largely avoided. "Alpha-1-Mobile" was well accepted, practical, and safe.

Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that is associated with low levels of circulating alpha-1-antitrypsin in serum. In comparison to the genotype PiZZ, PiSZ usually leads to lower risk of emphysema, better lung function and better survival. The aim of this study was to analyze the relationship between cigarette smoking (packyears) and the AATD genotypes (PiZZ and PiSZ) concerning quality of life (SGRQ), transfer factor of the lung for carbon monoxide (TLCO), forced expiratory volume in one second (FEV1) and exacerbation rate. METHODS: We compared PiZZ and PiSZ individuals from the German registry for individuals with AATD (AATDR) in univariate analysis and multivariate linear regression models. All subjects were stratified into three groups according to their cumulative nicotine consumption (0 py; 0 < py < 30; ?30 py). RESULTS: 868 PiZZ individuals (mean age 52.6 ± 12.8 years (43.5% female)) and 114 PiSZ individuals (mean age 50.3 ± 17.4 years (46.5% female)) were compared. In contrast to never- and intensive (ex-) smokers, moderate (ex-) smoking PiSZ individuals had a significantly better SGRQ total score (B = ?8.148; p = 0.020) and less exacerbations (B = ?0.354; p = 0.037) than individuals with PiZZ in multivariate analysis. CONCLUSIONS: The differences in quality of life and exacerbation frequency between PiZZ and PiSZ individuals diminish by intensive (ex-) smoking.

Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency - analysis from the German Registry.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary disease that is associated with a higher risk to develop chronic obstructive pulmonary disease and liver cirrhosis. Previous cross-sectional studies on AATD individuals have shown a relationship between worse St George's Respiratory Questionnaire (SGRQ) scores and elevated exacerbation rate or high cigarette consumption. There is a lack of longitudinal data on the relationship between the exacerbation rate and worsening of SGRQ during disease. The aim of this study was to provide not only cross-sectional data but also information about the deterioration in quality of life over a follow-up period up to 7 years (median follow-up period of 3.33 years). METHODS: We investigated questionnaire-based data of the German AATD registry concerning the relationship between SGRQ and exacerbation frequency, smoking history, forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusion capacity (DLCO) first in cross-sectional analysis and later in longitudinal analysis. RESULTS: Eight hundred sixty-eight individuals with protease inhibitor ZZ (PiZZ) genotype with an average age of 52.6±12.8 years had an SGRQ score of 45.7±20.6. SGRQ significantly correlated with the exacerbation frequency within the last 2 years (r=0.464; P<0.001), smoking history (r=0.233; P<0.001), FEV1 (r=-0.436; P<0.001), DLCO (r=-0.333; P<0.001), and patients' age (r=0.292; P<0.001). Individuals with occupational dust exposure had significantly worse quality of life (P<0.001). Mean annual deterioration of SGRQ in all patients with available follow-up data (n=286) was 1.21±4.45 points per year. Univariate and multivariate analysis showed a significant relationship between worsening of SGRQ/year and exacerbation frequency in the follow-up period (r=0.144; P=0.015). CONCLUSION: Worsening of SGRQ is associated with the exacerbation frequency in individuals with PiZZ AATD.

Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD patients.

BACKGROUND: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease. METHODS: Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort. The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles. The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities. RESULTS: Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD. AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT) compared with COPD patients without AATD. There were no significant differences between groups regarding indirect costs and HRQL. CONCLUSION: Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD. AT was not associated with lower costs or higher HRQL. TRIAL REGISTRATION: NCT01245933.

Health-Related Quality of Life in Patients With α1 Antitrypsin Deficency: A Cross Sectional Study. / Calidad de vida relacionada con la salud en pacientes con déficit de α1 antitripsina: estudio transversal.

