Semin Respir Crit Care Med 2015; 36(04): 575-591
DOI: 10.1055/s-0035-1556063
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management

Nirupama Putcha
1   Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
,
M. Bradley Drummond
1   Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
,
Robert A. Wise
1   Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
,
Nadia N. Hansel
1   Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
› Author Affiliations
Further Information

Publication History

Publication Date:
03 August 2015 (online)

Abstract

Comorbidities impact a large proportion of patients with chronic obstructive pulmonary disease (COPD), with over 80% of patients with COPD estimated to have at least one comorbid chronic condition. Guidelines for the treatment of COPD are just now incorporating comorbidities to their management recommendations of COPD, and it is becoming increasingly clear that multimorbidity as well as specific comorbidities have strong associations with mortality and clinical outcomes in COPD, including dyspnea, exercise capacity, quality of life, healthcare utilization, and exacerbation risk. Appropriately, there has been an increased focus upon describing the burden of comorbidity in the COPD population and incorporating this information into existing efforts to better understand the clinical and phenotypic heterogeneity of this group. In this article, we summarize existing knowledge about comorbidity burden and specific comorbidities in COPD, focusing on prevalence estimates, association with outcomes, and existing knowledge about treatment strategies.

 
  • References

  • 1 Almagro P, López García F, Cabrera F , et al; Grupo Epoc De La Sociedad Española De Medicina Interna. Comorbidity and gender-related differences in patients hospitalized for COPD. The ECCO study. Respir Med 2010; 104 (2) 253-259
  • 2 Anecchino C, Rossi E, Fanizza C, De Rosa M, Tognoni G, Romero M ; working group ARNO project. Prevalence of chronic obstructive pulmonary disease and pattern of comorbidities in a general population. Int J Chron Obstruct Pulmon Dis 2007; 2 (4) 567-574
  • 3 Areias V, Carreira S, Anciães M, Pinto P, Bárbara C. Co-morbidities in patients with gold stage 4 chronic obstructive pulmonary disease. Rev Port Pneumol 2014; 20 (1) 5-11
  • 4 Fumagalli G, Fabiani F, Forte S , et al. INDACO project: a pilot study on incidence of comorbidities in COPD patients referred to pneumology units. Multidiscip Respir Med 2013; 8 (1) 28
  • 5 Putcha N, Puhan MA, Hansel NN, Drummond MB, Boyd CM. Impact of co-morbidities on self-rated health in self-reported COPD: an analysis of NHANES 2001-2008. COPD 2013; 10 (3) 324-332
  • 6 García-Olmos L, Alberquilla A, Ayala V , et al. Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study. BMC Fam Pract 2013; 14: 11
  • 7 López Varela MV, Montes de Oca M, Halbert R , et al; PLATINO team. Comorbidities and health status in individuals with and without COPD in five Latin American cities: the PLATINO study. Arch Bronconeumol 2013; 49 (11) 468-474
  • 8 Noteboom B, Jenkins S, Maiorana A, Cecins N, Ng C, Hill K. Comorbidities and medication burden in patients with chronic obstructive pulmonary disease attending pulmonary rehabilitation. J Cardiopulm Rehabil Prev 2014; 34 (1) 75-79
  • 9 Vanfleteren LE, Spruit MA, Groenen M , et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 187 (7) 728-735
  • 10 Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40 (5) 373-383
  • 11 Divo M, Cote C, de Torres JP , et al; BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186 (2) 155-161
  • 12 de Torres JP, Casanova C, Marín JM , et al. Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE. Thorax 2014; 69 (9) 799-804
  • 13 Frei A, Muggensturm P, Putcha N , et al. Five comorbidities reflected the health status in patients with chronic obstructive pulmonary disease: the newly developed COMCOLD index. J Clin Epidemiol 2014; 67 (8) 904-911
  • 14 Garcia-Aymerich J, Gómez FP, Benet M , et al; PAC-COPD Study Group. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax 2011; 66 (5) 430-437
  • 15 Baty F, Putora PM, Isenring B, Blum T, Brutsche M. Comorbidities and burden of COPD: a population based case-control study. PLoS ONE 2013; 8 (5) e63285
  • 16 Thomsen M, Dahl M, Lange P, Vestbo J, Nordestgaard BG. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186 (10) 982-988
  • 17 Almagro P, Cabrera FJ, Diez J , et al; Working Group on COPD, Spanish Society of Internal Medicine. Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD: the EPOC en Servicios de Medicina Interna (ESMI) study. Chest 2012; 142 (5) 1126-1133
  • 18 Kinnunen T, Säynäjäkangas O, Tuuponen T, Keistinen T. Impact of comorbidities on the duration of COPD patients' hospital episodes. Respir Med 2003; 97 (2) 143-146
  • 19 Lin PJ, Shaya FT, Scharf SM. Economic implications of comorbid conditions among Medicaid beneficiaries with COPD. Respir Med 2010; 104 (5) 697-704
