Chronic Obstructive Pulmonary Disease Foundation Research Articles

Development and validation of a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality. In a retrospective study, we used probabilistic graphs to analyse clinical cross-sectional data (COPDGene cohort), including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data. COPDGene recruited current and former smokers, aged 45-80 years with >10 pack-years smoking history, from across the USA (Phase 1, 11/2007-4/2011) and invited them for a follow-up visit (Phase 2, 7/2013-7/2017). ECLIPSE cohort recruited current and former smokers (COPD patients and controls from USA and Europe), aged 45-80 with smoking history >10 pack-years (12/2005-11/2007). We applied graphical models on multi-modal data COPDGene Phase 1 participants to identify factors directly affecting all-cause and COPD-specific mortality (primary outcomes); and on Phase 2 follow-up cohort to identify additional molecular and social factors affecting mortality. We used penalized Cox regression with features selected by the causal graph to build VAPORED, a mortality risk prediction model. VAPORED was compared to existing scores (BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; ADO: age, dyspnoea, airflow obstruction) on the ability to rank individuals by mortality risk, using four evaluation metrics (concordance, concordance probability estimate (CPE), cumulative/dynamic (C/D) area under the receiver operating characteristic curve (AUC), and integrated C/D AUC). The results were validated in ECLIPSE. Graphical models, applied on the COPDGene Phase 1 samples (n=8610), identified 11 and 7 variables directly linked to all-cause and COPD-specific mortality, respectively. Although many appear in both models, non-lung comorbidities appear only in the all-cause model, while forced vital capacity (FVC %predicted) appears in COPD-specific mortality model only. Additionally, the graph model of Phase 2 data (n=3182) identified internet access, CD4 T cells and platelets to be linked to lower mortality risk. Furthermore, using the 7 variables linked to COPD-specific mortality (forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) ration, FVC %predicted, age, history of pneumonia, oxygen saturation, 6-min walk distance, dyspnoea) we developed VAPORED mortality risk score, which we validated on the ECLIPSE cohort (3-yr all-cause mortality data, n=2312). VAPORED performed significantly better than ADO, BODE, and updated BODE indices in predicting all-cause mortality in ECLIPSE in terms of concordance (VAPORED [0.719] vs ADO [0.693; FDR p-value 0.014], BODE [0.695; FDR p-value 0.020], and updated BODE [0.694; FDR p-value 0.021]); CPE (VAPORED [0.714] vs ADO [0.673; FDR p-value <0.0001], BODE [0.662; FDR p-value <0.0001], and updated BODE [0.646; FDR p-value <0.0001]); 3-year C/D AUC (VAPORED [0.728] vs ADO [0.702; FDR p-value 0.017], BODE [0.704; FDR p-value 0.021], and updated BODE [0.703; FDR p-value 0.024]); integrated C/D AUC (VAPORED [0.723] vs ADO [0.698; FDR p-value 0.047], BODE [0.695; FDR p-value 0.024], and updated BODE [0.690; FDR p-value 0.021]). Finally, we developed a web tool to help clinicians calculate VAPORED mortality risk and compare it to ADO and BODE predictions. Our work is an important step towards improving our identification of high-risk patients and generating hypotheses of potential biological mechanisms and social factors driving mortality in patients with COPD at the population level. The main limitation of our study is the fact that the analysed datasets consist of older people with extensive smoking history and limited racial diversity. Thus, the results are relevant to high-risk individuals or those diagnosed with COPD and the VAPORED score is validated for them. This research was supported by NIH [NHLBI, NLM]. The COPDGene study is supported by the COPD Foundation, through grants from AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.

Investigation of the Impact of Wellinks on the Quality of Life and Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease: Interventional Research Study.

