Featured Post
Pulmonary nocardiosis in immunocompetent patients: can COPD be the only risk factor?
Tool Identifies Degree Of 1-year Mortality Risk In Patients With Chronic Lung Disease, PH
August 26, 2025
4 min read
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
Key takeaways:A risk assessment tool including five factors identified whether patients with chronic lung disease and pulmonary hypertension face a high, intermediate or low risk for 1-year mortality, according to study results.
These findings were published in BMC Pulmonary Medicine.
"For frontline clinicians, the score offers several practical benefits: improved prognostication at the point of diagnosis; a framework to guide decisions regarding referral for lung transplantation, palliative care discussions or therapeutic escalation; and enhanced clarity in shared decision-making with patients and caregivers," Mario Naranjo-Tovar, MD, MHS, assistant professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, told Healio.
"Because the score relies exclusively on data routinely collected in clinical practice, it is both feasible and scalable for real-world implementation," Naranjo-Tovar said.
In a retrospective cohort study, Naranjo-Tovar and colleagues evaluated 793 patients (mean age, 63.3 years; 50.8% men; 49.9% non-Hispanic white) with chronic lung disease and pulmonary hypertension (PH) to determine predictors of 1-year mortality from time of PH diagnosis, create a risk assessment tool using this information and validate it.
"Patients with chronic lung diseases — like pulmonary fibrosis or COPD — often go on to develop PH, a condition that dramatically worsens survival," Naranjo-Tovar told Healio. "However, clinicians have lacked a validated, disease-specific tool to predict mortality in this high-risk group.
"Existing risk scores are designed for pulmonary arterial hypertension and don't adequately account for the unique pathophysiology seen in patients whose PH arises from underlying lung disease," he added.
The most common underlying lung disease in this population was COPD (41.6%), followed by pulmonary fibrosis without emphysema (31.7%), combined pulmonary fibrosis and emphysema (13.2%), advanced pulmonary sarcoidosis (8.8%) and non-fibrotic interstitial lung disease (4.7%).
Using multivariable Cox regression, researchers found five factors that significantly raised the risk for 1-year mortality and were deemed predictors:
"Notably, mean pulmonary artery pressure — a cornerstone metric for diagnosing PH — did not emerge as an independent predictor of 1-year mortality," Naranjo-Tovar told Healio. "This suggests that traditional hemodynamic severity may be less prognostically relevant in chronic lung disease-associated PH than previously assumed.
"These insights reinforced the notion that functional capacity (eg, 6-minute walk distance) and biomarkers of cardiac strain (eg, BNP) may offer superior predictive value over isolated hemodynamic metrics in this population," he continued.
The study reported that each predictor was given a point value based on its hazard ratio, meaning that pulmonary fibrosis without emphysema had the highest point value (4 points), age older than 65 and BNP greater than 200 pg/dL had the second highest point value (each 3 points) and 6MWD less than 150 m and PVR greater than 5 WU had the lowest point value (each 2 points).
Researchers outlined that a total score of 0 to 3 signaled low risk, a score of 4 to 10 signaled intermediate risk and a score of 11 to 14 signaled high risk. Using these ranges in the 407 patients with full data to calculate a risk score, 155 had low risk, 212 had intermediate risk and 40 had high risk.
Aligning with their calculated PVD-B65 tool risk score, the high-risk group had the highest proportion of patients who died by 1 year at 17.5%, according to the study. Following suit, the intermediate-risk group had the second highest proportion (9.4%) and the low-risk group had the lowest proportion (3.9%).
Researchers also found that the risk for 1-year mortality was significantly elevated among those with high vs. Low risk (HR = 6.2; 95% CI, 2.08-18.48) and those with intermediate vs. Low risk (HR = 2.59; 95% CI, 1.04-4.65) in Cox regression analysis.
Additionally, 1-year survival probability significantly differed between those with high vs. Intermediate risk and those with intermediate vs. Low risk in Kaplan-Meier survival analysis, according to the study.
Lastly, researchers reported that the PVD-B65 risk score calculator achieved internal validation in Cox regression with bootstrapping, noting that the findings were comparable to those observed above in the original Cox regression analysis.