  • 20 Budweiser S, Harlacher M, Pfeifer M, Jörres RA. Co-morbidities and hyperinflation are independent risk factors of all-cause mortality in very severe COPD. COPD 2014; 11 (4) 388-400
  • 21 Marti S, Muñoz X, Rios J, Morell F, Ferrer J. Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy. Eur Respir J 2006; 27 (4) 689-696
  • 22 Miller J, Edwards LD, Agustí A , et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med 2013; 107 (9) 1376-1384
  • 23 Koskela J, Kilpeläinen M, Kupiainen H , et al. Co-morbidities are the key nominators of the health related quality of life in mild and moderate COPD. BMC Pulm Med 2014; 14: 102
  • 24 Putcha N, Han MK, Martinez CH , et al; the COPDGene® Investigators. Comorbidities of COPD have a major impact on clinical outcomes, particularly in African Americans. Chronic Obstr Pulm Dis (Miami) 2014; 1 (1) 105-114
  • 25 Ekström MP, Jogréus C, Ström KE. Comorbidity and sex-related differences in mortality in oxygen-dependent chronic obstructive pulmonary disease. PLoS ONE 2012; 7 (4) e35806
  • 26 Singh B, Mielke MM, Parsaik AK , et al. A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment. JAMA Neurol 2014; 71 (5) 581-588
  • 27 Incalzi RA, Chiappini F, Fuso L, Torrice MP, Gemma A, Pistelli R. Predicting cognitive decline in patients with hypoxaemic COPD. Respir Med 1998; 92 (3) 527-533
  • 28 Dodd JW, Charlton RA, van den Broek MD, Jones PW. Cognitive dysfunction in patients hospitalized with acute exacerbation of COPD. Chest 2013; 144 (1) 119-127
  • 29 (GOLD) GIfCOLd. Global Strategy for Diagnosis, Management, and Prevention of COPD. Available at: http://www.goldcopd.org/.2014
  • 30 Tulek B, Atalay NB, Yildirim G, Kanat F, Süerdem M. Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories. Respirology 2014; 19 (6) 873-880
  • 31 Filipowski M, Bozek A, Kozlowska R, Czyżewski D, Jarzab J. The influence of hospitalizations due to exacerbations or spontaneous pneumothoraxes on the quality of life, mental function and symptoms of depression and anxiety in patients with COPD or asthma. J Asthma 2014; 51 (3) 294-298
  • 32 Dodd JW, Chung AW, van den Broek MD, Barrick TR, Charlton RA, Jones PW. Brain structure and function in chronic obstructive pulmonary disease: a multimodal cranial magnetic resonance imaging study. Am J Respir Crit Care Med 2012; 186 (3) 240-245
  • 33 Lahousse L, Vernooij MW, Darweesh SK , et al. Chronic obstructive pulmonary disease and cerebral microbleeds. The Rotterdam Study. Am J Respir Crit Care Med 2013; 188 (7) 783-788
  • 34 Li CH, Chen WC, Liao WC , et al. The association between chronic obstructive pulmonary disease and Parkinson's disease: a nationwide population-based retrospective cohort study. QJM 2015; 108 (1) 39-45
  • 35 Light RW, Merrill EJ, Despars JA, Gordon GH, Mutalipassi LR. Prevalence of depression and anxiety in patients with COPD. Relationship to functional capacity. Chest 1985; 87 (1) 35-38
  • 36 Al-shair K, Dockry R, Mallia-Milanes B, Kolsum U, Singh D, Vestbo J. Depression and its relationship with poor exercise capacity, BODE index and muscle wasting in COPD. Respir Med 2009; 103 (10) 1572-1579
  • 37 Di Marco F, Verga M, Reggente M , et al. Anxiety and depression in COPD patients: The roles of gender and disease severity. Respir Med 2006; 100 (10) 1767-1774
  • 38 Janssen DJ, Spruit MA, Leue C , et al; Ciro Network. Symptoms of anxiety and depression in COPD patients entering pulmonary rehabilitation. Chron Respir Dis 2010; 7 (3) 147-157
  • 39 Jennings JH, Digiovine B, Obeid D, Frank C. The association between depressive symptoms and acute exacerbations of COPD. Lung 2009; 187 (2) 128-135
  • 40 Kim KU, Park HK, Jung HY , et al. Association of depression with disease severity in patients with chronic obstructive pulmonary disease. Lung 2014; 192 (2) 243-249
  • 41 Qian J, Simoni-Wastila L, Langenberg P , et al. Effects of depression diagnosis and antidepressant treatment on mortality in Medicare beneficiaries with chronic obstructive pulmonary disease. J Am Geriatr Soc 2013; 61 (5) 754-761
  • 42 van Manen JG, Bindels PJ, Dekker FW, IJzermans CJ, van der Zee JS, Schadé E. Risk of depression in patients with chronic obstructive pulmonary disease and its determinants. Thorax 2002; 57 (5) 412-416
  • 43 Omachi TA, Katz PP, Yelin EH , et al. Depression and health-related quality of life in chronic obstructive pulmonary disease. Am J Med 2009; 122 (8) 778.e9-778.e15
  • 44 Ng TP, Niti M, Fones C, Yap KB, Tan WC. Co-morbid association of depression and COPD: a population-based study. Respir Med 2009; 103 (6) 895-901
  • 45 Ohayon MM. Chronic Obstructive Pulmonary Disease and its association with sleep and mental disorders in the general population. J Psychiatr Res 2014; 54: 79-84
  • 46 van den Bemt L, Schermer T, Bor H , et al. The risk for depression comorbidity in patients with COPD. Chest 2009; 135 (1) 108-114
  • 47 Atlantis E, Fahey P, Cochrane B, Smith S. Bidirectional associations between clinically relevant depression or anxiety and COPD: a systematic review and meta-analysis. Chest 2013; 144 (3) 766-777