BACKGROUND: Measures of health related quality of life (HRQoL) in patients with α1-antitrypsin deficiency (AATD) can help to determine the impact of the disease and provide an important insight into the intervention outcomes. There is few data regarding this issue in the literature. The aim of this study is to assess the relationship between HRQoL and gender, functional parameters and history of hospitalizations in patients with AATD. METHODS: This is a cross-sectional study of 26 patients with severe AATD recruited in the pulmonology outpatient clinic at a tertiary care medical center. Social-demographic, clinical and functional parameters were recorded and HRQoL was assessed with the Portuguese version of the medical outcome study short form-36 (SF-36) self-administered questionnaire. RESULTS: Older patients, females and patients with at least one hospitalization in the previous year due to respiratory disease had statistical lower scores in some dimensions of the SF-36 questionnaire. Superior FEV1 and higher distance mark in the 6-min walking test distance influenced positively several dimensions of the questionnaire. Higher scores in the mMRC scale influenced negatively the HRQoL. CONCLUSIONS: These data suggests that older and female patients with AATD have worse HRQoL. Hospitalizations and functional markers of respiratory disease progression influenced negatively the HRQoL, suggesting that the SF-36 questionnaire could be useful as an outcome for AATD patients with lung involvement.

Keeping Secrets or Educating Others: A Dyadic Analysis of Group Entitativity's Influence on Spouses' Label Management Connected to AATD.

In 1963, Goffman argued that forming a group based on shared stigma may provide benefits. However, there is no empirical research on whether perception that a separate, unique, coherent group exists (i.e., group entitativity) influences coping, such as educating others or secrecy, for the stigmatized individual or his or her spouse. Further, little is known about how spouses influence each other in terms of promoting the education of others about a stigmatizing condition, especially when it comes to the role of believing that stigma-based groups, to which they may both belong, exist. This study provides a step toward bridging this gap in the research by applying the label management model in efforts to understand coping for couples in which one spouse is diagnosed with genetic mutations leading to alpha-1 antitrypsin deficiency (AATD). This study included 50 married couples in which one spouse is diagnosed with genetic mutations leading to alpha-1 antitrypsin deficiency (AATD). We found that group entitativity related to those with AATD counterbalanced the influence of genetic stigma on spouses' intentions to keep the diagnosis secret or to educate others about it. Intrapersonal and interpersonal influences appeared among spouses. Attention is needed on the power of creating groups for stigmatized persons and their relatives. Indeed, people live within a dynamic world of group entities, and multiple social identities including spousal and familial. While attention has been paid to the diffusion of stigmas to loved ones, less has been paid to the uplift of group entities for them.

Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome.

OBJECTIVES: To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS. STUDY DESIGN: Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory (PedsQL) questionnaires were administered to 70 children with ALGS, 95 children with alpha-1-antitrypsin deficiency (A1ATD), and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent proxy PedsQL scores were recorded for children aged 2-18 years (98 ALGS, 123 A1ATD, and 68 IHC). RESULTS: Mean ages and total bilirubin (mg/dL) were ALGS 9.4 years; 4.4, A1ATD 9.5 years; 0.7, and IHC 10.3 years; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs 83; P = .001). Children with ALGS and IHC were similar, except in physical scores (73 vs 79; P = .05). Parents of children with ALGS perceived their children to have worse HRQOL than A1ATD (P ≤ .001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated international normalized ratio, and an intracardiac defect were predictive of poor parental scores (P ≤ .05). In multivariate analysis, only weight z-score remained significant for child- and parent-reported scores. CONCLUSIONS: HRQOL is impaired in children with ALGS compared with healthy and children with A1ATD, similar to children with IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL.

Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience.

The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.

The Swedish α1-Antitrypsin Screening Study: Health Status and Lung and Liver Function at Age 34.

