Baseline Chronic Obstructive Pulmonary Disease Research Articles

Longitudinal reciprocal association between rheumatoid arthritis and chronic obstructive pulmonary disease and mediation of inflammation.

To elucidate the longitudinal reciprocal association between rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD), and the mediating role of systemic inflammation in the association. 403045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox-proportional hazard regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association. At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of cross-lagged panel model revealed a bidirectional association between RA and COPD (β = 0.018, P < 0.001 for RA→COPD path; β = 0.010, P < 0.001 for COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients (Cox: HR = 1.65, 95% CI, 1.50-1.83; logistic: OR = 1.85, 95% CI, 1.66-2.07). In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up (Cox: HR = 1.67, 95% CI, 1.44-1.92; logistic: OR = 1.70, 95% CI, 1.47-1.97). Five inflammatory factors mediated the RA→COPD path, and C-reactive protein mediated the COPD→RA path (FDR < 0.05). A significant bidirectional association exists between RA and COPD, and it is partially mediated by systemic inflammation.

Epidemiology and clinical characteristics of interstitial lung disease in patients with rheumatoid arthritis from the JointMan database

Interstitial lung disease (ILD) is a progressive fibrotic disease associated with rheumatoid arthritis (RA); real-world data for evaluating RA–associated ILD (RA–ILD) are limited. We evaluated prevalence, time to onset, clinical characteristics and prognostic factors in patients diagnosed with RA (n = 8963) in the Discus Analytics JointMan database (2009–2019) with and without ILD. ILD prevalence was 4.1% (95% confidence interval 3.7–4.5); > 90% had an ILD diagnosis after RA diagnosis (mean time to onset 3.3 years). At baseline, a higher proportion of patients with RA–ILD were older (> 65 years), male, with history of chronic obstructive pulmonary disease (COPD) compared with patients in the RA cohort. Patients in the RA–ILD cohort were likely to have more severe RA characteristics and joint evaluation compared with patients without ILD, at baseline and before/after ILD diagnosis. In this large, real-world database patients with (vs without) ILD had a higher burden of RA characteristics. Previously established risk factors for RA–ILD were confirmed (age, baseline COPD, anti-cyclic citrullinated peptide positivity, C-reactive protein, Clinical Disease Activity Index score); thus, recognition of these factors and tracking routine disease activity metrics may help identify patients at higher risk of RA complications and lead to improved diagnosis and earlier treatment.

Associations of reproductive risk score and joint exposure to ambient air pollutants with chronic obstructive pulmonary disease: a cohort study in UK Biobank.

Reproductive risk factors and air pollution for developing chronic obstructive pulmonary disease (COPD) have been documented separately. However, the combined effects of overall reproductive risk status on COPD and the extent to which this can be impacted by air pollution are unknown. The aim of this study was to construct a reproductive risk score (RRS) and an air pollution score (APS) and assess independent and joint associations between the two with incident COPD risk. 78,027 female participants aged 40-69 years without baseline COPD from UK Biobank recruited between 2006 to 2010 were included in this study. RRS was constructed by 17 women's reproductive health-related items, and APS incorporating PM2.5, PM2.5-10, PM10, NO2, and NOx was calculated to assess the joint exposure level. The outcome of the incident COPD was identified through the in-patient hospital register. The associations of RRS and APS with COPD were examined by Cox proportional hazards regression. The risk of COPD reached its highest in the fourth quartile of the RRS (adjusted HR: 2.23, 95% CI: 1.76-2.82, P for trend < 0.001). A dose-response manner can also be observed between higher tertile APS with increased COPD risk and the highest risk was found in the third tertile of the APS (adjusted HR: 1.37, 95% CI: 1.19-1.58, P for trend < 0.001). The relative excess risk due to interaction (RERI) of 0.030 (95% CI: 0.012-0.048) showed additive interaction between RRS and APS on COPD was significant. In the joint analysis, the combinations of both higher RRS and APS signified higher incident COPD risk. High RRS and high APS were jointly associated with increased COPD risks in a dose-response pattern. Using comprehensive indicators to identify women's reproductive risk factors, together with the control of air pollution, is effective for COPD prevention.

