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Mustimbo E. P. Roberts, PhD1 Brandon W. Higgs, PhD1 Philip Brohawn, BS1 Fernanda Pilataxi, BA1 Xiang Guo, PhD1 Michael Kuziora, PhD1 Russell P. Bowler, MD, PhD2 Wendy I. White, PhD1
Author Affiliations
- MedImmune, Department of Translational Sciences, Gaithersburg, Maryland
- National Jewish Health, Department of Medicine, Denver, Colorado
Address correspondence to:
Wendy I. White, PhD
One MedImmune Way
Gaithersburg, MD 20878
Phone: 301-398-4335
Email: whitew@medimmune.com
Abstract
The heterogeneous clinical phenotypes of chronic obstructive pulmonary disease (COPD) challenge successful drug development. To identify COPD subgroups beyond clinical phenotypes, we interrogated blood immune cell profiles and ex-vivo responses of current and former smokers, with or without COPD, in the longitudinal COPD Genetic Epidemiology study (COPDGene) cohort. CD4+ and CD8+ T cells and monocytes were profiled by flow cytometry. Microarray analysis was performed on the RNA from the aforementioned isolated cells. T-cell directed whole blood ex-vivo stimulation was used to assess functional responses. Blood CD4+ T-cell transcript analysis distinguished patients with COPD from control smokers and also enriched for a subset of patients with COPD that had a history of exacerbations of the disease. Analogous analyses of CD8+ T cells and monocytes failed to discriminate patients with COPD from the control population. Patients with COPD had a diminished cytokine response, compared to control smokers, characterized by low levels of granulocyte-monocyte colony stimulation factor (GM-CSF), interferon gamma (IFN-ɣ), interleukin one-alpha (IL-1α), tumor necrosis factor-alpha (TNF-α) and tumor necrosis factor-beta (TNF-β) secreted in response to T-cell directed ex-vivo stimulation. This cytokine response associated with baseline disease severity (forced expiratory volume in 1 second [FEV1]% predicted), rapidly declining lung function, and emphysema. Our observations indicate that COPD phenotypes can be further differentiated based on blood CD4+ T-cell profiles and resultant immune responses, suggesting a role for these cells in COPD pathophysiology.
Citation
Citation: Roberts MEP, Higgs BW, Brohawn P, et al. CD4+ T-cell profiles and peripheral blood ex-vivo responses to T-cell directed stimulation delineate COPD phenotypes. Chronic Obstr Pulm Dis (Miami). 2015; 2(4): 268-280. doi: http://dx.doi.org/10.15326/jcopdf.2.4.2015.0131
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Chundak T Sherpa, MBBS1 Steven L. LeClerq, MPH2 Shakuntala Singh3 Neha Naithani, MBBS, MSPH2 Raju Pangeni, MD3 Arjun Karki, MD4 Ramesh K. Chokhani, MD5 MeiLan Han, MD6 Margaret Gyetko, MD6 James M. Tielsch, PhD7 William Checkley, MD, PhD1,2
Author Affiliations
- Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, Maryland
- Program in Global Disease Epidemiology and Control, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Nepal Nutrition Intervention Project Sarlahi (NNIPS), National Society for the Prevention of Blindness, Kathmandu, Nepal
- Department of Medicine, Patan Academy of Health Sciences, Kathmandu, Nepal
- Department of Pulmonary Medicine, Norvic International Hospital, Kathmandu, Nepal
- Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor
- Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC
Address correspondence to:
William Checkley, MD, PhD
Division of Pulmonary and Critical Care
School of Medicine
Johns Hopkins University
1800 Orleans Ave Suite 9121
Baltimore, MD 21205
Telephone: 443-287-8741
Fax: 410-955-0036
E-mail: wcheckl1@jhmi.edu
Abstract
The St. George’s Respiratory Questionnaire (SGRQ) is a standardized questionnaire for measuring impaired health and perceived well-being in chronic airway disease, but it is not available in the Nepali language. We translated the original SGRQ into Nepali and validated its use in 150 individuals aged 40 to 80 years with and without COPD.We also examined if the SGRQ could be used as a screening tool to identify individuals at risk for COPD. We translated the SGRQ following a standard protocol. The validation study was then conducted in both community and hospital-based settings in Nepal. We enrolled 100 participants from a community setting who were not actively seeking medical care, 50 of which met criteria for chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC]<70%) and 50 who did not. We also enrolled 50 participants with an established diagnosis of COPD who attended outpatient pulmonary clinics. All participants completed the questionnaire. We used linear regressions to compare average SGRQ scores by disease status categories and by lung function values, adjusted for age, sex, height and body mass index (BMI).All 150 participants (mean age 59.8 years, 48% male, mean BMI 20.5 kg/m2) completed the SGRQ. In multivariable regression, the average SGRQ total score was 23.9 points higher in established cases of COPD and 18.1 points higher in community cases of COPD when compared to participants without COPD living in the community (all p<0.001). The SGRQ total score also increased by an average of 2.1 points for each 100 mL decrease in post-FEV1 (p<0.001). The area-under-the-curve for the SGRQ total score as a predictor of COPD was 0.77 (95% confidence interval [CI] 0.68 to 0.85) and the optimal cutoff to identify COPD was 33 points.We developed a Nepali-validated version of SGRQ, which correlated well with both disease status and severity.
