The Comorbidity of Chronic Obstructive Pulmonary Disease and Peripheral Artery Disease – A Systematic Review

Figures & data

Figure 1. Flow chart [7] presenting the study selection process.

Table 1. Studies of COPD patients.

	Journal title	Study aims	Population	Country	COPD severity	Smoking		PAD co-existence	Remarks
						Current	Previous
Castagna O. et al. 2008 [11]	European Journal of Cardiovascular Prevention and Rehabilitation	- to assess the prevalence of PAD and its implications for exercise capacity limitation in COPD patients	COPD patients from Toulon hospital clinically stable with the absence of respiratory exacerbation 2 months before the study and healthy control individuals (n = 151 + 73)	France	NR	100%		81.5%	Nonsmokers excluded
Pecci R. et al. 2012 [12]	International Angiology	- to determine the prevalence of PAD in a population of patients with COPD - to investigate the relationship between PAD and lung disease severity	COPD patients admitted consecutively to Department of Internal Medicine (n = 246)	Spain	GOLD I 2.4% II 48.0% III 41.1% IV 8.5%	23.2%	54.5%	34.1%
Chen W. et al. 2015 [13]	International Journal of COPD	- to investigate the association between asymptomatic PAD and walking endurance in COPD patients measured with the 6MWT - to analyze which factors were associated with the distance achieved in the 6MWT	COPD patients who volunteered to undergo ABI measurements and the 6MWT at the outpatient department of the Division of Pulmonary and Critical Care Medicine (n = 200)	Taiwan	GOLD I 14% II 48% III 31% IV 7%	47.0%	53.0%	8.5%	Symptomatic PAD patients and not current or former smokers with at least a 10-pack-year history excluded
Pizarro C. et al. 2016 [14]	ERJ Open research	- to determine the link between peripheral artery disease and chronic obstructive pulmonary disease	Patients aged ≥18 years receiving treatment at the Department of Pneumonology with clinically confirmed COPD and non-COPD control smokers (n = 107 + 22)	Germany	GOLD A 5.6% B 48.6% C 3.7% D 42.1%	20.6%	74.8%	80.4%
Houben-Wilke S. et al. 2017 [15]	American Journal of Respiratory and Critical Care Medicine	- to assess the prevalence of PAD in COPD compared with distinct control groups - to study the association between PAD and functional capacity as well as health status	Patients aged ≥40 years with a diagnosis of COPD referred to the study by pulmonologists and general practitioners (n = 2088)	Germany	GOLD I 9.4% II 42.5% III 37.5% IV 10.5%	26.3%	68.2%	8.8%
Crisafulli E. et al. 2017 [16]	European Journal of Preventive Cardiology	- to evaluate the impact of asymptomatic/silent PAD on maximal exercise capacity in COPD patients - to search for predictors of peripheral artery disease	Adult COPD out-patients of Lung Function Unit who were former or current smokers with a history of at least 10 pack-years and in a cardio-respiratory stable condition for at least six weeks prior to enrollment (n = 47)	Italy	NR	25.5%	74. 5%	51.1%	Symptomatic PAD patients and nonsmokers excluded

COPD: chronic obstructive pulmonary disease; NR: not reported; PAD: peripheral arterial disease; GOLD: global initiative for chronic obstructive lung disease classification [1]; 6MWT: six-minute walk test.

Table 2. Study of PAD patients.

	Journal title	Study aims	Population	Country	PAD severity	Smoking	COPD co- existence	Remarks
Tuleta I. et al. 2017 [17]	International Journal of COPD	- to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD	Hospitalized patients and out-patients with confirmation of atherosclerotic cerebral and/or peripheral artery disease in duplex sonography and with the ability to conduct properly breathing maneuvers during body plethysmography (n = 125 + 41)	Germany	F I 72% F IIa 10.4% F IIb 15.2% F III 0.8% F IV 1.6%	Not reported	27.2%	Patients with total lung capacity <80% of predicted value excluded

PAD: peripheral arterial disease; COPD: chronic obstructive pulmonary disease; F: Fontaine classification.