Wellinks is a remote disease management solution that provides novel chronic obstructive pulmonary disease (COPD) care delivery. This study evaluated the satisfaction, engagement, and clinical outcomes of Wellinks participants. This study also investigated the cadence of health coaching for patients with COPD. A 24-week interventional study was conducted by Wellinks and the COPD Foundation in 2022. Adults with COPD were recruited by the COPD Foundation in the United States and determined to be eligible if they had phone and internet access, owned a smartphone, and were not currently participating in pulmonary rehabilitation. All study participants provided written informed consent. The Wellinks solution included remote health coaching, pulmonary rehabilitation, and group education; participants were provided the Wellinks app and smart spirometry and pulse oximetry devices. Participants were offered 6 coaching sessions in the first 12 weeks. For the second 12-week period, participants either reduced frequency or discontinued coaching; all other components of the Wellinks solution remained unchanged. The COPD Self-Efficacy Scale, Modified Medical Research Council dyspnea scale, pulmonary function, pulse oximetry, and patient-reported healthcare resource utilization were the clinical outcome measures. Nonclinical outcomes included engagement and satisfaction with Wellinks and net promoter score. In total, 141 adults consented and completed Wellinks onboarding; 84.4% (n=119) of whom remained engaged throughout the 24-week study. Participants had a mean age of 70 (SD 7.8; range 48-88) years, and 55.7% (n=78) were female. Most participants (n=119, 84.4%) completed all 6 coaching sessions during the first 12-week period. Compliance with spirometer and pulse oximeter use was 82.3% and 89.4%, respectively, at week 1 but waned over the study period to 8.5% and 9.2%, respectively, at the end of the study. Participants indicated a high degree of satisfaction with Wellinks, with 95.5% (n=85) and 91% (n=81) of participants indicating that they agreed or strongly agreed that the educational content and health coaching, respectively, were valuable. At the end of the study, the net promoter score was +64 and +55 in the coaching continuation and discontinuation arms, respectively. A significant improvement from baseline to end of the study was observed in the COPD Self-Efficacy Scale total score (P<.001) and domain scores (P<.001 for each domain). In total, 35.1% (n=27) of participants improved by at least 1 category of change on the 5-point Modified Medical Research Council dyspnea scale from baseline to week 24. This study confirmed the feasibility of using a remote model of care delivery to support people living with COPD. The insights gained in this study have allowed for further refinement and personalization of the Wellinks care model. Findings related to the combined use of technology and personal care delivery should be considered by others developing remote disease management tools. ClinicalTrials.gov NCT05259280; https://clinicaltrials.gov/ct2/show/NCT05259280.

Unique and shared systemic biomarkers for emphysema in Alpha-1 Antitrypsin deficiency and chronic obstructive pulmonary disease.

SummaryBackgroundAlpha-1 Antitrypsin (AAT) deficiency (AATD), the most common genetic cause of emphysema presents with unexplained phenotypic heterogeneity in affected subjects. Our objectives to identify unique and shared AATD plasma biomarkers with chronic obstructive pulmonary disease (COPD) may explain AATD phenotypic heterogeneity.MethodsThe plasma or serum of 5,924 subjects from four AATD and COPD cohorts were analyzed on SomaScan V4.0 platform. Using multivariable linear regression, inverse variance random-effects meta-analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression we tested the association between 4,720 individual proteins or combined in a protein score with emphysema measured by 15th percentile lung density (PD15) or diffusion capacity (DLCO) in distinct AATD genotypes (Pi*ZZ, Pi*SZ, Pi*MZ) and non-AATD, PiMM COPD subjects. AAT SOMAmer accuracy for identifying AATD was tested using receiver operating characteristic curve analysis.FindingsIn PiZZ AATD subjects, 2 unique proteins were associated with PD15 and 98 proteins with DLCO. Of those, 68 were also associated with DLCO in COPD also and enriched for three cellular component pathways: insulin-like growth factor, lipid droplet, and myosin complex. PiMZ AATD subjects shared similar proteins associated with DLCO as COPD subjects. Our emphysema protein score included 262 SOMAmers and predicted emphysema in AATD and COPD subjects. SOMAmer AAT level <7.99 relative fluorescence unit (RFU) had 100% sensitivity and specificity for identifying Pi*ZZ, but it was lower for other AATD genotypes.InterpretationUsing SomaScan, we identified unique and shared plasma biomarkers between AATD and COPD subjects and generated a protein score that strongly associates with emphysema in COPD and AATD. Furthermore, we discovered unique biomarkers associated with DLCO and emphysema in PiZZ AATD.FundingThis work was supported by a grant from the Alpha-1 Foundation to RPB. COPDGene was supported by Award U01 HL089897 and U01 HL089856 from the National Heart, Lung, and Blood Institute. Proteomics for COPDGene was supported by NIH 1R01HL137995. GRADS was supported by Award U01HL112707, U01 HL112695 from the National Heart, Lung, and Blood Institute, and UL1TRR002535 to CCTSI; QUANTUM-1 was supported by the National Heart Lung and Blood Institute, the Office of Rare Diseases through the Rare Lung Disease Clinical Research Network (1 U54 RR019498-01, Trapnell PI), and the Alpha-1 Foundation. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.

