Publications by authors named "Victor Kim"

96 Publications

Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in Chronic Obstructive Pulmonary Disease.

Chest 2021 Nov 18. Epub 2021 Nov 18.

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

Background: Improved understanding of the pathways associated with airway pathophysiology in chronic obstructive pulmonary disease (COPD) will identify new predictive biomarkers and novel therapeutic targets.

Research Question: Which physiologic pathways are altered in the airways of subjects with COPD and predict exacerbations?

Study Design And Methods: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the SPIROMICS multi-center COPD study. Biomarkers elevated in sputa from subjects with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.

Results: Sputum supernatants from 980 subjects (77 healthy non-smokers [NS], 341 smokers with preserved spirometry [SPS], and 562 COPD subjects [178 GOLD 1, 303 GOLD 2, and 81 GOLD 3]) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (at FDR 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were strongly associated with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.

Interpretation: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiology. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum soluble phase biomarkers improves prediction of pulmonary exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.10.049DOI Listing
November 2021

Significance of FEV/FEV in recognition of early airway disease in smokers at risk of development of COPD: Analysis of the SPIROMICS cohort.

Chest 2021 Nov 9. Epub 2021 Nov 9.

Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States. Electronic address:

Background: Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease.

Research Question: Can FEV/FEV identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?

Study Design And Methods: We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV/FEV based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV and FEV. Regression modeling was used to evaluate the relationship between baseline FEV/FEV and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD.

Results: FEV/FEV
Interpretation: FEV/FEV is a routinely available and repeatable spirometric index which can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV/FEV can identify those at risk for future development of COPD and respiratory exacerbations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.10.046DOI Listing
November 2021

Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study.

PLoS One 2021 15;16(10):e0257892. Epub 2021 Oct 15.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States of America.

Background: Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up.

Methods: We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2-3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO).

Results: 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035).

Conclusions: Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257892PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519442PMC
November 2021

Comparative Impact of Depressive Symptoms and Fev1% on Chronic Obstructive Pulmonary Disease.

Ann Am Thorac Soc 2021 Aug 19. Epub 2021 Aug 19.

Johns Hopkins University, Medicine, Baltimore, Maryland, United States.

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions.

Objectives: Examine the impact of depressive symptoms compared to FEV1% on COPD morbidity.

Methods: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6 minute walk distance (6MWD) and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale (HADS) or FEV1% respectively. PROs consisted of in person completion of St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), and Modified Medical Research Council Dyspnea Scale (mMRC) measures.

Results: Of individuals analyzed (n=1830), 43% were females, 81% Caucasian with mean ±SD age of 65.1±8.1, and 52.7±27.5 pack-years smoking. Mean ±SD FEV1% was 60.9±23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher HADS scores and lower FEV1% each were associated with worse PROs at baseline (p≤0.001). Depression accounted for more baseline variance in SGRQ, CAT, and FACT-F than FEV1%, explaining 30-67% of heterogeneity. While FEV1% accounted for more baseline variance in mMRC and 6MWD than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs.

Conclusions: Depression is more strongly associated with many PROs at baseline and their change over time compared to FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202009-1187OCDOI Listing
August 2021

Ratio of FEV/Slow Vital Capacity of < 0.7 Is Associated With Clinical, Functional, and Radiologic Features of Obstructive Lung Disease in Smokers With Preserved Lung Function.

Chest 2021 07 1;160(1):94-103. Epub 2021 Feb 1.

Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.

Background: Mild expiratory flow limitation may not be recognized using traditional spirometric criteria based on the ratio of FEV/FVC.

Research Question: Does slow vital capacity (SVC) instead of FVC increase the sensitivity of spirometry to identify patients with early or mild obstructive lung disease?