Radiation and immune checkpoint inhibitor-mediated pneumonitis risk stratification in patients with locally advanced non-small cell lung cancer: role of functional lung radiomics?

BackgroundPatients undergoing chemoradiation and immune checkpoint inhibitor (ICI) therapy for locally advanced non-small cell lung cancer (NSCLC) experience pulmonary toxicity at higher rates than historical reports. Identifying biomarkers beyond conventional clinical factors and radiation dosimetry is especially relevant in the modern cancer immunotherapy era. We investigated the role of novel functional lung radiomics, relative to functional lung dosimetry and clinical characteristics, for pneumonitis risk stratification in locally advanced NSCLC.MethodsPatients with locally advanced NSCLC were prospectively enrolled on the FLARE-RT trial (NCT02773238). All received concurrent chemoradiation using functional lung avoidance planning, while approximately half received consolidation durvalumab ICI. Within tumour-subtracted lung regions, 110 radiomics features (size, shape, intensity, texture) were extracted on pre-treatment [99mTc]MAA SPECT/CT perfusion images using fixed-bin-width discretization. The performance of functional lung radiomics for pneumonitis (CTCAE v4 grade 2 or higher) risk stratification was benchmarked against previously reported lung dosimetric parameters and clinical risk factors. Multivariate least absolute shrinkage and selection operator Cox models of time-varying pneumonitis risk were constructed, and prediction performance was evaluated using optimism-adjusted concordance index (c-index) with 95% confidence interval reporting throughout.ResultsThirty-nine patients were included in the study and pneumonitis occurred in 16/39 (41%) patients. Among clinical characteristics and anatomic/functional lung dosimetry variables, only the presence of baseline chronic obstructive pulmonary disease (COPD) was significantly associated with the development of pneumonitis (HR 4.59 [1.69–12.49]) and served as the primary prediction benchmark model (c-index 0.69 [0.59–0.80]). Discrimination of time-varying pneumonitis risk was numerically higher when combining COPD with perfused lung radiomics size (c-index 0.77 [0.65–0.88]) or shape feature classes (c-index 0.79 [0.66–0.91]) but did not reach statistical significance compared to benchmark models (p > 0.26). COPD was associated with perfused lung radiomics size features, including patients with larger lung volumes (AUC 0.75 [0.59–0.91]). Perfused lung radiomic texture features were correlated with lung volume (adj R2 = 0.84–1.00), representing surrogates rather than independent predictors of pneumonitis risk.ConclusionsIn patients undergoing chemoradiation with functional lung avoidance therapy and optional consolidative immune checkpoint inhibitor therapy for locally advanced NSCLC, the strongest predictor of pneumonitis was the presence of baseline chronic obstructive pulmonary disease. Results from this novel functional lung radiomics exploratory study can inform future validation studies to refine pneumonitis risk models following combinations of radiation and immunotherapy. Our results support functional lung radiomics as surrogates of COPD for non-invasive monitoring during and after treatment. Further study of clinical, dosimetric, and radiomic feature combinations for radiation and immune-mediated pneumonitis risk stratification in a larger patient population is warranted.

Worsening of Renal Function Among Hospitalized Patients With Acute Heart Failure: Phenotyping, Outcomes, and Predictors

