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      Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database

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          Abstract

          Background

          Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) being two large subgroups. Claims database studies provide insights into the real-world treatment patterns and outcomes among these patients. However, claims data do not provide sufficient detail to assign the clinical subtype of PH required for identifying these patients.

          Methods

          A panel of PH clinical experts and researchers was convened to discuss methodologies to identify patients with Group 3 PH associated with COPD or ILD in retrospective claims databases. To inform the discussion, a literature review was conducted to identify claims-based studies of Group 3 PH associated with COPD or ILD published from 2010 through June 2020.

          Results

          Targeted title and abstract review identified 11 claims-based studies and two conference abstracts (eight based in the United States [US] and five conducted outside the US) that met search criteria. Based on insights from the panel and literature review, the following components were detailed across studies in the identification of Group 3 PH associated with COPD and ILD: (a) COPD or ILD identification, (b) PH identification, (c) defining the sequence between COPD/ILD and PH, and (d) other PH Group and Group 3 PH exclusions.

          Conclusion

          This article provides recommended approaches and considerations for identifying and studying patients with Group 3 PH associated with COPD or ILD using administrative claims data that provide the foundation for future validation studies.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00408-022-00521-6.

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          Most cited references28

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          Haemodynamic definitions and updated clinical classification of pulmonary hypertension

          Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management. Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup “pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers”, due to the specific prognostic and management of these patients, and a subgroup “PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement”, due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH.
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            Pulmonary hypertension in chronic lung disease and hypoxia

            Pulmonary hypertension (PH) frequently complicates the course of patients with various forms of chronic lung disease (CLD). CLD-associated PH (CLD-PH) is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. The aetiology of CLD-PH is complex and multifactorial, with differences in the pathogenic sequelae between the diverse forms of CLD. Haemodynamic evaluation of PH severity should be contextualised within the extent of the underlying lung disease, which is best gauged through a combination of physiological and imaging assessment. Who, when, if and how to screen for PH will be addressed in this article, as will the current state of knowledge with regard to the role of treatment with pulmonary vasoactive agents. Although such therapy cannot be endorsed given the current state of findings, future studies in this area are strongly encouraged.
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              Pulmonary hypertension in chronic lung diseases.

              Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.
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                Author and article information

                Contributors
                HERESIG@ccf.org
                bonnie.dean@xcenda.com
                hcastillo@unither.com
                Henry.Lee@xcenda.com
                pclassi@unither.com
                Dana.Stafkey-Mailey@xcenda.com
                akantorovich@unither.com
                kmorland@unither.com
                msketch@unither.com
                bwu@unither.com
                Christopher.King@inova.org
                Journal
                Lung
                Lung
                Lung
                Springer US (New York )
                0341-2040
                1432-1750
                29 March 2022
                29 March 2022
                2022
                : 200
                : 2
                : 187-203
                Affiliations
                [1 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Department of Pulmonary and Critical Care Medicine, Respiratory Institute, , Cleveland Clinic, ; Cleveland, OH US
                [2 ]Xcenda, LLC, 5025 Plano Pkwy, Carrollton, TX 75010 US
                [3 ]GRID grid.421987.1, ISNI 0000 0004 0411 3117, United Therapeutics Corporation, ; Research Triangle Park, Durham, NC US
                [4 ]GRID grid.417781.c, ISNI 0000 0000 9825 3727, Advanced Lung Disease and Lung Transplant Clinic, , Inova Fairfax Hospital, ; Falls Church, VA US
                Author information
                http://orcid.org/0000-0002-2062-3200
                Article
                521
                10.1007/s00408-022-00521-6
                9038884
                35348836
                398f8088-8bed-45cc-bb6c-faeb025f18df
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 November 2021
                : 14 February 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100007150, United Therapeutics Corporation;
                Categories
                Pulmonary Hypertension
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2022

                Respiratory medicine
                pulmonary hypertension,real-world evidence,retrospective claims studies,algorithm

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