Knowledge and Attitudes Concerning Herpes Zoster among People with COPD: An Interventional Survey Study.

Herpes zoster (HZ) is common in older adults with conditions such as chronic obstructive pulmonary disease (COPD). Effective prevention is available through vaccination, but HZ vaccine uptake remains incomplete. Using an online survey of people with self-reported COPD, ShiPPS assessed HZ risk awareness, HZ vaccine use and barriers, and the impact of an HZ educational video on vaccine intent. USA members of the COPD Foundation’s Patient-Powered Research Network aged >50 years were surveyed in fall 2020. The responses were analyzed using descriptive and comparative statistics. Of the 735 respondents (59.6% female, mean age 68.5 years), 192 (26.1%) reported previous HZ, of whom 49 (25.5%) reported increased COPD symptoms during HZ episodes. Most participants (94.0%) knew of HZ vaccines, but only 33.1% reported receiving the Advisory Committee on Immunization Practices-preferred recombinant HZ vaccination. The recall of receiving HZ vaccine recommendations differed by the site attended: 68.8% primary care, 26.6% pulmonology offices. Most (74.7%) were unaware that COPD increases HZ risk. Among unvaccinated participants, interest in getting the HZ vaccine increased from 32.0% to 73.5% after watching the video. These results highlight the need for people with COPD to receive further HZ education, such as the five-minute video, and HZ vaccine recommendations from healthcare professionals.

Endurance Time During Constant Work Rate Cycle Ergometry in COPD: Development of an Integrated Database From Interventional Studies.

The COPD Biomarkers Qualification Consortium (CBQC) was formed under COPD Foundation management, with the goal of qualifying biomarkers and clinical outcome assessments through established regulatory processes for chronic obstructive pulmonary disease (COPD). Within CBQC, a working group evaluated opportunities for qualification of an exercise endurance measure. In a recent publication (Chronic Obstr Pulm Dis. 2022; 9[2]:252-265), we described a conceptual framework establishing exercise endurance's direct relationship to an individual with COPD's experience of physical functioning in daily life, and that increase in exercise endurance is a patient-centered, meaningful treatment benefit. We further proposed endurance time during constant work rate cycle ergometery (CWRCE) as a useful efficacy endpoint in clinical therapeutic intervention trials. In this current publication, we describe the process of assembling an integrated database of endurance time responses to interventions in COPD. We sought participant-level data from published studies incorporating CWRCE as an outcome measure. A literature search screened 2993 publications and identified 553 studies for assessment. Two interventions had sufficient data across studies to warrant data extraction: bronchodilators and rehabilitative exercise training. Investigators were contacted and requested to provide participant-by-participant data from their published studies. The final dataset included data from 8 bronchodilator studies (2166) participants and 15 exercise training studies (3488 participants). The database includes 71 variables per participant, comprising demographic, pulmonary function, and detailed physiologic response data. This paper provides a detailed description of the analysis population, while analysis supporting the validation/qualification process and addressing other scientific questions will be described in subsequent publications.

Self-reported COPD Medication Use and Adherence in the COPD Foundation Patient- Powered Registry Network.

Pharmacotherapy is one cornerstone of Chronic Obstructive Pulmonary Disease (COPD) management. Published U.S. data seldom includes patient-reported COPD medication use and adherence. We add this patient perspective to the commonly reported administrative prescribing and fill data. This survey study used inhaler and nebulizer pictures and lists of oral COPD medications to query members of the COPD Foundation Patient-Powered Research Network, a national self-reported online registry. Medications used, adherence, inhaler education, cost concerns, previous exacerbations, and COPD Assessment Test scores were assessed and summarized using simple descriptive statistics and hazard ratios controlling for age, gender, and disease burden. Respondents mean age was 68 years, 60% were women, >69% with the COPD Assessment Test (CAT) scores >15, and >50% reported 2 or more exacerbations in the past 12 months. Overall, >98% used one or more inhaled COPD medications, 7.6% rescue inhaler only, 17.8% used long-acting bronchodilator only therapy (11.1% dual), and 72.8% using corticosteroid therapies, including 53% triple therapy. Nebulizers were used by 59.4% and 34.8% use oral COPD medications. Reported adherence rates were high (80.1%), but 41% reported trouble paying for medications, with 20.1% reported missing medications due to cost. In this population, COPD had a high burden with >50% of respondents using triple therapy, and one in eight maintenance oral corticosteroids. Self-reported adherence was high, but with significant cost concerns reported resulting in missed medications.

