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

Nirupama Putcha; M. Bradley Drummond; Robert A. Wise; Nadia N. Hansel

doi:10.1055/s-0035-1556063

Seminars in Respiratory and Critical Care Medicine, Table of Contents

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

¹Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland

,

M. Bradley Drummond

¹Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland

,

Robert A. Wise

¹Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland

,

Nadia N. Hansel

¹Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland

› Author Affiliations

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.

Keywords

COPD - comorbidity - clinical outcomes

Full Text

References

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