Study Design And Methods: We included 854 current and former smokers from the Subpopulations and Intermediate Outcome Measures in COPD Study cohort with a postbronchodilator FEV/FVC ≥ 0.7 and FEV % predicted of ≥ 80% at enrollment. We compared baseline characteristics, chest CT scan features, exacerbations, and progression to COPD (postbronchodilator FEV/FVC, < 0.7) during the follow-up period between 734 participants with postbronchodilator FEV/SVC of ≥ 0.7 and 120 with postbronchodilator FEV/SVC < 0.7 at the enrollment. We performed multivariate linear and logistic regression models and negative binomial and interval-censored proportion hazards regression models adjusted for demographics and smoking exposure to examine the association of FEV/SVC < 0.7 with those characteristics and outcomes.

Results: Participants with FEV/SVC < 0.7 were older and had lower FEV and more emphysema than those with FEV/SVC ≥ 0.7. In adjusted analysis, individuals with postbronchodilator FEV/SVC < 0.7 showed a greater percentage of emphysema by 0.45% (95% CI, 0.09%-0.82%), percentage of gas trapping by 2.52% (95% CI, 0.59%-4.44%), and percentage of functional small airways disease based on parametric response mapping by 2.78% (95% CI, 0.72%-4.83%) at baseline than those with FEV/SVC ≥ 0.7. During a median follow-up time of 1,500 days, an FEV/SVC < 0.7 was not associated with total exacerbations (incident rate ratio [IRR], 1.61; 95% CI, 0.97-2.64), but was associated with severe exacerbations (IRR, 2.60; 95% CI, 1.04-4.89). An FEV/SVC < 0.7 was associated with progression to COPD during a 3-year follow-up even after adjustment for demographics and smoking exposure (hazard ratio, 3.93; 95% CI, 2.71-5.72). We found similar results when we examined the association of prebronchodilator FEV/SVC < 0.7 or FEV/SVC less than the lower limit of normal with chest CT scan features and progression to COPD.

Interpretation: Low FEV to SVC in current and former smokers with normal spirometry results can identify individuals with CT scan features of COPD who are at risk for severe exacerbations and is associated with progression to COPD in the future.

Trial Registry: ClinicalTrials.gov; No.: NCT01969344T4; URL: www.clinicaltrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.01.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295909PMC
July 2021

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

Thorax 2021 04 6;76(4):343-349. Epub 2021 Jan 6.

Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB.

Methods: In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0-4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit.

Measurements And Main Results: Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively.

Conclusions: Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-215853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225550PMC
April 2021

Current smoking with or without chronic bronchitis is independently associated with goblet cell hyperplasia in healthy smokers and COPD subjects.

Sci Rep 2020 11 18;10(1):20133. Epub 2020 Nov 18.

University of California San Francisco, San Francisco, CA, USA.

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log transformed values. LogGCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high logGCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77229-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674445PMC
November 2020

Defining Chronic Mucus Hypersecretion Using the CAT in the SPIROMICS Cohort.

Int J Chron Obstruct Pulmon Dis 2020 13;15:2467-2476. Epub 2020 Oct 13.

GSK R&D, Discovery Medicine, Collegeville, PA, USA.

Background: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions.

Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status.

Results: In a population of 1431 participants (57% male; mean FEV% predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH- in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status.

Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S267002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568676PMC
June 2021

Customer is always right: optimising inhaler design to fit patient preferences in obstructive lung disease.

Thorax 2020 09 6;75(9):711-712. Epub 2020 Jul 6.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-215238DOI Listing
September 2020

Thoracic Computed Tomography Features of Coronavirus Disease 2019 Patients with Emphysema.

Chronic Obstr Pulm Dis 2020 Jul;7(3):290-296

Department of Thoracic Medicine and Surgery, Temple University Health System, Philadelphia, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.7.3.2020.0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857718PMC
July 2020

Obesity: Surgical and Device Interventions.

FP Essent 2020 May;492:30-36

Lahey Hospital & Medical Center, 41 Burlington Mall Road Burlington, MA 01805.