ObjectiveTo define clinical phenotyping and its associated outcome of worsening of renal function (WRF) in hospitalized acute heart failure (AHF) patients. Patients and MethodsLatent class analysis was performed in 113 AHF patients who developed WRF within 72 hours in the DOSE (Diuretic Optimization Strategies Evaluation) trial (from March 2008 to November 2009) and ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial (from September 2010 to March 2013) to identify potential WRF phenotypes. Clinical characteristics and outcome (in-hospital and post-discharge) were compared between different phenotypes. ResultsTwo WRF phenotypes were identified by latent class analysis, which we named WRF minimally responsive to diuretics (WRF-MRD) and WRF responsive to diuretics (WRF-RD). Among the population, 58 (9.5%) developed WRF-MRD and 55 (9.0%) developed WRF-RD. Patients with WRF-MRD had more comorbidities than WRF-RD. In WRF-MRD, there were an early increase in serum creatinine, a smaller amount of net fluid loss and weight loss, and a higher rate of worsening or persistent heart failure over 72 hours. In contrast, for those with WRF-RD, they had faster in-hospital net fluid loss and weight loss and a better 60-day survival after discharge even compared with patients without WRF (P=.004). Furthermore, baseline chronic obstructive pulmonary disease, diabetes, and cystatin C were independent predictors of WRF-MRD, whereas serum hemoglobin and sodium predicted WRF-RD. ConclusionsAmong hospitalized AHF patients, we identified two phenotypes of WRF with distinct response to heart failure treatment, predictors, and short-term prognosis after discharge. The results could help early differentiation of WRF phenotypes in clinical practice.

185-LB: Pulmonary Function and Diabetes Risk in a Cohort of Black and White Current and Former Smokers

The recent COVID-19 pandemic, which saw an increased risk of subsequent diabetes among persons with COVID-19 as well as greater casualties among persons with diabetes, has brought renewed attention to the role of lung function in diabetes. We tested the relationship of lung function and chronic obstructive pulmonary disease (COPD) with diabetes in a population of current and former smokers. Using data from the COPD Genetic Epidemiology (COPDGene) cohort, we conducted a diabetes follow-up (2012-2018) of a cohort of Black and White current and former smokers with (n=2442) and w/out (n=2214) COPD, aged 39-85 years and w/out diabetes at cohort entry. Lung function was modeled using Forced Expiratory Volume at 1 second % predicted (FEV1%P) . COPD was defined as the ratio of FEV1% to FVC% &amp;lt;0.7. Logistic regression was used to compute ORs (95% CIs) for risk of incident diabetes. The incidence of diabetes was 8% over the five years of follow-up, representing a 43% increase in prevalence. After controlling for age, sex, and race, COPD at baseline was a significant risk factor for diabetes (OR=1.51, 1.21-1.88) . Significant interaction existed between baseline COPD and baseline Fev1%p (p-interaction=0.01) , such that Fev1%p only predicted diabetes among those w/out (OR=0.98, 0.96-0.99) but not among those with COPD at baseline (OR=0.99, 0.99-1.00) . Upon stratification by race, Fev1%p was a significant predictor among Blacks but not Whites, but effect modification by race was not observed. Blacks were at twice the risk of diabetes overall (OR=2.04, 1.59-2.60) and were at 3 times the risk among those w/out COPD (OR=2.91, 1.98-4.27) . BMI increased risk in both races regardless of COPD status; however, a higher BMI was a stronger risk factor for diabetes among Whites than Blacks, particularly for those with baseline COPD (race*BMI interaction p=0.06) . In this large population of current and former smokers, our data suggest that lower lung function prior to the development of COPD is a risk factor for diabetes, particularly among Blacks. BMI is an important risk factor in both races, but appears to play a stronger role among Whites. Disclosure R. B. Conway: None. K. Young: None. Y. Li: Employee; Vertex Pharmaceuticals Incorporated. E. Austin: None. G. L. Kinney: None. Funding National Institutes of Health (U01HL089897)

The Impact Of Acute Heart Failure Related Length Of Stay On The 30-day All-Cause Readmission Rate.

The Impact Of Acute Heart Failure Related Length Of Stay On The 30-day All-Cause Readmission Rate.

Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease

AimsType 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) often co-exist, yielding increased risk of cardiovascular (CV) complications including heart failure (HF). We assessed risk of cardiorenal outcomes, mortality and safety in patients with versus without COPD in the EMPA-REG OUTCOME trial. MethodsPatients (n = 7,020) with T2DM and CV disease (CVD) were treated with empagliflozin (10 mg or 25 mg) or placebo. Cox regression was used to assess COPD subgroup (placebo only) associations with, and treatment effects of empagliflozin versus placebo on first hospitalization for HF (HHF), CV death, all-cause mortality, incident/worsening nephropathy, and all-cause hospitalization. ResultsAt baseline, patients with COPD (n = 707) had more HF and used insulin more frequently than those without COPD. During follow-up in the placebo group, those with baseline COPD had increased risk of HHF (HR 2.15 [95% CI 1.32, 3.49]), HHF/CV death (1.60 [1.10, 2.33]), incident/worsening nephropathy (1.68 [1.26, 2.24]), all-cause hospitalization (1.44 [1.19, 1.74]) and all-cause death (1.60 [1.09, 2.35]) compared to those without COPD. Empagliflozin consistently reduced all clinical outcomes, irrespective of COPD status (interaction p-values 0.14 to 0.96), with a confirmed safety profile. ConclusionsIn patients with T2DM and CVD, COPD increased the risk of mortality and cardiorenal outcomes, including HF. Empagliflozin consistently reduced these outcomes versus placebo regardless of COPD, suggesting that empagliflozin’s benefits in patients with T2DM and CVD are not mitigated by the presence of COPD.

Predictors of Transition to Frailty in Middle-Aged and Older People With HIV: A Prospective Cohort Study.

People with HIV (PWH) have increased frailty risk at younger ages compared with the general population. Multimorbidity is associated with frailty, yet effects of specific comorbidities on transition to frailty in PWH are unknown. Prospective study of 219 PWH age 45 years or older in the National NeuroAIDS Tissue Consortium. Frailty status was categorized using Fried frailty phenotype criteria. Comorbidities [bone disease, cardiovascular disease, cerebrovascular disease, liver disease, renal disease, diabetes, chronic obstructive pulmonary disease (COPD), hypertension, obesity, cancers, neuropsychiatric conditions] were assessed from longitudinal data. Associations between baseline comorbidities and transition to frailty within 30 months were analyzed using Kaplan-Meier and Cox regression models. Grip strength was assessed using mixed-effects models. At baseline, the median age was 61 years, 73% were male 98% were on antiretroviral therapy, 29% had ≥3 comorbidities, 27% were robust, and 73% were pre-frail. Cerebrovascular disease, diabetes, and COPD were independent predictors of transition to frailty within 30 months in models adjusted for age, sex, and multimorbidity (≥3 additional comorbidities) [hazard ratios (95% confidence intervals) 2.52 (1.29 to 4.93), 2.31 (1.12 to 4.76), and 1.82 (0.95 to 3.48), respectively]. Furthermore, cerebrovascular disease, diabetes, COPD, or liver disease co-occurring with multimorbidity was associated with substantially increased frailty hazards compared with multimorbidity alone (hazard ratios 4.75-7.46). Cerebrovascular disease was associated with decreased baseline grip strength (P = 0.0001), whereas multimorbidity, diabetes, and COPD were associated with declining grip strength (P < 0.10). In older PWH, cerebrovascular disease, diabetes, COPD, or liver disease co-occurring with multimorbidity is associated with substantially increased risk of becoming frail within 30 months. Interventions targeting these comorbidities may ameliorate frailty and age-related functional decline in PWH.

Oscillococcinum® for upper respiratory tract infections and exacerbations in COPD: an observational, prospective study (OXITUNIS).

