Testing For Alpha-1 Antitrypsin Deficiency Research Articles

An Electronic Health Record-Based Strategy to Enhance Detection of Alpha-1 Antitrypsin Deficiency.

Because alpha-1 antitrypsin deficiency is severely underrecognized and delayed diagnosis is associated with harm, strategies to enhance early detection of alpha-1 antitrypsin deficiency are needed. The study intervention was placing a reminder to test for alpha-1 antitrypsin deficiency within an electronic medical record health maintenance dashboard that houses prompts to providers to implement guideline-based recommendations. This recommendation was for all patients assigned a diagnosis of COPD based on relevant International Classification of Diseases, Tenth Revision codes. The rate of testing for and detecting individuals with alpha-1 antitrypsin deficiency was assessed in 12 one-month intervals before and after implementing the dashboard. After the prompt, whereas testing was still performed in only a small percentage of guideline-concordant instances, the rate of testing for alpha-1 antitrypsin deficiency increased 3.8-fold (ie, from 1.2% to 4.6%, P < .05). This did not result in detection of new patients with alpha-1 antitrypsin deficiency. The rate of testing increased both for alpha-1 antitrypsin serum levels and genotypes in each month after the intervention, though the rate of genotype testing was 2-5-fold lower than the rate of testing for serum level. The results of this preliminary study of a detection strategy for alpha-1 antitrypsin deficiency show that placing a reminder to test for alpha-1 antitrypsin deficiency when indicated in an electronic medical record health maintenance dashboard significantly increased the frequency of testing. Still, that only 4.6% of those in whom testing for alpha-1 antitrypsin deficiency was indicated were tested in the post-intervention period shows that, as for all other alpha-1 antitrypsin deficiency-targeted detection interventions to date, the impact of the intervention was marginal and that other strategies remain needed to mitigate underrecognition. A focus on combining targeted detection strategies (eg, coupling enhanced awareness with free testing) and population-based screening for alpha-1 antitrypsin deficiency is suggested.

European pathways of care in Alpha-1 Antitrypsin deficiency

BackgroundDespite initiatives to improve awareness and treatment of alpha-1 antitrypsin deficiency (AATD), country-level processes for AATD management remain unclear. ObjectivesWe conducted a pan-European physician survey to clarify the pathways for AATD care. MethodProfessionals involved in AATD diagnosis and/or management completed a web-based survey on the detection, evaluation, monitoring and treatment of AATD and the utilisation of European reference network centres for rare lung diseases (ERN-LUNG). ResultsSurveys were completed by 166 physicians from 18 European countries. Overall, 25 % of respondents were unaware of local specific AATD testing guidelines, and most (72 %) had referred <10 patients to a specialist. However, there was general agreement regarding reasons for referral and the types of patient referred. Approaches to AATD testing are heterogenous, with significant between-country differences in the sample testing and collection methods used. Alpha-1 antitrypsin therapy is most frequently monitored using spirometry (98 %), gas transfer (79 %) or symptoms (82 %). Overall, 28 % of respondents were unfamiliar with ERN-LUNG centres, with Portugal and Spain reporting the lowest familiarity, and use of these centres for patient evaluation varied widely. However, engagement with ERN-LUNG centres was widely agreed to be useful when it did occur (especially in Italy and Poland). Little cross-border use of ERN-LUNG centres for patient testing/evaluation was reported. ConclusionsEuropean care pathways for AATD are largely uniform, but with notable heterogeneity in testing approaches and a need for education and standardisation. Familiarity with and use of ERN-LUNG AATD services is variable, and increased awareness of these services is warranted.