Bariatric surgery remains the most effective intervention for long-term sustained weight loss and resolution of comorbidities. It should be considered for patients with a body mass index of 40 kg/m or greater regardless of comorbidities and for patients with a body mass index of 30 kg/m with significant comorbidities, such as diabetes and sleep apnea. For these patients, laparoscopic bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and duodenal switch, is safe with minimal perioperative risks of morbidity and mortality. Surgical management is associated with a survival benefit and resolution of common morbidities compared with nonsurgical management, despite the risk of postsurgical complications. These include gastroesophageal reflux disease, weight regain, bleeding, infection, and deep venous thrombosis. All patients who have undergone bariatric surgery require lifelong follow-up, including vitamin supplementation, annual laboratory testing, and multidisciplinary care (eg, dietary and psychological support). Bariatric surgery also has been shown to be safe in appropriate adolescent and elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2020

Low FVC/TLC in Preserved Ratio Impaired Spirometry (PRISm) is associated with features of and progression to obstructive lung disease.

Sci Rep 2020 03 20;10(1):5169. Epub 2020 Mar 20.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals. We examined the utility of FVC/TLC in identifying features of obstructive lung disease. The ratio of post-bronchodilator FVC and TLC from chest CT (FVC/TLC) among current and former smokers with PRISm (FEV/FVC ≥ 0.7 and FEV1 < 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low. We examined the associations between FVC/TLC quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality. Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLC quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p < 0.001) relative to the very high quartile. The very low FVC/TLC quartile was associated with increased total (IRR = 1.65; 95% CI [1.07-2.54]) and severe (IRR = 2.24; 95% CI [1.29-3.89]) respiratory exacerbations. Mortality was lower in the very high FVC/TLC quartile relative to the other quartiles combined. Reduced FVC/TLC ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61932-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083974PMC
March 2020

Association of birthplace and occupational exposures with chronic bronchitis in US Hispanics/Latinos, 2008-2011.

Occup Environ Med 2020 05 12;77(5):344-350. Epub 2020 Mar 12.

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, US

Objectives: In the US, chronic bronchitis (CB) is common and is associated with substantial morbidity and mortality. Data on CB in the Hispanic/Latino population-a large, diverse US minority-are scarce. We aimed to test whether the prevalence of CB varies across Hispanic/Latino heritages and to identify CB risk factors, including occupational exposures, in this population.

Methods: We analysed data from the Hispanic Community Health Study/Study of Latinos, a US population-based probability sample of participants aged 18-74 years (n=16 415) including those with Mexican, Puerto Rican, Dominican, Cuban, Central American and South American heritages. Participants who had a completed respiratory questionnaire and valid spirometric data were included in the analysis (n=13 259). CB, place of birth, heritage, occupational exposures and other risk factors were based on standardised questionnaires. The prevalence of CB was estimated using survey logistic regression-conditional marginal analysis.

Results: The estimated (mean (95% CI)) overall adjusted prevalence of CB was 12.1% (9.3 to 15.6), with a large variation across heritages. Dominican heritage had a fivefold higher prevalence than South American heritage. US-born participants had a higher adjusted prevalence than their non-US-born counterparts (16.8% (12.5 to 22.1) vs 11.0% (8.5 to 14.10); p=0.022). Compared with non-exposed participants, those exposed to cleaning or disinfecting solutions had a higher adjusted prevalence of CB (12.6% (9.1 to 17.1) vs 11.8% (9.2 to 15.1); p=0.024).

Conclusions: The prevalence of CB was higher among Dominicans than other Hispanic/Latino heritages. CB was more prevalent among US-born participants and those exposed to cleaning and disinfecting solutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/oemed-2019-106081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165031PMC
May 2020

Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis.

Int J Chron Obstruct Pulmon Dis 2019 20;14:2927-2938. Epub 2019 Dec 20.

Department of Medicine, University of Utah, Salt Lake City, UT, USA.

Objective: Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV (BDR) as a measure reflecting the change in flow and in FVC (BDR) reflecting the change in volume.

Methods: We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.

Results: A majority of COPD participants exhibited BDR (52.7%). BDR occurred more often in earlier stages of COPD, while BDR occurred more frequently in more advanced disease. When defined by increases in either FEV or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDR was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDR was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV.