RATIONALE: All Swedish newborn infants were screened for α1-antitrypsin (AAT) deficiency between 1972 and 1974. The cohort of 127 individuals with severe AAT deficiency (PiZZ) and 54 with moderate AAT deficiency (PiSZ) has been followed up regularly. OBJECTIVES: To compare smoking habits, quality of life, respiratory symptoms, and lung and liver function at the age of 34 years in this cohort and among 300 age-matched control subjects randomly selected from the Swedish population registry. METHODS: The study participants answered a questionnaire on smoking habits and symptoms; underwent spirometry, including FEV1 and FVC; and provided blood samples. Health-related quality of life was assessed by using the St. George's Respiratory Questionnaire (SGRQ). MEASUREMENTS AND MAIN RESULTS: One hundred sixteen PiZZ, 48 PiSZ, and 229 control subjects (normal AAT level [PiMM]) answered the questionnaire. Eighty-eight PiZZ (76%), 36 PiSZ (75%), and 144 PiMM (63%) subjects had never smoked (P = 0.02). No significant differences were found in lung function parameters between the protease inhibitor (Pi) subgroups, nor were any discovered between the smoking subgroups. In all Pi subgroups, the symptom score on the SGRQ was significantly lower in ever-smokers than in never-smokers (P = 0.01 for PiZZ, P = 0.009 for PiSZ, and P = 0.01 for PiMM). The mean plasma levels of liver enzymes and albumin were within normal range in all Pi subgroups. However, the mean γ-glutamyl transpeptidase and albumin levels were significantly higher in the PiZZ than in the PiMM subjects (P < 0.05). CONCLUSIONS: In this population-based study, no differences in lung function or symptoms were found between subjects with AAT deficiency and control subjects, but smoking frequency was significantly lower among the subjects with AAT deficiency than in the controls at age 34 years.

Alpha-1 Antitrypsin Deficiency-Associated Chronic Obstructive Pulmonary Disease: A Family Perspective.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is a genetic condition that can lead to the early onset of chronic obstructive pulmonary disease (COPD), a disorder that comprises elements of chronic bronchitis and emphysema. AATD is characterized by reduced levels of the AAT protease inhibitor, leading to unrestricted protease activity in the lung, which promotes destruction of lung tissue. In severe cases, patients with AATD have an increased mortality risk and, potentially, a poor quality of life due to more frequent COPD exacerbations and/or limitations on daily activity. However, the burden of AATD on members of the patient's immediate family who may serve as caregivers has not been described. Because the age range at which most patients are diagnosed with AATD may affect the economic status of an individual and/or of a family, it is likely that a diagnosis of AATD may have negative effects that extend beyond those on the diagnosed person to include immediate family members. Here, we review the literature to investigate the impact of the caregiver role of family members in disease states that affect an age group similar to AATD. Furthermore, we provide a case study showing the effect of AATD on immediate family members.

Classifying married adults diagnosed with alpha-1 antitrypsin deficiency based on spousal communication patterns using latent class analysis: insights for intervention.

Married adults are increasingly exposed to test results that indicate an increased genetic risk for adult-onset conditions. For example, a SERPINA1 mutation, associated with alpha-1 antitrypsin deficiency (AATD), predisposes affected individuals to diseases such as chronic obstructive pulmonary disease (COPD) and cancer, which are often detected in adulthood. Married adults are likely to discuss genetic test results with their spouses, and interpersonal research suggests that spouses' communication patterns differ. Latent class analysis was used to identify subgroups of spousal communication patterns about AATD results from a sample of married adults in the Alpha-1 Research Registry (N = 130). A five-class model was identified, and the subgroups were consistent with existing spousal-communication typologies. This study also showed that genetic beliefs (e.g., genetic stigma), emotions, and experiences (e.g., insurance difficulties) covaried with membership in particular subgroups. Understanding these differences can serve as the foundation for the creation of effective, targeted communications interventions to address the specific needs and conversational patterns of different kinds of couples.

The impact of age on outcomes in chronic obstructive pulmonary disease differs by relationship status.

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that can lead to early-onset chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the impact of age on psychological and clinical outcomes among individuals with AATD-associated COPD. 468 individuals with AATD-associated COPD (age 32-84 at baseline) completed questionnaires at baseline, 1- and 2-year follow-up. Age was examined as a predictor of depression, anxiety, health-related quality of life, and breathlessness at all three time points using linear mixed models. Age was associated with anxiety (b = -0.09, SE = 0.02, p < 0.001) and health-related quality of life (b = -0.29, SE = 0.09, p < 0.001). Age also had a statistically significant interaction with relationship status when predicting depression, health-related quality of life, and breathlessness. Among individuals who were single, younger age was associated with more symptoms of depression (b = -0.08, SE = 0.03, p < 0.01), worse health-related quality of life (b = -0.61, SE = 0.16, p < 0.001), and more breathlessness (b = -0.023, SE = 0.009, p < 0.01) throughout the 2-year study. Age was not associated with these three outcomes among individuals who were married/part of an unmarried couple. Results suggest that individuals who develop a chronic illness at a young age, particularly those who are single, may be more likely to have worse psychological and clinical outcomes.