Deep neural network analyses of spirometry for structural phenotyping of chronic obstructive pulmonary disease.

BACKGROUNDCurrently recommended traditional spirometry outputs do not reflect the relative contributions of emphysema and airway disease to airflow obstruction. We hypothesized that machine-learning algorithms can be trained on spirometry data to identify these structural phenotypes.METHODSParticipants enrolled in a large multicenter study (COPDGene) were included. The data points from expiratory flow-volume curves were trained using a deep-learning model to predict structural phenotypes of chronic obstructive pulmonary disease (COPD) on CT, and results were compared with traditional spirometry metrics and an optimized random forest classifier. Area under the receiver operating characteristic curve (AUC) and weighted F-score were used to measure the discriminative accuracy of a fully convolutional neural network, random forest, and traditional spirometry metrics to phenotype CT as normal, emphysema-predominant (>5% emphysema), airway-predominant (Pi10 > median), and mixed phenotypes. Similar comparisons were made for the detection of functional small airway disease phenotype (>20% on parametric response mapping).RESULTSAmong 8980 individuals, the neural network was more accurate in discriminating predominant emphysema/airway phenotypes (AUC 0.80, 95%CI 0.79-0.81) compared with traditional measures of spirometry, FEV1/FVC (AUC 0.71, 95%CI 0.69-0.71), FEV1% predicted (AUC 0.70, 95%CI 0.68-0.71), and random forest classifier (AUC 0.78, 95%CI 0.77-0.79). The neural network was also more accurate in discriminating predominant emphysema/small airway phenotypes (AUC 0.91, 95%CI 0.90-0.92) compared with FEV1/FVC (AUC 0.80, 95%CI 0.78-0.82), FEV1% predicted (AUC 0.83, 95%CI 0.80-0.84), and with comparable accuracy with random forest classifier (AUC 0.90, 95%CI 0.88-0.91).CONCLUSIONSStructural phenotypes of COPD can be identified from spirometry using deep-learning and machine-learning approaches, demonstrating their potential to identify individuals for targeted therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT00608764.FUNDINGThis study was supported by NIH grants K23 HL133438 and R21EB027891 and an American Thoracic Foundation 2018 Unrestricted Research Grant. The COPDGene study is supported by NIH grants NHLBI U01 HL089897 and U01 HL089856. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprising AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sunovion.

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort.

BACKGROUNDMitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown.METHODSCell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters - including FEV1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure - were examined.RESULTSU-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.CONCLUSIONU-mtDNA levels may help to identify distinct clinical phenotypes and underlying pathobiological differences in males versus females with COPD.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov ( NCT01969344).FUNDINGUS NIH, National Heart, Lung and Blood Institute, supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics, Boehringer-Ingelheim Pharmaceuticals Inc., Chiesi Farmaceutici S.p.A., Forest Research Institute Inc., GlaxoSmithKline, Grifols Therapeutics Inc., Ikaria Inc., Novartis Pharmaceuticals Corporation, Nycomed GmbH, ProterixBio, Regeneron Pharmaceuticals Inc., Sanofi, Sunovion, Takeda Pharmaceutical Company, and Theravance Biopharma and Mylan.