A Novel Provider Education Module to Enhance Detection of Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is the most common genetic risk factor for early-onset emphysema. However, AATD continues to be underrecognized and underdiagnosed. Provider awareness about AATD, concerns with testing costs, and limited understanding about therapeutic options contribute to its underdiagnosis. We hypothesized that provider education would improve awareness of AATD and improve screening. To evaluate the impact of a targeted provider education module on AATD screening. We developed a web-based education module to address barriers to screening for AATD, deployed the education module using the Medscape Education platform, assessed perceived healthcare provider confidence in AATD screening, and conducted a prospective pre and postintervention study of AATD testing practices at a high-volume academic outpatient subspecialty pulmonary clinic. A total of 11,385 healthcare providers, including eight pulmonologists at our institution, completed the web-based education module. Confidence in identifying patients at high risk for AATD improved after completing the module ("not confident" in AATD screening was 7.7% postintervention compared with 19.4% preintervention). The rate of screening patients at high risk for AATD improved more than twofold (AATD screening rate 9.7% preintervention vs. 20.4% postintervention; P = 0.004). Among patients screened for AATD in our cohort, 27.2% had a genotype/phenotype or low alpha-1 antitrypsin concentration consistent with AATD. Targeted healthcare provider education can improve the confidence in testing for AATD. Improvements in provider confidence corresponded to improvements in AATD screening in a subspecialty pulmonary clinic. More than one-fourth of screening tests suggested AATD, underpinning the value of testing in high-risk individuals.

Testing Patterns and Disparities for Alpha-1 Antitrypsin Deficiency

BackgroundAlpha-1 antitrypsin deficiency is an under-recognized genetic cause of chronic lung and liver disease; it remains unclear what the testing frequency and disparities are for alpha-1 antitrypsin deficiency. MethodsThis is a retrospective cohort study of people with newly diagnosed chronic obstructive pulmonary disease and liver disease identified at the University of Florida between January 1, 2012 and December 31, 2021. We performed incidence and prevalence analysis for alpha-1 antitrypsin (AAT) testing and point-biserial correlation analysis for tobacco use and AAT testing. We evaluated characteristics with AAT testing using adjusted multivariable logistic regression. ResultsAmong 75,810 subjects with newly diagnosed chronic obstructive pulmonary disease and liver disease between 2012 and 2021, 4248 (5.6%) were tested for AAT deficiency. All subjects had an AAT level performed, while 1654 (39%) had phenotype testing. Annual incidence of testing increased for subjects with newly diagnosed chronic obstructive pulmonary disease or liver disease from 2.8% and 5.4%, respectively, in 2012 to 4.1% and 11.3%, respectively, in 2021. Adjusted multivariable regression analysis showed factors favoring AAT testing were White race, and concomitant chronic obstructive pulmonary disease and liver disease. Increasing age, non-White race, current tobacco use, and being a male with chronic obstructive pulmonary disease had lower odds of AAT testing. ConclusionAlthough slowly improving, testing for AAT deficiency continues to have a low uptake in the clinical setting despite guidelines recommending broader testing. Individuals of White race and those with concomitant chronic obstructive pulmonary disease and liver disease are more likely to be tested, while older subjects, individuals of non-White race, current tobacco use, and men with chronic obstructive pulmonary disease are less favored to be tested.

Development of a risk score to increase detection of severe alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is an under-recognised genetic cause of chronic obstructive lung disease, and many fewer cases than estimated have been identified. Can a reported respiratory and hepatic disease history from a large AATD testing database be used to stratify a person's risk of severe AATD? We analysed data extracted from the AATD National Detection Program. Demographics and medical history were evaluated to predict AATD PI*ZZ genotype. Logistic regression and integer programming models identified predictors and obtained risk scores. These were internally validated on a subset of the data. Out of 301 343 subjects, 1529 (0.5%) had PI*ZZ genotype. Predictors of severe AATD were asthma, bronchitis, emphysema, allergies, bronchiectasis, family history of AATD, cirrhosis, hepatitis and history of abnormal liver function tests. The derived model establishes a subject's risk of severe AATD, and scores ≥0 had an estimated risk of 0.41%, sensitivity 84.62% and specificity 24.32%. A model simulating guideline recommendations had an estimated risk of 0.51% with a sensitivity of 37.98% and specificity 46.60%. By recommending screening for scores ≥0, we estimate that more subjects would be screened (75.7% versus 53.4%) and detected (84.6% versus 58.2%) compared to a guideline-simulated model. This medical history risk model is a useful predictive tool to detect subjects at greater risk of having severe AATD and improves sensitivity of detection. Scores <0 are at lower risk and may need not be screened; testing is recommended for scores ≥0 and consistent with current guidelines.