"The development of the PVD-B65 score represents a significant advancement in risk stratification for chronic lung disease-PH patients," Naranjo-Tovar told Healio. "By integrating five binary clinical variables, the model provides an intuitive, evidence-based method for estimating 1-year mortality risk."
Moving forward, Naranjo-Tovar said external validation is needed.
"Future investigations will focus on external validation across diverse patient cohorts and health care systems to assess the model's generalizability," Naranjo-Tovar told Healio.
"The PVD-B65 score fills a longstanding gap in pulmonary vascular medicine: a validated, lung disease-specific tool to predict 1-year mortality in patients with PH," he said. "It's clinically accessible, prognostically robust and offers a new lens through which clinicians can individualize care for a complex and vulnerable population."
For more information:Mario Naranjo-Tovar, MD, MHS, can be reached at mario.Naranjo-tovar@tuhs.Temple.Edu.
Perspective Back to Top PH in the context of chronic lung disease remains a formidable clinical challenge, often portending poor outcomes and limited therapeutic clarity. In this study, Gayen et al introduce the PVD-B65 risk score — a novel, internally validated tool designed to predict 1-year mortality in patients with PH in the setting of chronic lung disease. The retrospective cohort included 793 patients diagnosed with severe PH diagnosed via right heart catheterization (mPAP > 35 mmHg or mPAP 25 mmHg with reduced cardiac index in accordance with the 2015 guidelines, or PV > 5 WU in accordance with 2022 guidelines) between 2011 and 2023. Underlying lung diseases included COPD (42%), pulmonary fibrosis without emphysema (32%), CPFE (13%), sarcoidosis (9%) and non-fibrotic ILD (5%). The score integrates five variables: pulmonary fibrosis without emphysema, pulmonary vascular resistance (PVR) greater than 5 WU, 6MWD less than 150 m, BNP greater than 200 pg/mL and age greater than 65 years. The score stratifies patients into low, intermediate and high-risk categories with statistically significant survival differences. Clinically, this tool has the potential to address an important gap. Existing risk models, largely derived from PAH cohorts, fail to account for the heterogeneity and complexity of PH in chronic lung disease. Further, the components of the risk score (PVR, 6MWD, BNP, type of chronic lung disease) are already widely used in clinical practice, increasing its appeal for "real world" applications. When a patient scores in the intermediate or high-risk categories, for example, clinicians may be prompted to augment therapy (when feasible) or refer for consideration of lung transplant, if appropriate. External validation of the tool is certainly warranted and will likely be quite informative. Going forward, risk stratification tools tailored toward specific types of chronic lung disease — which are both clinically and physiologically heterogeneous — would be invaluable, particularly as treatment options continue to evolve. Nonetheless, the PVD-B65 risk score's simplicity and applicability make it a promising candidate for integration into routine practice. Kathryn T. Del Valle, MD Assistant Program Director and Assistant Professor of Medicine, Mayo Clinic Pulmonary Hypertension Fellowship ProgramDisclosures: Del Valle reports no relevant financial disclosures.
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
Chronic Obstructive Pulmonary Disease - Nature
Vestbo, J. Et al. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. Am. J. Respir. Crit. Care Med. 187, 347–365 (2013). This strategy document is often regarded as the COPD standard and is the basis for most national guidelines.
Article CAS PubMed Google Scholar
Lange, P. Et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N. Engl. J. Med. 373, 111–122 (2015).
Article CAS PubMed Google Scholar
Lozano, R. Et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2013).
Article Google Scholar
Burney, P. G., Patel, J., Newson, R., Minelli, C. & Naghavi, M. Global and regional trends in COPD mortality, 1990–2010. Eur. Respir. J. 45, 1239–1247 (2015). This paper demonstrates that the cross-sectional association found between mortality from chronic lung disease and gross national income is also reflected in an association between the change in mortality from chronic lung disease and the change in gross national income. The association is less prone to confounding by other large differences between regions.
Article PubMed PubMed Central Google Scholar
Gershon, A. S., Warner, L., Cascagnette, P., Victor, J. C. & To, T. Lifetime risk of developing chronic obstructive pulmonary disease: a longitudinal population study. Lancet 378, 991–996 (2011).
Article PubMed Google Scholar
Yawn, B. Et al. Prevalence of COPD among symptomatic patients in a primary care setting. Curr. Med. Res. Opin. 25, 2671–2677 (2009).