BackgroundUpper respiratory tract infections (URTIs) are a major cause of exacerbations in patients with chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of Oscillococcinum® in the protection from URTIs in patients with COPD who had been vaccinated against influenza infection over the 2018–2019 winter season.MethodsPatients (n=106; mean ± standard deviation age: 66.0 ± 10.3 years; 89.6% men) were randomized into two groups: group V received influenza vaccination only and group OV received influenza vaccination plus Oscillococcinum® (one oral dose per week from inclusion in the study until the end of follow-up, with a maximum of 6 months follow-up over the winter season). The primary endpoint was the incidence rate of URTIs (number of URTIs/1000 patient-treatment exposure days) during follow-up compared between the two groups.ResultsThere was no significant difference in any of the demographic characteristics, baseline COPD, or clinical data between the two treatment groups (OV and V). The URTI incidence rate was significantly higher in group V than in group OV (2.9 versus 1.2 episodes/1000 treatment days, difference OV–V = −1.7; p=0.0312). There was a significant delay in occurrence of an URTI episode in the OV group versus the V group (mean ± standard error: 48.7 ± 3.0 versus 67.0 ± 2.8 days, respectively; p=0.0158). Limitations to this study include its small population size and the self-recording by patients of the number and duration of URTIs and exacerbations.ConclusionOscillococcinum may decrease the incidence rate and delay the appearance of URTIs in patients with COPD.

COVID-19-Related Spontaneous Aortic Arch Thrombus With Delayed Embolization.

Presentation of a 62-year-old man with baseline chronic obstructive pulmonary disease admitted to the hospital with dyspnea and newly diagnosed COVID-19 infection. CT scan of the chest was obtained to rule out pulmonary embolism. This revealed a mural thrombus of the inner curvature of the aortic arch with a floating component. Therapeutic full dose anticoagulation was initiated in combination with close clinical observation and treatment for modest hypoxia. He did well for 1month and then returned with ischemic rest pain of the right foot. Angiography revealed thrombosis of all 3 tibial arteries in the right leg. Percutaneous mechanical thrombectomy with tissue plasminogen activator injection and angioplasty was performed with success in 1 tibial artery to achieve in line flow to the foot. After continued anticoagulation, the remainder of the tibial arteries autolysed and the aortic thrombus was noted to be resolved 4 months later. A brief pathophysiology discussion is included.

Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort

BackgroundThere is a lack of mechanism-driven, clinically relevant biomarkers in chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction, a proposed disease mechanism in COPD, is associated with the release of mitochondrial DNA (mtDNA), but plasma cell-free mtDNA has not been previously examined prospectively for associations with clinical COPD measures.MethodsP-mtDNA, defined as copy number of mitochondrially-encoded NADH dehydrogenase-1 (MT-ND1) gene, was measured by real-time quantitative PCR in 700 plasma samples from participants enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Associations between p-mtDNA and clinical disease parameters were examined, adjusting for age, sex, smoking status, and for informative loss to follow-up.ResultsP-mtDNA levels were higher in participants with mild or moderate COPD, compared to smokers without airflow obstruction, and to participants with severe COPD. Baseline increased p-mtDNA levels were associated with better CAT scores in female smokers without airflow obstruction and female participants with mild or moderate COPD on 1-year follow-up, but worse 6MWD in females with severe COPD. Higher p-mtDNA levels were associated with better 6MWD in male participants with severe COPD. These associations were no longer significant after adjusting for informative loss to follow-up.ConclusionIn this study, p-mtDNA levels associated with baseline COPD status but not future changes in clinical COPD measures after accounting for informative loss to follow-up. To better characterize mitochondrial dysfunction as a potential COPD endotype, these results should be confirmed and validated in future studies.Trial Registration: ClinicalTrials.gov NCT01969344 (SPIROMICS)

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers

ImportanceWhile cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case–controls studies, their corelationship is not well...