Impact of a Computerized Clinical Decision Support System to Improve Chronic Obstructive Pulmonary Disease Diagnosis and Testing for Alpha-1 Antitrypsin Deficiency.

Rationale: Chronic obstructive pulmonary disease (COPD) and alpha-1 antitrypsin deficiency (AATD) are underrecognized diseases. This is in part due to the underdiagnosis and lack of confirmation of COPD but also from poor adherence to AATD screening recommendations. Objectives: A clinical decision support system (CDSS) to guide primary care providers improves spirometry testing and confirmation of COPD diagnosis in subjects at risk and improves AATD screening in patients with confirmed COPD. Methods: A CDSS was created to be applied to all Veterans attending single-center Veterans Affairs primary care clinics. The CDSS had an algorithmic dialogue with components executed in phases during different clinic visits: screening for COPD risk using the COPD population screening (COPD-PS) questionnaire, spirometry recommendation, and ordering tool for subjects with a prior diagnosis of COPD or subjects considered high risk by the COPD-PS, dialogue to confirm or discard the diagnosis of COPD, and recommendations for AATD screening in subjects with confirmed COPD. The latter was performed by ordering alpha-1 antitrypsin (AAT) serum levels. Each step of the CDSS algorithm approach was recorded and available to be retrieved at a later date for analysis. Results: Over 6 years, a total of 6,235 Veterans >40 years of age completed the CDSS. According to the COPD-PS questionnaire, 962 (18.5%) subjects were identified as high risk for COPD. An additional 579 subjects with a prior diagnosis of COPD also entered the subsequent steps of the CDSS algorithm. Of the high-risk cohort, the CDSS led to an increase in spirometry testing from 24% to 83% and led to a new diagnosis of COPD in 342 (43%). In the prior COPD diagnosis group, spirometry testing increased from 58% to 84%, leading to COPD reconfirmation in only 326 (67%). A total of 489 (68%) subjects with confirmed COPD completed AAT testing prompted by the CDSS, with 23 subjects identified with AATD and one with severe AATD. Conclusions: In the Veterans Affairs system, the use of a clinical decision support system algorithm that incorporates screening for COPD and AATD improves COPD over- and underdiagnosis and screening rates of AATD in a primary care setting.

A Novel Detection Method to Identify Individuals with Alpha-1 Antitrypsin Deficiency: Linking Prescription of COPD Medications with the Patient-Facing Electronic Medical Record.

Alpha-1 antitrypsin deficiency (AATD) is under-recognized, prompting the need for enhanced detection strategies. The primary aim of this study is to determine the feasibility of using the electronic medical record (EMR) and linked electronic patient messages (EPM) to encourage AATD testing by patients with chronic obstructive pulmonary disease (COPD). Study participants were eligible, untested adult patients who were prescribed an inhaled medication which is exclusively Food and Drug Administration-approved for treating COPD. Eligible patients received a message with basic information about AATD and availability of free, home-based AATD testing. Through a collaboration with the Alpha-1 Foundation's Alpha-1 Coded Testing (ACT) study, patients referred to home-based testing through EPM were flagged. The effectiveness of the electronic message was evaluated by the proportion of patients who underwent testing, and the rate of detecting individuals with severe deficiency of AAT among those tested. A total of 12,369 patients on eligible inhalers were screened; 5430 patients met all criteria and received an EPM. During the study, 396 patients (7.3%) fully requested an ACT kit. Of these, 209 patients (52.8%) returned the test sample and received genotyping results; 65.5%, had a normal AAT genotype (PI*MM), 31.6% were heterozygotes for a deficient allele (PI*MS, PI*MZ and PI*M/Null rare), and 2.9% had severe deficiency of alpha-1 antitrypsin (PI*SZ, PI*ZZ, PI*S/Null rare). While the response rate and test return rate were low, the rate of detecting individuals with AATD using this detection strategy exceeds that of many prior strategies. As such, while requiring independent validation in other populations, this detection strategy holds promise.