Conclusion: With advanced airflow obstruction in COPD, BDR is more prevalent in comparison to BDR and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV, BDR itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.

Clinical Trials Registration: ClinicalTrials.gov: NCT01969344T4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S220164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930016PMC
July 2020

COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

Chronic Obstr Pulm Dis 2019 Nov;6(5):384-399

Northeastern University, Boston, Massachusetts.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.

Methods: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.

Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.

Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.5.2019.0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020846PMC
November 2019

Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial.

BMJ Open Respir Res 2019 4;6(1):e000431. Epub 2019 May 4.

Division of Infection, Immunity and Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, The University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Rationale: Systemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts.

Objectives: Relate systemic levels of those proteins to forced expiratory volume in 1 s (FEV) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial.

Methods: Participants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender.

Results: Systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV, FEV decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months.

Conclusions: In COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD.

Trial Registration Number: NCT01313676.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjresp-2019-000431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561388PMC
July 2020

Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probe disease severity in COPD.

Eur Respir J 2019 08 1;54(2). Epub 2019 Aug 1.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Perturbations in airway mucus properties contribute to lung function decline in patients with chronic obstructive pulmonary disease (COPD). While alterations in bulk mucus rheology have been widely explored, microscopic mucus properties that directly impact on the dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated.We hypothesised that a tightened mesh structure of spontaneously expectorated mucus ( sputum) would contribute to increased COPD disease severity. Here, we investigated whether the mesh size of COPD sputum, quantified by muco-inert nanoparticle (MIP) diffusion, correlated with sputum composition and lung function measurements.The microstructure of COPD sputum was assessed based on the mean squared displacement (MSD) of variously sized MIPs measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. In total, 33 samples collected from COPD or non-COPD individuals were analysed.We found that 100 nm MIPs differentiated microstructural features of COPD sputum. The mobility of MIPs was more hindered in sputum samples from patients with severe COPD, suggesting a tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function.These findings suggest that sputum microstructure may serve as a novel risk factor for COPD progression and severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00088-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081045PMC
August 2019

Clinical Epidemiology of COPD: Insights From 10 Years of the COPDGene Study.

Chest 2019 08 30;156(2):228-238. Epub 2019 May 30.

Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO. Electronic address:

The Genetic Epidemiology of COPD (COPDGene) study is a noninterventional, multicenter, longitudinal analysis of > 10,000 subjects, including smokers with a ≥ 10 pack-year history with and without COPD and healthy never smokers. The goal was to characterize disease-related phenotypes and explore associations with susceptibility genes. The subjects were extensively phenotyped with the use of comprehensive symptom and comorbidity questionnaires, spirometry, CT scans of the chest, and genetic and biomarker profiling. The objective of this review was to summarize the major advances in the clinical epidemiology of COPD from the first 10 years of the COPDGene study. We highlight the influence of age, sex, and race on the natural history of COPD, and the impact of comorbid conditions, chronic bronchitis, exacerbations, and asthma/COPD overlap.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2019.04.135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198872PMC
August 2019

Chronic Bronchitis: Where Are We Now?

Chronic Obstr Pulm Dis 2019 Apr;6(2):178-192

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15326/jcopdf.6.2.2018.0151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596437PMC
April 2019

The St. George's Respiratory Questionnaire Definition of Chronic Bronchitis May Be a Better Predictor of COPD Exacerbations Compared With the Classic Definition.

Chest 2019 10 15;156(4):685-695. Epub 2019 May 15.

Lewis Katz School of Medicine at Temple University, Philadelphia, PA.

Background: Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown.

Methods: We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB or classic CB, using the classic definition. In addition, subjects were divided into SGRQ CB or SGRQ CB. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates.

