Pulmonary Subtypes Exhibit Differential Global Initiative for Chronic Obstructive Lung Disease Spirometry Stage Progression: The COPDGene® Study.

Rationale We classified individuals into pulmonary disease subtypes based on 2 underlying pathophysiologic disease axes (airway-predominant and emphysema-predominant) and their increased mortality risk. Our next objective was to determine whether some subcomponents of these subtypes are additionally associated with unique patterns of Global initiative for chronic Obstructive Lung Disease (GOLD) spirometry stage progression. Methods After accounting for intra-individual measurement variability in spirometry measures between baseline (Phase 1) and the 5-year follow up (Phase 2) of the COPD Genetic Epidemiology (COPDGene®) study, 4615 individuals had complete data that would characterize patterns of disease progression over 5 years (2033 non-Hispanic whites; 827 African Americans; 48% female). Individuals could express increased risk for mortality on one or both of the primary subtype axes (airway-predominant or emphysema-predominant) and thus they were further classified into 6 groups: high-risk airway-predominant disease only (APD-only), moderate-risk airway-predominant disease only (MR-APD-only), high-risk emphysema-predominant disease only (EPD-only), combined high-risk airway- and emphysema-predominant disease (combined APD-EPD), combined moderate-risk airway- and emphysema-predominant disease (combined MR-APD-EPD), and no high-risk pulmonary subtype. Outcomes were dichotomized for GOLD spirometry stage progression from Phase 1 to Phase 2. Logistic regression of the progression outcomes on the pulmonary subtypes were adjusted for age, sex, race, and change in smoking status. Results The MR-APD-only group was associated with conversion from GOLD 0 to preserved ratio-impaired spirometry (PRISm) status (odds ratio [OR] 11.3, 95% confidence interval [CI] 5.7-22.1) and GOLD 0 to GOLD 2-4 (OR 6.0, 95% CI 2.0-18.0). The EPD-only group was associated with conversion from GOLD 0 to GOLD 1 (OR 2.4, 95% CI 1.2-4.6), and GOLD 1 to GOLD 2-4 (OR 2.6, 95% CI 1.0-6.9). Conversion between PRISm and GOLD 2-4 (31%-38%) occurred in both the APD-only and the MR-APD-only groups. Conclusion Differential conversion occurs from GOLD 0 to PRISm and GOLD 0 to GOLD 1 based on groups expressing airway-predominant disease or emphysema-predominant disease independently or in combination. Airway-predominant and emphysema-predominant subtypes are highly important in determining patterns of early disease progression.

[1]  E. Regan,et al.  Subtypes of COPD Have Unique Distributions and Differential Risk of Mortality. , 2019, Chronic obstructive pulmonary diseases.

[2]  J. Curtis,et al.  Radiographic lung volumes predict progression to COPD in smokers with preserved spirometry in SPIROMICS , 2019, European Respiratory Journal.

[3]  Raúl San José Estépar,et al.  Imaging Advances in Chronic Obstructive Pulmonary Disease. Insights from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study , 2019, American journal of respiratory and critical care medicine.

[4]  Camille M. Moore,et al.  Airway wall thickening on CT: Relation to smoking status and severity of COPD. , 2019, Respiratory medicine.

[5]  E. Regan,et al.  Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study , 2018, American journal of respiratory and critical care medicine.

[6]  Jennifer G. Dy,et al.  Identification of Chronic Obstructive Pulmonary Disease Axes That Predict All-Cause Mortality: The COPDGene Study , 2018, American journal of epidemiology.

[7]  S. Zeng,et al.  Lung volume indices predict morbidity in smokers with preserved spirometry , 2018, Thorax.

[8]  G. A. Whitmore,et al.  Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction , 2017, American journal of respiratory and critical care medicine.

[9]  A. Menezes,et al.  The PLATINO study: description of the distribution, stability, and mortality according to the Global Initiative for Chronic Obstructive Lung Disease classification from 2007 to 2017 , 2017, International journal of chronic obstructive pulmonary disease.

[10]  Y. Oh,et al.  Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease , 2015, International journal of chronic obstructive pulmonary disease.

[11]  Meilan K. Han,et al.  Clinical and Radiologic Disease in Smokers With Normal Spirometry. , 2015, JAMA internal medicine.

[12]  M. Lebowitz,et al.  The "horse-racing effect" and predicting decline in forced expiratory volume in one second from screening spirometry. , 2015, The American review of respiratory disease.

[13]  N. Metzdorf,et al.  Does the 2013 GOLD classification improve the ability to predict lung function decline, exacerbations and mortality: a post-hoc analysis of the 4-year UPLIFT trial , 2014, BMC Pulmonary Medicine.

[14]  Edwin K Silverman,et al.  Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene , 2014, Respiratory Research.

[15]  L. Edwards,et al.  Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort , 2013, European Respiratory Journal.

[16]  E. Regan,et al.  Automated Telecommunication to Obtain Longitudinal Follow-up in a Multicenter Cross-sectional COPD Study , 2012, COPD.

[17]  L. Edwards,et al.  Changes in forced expiratory volume in 1 second over time in COPD. , 2011, The New England journal of medicine.

[18]  E. Regan,et al.  Genetic Epidemiology of COPD (COPDGene) Study Design , 2011, COPD.

[19]  Yasutaka Nakano,et al.  Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. , 2008, American journal of respiratory and critical care medicine.

[20]  D. Lynch,et al.  Phenotypes of Chronic Obstructive Pulmonary Disease , 2007, COPD.

[21]  A. Lindberg,et al.  Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking Report from the Obstructive Lung Disease in Northern Sweden Studies. , 2006, Respiratory medicine.

[22]  K Larsson,et al.  Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies. , 2003, Respiratory medicine.

[23]  John E Connett,et al.  Smoking and lung function of Lung Health Study participants after 11 years. , 2002, American journal of respiratory and critical care medicine.

[24]  J. Vestbo,et al.  Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? , 2002, American journal of respiratory and critical care medicine.

[25]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[26]  ATS statement: guidelines for the six-minute walk test. , 2002, American journal of respiratory and critical care medicine.