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.

Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the SERPINA1 gene, which encodes the alpha-1 antitrypsin (AAT) protein. Currently, over 200 SERPINA1 variants have been identified, many of which cause the quantitative and/or qualitative changes in AAT responsible for AATD-associated lung and liver disease. The types of these pathogenic mutations are varied, often resulting in misfolding, or truncating of the AAT amino acid sequence, and improvements in sequencing technology are helping to identify known and novel genetic variants. However, due to the diversity and novelty of rare variants, the clinical significance of many is largely unknown. There is, therefore, a lack of guidance on how patients should be monitored and treated when the clinical significance of their variant combination is unclear or variable. Nevertheless, it is important that physicians understand the advantages and disadvantages of the different testing methodologies available to diagnose AATD. Owing to the autosomal inheritance of the genetic mutations responsible for AATD, genetic testing should be offered not only to patients at increased AATD risk (e.g. patients with chronic obstructive pulmonary disease), but also to relatives of those with an abnormal result. Genetic counseling may help patients and family members understand the possible outcomes of testing and the implications for the family. While stress/anxiety can arise from genetic diagnosis or confirmation of carrier status, there can be positive consequences to genetic testing, including improved lifestyle choices, directed medical care, and empowered family planning. As genetic testing technology grows and becomes more popular, testing without physician referral is becoming more prevalent, irrespective of the availability of genetic counseling. Therefore, the Alpha-1 Foundation offers genetic counseling, as well as other support and educational material, for patients with AATD, as well as their families and physicians, to help improve the understanding of potential benefits and consequences of genetic testing.

Improving Screening for Alpha-1 Antitrypsin Deficiency with Direct Testing in the Pulmonary Function Testing Laboratory.

Alpha-1 antitrypsin deficiency (AATD) is a common but highly underdiagnosed genetic disorder that may lead to chronic obstructive pulmonary disease (COPD), bronchiectasis, and liver disease. Early diagnosis is key to altering the course of disease as well as informing family members of potential risk. This randomized, prospective observational study compares the different testing modalities for AATD testing of at-risk patients initiated in the pulmonary function testing (PFT) laboratory. Providing a recommendation with a prescription for serologic testing, providing a finger-stick testing method (AlphaKit), and providing a buccal swab testing method (AlphaID) were compared to the community standard of referring the patient back to the PFT-ordering provider only. Results show that testing directly in the PFT laboratory has an odds ratio (OR) for completing testing of 35.14 (5.33 - 999.99), p-value of <0.0001, for buccal swab testing and an OR of 17.09 (2.58 - 729.99), p-value of 0.0002, for finger-stick testing compared to the community standard. Providing a prescription was no better than referral back to the PFT-ordering provider with an OR of 2.61(0.33 - 119.36), p-value of 0.6412. Resources needed to have testing performed by the Respiratory Therapy department were minimal with an average time of 1 to 5 minutes per patient tested. Causes of testing refusal were also identified. In conclusion, direct testing for AATD by respiratory therapists at the conclusion of PFT testing shows a significant improvement in rates of testing, especially with testing that utilizes buccal swab sample collection.

Alpha-1 antitrypsin deficiency is under-recognized in individuals with cirrhosis undergoing liver transplantation.