  • 48 Qian J, Simoni-Wastila L, Rattinger GB , et al. Associations of depression diagnosis and antidepressant treatment with mortality among young and disabled Medicare beneficiaries with COPD. Gen Hosp Psychiatry 2013; 35 (6) 612-618
  • 49 Lou P, Chen P, Zhang P , et al. Effects of smoking, depression, and anxiety on mortality in COPD patients: a prospective study. Respir Care 2014; 59 (1) 54-61
  • 50 Stage KB, Middelboe T, Pisinger C. Depression and chronic obstructive pulmonary disease (COPD). Impact on survival. Acta Psychiatr Scand 2005; 111 (4) 320-323
  • 51 von Leupoldt A, Taube K, Lehmann K, Fritzsche A, Magnussen H. The impact of anxiety and depression on outcomes of pulmonary rehabilitation in patients with COPD. Chest 2011; 140 (3) 730-736
  • 52 Gudmundsson G, Gislason T, Janson C , et al. Depression, anxiety and health status after hospitalisation for COPD: a multicentre study in the Nordic countries. Respir Med 2006; 100 (1) 87-93
  • 53 Hynninen MJ, Pallesen S, Nordhus IH. Factors affecting health status in COPD patients with co-morbid anxiety or depression. Int J Chron Obstruct Pulmon Dis 2007; 2 (3) 323-328
  • 54 Quint JK, Baghai-Ravary R, Donaldson GC, Wedzicha JA. Relationship between depression and exacerbations in COPD. Eur Respir J 2008; 32 (1) 53-60
  • 55 Hilmarsen CW, Wilke S, Engan H , et al. Impact of symptoms of anxiety and depression on COPD Assessment Test scores. Eur Respir J 2014; 43 (3) 898-900
  • 56 Gudmundsson G, Gislason T, Janson C , et al. Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression. Eur Respir J 2005; 26 (3) 414-419
  • 57 Al-shair K, Kolsum U, Dockry R, Morris J, Singh D, Vestbo J. Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD. Respir Res 2011; 12: 3
  • 58 Janssen DJ, Müllerova H, Agusti A , et al; Eclipse Investigators. Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. Respir Med 2014; 108 (11) 1647-1654
  • 59 Dinicola G, Julian L, Gregorich SE, Blanc PD, Katz PP. The role of social support in anxiety for persons with COPD. J Psychosom Res 2013; 74 (2) 110-115
  • 60 Jordan N, Lee TA, Valenstein M, Weiss KB. Effect of care setting on evidence-based depression treatment for veterans with COPD and comorbid depression. J Gen Intern Med 2007; 22 (10) 1447-1452
  • 61 Pooler A, Beech R. Examining the relationship between anxiety and depression and exacerbations of COPD which result in hospital admission: a systematic review. Int J Chron Obstruct Pulmon Dis 2014; 9: 315-330
  • 62 Eiser N, Harte R, Spiros K, Phillips C, Isaac MT. Effect of treating depression on quality-of-life and exercise tolerance in severe COPD. COPD 2005; 2 (2) 233-241
  • 63 Tselebis A, Bratis D, Pachi A , et al. A pulmonary rehabilitation program reduces levels of anxiety and depression in COPD patients. Multidiscip Respir Med 2013; 8 (1) 41
  • 64 Paz-Díaz H, Montes de Oca M, López JM, Celli BR. Pulmonary rehabilitation improves depression, anxiety, dyspnea and health status in patients with COPD. Am J Phys Med Rehabil 2007; 86 (1) 30-36
  • 65 Garuti G, Cilione C, Dell'Orso D , et al. Impact of comprehensive pulmonary rehabilitation on anxiety and depression in hospitalized COPD patients. Monaldi Arch Chest Dis 2003; 59 (1) 56-61
  • 66 Franco CB, Paz-Filho G, Gomes PE , et al. Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D. Osteoporos Int 2009; 20 (11) 1881-1887
  • 67 Heerema-Poelman A, Stuive I, Wempe JB. Adherence to a maintenance exercise program 1 year after pulmonary rehabilitation: what are the predictors of dropout?. J Cardiopulm Rehabil Prev 2013; 33 (6) 419-426
  • 68 Silverberg DS, Mor R, Weu MT, Schwartz D, Schwartz IF, Chernin G. Anemia and iron deficiency in COPD patients: prevalence and the effects of correction of the anemia with erythropoiesis stimulating agents and intravenous iron. BMC Pulm Med 2014; 14: 24
  • 69 Krishnan G, Grant BJ, Muti PC , et al. Association between anemia and quality of life in a population sample of individuals with chronic obstructive pulmonary disease. BMC Pulm Med 2006; 6: 23
  • 70 Chambellan A, Chailleux E, Similowski T ; ANTADIR Observatory Group. Prognostic value of the hematocrit in patients with severe COPD receiving long-term oxygen therapy. Chest 2005; 128 (3) 1201-1208
  • 71 Boutou AK, Karrar S, Hopkinson NS, Polkey MI. Anemia and survival in chronic obstructive pulmonary disease: a dichotomous rather than a continuous predictor. Respiration 2013; 85 (2) 126-131
  • 72 Haja Mydin H, Murphy S, Clague H, Sridharan K, Taylor IK. Anemia and performance status as prognostic markers in acute hypercapnic respiratory failure due to chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2013; 8: 151-157
  • 73 Rasmussen L, Christensen S, Lenler-Petersen P, Johnsen SP. Anemia and 90-day mortality in COPD patients requiring invasive mechanical ventilation. Clin Epidemiol 2011; 3: 1-5
  • 74 Martinez-Rivera C, Portillo K, Muñoz-Ferrer A , et al. Anemia is a mortality predictor in hospitalized patients for COPD exacerbation. COPD 2012; 9 (3) 243-250