Genetics' influence on patient experiences with a rare chronic disorder: a photovoice study of living with alpha-1 antitrypsin deficiency.

Patients with rare chronic disorders and their caregivers increasingly form communities to support and exchange social experiences. Because up to 10% of the United States population is affected by one of 5000 to 6000 rare disorders, efforts to understand the individuals and affected communities are important. This study was conducted using community-based participatory research approaches within a community of patients and caregivers living with alpha-1 antitrypsin (AAT) deficiency. Patient populations at some risk for lung transplant include individuals who smoked cigarettes and patients who underwent liver transplant in infancy and later adulthood due to accumulation of misfolded AAT within hepatocytes.

Alpha1-antitrypsin deficiency - diagnostic testing and disease awareness in Germany and Italy.

BACKGROUND: Alpha1-antitrypsin (AAT) deficiency, although largely under-diagnosed, is the underlying cause of approximately 1% of COPD cases. Lack of awareness leads to long delays in diagnostic testing. Subsequently, lifestyle and treatment choices with potentially positive effects on prognosis may be postponed. METHODS: Data on the testing and diagnostic practices for AAT deficiency were derived from the University of Pavia, Italy, and the University of Marburg, Germany. In addition, a survey of physicians was undertaken to explore their awareness and attitudes toward AAT deficiency. RESULTS: In Pavia and Marburg, 125 and 729 patients, respectively, were identified with severe AAT deficiency between July 2006 and June 2011. The median time interval between the onset of symptoms and diagnosis was 6 years (interquartile range [IQR], 11; range, 0-40) and 7 years (IQR, 13; range, 0-73), respectively. Augmentation therapy was initiated almost immediately in Germany while treatment was delayed by 3 months in Italy (IQR, 5.25; range, 1-118). Survey data (Italy, n = 181; Germany, n = 180) revealed that pulmonologists had greater knowledge of AAT deficiency than internists and general practitioners, however, overall, only 18-25% of physicians tested all COPD patients. One-third of the respondents stated that they "sometimes" offered augmentation therapy to patients diagnosed with AAT deficiency. CONCLUSIONS: Major obstacles to AAT deficiency testing are physicians' attitudes and lack of understanding of the condition. A greater adherence to the guidelines that recommend diagnostic testing of all COPD patients, coupled with simpler testing protocols, may decrease delays and positively impact patient outcomes.

Differences in adjustment between individuals with alpha-1 antitrypsin deficiency (AATD)-associated COPD and non-AATD COPD.

Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for developing COPD earlier in life than smokers without AATD, and are likely to experience challenges adjusting to their illness because they are in a highly productive life stage when they are diagnosed with COPD. This study examined whether individuals with AATD-associated COPD differ from individuals with non-AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality of life (HRQL). Cross-sectional data were collected via self-report questionnaires completed by 480 individuals with non-AATD COPD and 578 individuals with AATD-associated COPD under protocols with IRB approval. Multiple linear regression models were used to test whether individuals with non-AATD COPD differed from individuals with AATD-associated COPD with regard to depression, anxiety, dyspnea, and HRQL. All models adjusted for demographic and health characteristics. Individuals with AATD-associated COPD did not report more symptoms of depression or anxiety; however, they did report more dyspnea (B = 0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with AATD-associated COPD were more likely to be a member of a couple (rather than single) and had a higher level of education when compared to individuals with non-AATD COPD. Resources available to persons with AATD-associated COPD, such as being in a serious relationship and having higher education, may offset the effect of age when considering symptoms of depression and anxiety in patients with COPD.

The Alpha-1 Association Genetic Counseling Program: an innovative approach to service.