Under-recognition of alpha-1 antitrypsin deficiency (AATD) is well documented in AATD-lung disease but is rarely reported in patients with liver cirrhosis requiring liver transplantation. This report examines the frequency of newly diagnosed AATD based on pathologic examination of explanted livers following liver transplantation, trends in diagnosis over time, and prognostic correlates of under-recognition outcomes following liver transplantation. This study retrospectively reviewed 1473 pathology reports from adult patients (>18 years) undergoing liver transplantation at Cleveland Clinic between 2004 and 2017. Pathology reports of explanted livers exhibiting periodic acid-Schiff, diastase-resistant inclusion bodies (PAS+G) suggestive of AATD were included and medical records were reviewed regarding demographics, AATD genotype, alternative etiologies for cirrhosis, presence of emphysema, and survival outcomes. Kaplan-Meier estimates of survival outcomes were compared between patients diagnosed pre-liver transplantation and that newly diagnosed post-liver transplantation. Of 1473 explanted liver pathology reports examined, 117 (7.9%) showed PAS+G suggestive of AATD. The diagnosis of AATD in these 117 patients was established pre-liver transplantation in 36 (30.8%, group 1) and in 46 (39.3%) post-liver transplantation (group 2a). Testing for AATD was not undertaken in 35 (29.9%) of patients despite having PAS+G on explanted livers (group 2b). Post-liver transplantation survival analysis showed a trend (P = 0.098) towards enhanced survival in group 1 vs. group 2 at 10 years. This study shows that diagnosis of AATD is overlooked and frequently delayed in patients with cirrhosis undergoing liver transplantation. The observed trend towards higher survival in patients diagnosed with AATD pre-liver transplantation suggests the opportunity to enhance outcomes by earlier recognition of AATD.

RECURRENT PNEUMOTHORACES IN A YOUNG, NON-SMOKING WOMAN

SESSION TITLE: Medical Student/Resident Genetic and Developmental Disorders Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is known to affect the lungs and liver by causing the early development of emphysema and liver disease. We present a case of a non-smoker who developed emphysema in her early 40s. CASE PRESENTATION: 42 year old non-smoking female with a past medical history of multiple spontaneous pneumothoraces presented to her primary care physician (PCP) with complaints of right-sided chest pain and was found to have decreased breath sounds on the right side. She was sent for a 2-view chest x-ray and d-dimer. The posteroanterior and lateral chest x-ray showed a right side pneumothorax and she was instructed to go to the emergency department (ED) for chest tube placement. Examination in the ED revealed normal vital signs and no breath sounds on the right chest. D-dimer was unremarkable. She was seen by pulmonology who recommended further imaging. CT chest with contrast demonstrated small subpleural blebs along the medial aspect of the right lung apex, the suspected source of the spontaneous pneumothorax, and a lobulated lesion in the posterior segment of the right lobe of the liver. Given the liver findings, a MRI abdomen was done showing a mildly complex, septated cyst in the posterior right hepatic lobe measuring up to 4.4cm without enhancement consistent with a biliary cystadenoma. Serial chest x-rays were done to monitor the pneumothorax regression. The chest tube was removed three days later after absence of pneumothorax on water seal. She was discharged with a referral to thoracic surgery and had an office visit two weeks later for right-sided robotic-assisted thoracoscopic surgery with wedge excision of right apical bleb and mechanical pleurodesis. Pathology from the bleb tissue showed subpleural fibrosis and emphysematous change. AATD testing sent during her hospitalization was significant for alpha-1 antitrypsin (AAT) phenotype of SS, with an incidence of 0.1% and an AAT level of 105 mg/dL, the lower end of the normal range for her age. Pulmonary function testing did not reveal any obstructive findings. DISCUSSION: Our case demonstrates a rare presentation of the development emphysema in a non-smoker found to have the SS phenotype with low normal level of alpha-1 antitrypsin. This patient developed emphysema earlier than expected given the phenotype of AATD. Although our patient did not have classic liver manifestations, she was found to have a biliary cystadenoma. Patients with the SS phenotype are at risk to develop liver disease and early manifestations of emphysema; however they have a minimally increased risk of developing COPD, as the SS allele is related to a mild decrease in alpha-1 antitrypsin levels. CONCLUSIONS: Given the rarity of the SS phenotype, more research is needed in order to truly determine the incidence of developing lung and/or liver disease. It will be vital to help prognosticate and treat patients with alpha-1 antitrypsin deficiency. Reference #1: Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis. 2008;3:16. Reference #2: Parr DG, Stoel BC, Stolk J, Stockley RA. Pattern of Emphysema Distribution in alpha1-Antitrypsin Deficiency Influences Lung Function Impairment. Am J Respir Crit Care Med. 2004;170:1172-8. Reference #3: Kelly E, Greene CM, Carroll TP, McElvaney NG, O’Neill SJ. Alpha-1 antitrypsin deficiency. Respir Med. 2010;104:763-72. DISCLOSURES: No relevant relationships by Patrick Koo, source=Web Response No relevant relationships by Jetina Okereke, source=Web Response