Article PubMed Google Scholar
Buist, A. S. Et al. International variation in the prevalence of COPD (the BOLD study): a population-based prevalence study. Lancet 370, 741–750 (2007).
Article PubMed Google Scholar
Menezes, A. M. Et al. Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America. Eur. Respir. J. 30, 1180–1185 (2007).
Article CAS PubMed Google Scholar
Hooper, R. Et al. Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project. Eur. Respir. J. 39, 1343–1353 (2012).
Article PubMed Google Scholar
Blanc, P. D. Et al. Further exploration of the links between occupational exposure and chronic obstructive pulmonary disease. J. Occup. Environ. Med. 51, 804–810 (2009).
Article PubMed PubMed Central Google Scholar
Chinn, S., Florey, C. D., Baldwin, I. G. & Gorgol, M. The relation of mortality in England and Wales1969–1973 to measurements of air pollution. J. Epidemiol. Commun. Health 35, 174–179 (1981).
Article CAS Google Scholar
Salvi, S. & Barnes, P. Chronic obstructive pulmonary disease in non-smokers. Lancet 374, 733–743 (2009).
Article PubMed Google Scholar
Burnett, R. T. Et al. An integrated risk function for estimating the global burden of disease attributable to ambient fine particulate patter exposure. Environ. Health Persp. 122, 397–403 (2014).
Article Google Scholar
Romieu, I. Et al. Improved biomass stove intervention in rural Mexico: impact on the respiratory health of women. Am. J. Respir. Crit. Care Med. 180, 649–656 (2009).
Article PubMed Google Scholar
Zhou, Y. Et al. Lung function and incidence of chronic obstructive pulmonary disease after improved cooking fuels and kitchen ventilation: a 9-year prospective cohort study. PLoS Med. 11, e1001621 (2014).
Article PubMed PubMed Central Google Scholar
Smith, M. Et al. Prevalence and correlates of airflow obstruction in 317,000 never-smokers in China. Eur. Respir. J. 44, 66–77 (2014).
Article PubMed PubMed Central Google Scholar
Burney, P. Et al. Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty — a BOLD analysis. Thorax 69, 465–473 (2014). This paper shows that the prevalence of airflow obstruction is strongly associated with the prevalence of smoking, as judged by the mean pack years smoked, and that the prevalence of a low FVC is strongly associated with poverty. The prevalence of a low FVC is most closely associated with mortality rates.
Article PubMed Google Scholar
Office of Population Censuses and Surveys. Occupational Mortality: The Registrar General's Decennial Supplement for Great Britain, 1979–80, 1982–1983 (Her Majesty's Stationery Office, 1986).
Marks, G. & Burney, P. In The Health of Adult Britain 1841–1991 Vol. 2 (eds Charlton, J. & Murphy, M. ) 93–113 (Her Majesty's Stationery Office, 1997).
Google Scholar
Barker, D. J. & Osmond, C. Childhood respiratory infection and adult chronic bronchitis in England and Wales. BMJ (Clin. Res. Ed.) 293, 1271–1275 (1986). This is an early paper from Barker and Osmond showing that mortality rates from chronic airway disease later in adult life is associated with mortality in the same areas from bronchitis and pneumonia among children half a century earlier. This association was not true for lung cancer rates, and Barker and Osmond suggest that this is evidence that the environment encountered during early life has an important impact on subsequent lung health.
Article CAS Google Scholar
Gnatiuc, L. Et al. Gaps in using bronchodilators, inhaled corticosteroids and influenza vaccine among 23 high- and low-income sites. Int. J. Tuberc. Lung Dis. 19, 21–30 (2015).
Article CAS PubMed Google Scholar
Ingebrigtsen, T. Et al. Genetic influences on chronic obstructive pulmonary disease — a twin study. Respir. Med. 104, 1890–1895 (2010).
Article PubMed Google Scholar
McCloskey, S. C. Et al. Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am. J. Respir. Crit. Care Med. 164, 1419–1424 (2001).
Article CAS PubMed Google Scholar
Silverman, E. K. Et al. Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease: risk to relatives for airflow obstruction and chronic bronchitis. Am. J. Respir. Crit. Care Med. 157, 1770–1778 (1998).