Systemic Biomarkers of Lung Function and FEV &lt;sub&gt;1&lt;/sub&gt; Decline Across Multiple Cohorts

Background: Chronic obstructive pulmonary disease (COPD) is a common, complex respiratory disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. We tested whether aptamer-based protein profiling could identify markers and pathways related to impaired pulmonary function and lung function decline in multiple studies. Methods: We studied 3,827 non-Hispanic/European White participants across six cohort studies with both aptamer-based proteomic and spirometry data. In linear regression models we examined protein associations with baseline FEV1 and FEV1/FVC. In linear mixed effects models we investigated the associations of baseline protein levels with rate of FEV1 decline (mL/year) in 2,636 participants with up to 7 years of follow-up spirometry. Findings: We identified 198 proteins associated with FEV1, twelve of the proteins were also significantly associated with FEV1/FVC, including retinal binding protein 4 FEV1 : β=0·0307, Q= 2·18×10-4; FEV1/FVC: β=0·008, Q =4·0×10-3 ) and bactericidal permeability-increasing protein (FEV1 : β=-0·0280, Q =6·80×10-3; FEV1/FVC: β=0·0050, Q =0·04). We further identified 15 proteins associated with the rate of FEV1 decline ( Q <0·05), including coagulation-related tissue factor and basement membrane-associated nidogen (β=-5·21 mL/year, Q =0·016 and β=-4·90 mL/year, Q =0·020, respectively). Pathways and processes associated with lung function included extracellular matrix organization, coagulation, and angiogenesis. Interpretation: In this study, we identified novel biomarkers and pathways associated with lung function and lung function decline. Additionally, several protein findings support previously reported genetic signals, highlighting the plausibility of certain biologic pathways. These novel proteins might represent disease markers of at-risk individuals and/or novel molecular targets with the potential to modify COPD clinical course. Funding Statement: COPDGene Phase 3: Grant Support and Disclaimer: The project described was supported by Award Number U01 HL089897 and Award Number U01 HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health; COPD Foundation Funding: The COPDGene® project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, and Sunovion; FHS: This work was supported by R01HL132320 and R01HL133870. The Framingham Heart Study (FHS) acknowledges the support of contracts NO1-HC25195, HHSN268201500001I and 75N92019D00031. KORA: The KORA study was initiated and financed by the Helmholtz Zentrum Munchen – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. This work was also supported by the Comprehensive Pneumology Center Munich (CPC-M) as member of the German Center for Lung Research (DZL). LSC: This work was supported by funding from the State of New Mexico. MESA-TOPMed/MESA Lung Support: Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung and Blood Institute (NHLBI), with core services provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I) and the TOPMed Data Coordinating Center (3R01HL120393-2S1; contract HHSN268201800001I). Proteomics data for the MultiEthnic Study of Atherosclerosis MESA; phs001416) were generated through the TOPMed MESA Multi-Omics project (HHSN2682015000031/HHSN26800004). The MESA Lung Study is supported by R01-HL077612 and R01-HL093081. SPIROMICS. This work was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C), grants from the NIH/NHLBI (U01 HL137880 and U24 HL141762), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; BoehringerIngelheim Pharmaceuticals, Inc.; Chiesi Farmaceutici S.p.A.; Forest Research Institute, Inc.; GlaxoSmithKline; Grifols Therapeutics, Inc.; Ikaria, Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals, Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. Declaration of Interests: None. Ethics Approval Statement: The respective local Institutional Review Boards approved all study protocols and informed consent was obtained from all participants.

The Burden of Cough and Phlegm in People With COPD: A COPD Patient-Powered Research Network Study.

Cough and phlegm are common symptoms of chronic obstructive pulmonary disease (COPD) and may significantly affect quality of life. This study assessed the burden of cough and phlegm on clinical outcomes and quality of life among people with a self-reported physician diagnosis of COPD. Patient-reported data from the COPD Foundation's Patient-Powered Research Network (COPD PPRN) were utilized. Cough and phlegm severity and frequency were assessed by responses to questions on the COPD Assessment Test (CAT) and categorized into none/low, moderate and severe. Quality of life domains were evaluated using the Patient-Reported Outcome Measurement Information System (PROMIS-29). Associations between cough and phlegm levels and PROMIS-29 domains were examined using multivariate analysis of variance (MANOVA). The 5286 participants were average age 64.4 years (SD=11.4), 87.9% white, 60.4% female, 51.2% married, and 42.2% with caregivers. Approximately three-fourths of the participants had moderate or severe cough or phlegm levels. Respondents with moderate and high cough or phlegm had significantly worse dyspnea (p<0.0001), more exacerbations in the previous one year (p<0.0001), worse physical and social functioning, and more symptoms of anxiety and depression on PROMIS-29 compared to those with no/low cough and phlegm. In this group of people with COPD, higher levels of cough and phlegm are associated with worse clinical and quality of life outcomes.