Chronic obstructive pulmonary disease is associated with increased mortality in patients undergoing MitraClip therapy: A systematic review and meta-analysis

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent in patients undergoing MitraClip with up to 39% reported. Nonetheless, whether COPD has effect on mortality in this patient population remains unclear. We conduct a systematic review and meta-analysis to evaluate the effect of COPD on the outcome in patient undergoing MitraClip therapy. Methods: We comprehensively searched the data bases of MEDLINE and EMBASE from inception to August 2020. Published cohort and randomized controlled trials of patients undergoing MitraClip therapy which reported univariate or multivariate analyses on the effect of COPD to mortality were included. Data were integrated using the random-effects, generic inverse variance method of DerSimonian and Laird. Results: Six studies from 2014-2018 involving 5,076 patients undergoing MitraClip therapy were included. Baseline COPD was associated with increased mortality (Risk Ratio [RR]=1.22, 95% Confidence Interval [CI]: 1.07-1.38, p=0.002, I2=0.00%). Conclusion: COPD is associated with increased mortality in patient undergoing MitraClip therapy up to 1.22 folds. Therefore, COPD could be a predictor of outcome in patients undergoing Mitraclip therapy and could be potentially integrated in risk stratification in this patient population.

Low-Dose Radiation Therapy in the Management of Coronavirus Disease 2019 (COVID-19) Pneumonia (LOWRAD-Cov19): Preliminary Report

PurposeLow-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia.Materials and MethodsWe conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT.ResultsNine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia.ConclusionsOur preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.

ANALYSIS OF PULMONARY-RELATED CLINICAL MANIFESTATIONS AND HEALTH RESOURCE UTILIZATION IN PATIENTS WITH SEVERE AND NON-SEVERE ALPHA-1 ANTITRYPSIN DEFICIENCY IN THE UNITED STATES

SESSION TITLE: Monday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Pulmonary manifestations (PM) of alpha-1 antitrypsin deficiency (AATD) can inflict a severe clinical course for patients and require increased healthcare resource use (HRU). This study aimed to describe the real-world burden of AATD with PM in the U.S. METHODS: Patient-level healthcare claims from the Truven Health MarketScan® database were retrospectively analyzed. Patients with a second primary diagnosis of AATD between 6/1/2008-12/31/2017 and continuous enrollment in the 6 months preceding the second diagnosis date were included. Patient characteristics and AATD-associated PM events of Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, emphysema and bronchiectasis were assessed among all identified patients. All-cause HRU was assessed separately among patients with severe PM (≥1 event with hospitalization within 1 calendar day) and non-severe PM (events with no hospitalization within 1 calendar day). Incidence rates (IR) and associated 95% confidence intervals (CI) of the defined PM and HRU were measured from day 1 after the date of hospital discharge for severe events and the date of first PM event claim for non-severe events to the end of data or continuous eligibility. IR were summarized descriptively and compared using standardized differences (d). RESULTS: Of 5109 cases, 2674 (52.3%) had ≥1 of the defined PM events. Severe AATD patients (N=711) were older (mean age 57.9 vs 52.8 years; d=0.37) vs non-severe patients (N=1963), had a greater baseline morbidity (higher mean CCI score [2.2 vs 1.4; d=0.497]), had a higher prevalence of baseline COPD (75.8% vs 56.9%; d=0.41) and emphysema (33.8% vs 23.8%; d=0.22), and increased hospitalization frequency (mean 0.7 vs 0.13; d=0.70). Pulmonary exacerbations were the most frequent manifestation. IR for severe exacerbations was 522.4 (95% CI: 485.4-562.2) and 231.6 (221.6-242.1) for non-severe per 100 person-years. The IR for severe and non-severe COPD, chronic bronchitis, emphysema, and bronchiectasis were: 234.5 [216.8-253.6] and 82.3 [78.2-86.6], 65.9 [60.4-71.8] and 26.6 [24.8-28.4], 46.8 [42.5-51.6] and 20.4 [18.9-22.0], and 7.9 [6.6-9.5] and 4.3 [3.7-5.0] per 100 person-years respectively. Patients with severe PE had intensified HRU based on significantly higher mean annual frequencies of emergency room (1.2 vs 0.5; d=0.16), inpatient (1.3 vs 0.08; d=0.68), outpatient (10.3 vs 6.4; d=0.28), other visits (4.0 vs 2.0; d=0.21), and significantly longer hospitalizations (mean, 8.8 days vs 5.4 days; d=0.49). CONCLUSIONS: Patients with severe AATD-related PM requiring hospitalization are substantially burdened by more frequent events, more severe clinical course and higher HRU. CLINICAL IMPLICATIONS: These findings characterize patients with pulmonary-related AATD and highlight the importance of strategies to reduce the frequency and severity of PM through disease modification. DISCLOSURES: Employee relationship with Takeda Pharmaceuticals Please note: >$100000 Added 03/18/2019 by Emily Brouwer, source=Web Response, value=Stocks Employee relationship with Takeda Please note: >$100000 Added 03/18/2019 by Emily Brouwer, source=Web Response, value=Salary Employee relationship with Takeda Pharmaceuticals Please note: $1-$1000 Added 03/15/2019 by Corey Joseph, source=Web Response, value=I am an employee of Takeda Employee relationship with Takeda Pharmaceutical Company Limited Please note: >$100000 Added 03/12/2019 by Ernesto Mayen Herrera, source=Web Response, value=Salary