Article CAS PubMed Google Scholar
Zhou, J. J. Et al. Heritability of chronic obstructive pulmonary disease and related phenotypes in smokers. Am. J. Respir. Crit. Care Med. 188, 941–947 (2013).
Article PubMed PubMed Central Google Scholar
Silverman, E. K. & Sandhaus, R. A. Clinical practice. Alpha1-antitrypsin deficiency. N. Engl. J. Med. 360, 2749–2757 (2009).
Article CAS PubMed Google Scholar
Sorheim, I. C. Et al. α1-Antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. Chest 138, 1125–1132 (2010).
Article PubMed PubMed Central Google Scholar
Molloy, K. Et al. Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes. Am. J. Respir. Crit. Care Med. 189, 419–427 (2014).
Article CAS PubMed PubMed Central Google Scholar
Rodriguez-Revenga, L. Et al. A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa. Arch. Dermatol. 140, 1135–1139 (2004).
Article CAS PubMed Google Scholar
Kelleher, C. M. Et al. A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease. Am. J. Respir. Cell. Mol. Biol. 33, 355–362 (2005).
Article CAS PubMed PubMed Central Google Scholar
Wain, L. V. Et al. Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction. PLoS Genet. 10, e1004314 (2014).
Article CAS PubMed PubMed Central Google Scholar
Castaldi, P. J. Et al. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Hum. Mol. Genet. 19, 526–534 (2010).
Article CAS PubMed Google Scholar
Smolonska, J., Wijmenga, C., Postma, D. S. & Boezen, H. M. Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years' research. Am. J. Respir. Crit. Care Med. 180, 618–631 (2009).
Article CAS PubMed Google Scholar
Cho, M. H. Et al. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respir. Med. 2, 214–225 (2014). This collaborative genome-wide association study identifies four genetic loci for moderate-to-severe COPD and two additional loci for severe COPD. Although highly significant, these genetic loci are of modest effect size.
CAS Google Scholar
Hancock, D. B. Et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat. Genet. 42, 45–52 (2010).
Article CAS PubMed Google Scholar
Repapi, E. Et al. Genome-wide association study identifies five loci associated with lung function. Nat. Genet. 42, 36–44 (2010).
Article CAS PubMed Google Scholar
Soler Artigas, M. Et al. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nat. Genet. 43, 1082–1090 (2011).
Article CAS PubMed Google Scholar
Castaldi, P. J. Et al. Genome-wide association identifies regulatory loci associated with distinct local histogram emphysema patterns. Am. J. Respir. Crit. Care Med. 190, 399–409 (2014).
Article CAS PubMed PubMed Central Google Scholar
Siedlinski, M. Et al. Genome-wide association study of smoking behaviours in patients with COPD. Thorax 66, 894–902 (2011).
Article PubMed Google Scholar
Thorgeirsson, T. E. Et al. Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior. Nat. Genet. 42, 448–453 (2010).
Article CAS PubMed PubMed Central Google Scholar
Amos, C. I. Et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat. Genet. 40, 616–622 (2008).
Article CAS PubMed PubMed Central Google Scholar
Thorgeirsson, T. E. Et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452, 638–642 (2008).
Article CAS PubMed PubMed Central Google Scholar
DeMeo, D. L. Et al. Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene. Am. J. Hum. Genet. 85, 493–502 (2009).
Article CAS PubMed PubMed Central Google Scholar
Siedlinski, M. Et al. Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility. Hum. Genet. 132, 431–441 (2013).
Article PubMed PubMed Central Google Scholar
Zhou, X. Et al. Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Hum. Mol. Genet. 21, 1325–1335 (2012). With a COPD genome-wide association study region, chromatin interaction studies followed by functional analyses identified a likely functional genetic variant. This is one of the first examples of functional variant identification with a complex disease genome-wide association study locus.
Article CAS PubMed Google Scholar
Lao, T. Et al. Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring. Genome Med. 7, 12 (2015).
Article CAS PubMed PubMed Central Google Scholar
Castaldi, P. J. Et al. Genetic control of gene expression at novel and established chronic obstructive pulmonary disease loci. Hum. Mol. Genet. 24, 1200–1210 (2015).
Article CAS PubMed Google Scholar
Qiu, W. Et al. Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function. Am. J. Respir. Crit. Care Med. 185, 373–381 (2012).