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Vickram Tejwani, MD1 Xiao-Feng Wang, PhD2 James K. Stoller, MD, MS3
Author Affiliations
- Internal Medicine, Cleveland Clinic, Ohio
- Quantitative Health Sciences, Cleveland Clinic, Ohio
- Education Institute, Respiratory Institute, Cleveland Clinic, Ohio
Address correspondence to:
Vickram Tejwani, MD
9500 Euclid Avenue, NA10
Cleveland, OH 44195
(216) 444-2336
tejwanv@ccf.org
Abstract
PI*ZZ alpha-1 antitrypsin (AAT) deficiency poses risk for lung disease through 2 different mechanisms: a toxic loss of function in which deficient AAT levels cause a depleted proteolytic screen and, separately, a proinflammatory effect of Z polymers produced both by alveolar macrophages and by the liver. Ample data support the first mechanism, while the possible contribution of the second 2 proinflammatory mechanisms is currently unknown.
Experience with a 74 year-old PI*ZZ female who underwent single lung transplantation and subsequent orthotopic liver transplantation (OLT) may shed light on the relative contributions of each of the potential mechanisms. Availability of multiple pulmonary function tests (PFT) measurements uniquely permitted calculation of rates of lung function change before and after OLT. The rate of forced expiratory volume in 1 second (FEV1) decline normalized post-OLT (from -60 to -21 ml/yr). Her course suggests that restoring the normal serum AAT levels or, alternately, eliminating liver-derived polymers, exerted a greater effect on preventing emphysema progression than local Z polymer production contributed to furthering emphysema.
Citation
Citation:Tejwani V, Wang XF, Stoller JK. The natural history of lung function in severe deficiency of alpha-1 antitrypsin following orthotopic liver transplantation: A case report. Chronic Obstr Pulm Dis (Miami). 2015; 2(4): 290-295. doi: http://dx.doi.org/10.15326/jcopdf.2.4.2015.0141
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Mark Weir, MBChB1 Nathaniel Marchetti, DO1 Aaron Czysz, MD1 Nicholas Hill, MD2 Frank Sciurba, MD3 Patrick Strollo, MD3 Gerard J. Criner, MD1
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
- Division of Pulmonary and Critical Care Medicine, Tufts Medical Center, Boston, Massachusetts
- University of Pittsburgh Medical Center, Division of Pulmonary, Allergy and Critical Care Medicine, Montefiore Hospital, Pittsburgh, Pennsylvania
Address correspondence to:
Mark Weir, MBChB
Division of Pulmonary and Critical Care Medicine
Temple University School of Medicine
745 Parkinson Pavilion
3401 North Broad Street
Philadelphia Pa, 19140
Phone: 215-707-5864
Fax: 215-707-6867
Email: mark.weir@tuhs.temple.edu
Abstract
Introduction: High intensity non-invasive positive pressure ventilation (HI-NPPV) is an algorithm of non-invasive ventilation that has been shown to improve partial pressure of carbon dioxide (PaCO2), health-related quality of life and mortality in hypercapnic chronic obstructive pulmonary disease (COPD) patients.
Objective: Assess 3 months of HI-NPPV in stable hypercapnic COPD patients.
Methods: A single arm, non-randomized pilot study of HI-NPPV. Patients were eligible if they had clinically stable COPD and daytime arterial PaCO2 >50 mmHg.