In an era of specialty medicine, genetic counselors are becoming increasingly focused in their service provision. The Alpha-1 Association Genetic Counseling Program, established in September 2007, specializes in confidential toll-free genetic counseling provided by a certified genetic counselor for Alpha-1 Antitrypsin deficiency, a co-dominant condition associated with lung and/or liver disease. The program received more than 600 callers in its first 2 years. Sixty-seven percent of new callers were family members, carriers, or health professionals. The number of callers increased between the first 2 years, with the greatest increases being family members and health professionals. Testing options and explanation of results encompassed 60% of initial reasons for calls. Seventy-two percent of referrals came from family and friends, test result letters, and the Alpha-1 Association. Between year 1 and 2 family member referrals showed the largest increase. This disease-specific genetic counseling program provides a model that may be useful for other rare disease communities.

"Am I my genes?": Questions of identity among individuals confronting genetic disease.

PURPOSE: : To explore many questions raised by genetics concerning personal identities that have not been fully investigated. METHODS: : We interviewed in depth, for 2 hours each, 64 individuals who had or were at risk for Huntington disease, breast cancer, or alpha-1 antitrypsin deficiency. RESULTS: : These individuals struggled with several difficult issues of identity. They drew on a range of genotypes and phenotypes (e.g., family history alone; mutations, but no symptoms; or symptoms). They often felt that their predicament did not fit preexisting categories well (e.g., "sick," "healthy," "disabled," "predisposed"), due in part to uncertainties involved (e.g., unclear prognoses, since mutations may not produce symptoms). Hence, individuals varied in how much genetics affected their identity, in what ways, and how negatively. Factors emerged related to disease, family history, and other sources of identity. These identities may, in turn, shape disclosure, coping, and other health decisions. CONCLUSIONS: : Individuals struggle to construct a genetic identity. They view genetic information in highly subjective ways, varying widely in what aspects of genetic information they focus on and how. These data have important implications for education of providers (to assist patients with these issues), patients, and family members; and for research, to understand these issues more fully.

Barriers to genetic testing among persons at risk for alpha-1 antitrypsin deficiency.

The alpha coded testing (ACT) study offers free and confidential testing for alpha-1 antitrypsin deficiency (AATD) and includes surveys to provide data to study the psychosocial correlates of genetic testing. The purpose of the current study is to better understand reasons why some individuals complete genetic testing while others do not. Survey measures were compared between participants who requested and returned a genetic test for AATD (n = 703), and a random sample of individuals who requested a test kit, but did not return it within 3 months of their request (n = 83). Increasing decile of age (odds ratio [OR] = 0.74 [95% confidence interval = 0.60-0.82]) and fingerstick fear (OR = 0.74 [0.60-0.93]) were associated with a decreased likelihood of returning the test, while assurance of confidentiality was associated with an increased likelihood (OR = 1.26 [1.01-1.57]) of returning the genetic test. General anxiety as measured by the Beck Anxiety Inventory, family functioning as measured by the general functioning subscale of the Family Assessment Device, and stress induced by genetic testing as measured by the Impact of Events Scale did not significantly differ between responder groups (p = not significant). Results of this study help characterize factors driving genetic testing in AATD and may offer insight into population responses with other genetic tests.

Anxiety related to genetic testing for alpha-1 antitrypsin deficiency and cystic fibrosis in COPD and/or bronchiectasis patients.

OBJECTIVE: To describe the psychological reaction to information about diagnostic genetic testing for alpha-1 antitrypsin deficiency (Alpha-1) and cystic fibrosis (CF) in chronic obstructive pulmonary disease and/or bronchiectasis patients who were tested but did not know the results. METHODS: One hundred and three adults took the State-Trait Anxiety Inventory before and after a standardized educational intervention and responded to a questionnaire. RESULTS: Information about the limitations, risks and benefits of Alpha-1 and CF testing did not raise mean anxiety levels. Mean anxiety was slightly lower after the educational intervention than at baseline (mean pretest score 35.0, posttest score 33.7; p < 0.05). Participants whose physician preinformed them of genetic testing had slightly higher mean anxiety than other participants, both before and after the intervention, but scores were comparable to those in a normative sample of general medical and surgical patients. CONCLUSIONS: Disclosure of information regarding Alpha-1 and CF testing appears to be potentially acceptable to patients and unlikely to prevent clinicians from conducting useful diagnostic procedures. This study is a step in alleviating concerns about raising issues related to genetic testing for Alpha-1 and CF in chronic obstructive pulmonary disease patients during the informed consent process.