Results: There were 1,434 classic CB subjects and 2,290 SGRQ CB subjects. The classic CB group had a greater exacerbation frequency compared with the classic CB group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P < .0001) and a greater severe exacerbation frequency (0.26 ± 0.74 vs 0.13 ± 0.46 severe exacerbations per patient per year; P < .0001). There were similar differences between the SGRQ CB and SGRQ CB groups. In multivariable analysis, both SGRQ CB and classic CB were independent predictors of exacerbation frequency, but SGRQ CB had a higher regression coefficient. In addition, SGRQ CB was an independent predictor of severe exacerbation frequency whereas classic CB was not.

Conclusions: The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2019.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859248PMC
October 2019

Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease.

Ann Am Thorac Soc 2019 07;16(7):826-835

6 UAB Lung Imaging Core, Lung Health Center, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: ) No-BDR, no BDR in either FEV or FVC; ) FEV-BDR, BDR in FEV but no BDR in FVC; ) FVC-BDR, BDR in FVC but no BDR in FEV; and ) Combined-BDR, BDR in both FEV and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, -1.67; 95% confidence interval [CI], -2.68 to -0.65;  = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03-1.50;  = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05-1.71;  = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58-0.99;  = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. BDR in both FEV and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.201809-601OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600841PMC
July 2019

Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort.

J Psychosom Res 2019 03 7;118:18-26. Epub 2019 Jan 7.

Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Pulmonary, Critical Care, and Sleep Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address:

Objectives: To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms.

Methods: Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms.

Key Results: Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%-12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%-17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25-3.87), male gender (adjusted OR 1.93, 95% CI 1.57-2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30-4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04-2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62-3.02).

Conclusions: Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics.

Primary Funding Source: National Institutes of Health and The COPD Foundation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychores.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383809PMC
March 2019

Looking at the Definition of Airflow Obstruction through a New Lens: Time for a Change?

Authors:
Victor Kim

Ann Am Thorac Soc 2019 02;16(2):191-192

Temple University-Pulmonary and Critical Care Medicine, Temple University, Philadelphia, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.201810-679EDDOI Listing
February 2019

Safety and Tolerability of Comprehensive Research Bronchoscopy in Chronic Obstructive Pulmonary Disease. Results from the SPIROMICS Bronchoscopy Substudy.

Ann Am Thorac Soc 2019 04;16(4):439-446

4 Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan.

Rationale: There is an unmet need to investigate the lower airways in chronic obstructive pulmonary disease (COPD) to define pathogenesis and to identify potential markers to accelerate therapeutic development. Although bronchoscopy is well established to sample airways in various conditions, a comprehensive COPD research protocol has yet to be published.

Objectives: To evaluate the safety and tolerability of a comprehensive research bronchoscopy procedure suitable for multicenter trials and to identify factors associated with adverse events.

Methods: We report the detailed methodology used to conduct the bronchoscopy used in SPIROMICS (the Subpopulations and Intermediate Outcome Measures in COPD Study). The protocol entailed collection of tongue scrapings and oral rinses as well as bronchoscopy with airway inspection, bronchoalveolar lavage (BAL), protected brushings, and endobronchial biopsies. Visual airway characteristics were graded on a scale of 0 (normal appearance) to 3 (severe abnormality) in four domains: erythema, edema, secretions, and friability. Adverse events were defined as events requiring intervention. Logistic regression modeling assessed associations between adverse event occurrence and key variables.

Results: We enrolled 215 participants. They were 61 ± 9 years old, 71% were white, 53% were male, and post-bronchodilator forced expiratory volume in 1 second was 89 ± 19% predicted. Self-reported asthma was present in 22% of bronchoscopy participants. Oral samples were obtained in greater than or equal to 99% of participants. Airway characteristics were recorded in 99% and were most often characterized as free of edema (61.9%). Less than 50% reported secretions, friability, or erythema. BAL yielded 111 ± 57 ml (50%) of the 223 ± 65 ml of infusate, brushes were completed in 98%, and endobronchial biopsies were performed in 82% of procedures. Adverse events requiring intervention occurred in 14 (6.7%) of 208 bronchoscopies. In logistic regression models, female sex (risk ratio [RR], 1.10; 95% confidence interval [CI], 1.02-1.19), self-reported asthma (RR, 1.17; 95% CI, 1.02-1.34), bronchodilator reversibility (RR, 1.17; 95% CI, 1.04-1.32), COPD (RR, 1.10; 95% CI, 1.02-1.20), forced expiratory volume in 1 second (RR, 0.97; 95% CI, 0.95-0.99), and secretions (RR, 1.85; 1.08-3.16) or friability (RR, 1.64; 95% CI, 1.04-2.57) observed during bronchoscopy were associated with adverse events.