  • 75 Nguyen HQ, Chu L, Amy Liu IL , et al. Associations between physical activity and 30-day readmission risk in chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014; 11 (5) 695-705
  • 76 Barba R, de Casasola GG, Marco J , et al. Anemia in chronic obstructive pulmonary disease: a readmission prognosis factor. Curr Med Res Opin 2012; 28 (4) 617-622
  • 77 Copur AS, Fulambarker A, Molnar J , et al. Role of Anemia in Home Oxygen Therapy in Chronic Obstructive Pulmonary Disease Patients. Am J Ther 2013;
  • 78 Boutou AK, Stanopoulos I, Pitsiou GG , et al. Anemia of chronic disease in chronic obstructive pulmonary disease: a case-control study of cardiopulmonary exercise responses. Respiration 2011; 82 (3) 237-245
  • 79 Ali Zohal M, Yazdi Z, Kazemifar AM. Daytime sleepiness and quality of sleep in patients with COPD compared to control group. Glob J Health Sci 2013; 5 (3) 150-155
  • 80 Zohal MA, Yazdi Z, Kazemifar AM, Mahjoob P, Ziaeeha M. Sleep Quality and Quality of Life in COPD Patients with and without Suspected Obstructive Sleep Apnea. Sleep Disord 2014; 2014: 508372
  • 81 Krieger AC, Patel N, Green D , et al. Respiratory disturbance during sleep in COPD patients without daytime hypoxemia. Int J Chron Obstruct Pulmon Dis 2007; 2 (4) 609-615
  • 82 Bednarek M, Plywaczewski R, Jonczak L, Zielinski J. There is no relationship between chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: a population study. Respiration 2005; 72 (2) 142-149
  • 83 Sanders MH, Newman AB, Haggerty CL , et al; Sleep Heart Health Study. Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med 2003; 167 (1) 7-14
  • 84 Rizzi M, Palma P, Andreoli A , et al. Prevalence and clinical feature of the “overlap syndrome”, obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), in OSA population. Sleep Breath 1997; 2 (3) 68-72
  • 85 Chaouat A, Weitzenblum E, Krieger J, Ifoundza T, Oswald M, Kessler R. Association of chronic obstructive pulmonary disease and sleep apnea syndrome. Am J Respir Crit Care Med 1995; 151 (1) 82-86
  • 86 Turcani P, Skrickova J, Pavlik T, Janousova E, Orban M. The prevalence of obstructive sleep apnea in patients hospitalized for COPD exacerbation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; . doi: 10.5507/bp.2014.002 [e-pub ahead of print]
  • 87 Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med 2010; 182 (3) 325-331
  • 88 Shaya FT, Lin PJ, Aljawadi MH, Scharf SM. Elevated economic burden in obstructive lung disease patients with concomitant sleep apnea syndrome. Sleep Breath 2009; 13 (4) 317-323
  • 89 Ganga HV, Nair SU, Puppala VK, Miller WL. Risk of new-onset atrial fibrillation in elderly patients with the overlap syndrome: a retrospective cohort study. J Geriatr Cardiol 2013; 10 (2) 129-134
  • 90 Shiina K, Tomiyama H, Takata Y , et al. Overlap syndrome: additive effects of COPD on the cardiovascular damages in patients with OSA. Respir Med 2012; 106 (9) 1335-1341
  • 91 Sharma B, Neilan TG, Kwong RY , et al. Evaluation of right ventricular remodeling using cardiac magnetic resonance imaging in co-existent chronic obstructive pulmonary disease and obstructive sleep apnea. COPD 2013; 10 (1) 4-10
  • 92 McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med 2009; 180 (8) 692-700
  • 93 Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014; 311 (8) 806-814
  • 94 Dimov D, Tacheva T, Koychev A, Ilieva V, Prakova G, Vlaykova T. Obesity in Bulgarian patients with chronic obstructive pulmonary disease. Chron Respir Dis 2013; 10 (4) 215-222
  • 95 Rodríguez DA, Garcia-Aymerich J, Valera JL , et al; PAC-COPD Study Group. Determinants of exercise capacity in obese and non-obese COPD patients. Respir Med 2014; 108 (5) 745-751
  • 96 García-Rio F, Soriano JB, Miravitlles M , et al. Impact of obesity on the clinical profile of a population-based sample with chronic obstructive pulmonary disease. PLoS ONE 2014; 9 (8) e105220
  • 97 Cecere LM, Littman AJ, Slatore CG , et al. Obesity and COPD: associated symptoms, health-related quality of life, and medication use. COPD 2011; 8 (4) 275-284
  • 98 Vozoris NT, O'Donnell DE. Prevalence, risk factors, activity limitation and health care utilization of an obese, population-based sample with chronic obstructive pulmonary disease. Can Respir J 2012; 19 (3) e18-e24
  • 99 Aiello M, Teopompi E, Tzani P , et al. Maximal exercise in obese patients with COPD: the role of fat free mass. BMC Pulm Med 2014; 14: 96
  • 100 Bautista J, Ehsan M, Normandin E, Zuwallack R, Lahiri B. Physiologic responses during the six minute walk test in obese and non-obese COPD patients. Respir Med 2011; 105 (8) 1189-1194
  • 101 Laviolette L, Sava F, O'Donnell DE , et al. Effect of obesity on constant workrate exercise in hyperinflated men with COPD. BMC Pulm Med 2010; 10: 33
  • 102 Ora J, Laveneziana P, Ofir D, Deesomchok A, Webb KA, O'Donnell DE. Combined effects of obesity and chronic obstructive pulmonary disease on dyspnea and exercise tolerance. Am J Respir Crit Care Med 2009; 180 (10) 964-971