PULMONARY REHABILITATION AWARENESS AND UPTAKE IN AN ENGAGED COHORT OF PEOPLE WITH COPD

PULMONARY REHABILITATION AWARENESS AND UPTAKE IN AN ENGAGED COHORT OF PEOPLE WITH COPD

Association Between Health Literacy, Electronic Health Literacy, Disease-Specific Knowledge, and Health-Related Quality of Life Among Adults With Chronic Obstructive Pulmonary Disease: Cross-Sectional Study.

BackgroundDespite the relatively high prevalence of low health literacy among individuals living with chronic obstructive pulmonary disease (COPD), limited empirical attention has been paid to the cognitive and health literacy–related skills that can uniquely influence patients’ health-related quality of life (HRQoL) outcomes.ObjectiveThe aim of this study was to examine how health literacy, electronic health (eHealth) literacy, and COPD knowledge are associated with both generic and lung-specific HRQoL in people living with COPD.MethodsAdults from the COPD Foundation’s National Research Registry (n=174) completed a cross-sectional Web-based survey that assessed sociodemographic characteristics, comorbidity status, COPD knowledge, health literacy, eHealth literacy, and generic/lung-specific HRQoL. Hierarchical linear regression models were tested to examine the roles of health literacy and eHealth literacy on generic (model 1) and lung-specific (model 2) HRQoL, after accounting for socioeconomic and comorbidity covariates. Spearman rank correlations examined associations between ordinal HRQoL items and statistically significant hierarchical predictor variables.ResultsAfter adjusting for confounding factors, health literacy, eHealth literacy, and COPD knowledge accounted for an additional 9% of variance in generic HRQoL (total adjusted R2=21%; F9,164=6.09, P<.001). Health literacy (b=.08, SE 0.02, 95% CI 0.04-0.12) was the only predictor positively associated with generic HRQoL (P<.001). Adding health literacy, eHealth literacy, and COPD knowledge as predictors explained an additional 7.40% of variance in lung-specific HRQoL (total adjusted R2=26.4%; F8,161=8.59, P<.001). Following adjustment for covariates, both health literacy (b=2.63, SE 0.84, 95% CI 0.96-4.29, P<.001) and eHealth literacy (b=1.41, SE 0.67, 95% CI 0.09-2.73, P<.001) were positively associated with lung-specific HRQoL. Health literacy was positively associated with most lung-specific HRQoL indicators (ie, cough frequency, chest tightness, activity limitation at home, confidence leaving home, sleep quality, and energy level), whereas eHealth literacy was positively associated with 5 of 8 (60%) lung-specific HRQoL indicators. Upon controlling for confounders, COPD knowledge (b=−.56, SE 0.29, 95% CI −1.22 to −0.004, P<.05) was inversely associated with lung-specific HRQoL.ConclusionsHealth literacy, but not eHealth literacy, was positively associated with generic HRQoL. However, both health literacy and eHealth literacy were positively associated with lung-specific HRQoL, with higher COPD knowledge indicative of lower lung-specific HRQoL. These results confirm the importance of considering health and eHealth literacy levels when designing patient education programs for people living with COPD. Future research should explore the impact of delivering interventions aimed at improving eHealth and health literacy among patients with COPD, particularly when disease self-management goals are to enhance HRQoL.

Patient-Reported Consequences of Community-Acquired Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.

Community acquired pneumonia (CAP) carries high morbidity, mortality, and economic burden, which is even higher in adults diagnosed with chronic obstructive pulmonary disease (COPD). While several studies have assessed the clinical burden and mortality risk of CAP and COPD, very few studies focus on CAP burden from a COPD patient perspective. Individuals recently diagnosed with CAP and with pre-existing COPD were recruited through the COPD Foundation. The CAP Burden of Illness Questionnaire (CAP-BIQ), a content validated questionnaire assessing CAP symptomatology, duration of symptoms and CAP impact on work, activities and family, was administered at baseline and at 30-days follow-up. Of the 490 participants recruited, 481 had data sufficient for analysis. The prevalence of respiratory-related symptoms was very high (>90%) at the time of diagnosis with other generalized symptoms such as fatigue, trouble sleeping, headaches and confusion present in more than 60% of participants. Mean duration of symptoms varied from approximately 2 weeks for headaches and fever to more than a month for fatigue, wheezing, dyspnea, and cough. Employed participants missed an average of 21 days of work and those not employed missed 36 days of usual activities. Over 84% required help from family, friends or care givers. CAP is a serious and burdensome condition for people with COPD, a condition that can impair activities for weeks, frequently requires care from family or friends, and includes lingering symptoms. The patient-reported impact of CAP reported in this study underscores the need for prevention strategies in this population.