Results: Nine patients completed therapy. Patient characteristics: 2 male: 7 female, mean age of 64.4 years (SD ±6.6), mean forced expiratory volume in 1 second (FEV1) of 26% (SD±6.73), 8 patients on long term oxygen therapy (LTOT) and a median body mass index (BMI) of 26.6 (interquartile range [IQR] 25.5 – 32.5).
Outcomes: There was a mean reduction in daytime PaCO2 by 4.66 mmHg (p=0.01) and bicarbonate by 2.16 mmHg (p=0.005). There was no statistically significant difference in lung function, maximal inspiratory pressures or 6 minute walk distance. There was no statistically significant difference in sleep duration, efficiency or percentage of sleep stage 3 ( N3) or rapid eye movement (REM). The Chronic Respiratory Questionnaire (CRQ) showed a trend towards improvement with an increase of 2.69 points (p=0.054), the dyspnea domain showed a statistically significant improvement (p=0.03). The Calgary Sleep Apnea Quality of Life Index (SAQLI) detected an improvement in daily functioning (p=0.007). The Severe Respiratory Insufficiency (SRI) Questionnaire showed a trend to improvement overall (p=0.05). Four patients had COPD exacerbations during the follow up period.
Conclusions: HI-NPPV is able to substantially reduce PaCO2 in hypercapnic COPD patients; we detected a positive effect on quality of life measures with no significant change in sleep quality.
Citation
Citation: Weir M, Marchetti N, Czysz A, et al. High intensity non-invasive positive pressure ventilation for stable hypercapnic chronic obstructive pulmonary disease patients. Chronic Obstr Pulm Dis (Miami). 2015; 2(4): 313-320. doi: http://dx.doi.org/10.15326/jcopdf.2.4.2015.0145
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Abdulbaset Kamour, DrPH, MMedSci, MBChB1 David Mannino, MD2 Sarojini Kanotra, PhD, MPH, CHES3
Author Affiliations
- Department of Epidemiology, University of Kentucky, Lexington
- Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington
- Kentucky Department for Public Health, Frankfort
Address correspondence to:
Abdulbaset Kamour
Department of Epidemiology,
University of Kentucky College of Public Health
111 Washington Avenue, Lexington, KY 40536
Telephone: (859) 420-7380
Email: ahka222@uky.edu
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in Kentucky, and precise estimates of the prevalence of this disease and its comorbidities are needed. This study aimed to determine the prevalence of both COPD and its comorbidities and risk differences of COPD comorbidities across Area Development Districts (ADDs) and gender.
Methods: The demographic characteristics, prevalence of self- reported COPD and its comorbidities were determined by using data from the 2011 Kentucky Behavioral Risk Factor Survey (KyBRFS). Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD and comorbidities.
Results: The overall prevalence of age adjusted COPD was 10.09% (95% confidence interval [CI] 9.99, 10.19), 8.85% for men (95% CI 8.76, 8.93), and 10.78% for women (95% CI 10.67, 10.88). Odds ratios for risk of angina or coronary heart disease (CHD), and arthritis among patients with COPD, by sex and ADDs varied significantly (pooled overall OR=3.43, 95% CI 2.70–4.34, heterogeneity p=0.0001) and (pooled overall OR=2.16, 95% CI 1.75–2.67, heterogeneity p=0.0001), respectively. ORs for risk of depression (pooled OR=2.61, 95% CI 1.78–3.70, heterogeneity p=0.028) and hypertension (pooled OR=1.67, 95% CI 1.16–2.42, heterogeneity p=0. 006) only varied significantly in men. Odds ratios for risk of diabetes was not significant across ADDs and gender (pooled overall OR=2.02, 95% CI 1.61–2.53, heterogeneity p=0.709).
Conclusion: Gender differences account for the discrepancy in the risk of comorbidities in patients with COPD across Kentucky’s Area Development Districts. This should guide public health officials and physicians to create gender-based prevention interventions.
Citation
Citation: Kamour A, Mannino D, Kanotra S. Prevalence and comorbidities of chronic obstructive pulmonary disease among adults in Kentucky across gender and area development districts, 2011. Chronic Obstr Pulm Dis (Miami). 2015; 2(4): 296-312. doi: http://dx.doi.org/10.15326/jcopdf.2.4.2015.0138
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