  • 103 O'Donnell DE, Deesomchok A, Lam YM , et al. Effects of BMI on static lung volumes in patients with airway obstruction. Chest 2011; 140 (2) 461-468
  • 104 Boiselle PM, Litmanovich DE, Michaud G , et al. Dynamic expiratory tracheal collapse in morbidly obese COPD patients. COPD 2013; 10 (5) 604-610
  • 105 Breyer MK, Spruit MA, Celis AP, Rutten EP, Janssen PP, Wouters EF ; CIRO Network. Highly elevated C-reactive protein levels in obese patients with COPD: a fat chance?. Clin Nutr 2009; 28 (6) 642-647
  • 106 Bridevaux PO, Gerbase MW, Schindler C , et al. Sex-specific effect of body weight gain on systemic inflammation in subjects with COPD: results from the SAPALDIA cohort study 2. Eur Respir J 2009; 34 (2) 332-339
  • 107 Poulain M, Doucet M, Drapeau V , et al. Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease. Chron Respir Dis 2008; 5 (1) 35-41
  • 108 Stanciu S, Iordache M, Busuioceanu A , et al. The metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease. Rom J Intern Med 2009; 47 (2) 123-132
  • 109 Barbarito N, De Mattia E. Grading the severity of obstruction in patients with chronic obstructive pulmonary disease and morbid obesity. Monaldi Arch Chest Dis 2013; 79 (3-4) 121-127
  • 110 Collins BF, Feemster LC, Rinne ST, Au DH. Factors predictive of airflow obstruction among veterans with presumed empirical diagnosis and treatment of COPD. Chest 2015; 147 (2) 369-376
  • 111 Minas M, Kostikas K, Papaioannou AI , et al. The association of metabolic syndrome with adipose tissue hormones and insulin resistance in patients with COPD without co-morbidities. COPD 2011; 8 (6) 414-420
  • 112 Park BH, Park MS, Chang J , et al. Chronic obstructive pulmonary disease and metabolic syndrome: a nationwide survey in Korea. Int J Tuberc Lung Dis 2012; 16 (5) 694-700
  • 113 Akpınar EE, Akpınar S, Ertek S, Sayın E, Gülhan M. Systemic inflammation and metabolic syndrome in stable COPD patients. Tuberk Toraks 2012; 60 (3) 230-237
  • 114 Marquis K, Maltais F, Duguay V , et al. The metabolic syndrome in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2005; 25 (4) 226-232 , discussion 233–234
  • 115 Park SK, Larson JL. The relationship between physical activity and metabolic syndrome in people with chronic obstructive pulmonary disease. J Cardiovasc Nurs 2014; 29 (6) 499-507
  • 116 Breyer MK, Spruit MA, Hanson CK , et al. Prevalence of metabolic syndrome in COPD patients and its consequences. PLoS ONE 2014; 9 (6) e98013
  • 117 Ozgen Alpaydin A, Konyar Arslan I, Serter S , et al. Metabolic syndrome and carotid intima-media thickness in chronic obstructive pulmonary disease. Multidiscip Respir Med 2013; 8 (1) 61
  • 118 Díez-Manglano J, Barquero-Romero J, Almagro P , et al; Working Group on COPD; Spanish Society of Internal Medicine. COPD patients with and without metabolic syndrome: clinical and functional differences. Intern Emerg Med 2014; 9 (4) 419-425
  • 119 Watz H, Waschki B, Kirsten A , et al. The metabolic syndrome in patients with chronic bronchitis and COPD: frequency and associated consequences for systemic inflammation and physical inactivity. Chest 2009; 136 (4) 1039-1046
  • 120 Chung JH, Hwang HJ, Han CH, Son BS, Kim DH, Park MS. Association between sarcopenia and metabolic syndrome in chronic obstructive pulmonary disease: The Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011. COPD 2015; 12 (1) 82-89
  • 121 Fritzsche A, Watz H, Magnussen H, Tuinmann G, Löwe B, von Leupoldt A. Cognitive biases in patients with chronic obstructive pulmonary disease and depression—a pilot study. Br J Health Psychol 2013; 18 (4) 827-843
  • 122 Küpeli E, Ulubay G, Ulasli SS, Sahin T, Erayman Z, Gürsoy A. Metabolic syndrome is associated with increased risk of acute exacerbation of COPD: a preliminary study. Endocrine 2010; 38 (1) 76-82
  • 123 Leone N, Courbon D, Thomas F , et al. Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am J Respir Crit Care Med 2009; 179 (6) 509-516
  • 124 Stanciu S, Marinescu R, Iordache M, Dumitrescu S, Mureşan M, Bogdan MA. Are systemic inflammatory profiles different in patients with COPD and metabolic syndrome as compared to those with COPD alone?. Rom J Intern Med 2009; 47 (4) 381-386
  • 125 Vanfleteren LE, van Meerendonk AM, Franssen FM , et al. A possible link between increased metabolic activity of fat tissue and aortic wall inflammation in subjects with COPD. A retrospective 18F-FDG-PET/CT pilot study. Respir Med 2014; 108 (6) 883-890
  • 126 Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J 2008; 32 (4) 962-969
  • 127 Rogliani P, Calzetta L, Segreti A, Barrile A, Cazzola M. Diabetes mellitus among outpatients with COPD attending a university hospital. Acta Diabetol 2014; 51 (6) 933-940
  • 128 Lee CT, Mao IC, Lin CH, Lin SH, Hsieh MC. Chronic obstructive pulmonary disease: a risk factor for type 2 diabetes: a nationwide population-based study. Eur J Clin Invest 2013; 43 (11) 1113-1119
