Ashraf Fawzy

Background: Guidelines recommend aspirin (75–100 mg daily) for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, it is unknown if people with a history of ASCVD and chronic obstructive pulmonary disease (COPD) or asthma, which are independent risk factors for ASCVD, would benefit from higher dose aspirin. Methods: We evaluated the effectiveness and safety of 2 aspirin doses among individuals with and without COPD/asthma in the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial. The ADAPTABLE study was an open‐label, randomized clinical trial that assigned people with ASCVD to aspirin 81 or 325 mg. We performed a secondary analysis of data from the ADAPTABLE study to investigate the difference in clinical effectiveness and safety among people with and without COPD or asthma randomized to aspirin 325 versus 81 mg. We assessed if history of COPD/asthma modified the association between aspirin dose and outcomes. Results: Among the 14 662 participants, 2778 had a history of COPD or asthma and 11 884 had no history of COPD or asthma. We observed no significant interaction between aspirin dose and history of COPD/asthma in our adjusted primary composite outcome (adjusted hazard ratio [aHR], 1.15 [95% CI, 0.92–1.43]; P value=0.349). We observed individuals with a history of COPD/asthma treated with aspirin 81 mg had a significantly higher risk of stroke (aHR, 2.41 [95% CI, 1.27–4.57]) compared with a treatment strategy of aspirin 325 mg. Conclusions: Among people with ASCVD and COPD/asthma, there were no significant differences in ASCVD outcomes based on aspirin dosing except stroke. Further evaluation of stroke prevention in this population is warranted.

Background: Current guidelines for the evaluation of chronic obstructive pulmonary disease (COPD) do not recommend screening for pulmonary hypertension (PH), despite the high prevalence and impact on outcomes. A simple screening tool to identify patients with an elevated pulmonary vascular resistance (PVR) is urgently needed, as they may benefit from PH-specific therapy and more urgent referral for lung transplantation. Research question: We sought to examine whether a ratio of forced expiratory volume in 1 s (FEV ₁ ) to diffusing capacity (DLCO) predicts haemodynamic patterns in COPD. Study design and methods: Individuals with COPD who underwent right heart catheterisation from two academic medical centres were included. Adjusted multinomial models tested associations between FEV ₁ /DLCO and haemodynamic patterns. Receiver operating curves were generated to assess the discriminative performance of the FEV ₁ /DLCO ratio in predicting PH with an elevated PVR. Results: Approximately 40% of the 411 individuals included had PH with an elevated PVR. For every 0.1 increase in the FEV ₁ /DLCO ratio, there was a 12–14% increased rate of PH with an elevated PVR compared with No PH. FEV ₁ /DLCO ratio had moderate discriminative performance (C-statistic 0.68–0.72), which was strengthened when combined in a model with elevated tricuspid regurgitant jet velocity on echocardiography (C-statistic 0.78–0.82). Above a threshold of 1.4, FEV ₁ /DLCO demonstrated good specificity (75%) in predicting PH with an elevated PVR. Interpretation: These findings suggest that disproportionate reductions in DLCO predict PH with an elevated PVR in a COPD population. The FEV ₁ /DLCO ratio should be considered in the evaluation of PH in COPD.

Rationale: Serum IgG deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD), but it is unclear whether concentrations in the lower end of the normal range still confer risk. Objectives: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. Methods: Former and current smokers in SPIROMICS (the Subpopulations and Intermediate Outcome Measures of COPD study) (n = 1,497) were studied: 1,026 with COPD and 471 at risk for COPD. In a subset (n = 1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographic characteristics, current smoking, smoking history, FEV1 percent predicted, inhaled corticosteroids, and serum IgA. Measurements and Main Results: The 35th percentile (1,225 mg/dl in this cohort) of IgG was the best cutoff by Akaike information criterion. Below this, there was increased exacerbation risk (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.08–1.51). Among subclasses, IgG1 and IgG2 below the 35th percentile (354 and 105 mg/dl, respectively) were associated with increased risks of severe exacerbation (IgG1, IRR, 1.39; 95% CI, 1.06–1.84; IgG2, IRR, 1.50; 95% CI, 1.14–1.1.97). These associations remained significant when additionally adjusting for a history of exacerbations. Conclusions: Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting that subtle impairment of humoral immunity may be associated with exacerbations.

Rationale: In chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared analytic methods for estimating rate of forced expiratory volume in one second (FEV₁) change from EHR data. Methods: We estimated rate of FEV₁ change in patients with COPD from a single centre who had ≥3 outpatient tests spanning at least 1 year. Estimates were calculated as both an absolute mL/year and a relative %/year using non-regressive (Total Change, Average Change) and regressive (Quantile, RANSAC, Huber) methods. We compared distributions of the estimates across methods focusing on extreme values. Univariate zero-inflated negative binomial regressions tested associations between estimates and all-cause or COPD hospitalisations. Results were validated in an external cohort. Results: Among 1417 participants, median rate of change was approximately −30 mL/year or −2%/year. Non-regressive methods frequently generated erroneous estimates due to outlier first measurements or short intervals between tests. Average change yielded the most extreme estimates (minimum=−3761 mL/year), while regressive methods, and Huber specifically, minimised extreme estimates. Huber, Total Change and Quantile FEV₁ slope estimates were associated with all-cause hospitalisations (Huber incidence rate ratio 0.98, 95% CI 0.97 to 0.99, p1 rate of change is clinically applicable but sensitive to challenges intrinsic to clinically obtained data. While no analytic method will fully overcome these complexities, we identified Huber regression as useful in defining an individual’s lung function change using EHR data.

Background: Elevated urine 11-dehydro-thromboxane B2 is associated with worse respiratory outcomes in COPD, suggesting a role for platelet activation. Question: Are specific platelet activation pathways associated with COPD morbidity? Methods: Multicolor flow cytometry was used to measure platelet surface expression of P-selectin, CD40L, CD63, and activated glycoprotein IIb/IIIa (PAC1) in platelet rich plasma and platelet-monocyte and platelet-neutrophil conjugates in whole blood of 40 former smokers with COPD without cardiovascular disease (CVD) and low coronary calcium. Multivariable linear regression adjusted for age, sex, aspirin use, platelet count, and FEV1% evaluated the association of platelet surface markers, platelet-monocyte and platelet-neutrophil conjugates (% positive) with clinical outcomes. Results: Greater platelet surface expression of α-granule constituents P-selectin and CD40L and dense granule constituent CD63 was associated with higher CAT, SGRQ, and CCQ scores. There were no consistent associations between PAC1 expression (platelet-endothelial interaction), platelet-monocyte, or platelet-neutrophil conjugates with respiratory morbidity. Conclusions: Among former smokers with COPD without CVD, in vivo platelet degranulation is associated with more severe respiratory symptoms, worse health status, and quality of life. Whether cytokines and chemokines released from platelet granules impact COPD morbidity remains unknown. erj;64/suppl_68/PA3090/F1 F1 F1