Table

	PAD terms
1	Peripheral Arterial Disease
2	Intermittent Claudication
3	1 OR 2
	COPD terms
4	Pulmonary Disease, Chronic Obstructive
5	Lung Diseases
6	Respiratory Tract Diseases
7	4 OR 5 OR 6
8	3 AND 7
9	Human
10	8 AND 9

PAD: peripheral arterial disease; COPD: chronic obstructive pulmonary disease.

Table

	PAD terms
1	peripheral occlusive artery disease
2	intermittent claudication
3	1 OR 2
	COPD terms
4	chronic obstructive lung disease
5	lung disease
6	respiratory tract disease
7	4 OR 5 OR 6
8	3 AND 7
9	Human
10	8 AND 9

PAD: peripheral arterial disease; COPD: chronic obstructive pulmonary disease.

Table

	PAD terms
1	Peripheral Arterial Disease
2	Intermittent Claudication
3	1 OR 2
	COPD terms
4	Pulmonary Disease, Chronic Obstructive
5	Lung Diseases
6	Respiratory Tract Diseases
7	4 OR 5 OR 6
8	3 AND 7

PAD: peripheral arterial disease; COPD: chronic obstructive pulmonary disease.

Table

	Castagna O. et al. 2008 [1]	Pecci R. et al. 2012 [2]	Chen W. et al. 2015 [3]	Pizarro C. et al. 2016 [4]	Houben-Wilke S. et al. 2017 [5]	Crisafulli E. et al. 2017 [6]	Tuleta I. et al. 2017 [7]
Were the criteria for inclusion in the sample clearly defined?
Were the study subjects and the setting described in detail?
Was the exposure measured in a valid and reliable way?
Were objective, standard criteria used for measurement of condition?
Were confounding factors identified?
Were strategies to deal with confounding factors stated?						NA
Were the outcomes measured in a valid and reliable way?
Was appropriate statistical analysis used?

NA: not applicable, because the differences in the confounding parameters between compared groups were statistically insignificant.

Appendix 3. Characteristics of the analyzed studies.