EFFICACY OF NEBULIZED ARFORMOTEROL FOR THE TREATMENT OF PATIENTS WITH COPD: A ROLE FOR LONG-ACTING BRONCHODILATORS IN TREATING LONG-TERM CARE PATIENTS WITH COPD

SESSION TITLE: Monday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and increased health care resource utilization in long-term care (LTC) nursing home facilities in the US. Although GOLD guidelines recommend the use of long-acting bronchodilators (LABDs) for the treatment of COPD, as they are more effective and convenient than regular treatment with short-acting bronchodilators (SABDs), a large proportion of nursing home residents with a diagnosis of COPD do not receive any respiratory medication. Arformoterol tartrate (ARF; 15 μg twice daily [BID]) is a nebulized long-acting beta2-agonist (LABA) indicated for the maintenance treatment of bronchoconstriction in patients with COPD; ARF should not be used as rescue medication. In this post-hoc analysis, the efficacy of ARF was assessed in older COPD patients and in patients with very severe COPD. METHODS: Data from two identical, 12-week, multicenter, double-dummy, randomized Phase III trials (NCT00685841 and NCT00064402) evaluating improvement in airway function with ARF treatment in patients with COPD were pooled for analysis. Patients (n=1456; mean predicted forced expiratory volume in 1 second [FEV1]=40.6% [standard deviation: 12.8]) received nebulized ARF 15 μg BID, 25 μg BID, or 50 μg once daily (QD), salmeterol 42 μg BID (via metered dose inhaler), or placebo BID for 12 weeks. In order to assess the efficacy of ARF in patients with COPD representative of an LTC population, an analysis of improvement in airway function (as measured by FEV1) was performed comparing ARF 15 ug BID with placebo (BID) in a subset of patients defined by age (≥75 years; n=160) and baseline COPD disease severity (FEV1 <30% predicted; n=410). RESULTS: In the overall study population, the median % change in FEV1 was 2.05% among patients receiving placebo and 12.72% in patients treated with ARF 15 μg BID. In patients ≥75 years of age, the median % change in FEV1 was −5.22% in patients receiving placebo compared with 18.62% improvement in patients treated with ARF 15 μg BID. In patients with severe COPD disease (<30% FEV1 % predicted), the median % change in FEV1 was 5.13% among patients receiving placebo compared with 22.58% in patients treated with ARF 15 μg BID. CONCLUSIONS: Despite the recommendations for use of LABDs by GOLD guidelines, many LTC nursing home residents with COPD do not receive any respiratory medications. In this post-hoc analysis of patients with COPD representative of nursing facility residents (≥75 years of age; severe baseline disease), treatment with ARF 15 μg BID resulted in greater improvements in lung function when compared with placebo. CLINICAL IMPLICATIONS: LABDs such as ARF should be considered as a treatment option for residents in an LTC setting with a diagnosis of COPD. DISCLOSURES: Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/11/2019 by Thomas Goodin, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/12/2019 by Ayca Ozol-Godfrey, source=Admin input, value=Salary Employee relationship with Sunovion Pharmaceuticals Please note: >$100000 Added 03/13/2019 by Barry Price, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: >$100000 Added 03/14/2019 by Shahin Sanjar, source=Web Response, value=Salary Employee relationship with Sunovion Pharmaceuticals Inc. Please note: $20001 - $100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary Removed 03/11/2019 by Sanjay Sharma, source=Web Response Employee relationship with Sunovion Pharmaceuticals, Inc. Please note: >$100000 Added 03/11/2019 by Sanjay Sharma, source=Web Response, value=Salary