Article CAS PubMed PubMed Central Google Scholar
Hogg, J. C. & Timens, W. The pathology of chronic obstructive pulmonary disease. Annu. Rev. Pathol. 4, 435–459 (2009).
Article CAS PubMed Google Scholar
McDonough, J. E. Et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N. Engl. J. Med. 365, 1567–1575 (2011).
Article CAS PubMed PubMed Central Google Scholar
Galban, C. J. Et al. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat. Med. 18, 1711–1715 (2012).
Article CAS PubMed PubMed Central Google Scholar
Peinado, V. I., Pizarro, S. & Barbera, J. A. Pulmonary vascular involvement in COPD. Chest 134, 808–814 (2008).
Article CAS PubMed Google Scholar
Seeger, W. Et al. Pulmonary hypertension in chronic lung diseases. J. Am. Coll. Cardiol. 62, D109–D116 (2013).
Article PubMed Google Scholar
Barnes, P. J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 35, 71–86 (2014).
Article PubMed Google Scholar
Brusselle, G. G., Joos, G. F. & Bracke, K. R. New insights into the immunology of chronic obstructive pulmonary disease. Lancet 378, 1015–1026 (2011).
Article CAS PubMed Google Scholar
Barnes, P. J. Immunology of asthma and chronic obstructive pulmonary disease. Nat. Immunol. Rev. 8, 183–192 (2008).
Article CAS Google Scholar
McAleer, J. P. & Kolls, J. K. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense. Immunol. Rev. 260, 129–144 (2014).
Article CAS PubMed PubMed Central Google Scholar
Barrecheguren, M., Esquinas, C. & Miravitlles, M. The asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS): opportunities and challenges. Curr. Opin. Pulm. Med. 21, 74–79 (2015).
Article CAS PubMed Google Scholar
Barnes, P. J. Cytokine networks in asthma and chronic obstructive pulmonary disease. J. Clin. Invest. 118, 3546–3556 (2008).
Article CAS PubMed PubMed Central Google Scholar
Di Stefano, A. Et al. Increased expression of NF-κB in bronchial biopsies from smokers and patients with COPD. Eur. Respir. J. 20, 556–563 (2002).
Article CAS PubMed Google Scholar
Renda, T. Et al. Increased activation of p38 MAPK in COPD. Eur. Respir. J. 31, 62–69 (2008).
Article CAS PubMed Google Scholar
Ito, K. Et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl. J. Med. 352, 1967–1976 (2005). This study demonstrates that COPD lungs have decreased expression and activity of the nuclear enzyme HD2, which is required for corticosteroids to switch off inflammatory genes. This result explains the amplified inflammation and corticosteroid resistance in patients with COPD.
Article CAS PubMed Google Scholar
Taylor, A. E. Et al. Defective macrophage phagocytosis of bacteria in COPD. Eur. Respir. J. 35, 1039–1047 (2010).
Article CAS PubMed Google Scholar
Donnelly, L. E. & Barnes, P. J. Defective phagocytosis in airways disease. Chest 141, 1055–1062 (2012).
Article PubMed Google Scholar
Singh, R. Et al. Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease. Respir. Res. 15, 114 (2014).
Article CAS PubMed PubMed Central Google Scholar
Mukaro, V. R. & Hodge, S. Airway clearance of apoptotic cells in COPD. Curr. Drug Targets 12, 460–468 (2011).
Article CAS PubMed Google Scholar
Kirkham, P. A. Et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of COPD. Am. J. Respir. Crit. Care Med. 184, 796–802 (2011).
Article CAS PubMed PubMed Central Google Scholar
Barnes, P. J. Chronic obstructive pulmonary disease: effects beyond the lungs.PLoS Med. 7, e1000220 (2010).
Article PubMed PubMed Central Google Scholar
Agusti, A. Et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS ONE 7, e37483 (2012).
Article CAS PubMed PubMed Central Google Scholar
Ito, K. & Barnes, P. J. COPD as a disease of accelerated lung aging. Chest 135, 173–180 (2009).
Article PubMed Google Scholar
Mercado, N., Ito, K. & Barnes, P. J. Accelerated ageing in chronic obstructive pulmonary disease: new concepts. Thorax 70, 482–489 (2015). A review of the accelerated ageing process in COPD and the molecular mechanisms involved; this article also identifies novel targets for future therapies.