Author and publication year	Castagna O. et al. 2008 [1]	Pecci R. et al. 2012 [2]	Chen W. et al. 2015 [3]	Pizarro C. et al. 2016 [4]	Houben-Wilke S. et al. 2017 [5]	Crisafulli E. et al. 2017 [6]	Tuleta I. et al. 2017 [7]
Publication title	Peripheral arterial disease: an underestimated etiology of exercise intolerance in chronic obstructive pulmonary disease patients	Peripheral arterial disease in patients with chronic obstructive pulmonary disease	Is asymptomatic peripheral arterial disease associated with walking endurance in patients with COPD?	Lower extremity and carotid artery disease in COPD	Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences– Comorbidities Network Study	Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation	High prevalence of COPD in atherosclerosis patients
Publication type	Article	Article	Article	Article	Article	Article	Article
Journal title	European Journal of Cardiovascular Prevention and Rehabilitation	International Angiology	International Journal of COPD	European Respiratory Journal Open research	American Journal of Respiratory and Critical Care Medicine	European Journal of Preventive Cardiology	International Journal of COPD
Study type	Cross-sectional study	Cross-sectional study	Cross-sectional study	Cross-sectional study	Cross-sectional study	Cross-sectional study	Cross-sectional study
Study aims	- to assess the prevalence of peripheral arterial disease and its implications for exercise limitation in COPD patients	- to determine the prevalence of PAD in a population of patients with COPD - to investigate the relationship between PAD and lung disease severity	- to investigate the association between asymptomatic PAD and walking endurance, measured by the 6MWT in COPD patients - to analyze which factors were associated with the distance achieved on the 6MWT	- to determine the linkage between PAD and COPD	- to assess the prevalence of PAD in COPD compared with distinct control groups - to study the association between PAD and functional capacity as well as health status	- to evaluate in COPD patients the impact of asymptomatic/silent PAD on maximal exercise capacity - to search for predictors of PAD	- to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease - to assess factors associated with the presence of COPD
Inclusion criteria	- COPD patients from Toulon’s hospital clinically stable with the absence of respiratory exacerbation within 2 months before the study - healthy control individuals	- Patients with COPD	- COPD patients who volunteered to undergo ABI measurements and the 6MWT enrolled in the CMPICO study [8]	- Patients aged ≥18 years receiving treatment for spirometrically and clinically confirmed COPD - nonCOPD control smokers	- Patients aged ≥40 years having a diagnosis of COPD or symptoms of chronic bronchitis	- Adult COPD patients having a former or current smoking history of at least 10 pack-years and in a cardio-respiratory stable condition for at least six weeks previous the enrollment	- Confirmation of atherosclerotic cerebral and/or PAD in duplex sonography and the ability of the patient to conduct properly breathing maneuvers during body plethysmography
Exclusion criteria	- Taking medications that were prone to interfere with the tests	NR	- Obvious symptoms of PAD - not current or former smokers with at least a 10-pack-year history - history of bronchial asthma and other structural lung diseases	- Previously diagnosed LEAD and carotid artery disease (including cerebrovascular disorders) - acute exacerbated COPD at the time of evaluation	- Patients with missing ABI or lung function data - unclassified patients - patients with alpha1 deficiency	- Concomitant respiratory disease other than COPD, such as asthma or bronchiectasis - chronic respiratory failure needing long-term oxygen therapy - any signs or symptoms potentially attributable to a PAD	- Restrictive pattern defined as total lung capacity <80% of a predicted value
Geographical location	France	Spain	Taiwan	Germany	Germany	Italy	Germany
Recruitment population	COPD patients hospitalized in Toulon’s hospital	COPD patients admitted consecutively in the Internal Medicine Department	COPD patients at the outpatient department of the Division of Pulmonary and Critical Care Medicine	Patients receiving treatment at the Department of Pneumonology and non COPD smokers	Patients referred to the study by pulmonologists and general practitioners	COPD out-patients of Lung Function Unit	Hospitalized patients and out-patients with confirme atherosclerotic cerebral and/or peripheral artery disease
Recruited population size	224	246	200	129	2088	47	166
PAD population size	123	84	17	86	184	24	125
COPD population size	151	246	200	107	2088	47	36^a
PAD diagnostic criteria	ABI	ABI	ABI	ABI	ABI	ABI	ABI
COPD diagnostic criteria	GOLD	GOLD	GOLD	GOLD	GOLD	GOLD	GOLD
PAD stage	NA	NA	NA	NA	NA	NA	F I 72.0% F IIa 10.4% F IIb 15.2% F III 0.8% F IV 1.6%
COPD stage	NR	GOLD I 2.4% II 48.0% III 41.1% IV 8.5%	GOLD I 14% II 48% III 31% IV 7%	GOLD A 5.6% B 48.6% C 3.7% D 42.1%	GOLD I 9.4% II 42.5% III 37.5% IV 10.5%	NR	NA
Age of patients in PAD group (years ± SD)	NR	71.9 ± 10.6	71.9 ± 9	NR	68.5 ± 7	68.7 ± 8.4	NR
Age of patients in COPD group (years ± SD)	67 ± 3.1	70.2 ± 11.0	70.9 ± 8.9	64.6 ± 10.4	65.3 ± 8.2	68.3 ± 7.1	72.4 ± 8.6^a
Number of PAD patients among COPD patients (%)	123 (81.5)	84 (34.1)	17 (8.5)	86 (80.4)	184 (8.8)	24 (51.1)	NA
Number of COPD patients among PAD patients	NA	NA	NA	NA	NA	NA	34 (27.2)
Number of smoking patients (%)	-- COPD group: - current or former 151 (100) -- PAD group - current or former - NR	-- COPD group: - current 57 (23.2) - former 134 (54.5) -- PAD group: - current 19 (22.6) - former 58 (69.0)	-- COPD group: - current 94 (47.0) - former 106 (53.0) -- PAD group: - current 8 (47.1) - former 9 (52.9)	-- COPD group: - current 22 (20.6) - former 80 (74.8) -- PAD group: - current - NR - former - NR	-- COPD group: - current 550 (26.3) - former 1424 (68.2) -- PAD group: - current 64 (34.8) - former 116 (63.0)	-- COPD group: - current 12 (25.5) - former 35 (74.5) -- PAD group: - current 8 (33.3) - former 16 (66.7)	-- COPD group^a: - current 3 (8.3) - former 23 (63.9) -- PAD group: - current - NR - former - NR
Remarks	Nonsmokers excluded		Symptomatic PAD patients and not current or former smokers with at least a 10-pack-year history excluded			Symptomatic PAD patients and nonsmokers excluded	Patients with total lung capacity <80% of a predicted value excluded