  • 129 Rana JS, Mittleman MA, Sheikh J , et al. Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. Diabetes Care 2004; 27 (10) 2478-2484
  • 130 Parappil A, Depczynski B, Collett P, Marks GB. Effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of COPD. Respirology 2010; 15 (6) 918-922
  • 131 Sandler M, Bunn AE, Stewart RI. Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus. Am Rev Respir Dis 1987; 135 (1) 223-229
  • 132 Klein OL, Meltzer D, Carnethon M, Krishnan JA. Type II diabetes mellitus is associated with decreased measures of lung function in a clinical setting. Respir Med 2011; 105 (7) 1095-1098
  • 133 Kinney GL, Black-Shinn JL, Wan ES , et al; COPDGene Investigators. Pulmonary function reduction in diabetes with and without chronic obstructive pulmonary disease. Diabetes Care 2014; 37 (2) 389-395
  • 134 Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression. Am J Med 2010; 123 (11) 1001-1006
  • 135 O'Byrne PM, Rennard S, Gerstein H , et al. Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids. Respir Med 2012; 106 (11) 1487-1493
  • 136 Bolton CE, Evans M, Ionescu AA , et al. Insulin resistance and inflammation - a further systemic complication of COPD. COPD 2007; 4 (2) 121-126
  • 137 Cazzola M, Calzetta L, Bettoncelli G , et al. Cardiovascular disease in asthma and COPD: a population-based retrospective cross-sectional study. Respir Med 2012; 106 (2) 249-256
  • 138 Curkendall SM, DeLuise C, Jones JK , et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol 2006; 16 (1) 63-70
  • 139 de Miguel-Díez J, Carrasco-Garrido P, Rejas-Gutierrez J , et al. The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings. BMC Cardiovasc Disord 2010; 10: 8
  • 140 Feary JR, Rodrigues LC, Smith CJ, Hubbard RB, Gibson JE. Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care. Thorax 2010; 65 (11) 956-962
  • 141 Huiart L, Ernst P, Suissa S. Cardiovascular morbidity and mortality in COPD. Chest 2005; 128 (4) 2640-2646
  • 142 Mapel DW, Dedrick D, Davis K. Trends and cardiovascular co-morbidities of COPD patients in the Veterans Administration Medical System, 1991-1999. COPD 2005; 2 (1) 35-41
  • 143 Mapel DW, Hurley JS, Frost FJ, Petersen HV, Picchi MA, Coultas DB. Health care utilization in chronic obstructive pulmonary disease. A case-control study in a health maintenance organization. Arch Intern Med 2000; 160 (17) 2653-2658
  • 144 Müllerova H, Agusti A, Erqou S, Mapel DW. Cardiovascular comorbidity in COPD: systematic literature review. Chest 2013; 144 (4) 1163-1178
  • 145 McGarvey LP, John M, Anderson JA, Zvarich M, Wise RA ; TORCH Clinical Endpoint Committee. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax 2007; 62 (5) 411-415
  • 146 Zielinski J, MacNee W, Wedzicha J , et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch Chest Dis 1997; 52 (1) 43-47
  • 147 Mannino DM, Doherty DE, Sonia Buist A. Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med 2006; 100 (1) 115-122
  • 148 Campo G, Guastaroba P, Marzocchi A , et al. Impact of COPD on long-term outcome after ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention. Chest 2013; 144 (3) 750-757
  • 149 Konecny T, Somers K, Orban M , et al. Interactions between COPD and outcomes after percutaneous coronary intervention. Chest 2010; 138 (3) 621-627
  • 150 Sidney S, Sorel M, Quesenberry Jr CP, DeLuise C, Lanes S, Eisner MD. COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program. Chest 2005; 128 (4) 2068-2075
  • 151 Black-Shinn JL, Kinney GL, Wise AL , et al; COPDGene Investigators. Cardiovascular disease is associated with COPD severity and reduced functional status and quality of life. COPD 2014; 11 (5) 546-551
  • 152 Patel AR, Donaldson GC, Mackay AJ, Wedzicha JA, Hurst JR. The impact of ischemic heart disease on symptoms, health status, and exacerbations in patients with COPD. Chest 2012; 141 (4) 851-857
  • 153 Dalal AA, Shah M, Lunacsek O, Hanania NA. Clinical and economic burden of patients diagnosed with COPD with comorbid cardiovascular disease. Respir Med 2011; 105 (10) 1516-1522
  • 154 Gale NS, Duckers JM, Enright S, Cockcroft JR, Shale DJ, Bolton CE. Does pulmonary rehabilitation address cardiovascular risk factors in patients with COPD?. BMC Pulm Med 2011; 11: 20
  • 155 Bor S, Kitapcioglu G, Solak ZA, Ertilav M, Erdinc M. Prevalence of gastroesophageal reflux disease in patients with asthma and chronic obstructive pulmonary disease. J Gastroenterol Hepatol 2010; 25 (2) 309-313
  • 156 García Rodríguez LA, Ruigómez A, Martín-Merino E, Johansson S, Wallander MA. Relationship between gastroesophageal reflux disease and COPD in UK primary care. Chest 2008; 134 (6) 1223-1230
  • 157 Kim J, Lee JH, Kim Y , et al. Association between chronic obstructive pulmonary disease and gastroesophageal reflux disease: a national cross-sectional cohort study. BMC Pulm Med 2013; 13: 51
  • 158 Mokhlesi B, Morris AL, Huang CF, Curcio AJ, Barrett TA, Kamp DW. Increased prevalence of gastroesophageal reflux symptoms in patients with COPD. Chest 2001; 119 (4) 1043-1048