Article PubMed Google Scholar
Paschalaki, K. E. Et al. Dysfunction of endothelial progenitor cells from smokers and COPD patients due to increased DNA damage and senescence. Stem Cells 31, 2813–2826 (2013).
Article CAS PubMed PubMed Central Google Scholar
Barnes, P. J. Mechanisms of development of multimorbidity in the elderly. Eur. Respir. J. 45, 790–806 (2015).
Article CAS PubMed Google Scholar
Madeo, F., Zimmermann, A., Maiuri, M. C. & Kroemer, G. Essential role for autophagy in life span extension. J. Clin. Invest. 125, 85–93 (2015).
Article PubMed PubMed Central Google Scholar
Mizumura, K., Cloonan, S. M., Haspel, J. A. & Choi, A. M. The emerging importance of autophagy in pulmonary diseases. Chest 142, 1289–1299 (2012).
Article CAS PubMed PubMed Central Google Scholar
Kirkham, P. A. & Barnes, P. J. Oxidative stress in COPD. Chest 144, 266–273 (2013).
Article CAS PubMed Google Scholar
Caramori, G. Et al. Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer. Thorax 66, 521–527 (2011).
Article PubMed Google Scholar
Barnes, P. J. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 131, 636–645 (2013).
Article CAS PubMed Google Scholar
Nakamaru, Y. Et al. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J. 23, 2810–2819 (2009).
Article CAS PubMed Google Scholar
Malhotra, D. Et al. Expression of concern: decline in NRF2 regulated antioxidants in COPD lungs due to loss of its positive regulator DJ-1. Am. J. Respir. Crit. Care Med. 178, 592–604 (2008).
Article CAS PubMed PubMed Central Google Scholar
Mercado, N. Et al. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress. Biochem. Biophys. Res. Commun. 406, 292–298 (2011).
Article CAS PubMed PubMed Central Google Scholar
Hara, H. Et al. Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence. Am. J. Physiol. Lung Cell. Mol. Physiol. 305, L737–L746 (2013).
Article CAS PubMed Google Scholar
Mizumura, K. Et al. Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. J. Clin. Invest. 124, 3987–4003 (2014).
Article CAS PubMed PubMed Central Google Scholar
Guenette, J. A., Webb, K. A. & O'Donnell, D. E. Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD? Eur. Respir. J. 40, 322–329 (2012).
Article PubMed Google Scholar
Wedzicha, J. A. & Seemungal, T. A. COPD exacerbations: defining their cause and prevention. Lancet 370, 786–796 (2007). This paper provides an excellent insight into the nature of exacerbations of COPD, their importance, clinical consequences and prevention of their occurrence.
Article PubMed PubMed Central Google Scholar
Seemungal, T. Et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 164, 1618–1623 (2001).
Article CAS PubMed Google Scholar
George, S. N. Et al. Human rhinovirus infection during naturally occurring COPD exacerbations. Eur. Respir. J. 44, 87–96 (2014).
Article PubMed Google Scholar
Peacock, J. L. Et al. Outdoor air pollution and respiratory health in patients with COPD. Thorax 66, 591–596 (2011).
Article PubMed Google Scholar
Seemungal, T. A. Et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 157, 1418–1422 (1998).
Article CAS PubMed Google Scholar
Hurst, J. R. Et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N. Engl. J. Med. 363, 1128–1138 (2010).
Article CAS PubMed Google Scholar
Wedzicha, J. A., Brill, S. E., Allinson, J. P. & Donaldson, G. C. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease. BMC Med. 11, 181 (2013).
Article PubMed PubMed Central Google Scholar
Celli, B. R. & MacNee, W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur. Respir. J. 23, 932–946 (2004).
Article CAS PubMed Google Scholar
Barr, R. G. Et al. Physician and patient perceptions in COPD: the COPD Resource Network Needs Assessment Survey. Am. J. Med. 118, 1415 (2005).
Article PubMed Google Scholar
Cote, C. G. & Chapman, K. R. Diagnosis and treatment considerations for women with COPD. Int. J. Clin. Pract. 63, 486–493 (2009).