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

IntroductionAlpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States.MethodsUsing data from the 2012–2017 PharMetrics Plus Administrative Claims Database and 2011–2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD.ResultsA cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant.DiscussionSignificant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

Focussing on The Patient: Future Prospects in Alpha 1 Management

With new patient-centric and scientific networks being created, Prof Chorostowska-Wynimko explored how these initiatives, such as the European Alpha-1 Research Collaboration (EARCO) and the European Reference Network-LUNG Alpha1 Antitrypsin Deficiency (ERN-LUNG AATD Core Network), will help to advance the management of alpha 1-antitrypsin deficiency (AATD) patients. EARCO plans to create a registry to gather information from centres across Europe and ERN-LUNG AATD plans to ensure highly specialised healthcare for AATD patients, including reliable AATD diagnostics across European laboratories. Explaining in more detail the plans for the new EARCO registry, Dr Barrecheguren argued the case for another AATD registry to gather large-scale data that clinical trials cannot provide. She provided an overview of the new EARCO prospective follow-up registry, to be launched next year, which will integrate existing national AATD registries, enhance long-term follow-up and quality of data, and facilitate research and quality improvements across healthcare systems. Discussing one of the first initiatives of the ERN-LUNG AATD Core Network, Dr Ferrarotti explored how to align AATD testing across Europe with the creation of European LAB-NET, an initiative first involving six European centres that will co-operate to collect, develop, verify, and make reference materials available for molecular and biochemical tests to correctly diagnose AATD and provide quality control in the laboratory diagnosis. Dr Greulich reported on a post-hoc pooled analysis from the RAPID-randomised controlled trial (RAPID-RCT) and the RAPID-open label extension (RAPID-OLE) study, which compared the safety and tolerability of adverse event (AE) rates for two different alpha-1 antitrypsin (AAT) dosing patterns, weekly infusions of 60 mg/kg AAT, and bi-weekly infusions of 120 mg/kg AAT. Results showed there were no significant differences for exposure-adjusted event rates (p=0.850), infusion-adjusted event rates (p=0.344), and serious treatment emergent AE (TEAE) (p=1.0); TEAE occurring in the first 24 and 48 hours were comparable for both groups. Prof Sandhaus presented the results of a telephone survey from the USA AlphaNet organisation of self-infusion practices in 555 patients with AATD. The survey found that 7.9% of respondents self-administered AAT and 92.1% who did not. Of the 44 patients who self-administered AAT, 95.4% reported being very satisfied and 4.6% were satisfied with their treatment.