Introducing the New COPD Pocket Consultant Guide App: Can A Digital Approach Improve Care? A Statement of the COPD Foundation.

The COPD Foundation has tried to address gaps in chronic obstructive pulmonary disease (COPD) care by providing COPD Pocket Consultant Guide cards to U.S. health care providers. Since launching the card in 2007, there have been numerous updates and more than 800,000 of these cards have been distributed at no charge to health care professionals. The most recent versions have concentrated on presenting an algorithm for COPD management based on 7 severity domains: spirometry, symptoms, exacerbations, oxygen requirements, the presence of chronic bronchitis or emphysema and comorbidities. To increase the usability and reach of this tool, the COPD Pocket Consultant Guide is now available as an app for iOS and Android. This updated version of the app includes new COPD and asthma/COPD overlap flow charts; an interactive therapy chart that takes into account modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and spirometry scores; anxiety and depression screeners; up-to-date medication charts in both brand and generic formats; a checklist to aid in determining when a patient should be referred to a pulmonologist and more. Potential use of the COPD Pocket Consultant Guide app in clinical care is discussed.

COPD: A New Diagnostic Paradigm.

The disease we know as chronic obstructive pulmonary disease (COPD) continues a circuitous journey in its definition, characterization and clinical course. The article by Lowe et al in this issue of Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation expands our understanding of the diagnosis, progression and mortality of this heterogeneous group of disorders.1 The definition of COPD is expanded and a new diagnostic term is introduced – COPDGene® 2019. This perspective provides insights on the importance of this manuscript to clinicians, clinical researchers, and patients. Four questions are raised by this new definition of COPD: · Does COPDGene® 2019 differ from the current definition of COPD? · Is COPDGene® 2019 clinically important? · Are there opportunities for future research to improve the implementation and management of COPDGene® 2019? · How can clinicians employ COPDGene® 2019 in the management of their patients?

Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene.

Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD). We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on >95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts. Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%-16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0-0.74] versus 0 [0-0.80] events/year and 0.9 [0.5-2] versus 0.5 [0-1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00-2.90; and OR, 3.03; 95%CI, 1.02-9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23-1.7; and IRR, 1.24; 95%CI, 1.03-1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively. Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD. ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01 CX000911 to JLC; R01 (R01HL102371, R01HL126596) and VA Merit (I01BX001756) to AG. SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) is funded by contracts from the NHLBI (HHSN268200900013C, HHSN268200900014C,HHSN268200900015C HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and a grant from the NIH/NHLBI (U01 HL137880), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals Inc.; Chiesi Farmaceutici; Forest Research Institute Inc.; GlaxoSmithKline; Grifols Therapeutics Inc.; Ikaria Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. COPDGene is funded by the NHLBI (R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

Internet Health Behaviors of Patients with Chronic Obstructive Pulmonary Disease and Assessment of Two Disease Websites.

Background: Little is known about patients' use of the internet to search for information about chronic obstructive pulmonary disease (COPD) and their perspectives on disease content on websites. Objectives: To determine the interests and behavior of patients with COPD who search the internet for disease information and to assess their perspectives about 2 COPD educational websites. Methods: Individuals with COPD who had registered for a consumer panel were invited electronically to participate in a survey which included general use of the internet, online health behaviors about COPD, and assessment of 2 COPD educational websites. Results: A total of 445 respondents completed the survey in 23 ± 12 minutes (72% response rate). A total of 95% reported that physicians were the primary source of information about COPD followed by internet searches about the disease (76%). The 3 major information priorities were "symptom control" (82%), "how COPD is affecting my body" (60%), and "treatments that might work better for me" (59%). Overall ratings (range, 1 - 10) were 7.4 ± 1.5 for the American Lung Association and 6.8 ±1.8 for the COPD Foundation websites. Ratings by respondents were higher for all 5 impression attributes and for 8 of 9 content attributes on the American Lung Association website compared with the COPD Foundation website. Conclusions: This report describes, for the first time, information priorities of patients with COPD about their disease and their assessment of 2 educational websites. Our survey results can be used by health care professionals to recommend online resources to their patients.