Article CAS PubMed Google Scholar
Lundback, B. Et al. Not 15 but 50% of smokers develop COPD? — Report from the Obstructive Lung Disease in Northern Sweden studies. Respir. Med. 97, 115–122 (2003).
Article CAS PubMed Google Scholar
Sood, A. Et al. Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers. Am. J. Respir. Crit. Care Med. 182, 1098–1104 (2010).
Article CAS PubMed PubMed Central Google Scholar
Celli, B. R., Halbert, R. J., Nordyke, R. J. & Schau, B. Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey. Am. J. Med. 118, 1364–1372 (2005).
Article PubMed Google Scholar
Stern, D. A., Morgan, W. J., Wright, A. L., Guerra, S. & Martinez, F. D. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet 370, 758–764 (2007).
Article PubMed PubMed Central Google Scholar
Sanchez-Salcedo, P. Et al. Disease progression in young patients with COPD: rethinking the Fletcher and Peto model. Eur. Respir. J. 44, 324–331 (2014).
Article PubMed Google Scholar
Erb-Downward, J. R. Et al. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS ONE 6, e16384 (2011).
Article CAS PubMed PubMed Central Google Scholar
Burgel, P. R. Et al. Clinical COPD phenotypes: a novel approach using principal component and cluster analyses. Eur. Respir. J. 36, 531–539 (2012).
Article Google Scholar
Garcia-Aymerich, J. Et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax 66, 430–437 (2011).
Article PubMed Google Scholar
Rennard, S. Et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann. Am. Thorac. Soc. 12, 303–312 (2014).
Article Google Scholar
Miller, M. R. Et al. Standardisation of spirometry. Eur. Respir. J. 26, 319–338 (2005).
Article CAS PubMed Google Scholar
Swanney, M. P. Et al. Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction. Thorax 63, 1046–1051 (2008).
Article CAS PubMed Google Scholar
Hankinson, J. L., Odencrantz, J. R. & Fedan, K. B. Spirometric reference values from a sample of the general U. S. Population. Am. J. Respir. Crit. Care Med. 159, 179–187 (1999).
Article CAS PubMed Google Scholar
Celli, B. R. Et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N. Engl. J. Med. 350, 1005–1012 (2004). This work provides the first objective evidence of the importance of non-pulmonary involvement in patients with COPD. In addition, it prospectively validates the measurement of a multidimensional index to prognosticate outcome in patients with COPD.
Article CAS PubMed Google Scholar
Watz, H. Et al. An official European Respiratory Society statement on physical activity in COPD. Eur. Respir. J. 44, 1521–1537 (2014).
Article PubMed Google Scholar
Nici, L., ZuWallack, R. & American Thoracic Society Subcommittee on Integrated Care of the COPD Patient. An official American Thoracic Society workshop report: the Integrated Care of the COPD Patient. Proc. Am. Thorac. Soc. 9, 9–18 (2012).
Article PubMed Google Scholar
Maltais, F. Et al. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 189, e15–e62 (2014).
Article PubMed PubMed Central Google Scholar
Puhan, M. A. Et al. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet 374, 704–711 (2009).
Article PubMed Google Scholar
Jones, R. C. Et al. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE index. Am. J. Respir. Crit. Care Med. 180, 1189–1195 (2009).
Article PubMed Google Scholar
Marin, J. M. Et al. Multicomponent indices to predict survival in COPD: the COCOMICS study. Eur. Respir. J. 42, 323–332 (2013).
Article PubMed Google Scholar
Divo, M. Et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 186, 155–161 (2012).
Article PubMed Google Scholar
Gietema, H. A. Et al. Quantifying the extent of emphysema: factors associated with radiologists' estimations and quantitative indices of emphysema severity using the ECLIPSE cohort. Acad. Radiol. 18, 661–671 (2011).
Article PubMed Google Scholar
de Torres, J. P. Et al. Lung cancer in patients with chronic obstructive pulmonary disease — incidence and predicting factors. Am. J. Respir. Crit. Care Med. 184, 913–919 (2011).
Article PubMed Google Scholar
Vestbo, J. Et al. Changes in forced expiratory volume in 1 second over time in COPD. N. Engl. J. Med. 365, 1184–1192 (2011).
Article CAS PubMed Google Scholar
Comments
Post a Comment