A Blast From the Past: A Novel Complication of Bronchopulmonary Dysplasia

SESSION TITLE: Imaging SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a pulmonary complication of pre-mature birth. BPD occurs in pre-mature infants experiencing respiratory distress syndrome (RDS) treated with mechanical ventilation (MV), resulting in an inflammatory condition characterized by diverse radiographic findings and histologically by fibrosis and smooth muscle hypertrophy in the pulmonary tissues. In this case, we describe unique radiographic sequelae of BPD manifesting in adulthood. CASE PRESENTATION: A 43-year-old Caucasian female with history of premature birth, supported with MV, presented to her primary care physician for a retirement physical. She endorsed mild dyspnea on exertion, but denied chest pain, cough, or shortness of breath at rest. On physical exam, lungs were clear bilaterally with good air movement in all fields. Chest radiograph was normal except a 6mm nodular density noted in the right lower lobe. A non-contrast computed tomography scan of the chest was performed revealing a 2mm calcified granuloma. In addition, there were global, mild, and uniform paraseptal emphysematous changes throughout the pleural surfaces of the lungs and the fissures. Pulmonary work up including spirometry, carbon monoxide diffusing capacity, and testing for alpha-1 antitrypsin deficiency was normal. DISCUSSION: The long term sequelae of BPD is heterogeneous and depends on the initial degree of insult. MV of the premature infant in the setting of RDS is the predominant risk factor. Mild-moderate BPD may have no long-term effects with normal to only mildly obstructed spirometry; these patients typically go on to have normal chest radiographs by adolescence. More severe cases may demonstrate bronchial wall thickening, air trapping, lung cysts, linear interstitial opacities and emphysema. Case series suggest infants with BPD have more frequent airway hyperreactivity in adulthood and may have increased susceptibility to respiratory infections. Our patient presented with minimal symptoms, a history of MV during premature infancy and a novel, bilateral paraseptal emphysematous pattern without other underlying etiology suggesting BPD as the cause. Prevention in premature infants is key to management of this disease and centers on minimizing airway pressures during MV, antenatal glucocorticoids and exogenous surfactant therapy. CONCLUSIONS: The sequela of BPD infrequently persists into adulthood. We postulate that the diffuse and symmetric paraseptal emphysema in this adult patient with no other pulmonary risk factors is a previously undescribed manifestation of bronchopulmonary dysplasia as a premature infant. Reference #1: Howling SJ, Northway WH Jr, Hansell DM, Moss RB, Ward S, Müller NL. Pulmonary sequelae of bronchopulmonary dysplasia survivors: high-resolution CT findings. AJR Am J Roentgenol. 2000 May;174(5):1323-6. DISCLOSURE: The following authors have nothing to disclose: Tyler Church, Kyle Keinath, Whittney Warren, John Sherner No Product/Research Disclosure Information

Pathophysiology of Alpha-1 Antitrypsin Lung Disease.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease-antiprotease balance in the lungs, allowing proteases, specifically neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar structures. Destruction of these lung structures classically leads to an increased risk of developing emphysema and chronic obstructive pulmonary disease (COPD), especially in individuals with a smoking history. It is estimated that 3.4 million people worldwide have AATD. However, AATD is considered to be significantly underdiagnosed and underrecognized by clinicians. Contributing factors to the diagnostic delay of approximately 5.6years are: inadequate awareness by healthcare providers, failure to implement recommendations from the American Thoracic Society/European Respiratory Society, and the belief that AATD testing is not warranted. Diagnosis can be attained using qualitative or quantitative laboratory testing. The only FDA approved treatment for AATD is augmentation therapy, although classically symptoms have been treated similarly to those of COPD. Future goals of AATD treatment are to use gene therapy using vector systems to produce therapeutic levels of AAT in the lungs without causing a systemic inflammatory response.

Alpha1-antitrypsin Deficiency—Increased Knowledge and Diagnostic Testing after Viewing Short Instructional Video

ABSTRACTMany individuals with Alpha-1 Antitrypsin Deficiency (AATD) are unaware of their diagnosis. In the absence of an AATD diagnosis, irreversible damage continues, and incorrect care is provided. Research demonstrates low levels of knowledge about AATD among health care providers. To address this ongoing issue, a short educational video was developed for health care providers with the goal of increasing knowledge and testing for AATD. A five-question test on the video material was developed. Invitations to participate in the study were sent via email to providers at both public teaching hospitals and private practices across the country. Respondents completed three parts online: pre-test, video, and post-test. To confirm retention of knowledge gained, providers who completed all three were invited to take the same test 3–6 months later. There were 683 providers who responded, and 213 completed all three portions; 105 of those providers completed the 3–6-months of follow-up testing. The average pre-test score of the 213 providers was 54.6% (std. dev. = 26.2%). The average post-test score immediately following the video viewing was 74.7% (std. dev. = 27.7%). The average follow-up test score 3–6 months later was 63.2% (std. dev. = 22.0%). During the follow-up period, 11 providers reported testing for AATD for the first time. This short educational video demonstrated both immediate and sustained improvement in knowledge and an increase in testing for AATD. Short digital videos may provide an effective platform for the ongoing effort to identify individuals with AATD.