Web-based Health Information Seeking and eHealth Literacy among Patients Living with Chronic Obstructive Pulmonary Disease (COPD)

ABSTRACTMany people living with Chronic Obstructive Pulmonary Disease (COPD) have low general health literacy; however, there is little information available on these patients’ eHealth literacy, or their ability to seek, find, understand, and appraise online health information and apply this knowledge to address or solve disease-related health concerns. A nationally representative sample of patients registered in the COPD Foundation’s National Research Registry (N = 1,270) was invited to complete a web-based survey to assess socio-demographic (age, gender, marital status, education), health status (generic and lung-specific health-related quality of life), and socio-cognitive (social support, self-efficacy, COPD knowledge) predictors of eHealth literacy, measured using the 8-item eHealth literacy scale (eHEALS). Over 50% of the respondents (n = 176) were female (n = 89), with a mean age of 66.19 (SD = 9.47). Overall, participants reported moderate levels of eHealth literacy, with more than 70% feeling confident in their ability to find helpful health resources on the Internet. However, respondents were much less confident in their ability to distinguish between high- and low-quality sources of web-based health information. Very severe versus less severe COPD (β = 4.15), lower lung-specific health-related quality of life (β = −0.19), and greater COPD knowledge (β = 0.62) were significantly associated with higher eHealth literacy. Higher COPD knowledge was also significantly associated with greater knowledge (ρ = 0.24, p = .001) and use (ρ = 0.24, p = .001) of web-based health resources. Findings emphasize the importance of integrating skill-building activities into comprehensive patient education programs that enable patients with severe cases of COPD to identify high-quality sources of web-based health information. Additional research is needed to understand how new social technologies can be used to help medically underserved COPD patients benefit from web-based self-management support resources.

The 2017 Update to the COPD Foundation COPD Pocket Consultant Guide.

The COPD Foundation Pocket Consultant Guide (PCG) was first released in 2007 as a practice tool for use at point of service for clinicians, especially primary care clinicians diagnosing and treating patients with chronic obstructive pulmonary disease (COPD). Over the years, the PCG has been supplemented with a mobile app that presents the tool in an online smart phone accessible version that also allows the clinician to enter patient specific data for guidance to next steps of diagnosis or management. In November 2016, a new update of the PCG was released that incorporates a flow diagram for stepped care that includes the newest recommendation for diagnosis, assessment and treatment; including the broad use of dual bronchodilator therapy and consideration of asthma COPD overlap syndrome (ACOS). The current controversy regarding when to add inhaled corticosteroids (ICSs) is addressed to support clinical decision making. The PCG comes in 2 versions, one with generic names for COPD drugs available in the United States and one with trade names for those drugs. The update continues to recommend spirometry for those at highest risk, also emphasizing the need to assess symptoms, exacerbation risks and comorbidity before selecting appropriate non-pharmacological as well as pharmacological therapy. The tool is designed to facilitate COPD management in daily practice.

Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease. Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium.

The COPD Foundation Biomarker Qualification Consortium (CBQC) is a unique public-private partnership established in 2010 between the COPD Foundation, the pharmaceutical industry, and academic chronic obstructive pulmonary disease (COPD) experts with advisors from the U.S. NHLBI and the Food and Drug Administration (FDA). This was a direct response to the 2009 publication of a guidance on qualification of drug development tools by the FDA. Although data were believed to be available from publicly funded and industry-funded studies that could support qualification of several tools, the necessary data resided in disparate databases. The initial intent of the CBQC was to integrate these data and submit a dossier for the qualification. This led to the FDA qualification of plasma fibrinogen as a prognostic or enrichment biomarker for all-cause mortality and COPD exacerbations in July 2015. It is the first biomarker drug development tool qualified for use in COPD under the FDA's drug development tool qualification program. This perspective summarizes the FDA's qualification process, the formation of the CBQC, and the effort that led to a successful outcome for plasma fibrinogen and discusses implications for future biomarker qualification efforts.