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      International Journal of COPD (submit here)

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

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          Abstract

          Introduction

          Alpha-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.

          Methods

          Using 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.

          Results

          A 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.

          Discussion

          Significant 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.

          Most cited references44

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          Comorbidity Measures for Use with Administrative Data

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            Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease.

            Patients with chronic obstructive pulmonary disease (COPD) are afflicted by comorbidities. Few studies have prospectively evaluated COPD comorbidities and mortality risk. To prospectively evaluate COPD comorbidities and mortality risk. We followed 1,664 patients with COPD in five centers for a median of 51 months. Systematically, 79 comorbidities were recorded. We calculated mortality risk using Cox proportional hazard, and developed a graphic representation of the prevalence and strength of association to mortality in the form of a "comorbidome". A COPD comorbidity index (COPD specific comorbidity test [COTE]) was constructed based on the comorbidities that increase mortality risk using a multivariate analysis. We tested the COTE index as predictor of mortality and explored whether the COTE index added predictive information when used with the validated BODE index. Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors. Of those, 12 predicted mortality and were integrated into the COTE index. Increases in the COTE index were associated with an increased risk of death from COPD-related (hazard ratio [HR], 1.13; 95% confidence interval, 1.08-1.18; P < 0.001) and non-COPD-related causes (HR, 1.18; 95% confidence interval, 1.15-1.21; P < 0.001). Further, increases in the BODE and COTE were independently associated with increased risk of death. A COTE score of greater than or equal to 4 points increased by 2.2-fold the risk of death (HR, 2.26-2.68; P < 0.001) in all BODE quartile. Comorbidities are frequent in COPD and 12 of them negatively influence survival. A simple disease-specific comorbidities index (COTE) helps assess mortality risk in patients with COPD.
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              Genetically distinct subsets within ANCA-associated vasculitis.

              Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding α(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P=6.2×10(-89), P=5.6×10(-12,) and P=2.6×10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P=2.1×10(-8)). This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.).
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                copd
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                05 October 2020
                2020
                : 15
                : 2389-2397
                Affiliations
                [1 ]Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health , Denver, CO, USA
                [2 ]Department of Pulmonary and Critical Care Medicine, Medical University of South Carolina , Charleston, SC, USA
                [3 ]Global Health Economics & Outcomes Research, Grifols Shared Services of North America, Inc , Research Triangle Park, NC, USA
                [4 ]Department of Public Health Sciences, College of Health and Human Services, University of North Carolina at Charlotte , Charlotte, NC, USA
                [5 ]Department of Kinesiology, College of Health and Human Services, University of North Carolina at Charlotte , Charlotte, NC, USA
                Author notes
                Correspondence: Glenda Stone Global Health Economics & Outcomes Research, Grifols Shared Services of North America, Inc , 79 T.W. Alexander Dr, 4101 Research Commons, Research Triangle Park, NC27709, USATel +1 (919)316-6415 Email glenda.stone@grifols.com
                Author information
                http://orcid.org/0000-0002-7937-2485
                http://orcid.org/0000-0002-8109-8067
                http://orcid.org/0000-0003-2155-2296
                Article
                263297
                10.2147/COPD.S263297
                7547287
                33116454
                d5ede3ae-c7d5-4a9b-9841-2fcbc3680614
                © 2020 Sandhaus et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 09 June 2020
                : 07 September 2020
                Page count
                Figures: 1, Tables: 7, References: 46, Pages: 9
                Categories
                Original Research

                Respiratory medicine
                chronic obstructive pulmonary disease,alpha-1 antitrypsin deficiency,comorbid,genetic

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