Detecting Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency is a widely underrecognized condition, with evidence of persisting long diagnostic delays and patients' frequent need to see multiple physicians before initial diagnosis. Reasons for underrecognition include inadequate understanding of alpha-1 antitrypsin deficiency by physicians and allied health care providers; failure to implement available, guideline-based practice recommendations; and the belief that effective therapy is unavailable. Multiple studies have described both the results of screening and targeted detection of individuals with alpha-1 antitrypsin deficiency, with both varying strategies employed to identify at-risk individuals and varying results of testing. Also, various strategies to enhance detection of affected individuals have been examined, including use of the electronic medical record to prompt testing and empowerment of allied health providers, especially respiratory therapists, to promote testing for alpha-1 antitrypsin deficiency. Such efforts are likely to enhance detection with the expected result that the harmful effects of delayed diagnosis can be mitigated.

The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult.

Background: The diagnosis and clinical management of adults with alpha-1 antitrypsin deficiency (AATD) have been the subject of ongoing debate, ever since the publication of the first American Thoracic Society guideline statement in 1989.1 In 2003, the "American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency" made a series of evidence-based recommendations, including a strong recommendation for broad-based diagnostic testing of all symptomatic adults with chronic obstructive pulmonary disease (COPD).2 Even so, AATD remains widely under-recognized. To update the 2003 systematic review and clinical guidance, the Alpha-1 Foundation sponsored a committee of experts to examine all relevant, recent literature in order to provide concise recommendations for the diagnosis and management of individuals with AATD. Purpose: To provide recommendations for: (1) the performance and interpretation of diagnostic testing for AATD, and (2) the current management of adults with AATD and its associated medical conditions. Methods: A systematic review addressing the most pressing questions asked by clinicians (clinician-centric) was performed to identify citations related to AATD that were published since the 2003 comprehensive review, specifically evaluating publications between January 2002 and December 2014. Important, more recent publications were solicited from the writing committee members as well. The combined comprehensive literature reviews of the 2003 document and this current review comprise the evidence upon which the committee's conclusions and recommendations are based. Results: Recommendations for the diagnosis and management of AATD were formulated by the committee. Conclusions: The major recommendations continue to endorse and reinforce the importance of testing for AATD in all adults with symptomatic fixed airflow obstruction, whether clinically labeled as COPD or asthma. Individuals with unexplained bronchiectasis or liver disease also should be tested. Family testing of first-degree relatives is currently the most efficient detection technique. In general, individuals with AATD and emphysema, bronchiectasis, and/or liver disease should be managed according to usual guidelines for these clinical conditions. In countries where intravenous augmentation therapy with purified pooled human plasma-derived alpha-1 antitrypsin is available, recent evidence now provides strong support for its use in appropriate individuals with lung disease due to AATD.

The Challenge of Detecting Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is relatively common but under-recognized. Indeed, fewer than 10% of the estimated 100,000 Americans with AATD have been diagnosed currently, with common reports of long delays between initial symptoms and first detection and the need to see multiple physicians before diagnosis. Because detection can confer benefits (e.g., identification of at-risk family members, lower smoking likelihood, consideration of augmentation therapy), targeted detection of AATD in at-risk groups such as all symptomatic adults with COPD has been endorsed.Two general approaches to detection have been studied: population-based screening (in which testing is performed in a group for whom no increased risk of having AATD exists) and targeted detection or case-finding (in which testing is confined to those with an attributable condition such as COPD or chronic liver disease). Studies to date have suggested that population-based screening is not cost-effective, whereas targeted detection of AATD has been advocated by official society guidelines.Efforts to enhance detection of AATD individuals have included various approaches, including educational campaigns, provision of free test kits, issuance of reminders with medical reports or within an electronic medical record, and empowering respiratory therapists to conduct testing for AATD in pulmonary function laboratories. Such programs have identified individuals with severe deficiency of alpha-1 antitrypsin in up to 12% of subjects, with considerable variation across series by testing criteria.Overall, the persistence of under-recognition of AATD underscores the need for continued efforts to optimize detection of this potentially debilitating genetic disease.