  • 159 Rascon-Aguilar IE, Pamer M, Wludyka P , et al. Role of gastroesophageal reflux symptoms in exacerbations of COPD. Chest 2006; 130 (4) 1096-1101
  • 160 Casanova C, Baudet JS, del Valle Velasco M , et al. Increased gastro-oesophageal reflux disease in patients with severe COPD. Eur Respir J 2004; 23 (6) 841-845
  • 161 Kamble NL, Khan NA, Kumar N, Nayak HK, Daga MK. Study of gastro-oesophageal reflux disease in patients with mild-to-moderate chronic obstructive pulmonary disease in India. Respirology 2013; 18 (3) 463-467
  • 162 Lee AL, Button BM, Denehy L , et al. Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary disease and bronchiectasis. Respirology 2014; 19 (2) 211-217
  • 163 Kempainen RR, Savik K, Whelan TP, Dunitz JM, Herrington CS, Billings JL. High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD. Chest 2007; 131 (6) 1666-1671
  • 164 Orr WC, Shamma-Othman Z, Allen M, Robinson MG. Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease. Chest 1992; 101 (6) 1521-1525
  • 165 Liang BM, Feng YL. Association of gastroesophageal reflux disease symptoms with stable chronic obstructive pulmonary disease. Lung 2012; 190 (3) 277-282
  • 166 Rascon-Aguilar IE, Pamer M, Wludyka P, Cury J, Vega KJ. Poorly treated or unrecognized GERD reduces quality of life in patients with COPD. Dig Dis Sci 2011; 56 (7) 1976-1980
  • 167 Martinez CH, Okajima Y, Murray S , et al; COPDGene Investigators. Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort. Respir Res 2014; 15: 62
  • 168 Ajmera M, Raval AD, Shen C, Sambamoorthi U. Explaining the increased health care expenditures associated with gastroesophageal reflux disease among elderly Medicare beneficiaries with chronic obstructive pulmonary disease: a cost-decomposition analysis. Int J Chron Obstruct Pulmon Dis 2014; 9: 339-348
  • 169 Sakae TM, Pizzichini MM, Teixeira PJ, Silva RM, Trevisol DJ, Pizzichini E. Exacerbations of COPD and symptoms of gastroesophageal reflux: a systematic review and meta-analysis. J Bras Pneumol 2013; 39 (3) 259-271
  • 170 Takada K, Matsumoto S, Kojima E , et al. Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire. Respir Med 2011; 105 (10) 1531-1536
  • 171 Terada K, Muro S, Sato S , et al. Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation. Thorax 2008; 63 (11) 951-955
  • 172 Sasaki T, Nakayama K, Yasuda H , et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc 2009; 57 (8) 1453-1457
  • 173 Boeree MJ, Peters FT, Postma DS, Kleibeuker JH. No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux. Eur Respir J 1998; 11 (5) 1070-1074
  • 174 Bhattacharyya P, Paul R, Ghosh M , et al. Prevalence of osteoporosis and osteopenia in advanced chronic obstructive pulmonary disease patients. Lung India 2011; 28 (3) 184-186
  • 175 Bolton CE, Stone MD, Edwards PH, Duckers JM, Evans WD, Shale DJ. Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease. Chron Respir Dis 2009; 6 (2) 81-87
  • 176 Ferguson GT, Calverley PM, Anderson JA , et al. Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest 2009; 136 (6) 1456-1465
  • 177 Graat-Verboom L, Spruit MA, van den Borne BE , et al; CIRO Network. Correlates of osteoporosis in chronic obstructive pulmonary disease: an underestimated systemic component. Respir Med 2009; 103 (8) 1143-1151
  • 178 Hattiholi J, Gaude GS. Prevalence and correlates of osteoporosis in chronic obstructive pulmonary disease patients in India. Lung India 2014; 31 (3) 221-227
  • 179 Jørgensen NR, Schwarz P, Holme I, Henriksen BM, Petersen LJ, Backer V. The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study. Respir Med 2007; 101 (1) 177-185
  • 180 Ogura-Tomomatsu H, Asano K, Tomomatsu K , et al. Predictors of osteoporosis and vertebral fractures in patients presenting with moderate-to-severe chronic obstructive lung disease. COPD 2012; 9 (4) 332-337
  • 181 Incalzi RA, Caradonna P, Ranieri P , et al. Correlates of osteoporosis in chronic obstructive pulmonary disease. Respir Med 2000; 94 (11) 1079-1084
  • 182 Graat-Verboom L, Smeenk FW, van den Borne BE , et al. Risk factors for osteoporosis in Caucasian patients with moderate chronic obstructive pulmonary disease: a case control study. Bone 2012; 50 (6) 1234-1239
  • 183 Silva DR, Coelho AC, Dumke A , et al. Osteoporosis prevalence and associated factors in patients with COPD: a cross-sectional study. Respir Care 2011; 56 (7) 961-968
  • 184 Kiyokawa H, Muro S, Oguma T , et al. Impact of COPD exacerbations on osteoporosis assessed by chest CT scan. COPD 2012; 9 (3) 235-242
  • 185 Sabit R, Bolton CE, Edwards PH , et al. Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007; 175 (12) 1259-1265
  • 186 Fattahi F, ten Hacken NH, Löfdahl CG , et al. Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study. Respir Res 2013; 14: 10
  • 187 Jamieson DB, Matsui EC, Belli A , et al. Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 188 (2) 187-192