Conclusions: A research bronchoscopy procedure that includes oral sampling, BAL, endobronchial biopsy, and brushing can be safely performed. Airway characteristics during bronchoscopy, demographics, asthma or COPD, and lung function may convey increased risk for procedure-related events necessitating intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.201807-441OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441692PMC
April 2019

Association of low income with pulmonary disease progression in smokers with and without chronic obstructive pulmonary disease.

ERJ Open Res 2018 Oct 12;4(4). Epub 2018 Nov 12.

Dept of Medicine, National Jewish Health, Denver, CO, USA.

Low socioeconomic status has been associated with chronic obstructive pulmonary disease (COPD) but little is known about its impact on disease progression. We assessed the association of income to symptoms, pulmonary disease severity and progression in smokers with and without COPD. The COPDGene cohort of 4826 smokers who reported annual income in phase 2 was analysed. Those who reported annual income
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00069-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230816PMC
October 2018

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

JCI Insight 2018 11 15;3(22). Epub 2018 Nov 15.

The SPIROMICS and COPDGene groups are detailed in the Supplemental Acknowledgments.

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Trial Registration: ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene).

Funding: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.123614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302944PMC
November 2018

Dawn of a New Era in the Diagnosis and Treatment of Airway Mucus Dysfunction.

Am J Respir Crit Care Med 2019 01;199(2):133-134

3 Department of Pulmonary Medicine University of Texas MD Anderson Cancer Center Houston, Texas.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201808-1444EDDOI Listing
January 2019

What is a COPD exacerbation? Current definitions, pitfalls, challenges and opportunities for improvement.

Eur Respir J 2018 11 15;52(5). Epub 2018 Nov 15.

The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

Chronic obstructive pulmonary disease (COPD) is a chronic illness that can be periodically punctuated by exacerbations, characterised by acute worsening of symptoms, including increased dyspnoea, cough, sputum production and sputum purulence. COPD exacerbations are common and have important clinical and economic consequences, including lost work productivity, increased utilisation of healthcare resources, temporary or permanent reductions in lung function and exercise capacity, hospitalisation, and sometimes death. Over the past two decades, clinicians and researchers have broadened their treatment goals for COPD to extend beyond improving lung function and symptoms, and have begun to address the importance of preventing and reducing exacerbations. However, despite the best efforts of clinicians and guideline committees, current definitions of COPD exacerbations are imperfect and fraught with problems. The cardinal symptoms of a COPD exacerbation are nonspecific and can result from acute cardiorespiratory illnesses other than COPD. A proposed definition, which may be more specific than current definitions, suggests that COPD exacerbation be defined as an acute or subacute worsening of dyspnoea (≥5 on a visual analogue scale that ranges from 0 to 10) sometimes but not necessarily accompanied by increased cough, sputum volume and/or sputum purulence. Necessary laboratory criteria for an exacerbation include oxygen desaturation ≤4% below that of stable state, elevated levels of circulating blood neutrophils or eosinophils (≥9000 neutrophils·mm or ≥2% blood eosinophils) and elevated C-reactive protein (≥3 mg·L), without evidence of pneumonia or pulmonary oedema on chest radiography and with negative laboratory test results for other aetiologies. Herein, we discuss the current state of the art with respect to how we define COPD exacerbations, associated pitfalls and challenges, and opportunities for improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.01261-2018DOI Listing
November 2018
-->