Tai Chi Movements for Wellbeing - evaluation of a British Lung Foundation pilot.

In breathless individuals with respiratory disease, pulmonary rehabilitation (PR) can improve exercise capacity, symptoms and ability to cope with their condition. However, access is often limited, and adherence can be poor. Thus, there is interest in developing alternative and complementary forms of exercise intervention and tai chi may be effective in this context. The British Lung Foundation worked in collaboration with 'Tai Chi Movements for Wellbeing' Training to train leaders to run community-based tai chi groups in the UK. Leaders received funding to run 3 months of once-a-week classes consisting of a 12 movement sequence of tai chi. Participants completed a questionnaire survey to evaluate the service at the start of their first session and again after 3 months. Ten tai chi groups recruited 128 participants, 65% women, mean (standard deviation (SD)) age 70.1 (7.4) years at baseline. Seventy individuals completed the follow-up questionnaire at 3 months. Participants demonstrated an improvement in Medical Research Council (MRC) Dyspnoea Score pre 3 (interquartile range (IQR) = 1.8), post 2 (IQR = 1), p = .013 and disease burden; chronic obstructive pulmonary disease (COPD) assessment test score pre 19.4 (8.7), post 17.9 (9.4), mean change -1.5 (confidence interval (CI): -2.89 to -0.127), p = .033. Those who completed the programme had a worse baseline COPD assessment test (CAT) score and were more likely to have participated in maintenance exercise previously. Qualitative feedback suggested that participants felt the classes had helped with breathlessness and relaxation. Establishing a tai chi for wellbeing programme for people with respiratory disease is feasible, with a reasonable level of compliance, and is perceived to be helpful by participants.

Changes in biomarkers of cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease.

Cardiac dysfunction is associated with a higher mortality in exacerbations of chronic obstructive pulmonary disease (COPD). It is unknown how the heart responds to treatment of COPD exacerbations. We followed cardiac biomarker levels during hospital admissions for exacerbations of COPD and hypothesised that these biochemical markers of cardiac dysfunction might be affected the severity and treatment of exacerbations of COPD. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured at admission, 12 h, 72 h, and clinical stability in 176 patients. In a second cohort (n = 93), associations between blood salbutamol concentrations and biomarker changes at 12 h were analysed. NT-proBNP increased from a geometric mean of 43 pmol/L at admission to 56 pmol/L at 12 h (p < 0.001), 53 pmol/L at 72 h (p = 0.045), and decreased to 25 pmol/L (p < 0.001) at stability. Troponin T levels decreased at 12 h (p < 0.001), but 15/174 (9%) patients had a clinically significant rise. Nebulised bronchodilator treatment and blood salbutamol concentrations were associated with greater increases in NT-proBNP rise at 12 h independently of baseline COPD or exacerbation severity and other treatments (p < 0.05). Nebulised bronchodilator and blood salbutamol concentrations also predicted rises in troponin T in univariate analyses (p < 0.05). NT-proBNP continues to rise after admission to hospital for COPD exacerbations and a minority of patients have clinically significant rises in cardiac troponins. These rises were associated with nebulised beta2-agonist treatment. These findings suggest that high doses of beta2-agonists may exacerbate cardiac dysfunction in COPD.