  • 188 Caillaud D, Chanez P, Escamilla R , et al; Initiatives BPCO Scientific Committee and Investigators. Association of chronic nasal symptoms with dyspnoea and quality-of-life impairment in chronic obstructive pulmonary disease. Respirology 2014; 19 (3) 346-352
  • 189 Drummond MB, Kirk GD. HIV-associated obstructive lung diseases: insights and implications for the clinician. Lancet Respir Med 2014; 2 (7) 583-592
  • 190 Diaz PT, Clanton TL, Pacht ER. Emphysema-like pulmonary disease associated with human immunodeficiency virus infection. Ann Intern Med 1992; 116 (2) 124-128
  • 191 Mitchell DM, Fleming J, Pinching AJ , et al. Pulmonary function in human immunodeficiency virus infection. A prospective 18-month study of serial lung function in 474 patients. Am Rev Respir Dis 1992; 146 (3) 745-751
  • 192 Petrache I, Diab K, Knox KS , et al. HIV associated pulmonary emphysema: a review of the literature and inquiry into its mechanism. Thorax 2008; 63 (5) 463-469
  • 193 Crothers K, Butt AA, Gibert CL, Rodriguez-Barradas MC, Crystal S, Justice AC ; Veterans Aging Cohort 5 Project Team. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest 2006; 130 (5) 1326-1333
  • 194 Crothers K, Huang L, Goulet JL , et al. HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med 2011; 183 (3) 388-395
  • 195 Gingo MR, Balasubramani GK, Kingsley L , et al. The impact of HAART on the respiratory complications of HIV infection: longitudinal trends in the MACS and WIHS cohorts. PLoS ONE 2013; 8 (3) e58812
  • 196 Madeddu G, Fois AG, Calia GM , et al. Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?. Infection 2013; 41 (2) 347-353
  • 197 Drummond MB, Kirk GD, Astemborski J , et al. Association between obstructive lung disease and markers of HIV infection in a high-risk cohort. Thorax 2012; 67 (4) 309-314
  • 198 Drummond MB, Merlo CA, Astemborski J , et al. The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort. AIDS 2013; 27 (8) 1303-1311
  • 199 Drummond MB, Kirk GD, McCormack MC , et al. HIV and COPD: impact of risk behaviors and diseases on quality of life. Qual Life Res 2010; 19 (9) 1295-1302
  • 200 Sigel K, Wisnivesky J, Gordon K , et al. HIV as an independent risk factor for incident lung cancer. AIDS 2012; 26 (8) 1017-1025
  • 201 Kirk GD, Merlo C, O' Driscoll P , et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis 2007; 45 (1) 103-110
  • 202 Lambert AA, Merlo CA, Kirk GD. Human immunodeficiency virus-associated lung malignancies. Clin Chest Med 2013; 34 (2) 255-272
  • 203 Kaviani N, Bukberg P, Manessis A, Yen V, Young I. Iatrogenic osteoporosis, bilateral HIP osteonecrosis, and secondary adrenal suppression in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted highly active antiretroviral therapy. Endocr Pract 2011; 17 (1) 74-78
  • 204 Mahlab-Guri K, Asher I, Gradstein S , et al. Inhaled fluticasone causes iatrogenic Cushing's syndrome in patients treated with Ritonavir. J Asthma 2011; 48 (8) 860-863
  • 205 de Torres JP, Bastarrika G, Wisnivesky JP , et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest 2007; 132 (6) 1932-1938
  • 206 Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data From the First National Health and Nutrition Examination Survey follow-up. Arch Intern Med 2003; 163 (12) 1475-1480
  • 207 Turner MC, Chen Y, Krewski D, Calle EE, Thun MJ. Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med 2007; 176 (3) 285-290
  • 208 Wilson DO, Weissfeld JL, Balkan A , et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med 2008; 178 (7) 738-744
  • 209 Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J 2009; 34 (2) 380-386
  • 210 Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE ; Lung Health Study Research Group. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med 2005; 142 (4) 233-239
  • 211 Ueda K, Jinbo M, Li TS, Yagi T, Suga K, Hamano K. Computed tomography-diagnosed emphysema, not airway obstruction, is associated with the prognostic outcome of early-stage lung cancer. Clin Cancer Res 2006; 12 (22) 6730-6736
  • 212 Sekine Y, Yamada Y, Chiyo M , et al. Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection. Ann Thorac Surg 2007; 84 (3) 946-950
  • 213 Wauters E, Smeets D, Coolen J , et al. The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema. Eur Respir J 2011; 38 (4) 924-931
  • 214 Young RP, Whittington CF, Hopkins RJ , et al. Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J 2010; 36 (6) 1375-1382
  • 215 Schembri F, Sridhar S, Perdomo C , et al. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci U S A 2009; 106 (7) 2319-2324
  • 216 Rooney C, Sethi T. The epithelial cell and lung cancer: the link between chronic obstructive pulmonary disease and lung cancer. Respiration 2011; 81 (2) 89-104
  • 217 de-Torres JP, Casanova C, Marín JM , et al. Exploring the impact of screening with low-dose CT on lung cancer mortality in mild to moderate COPD patients: a pilot study. Respir Med 2013; 107 (5) 702-707
  • 218 Mapel D. Insights into COPD comorbidities from the OLIN study and other large databases. COPD 2011; 8 (6) 397-399