COPD: chronic obstructive pulmonary disease; PAD: peripheral arterial disease; 6MWT: six-minute walk test; ABI: ankle-brachial index; CMPICO: Case Management Program and Integrated Care for Patients with COPD; GOLD: global initiative for chronic obstructive lung disease⁸; GOLD I-IV or A-D: global initiative for chronic obstructive lung disease classification⁸; NA: not applicable; NR: not reported; F: Fontaine classification⁹.

^aIn the group of patients with cerebral and/or peripheral artery disease.

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 PubMedGoogle Scholar

Pecci R, De La Fuente AJ, Sanjurjo Rivo AB, et al. Peripheral arterial disease in patients with chronic obstructive pulmonary disease. Int Angiol. 2012;31:444–453.

 PubMed Web of Science ®Google Scholar

Chen W, Lin M-S, Sun K-S, et al. Is asymptomatic peripheral arterial disease associated with walking endurance in patients with COPD? Int J Chron Obstruct Pulmon Dis. 2015;10:1487–1492.

 PubMed Web of Science ®Google Scholar

Pizarro C, Linnhoff F, van Essen F, et al. Lower extremity and carotid artery disease in COPD. ERJ Open Res. 2016;2:00037–02016. doi:10.1183/23120541.00037-2016.

 PubMedGoogle Scholar

Houben-Wilke S, Jörres RA, Bals R, et al. Peripheral artery disease and its clinical relevance in patients with chronic obstructive pulmonary disease in the COPD and Systemic Consequences-Comorbidities Network Study. Am J Respir Crit Care Med. 2017;195:189–197. doi:10.1164/rccm.201602-0354OC.

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 PubMed Web of Science ®Google Scholar

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 PubMedGoogle Scholar

Pecci R, De La Fuente AJ, Sanjurjo RA, et al. Peripheral arterial disease in patients with chronic obstructive pulmonary disease. Int Angiol. 2012;31:444–453.

 PubMed Web of Science ®Google Scholar

Chen W, Lin M-S, Sun K-S, et al. Is asymptomatic peripheral arterial disease associated with walking endurance in patients with COPD? Int J Chron Obstruct Pulmon Dis. 2015;10:1487–1492.

 PubMed Web of Science ®Google Scholar

Pizarro C, Linnhoff F, van Essen F, et al. Lower extremity and carotid artery disease in COPD. ERJ Open Res. 2016;2:00037–02016. doi:10.1183/23120541.00037-2016.

 PubMedGoogle Scholar

Houben-Wilke S, Jörres RA, Bals R, et al. Peripheral artery disease and its clinical relevance in patients with chronic obstructive pulmonary disease in the COPD and Systemic Consequences-Comorbidities Network Study. Am J Respir Crit Care Med. 2017;195:189–197. doi:10.1164/rccm.201602-0354OC.

 PubMed Web of Science ®Google Scholar

Crisafulli E, Scelfo C, Tzani P, et al. Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation. Eur J Prev Cardiol. 2017;24:990–999. doi:10.1177/2047487317695629.

 PubMed Web of Science ®Google Scholar

Tuleta I, Farrag T, Busse L, et al. High prevalence of COPD in atherosclerosis patients. Int J Chron Obstruct Pulmon Dis. 2017;12:3047–3053. doi:10.2147/COPD.S141988.

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