14
Chronic Obstructive Pulmonary Disease (COPD) Comorbidities Network Miguel J. Divo MD, Ciro Casanova MD, Jose M. Marin MD, Victor M. Pinto-Plata MD, Juan P. de-Torres MD, Javier Zulueta MD, Carlos Cabrera MD, Jorge Zagaceta MD, Pablo Sanchez-Salcedo MD, Juan Berto MD, Ana B. Alcaide MD, Claudia Cote MD, and Bartolome R. Celli MD The BODE Collaborative Group Online supplement Table E1. Demographic and anthropometric characteristics comparing the Non-COPD controls with a randomly selected matched COPD subset. Table E2. Comorbidities ranking by age category and group. Table E3. Prevalence comparison between Females and Males in the COPD cohort. Figure E1. Disease prevalence comparing COPD vs Control by age category. Figure E2. Disease prevalence comparing COPD vs Control by gender. Figure E3. Comorbidities network comparing COPD males and females. Figure E4. Comorbidities network comparing COPD and controls matched by total number of subjects, age, gender distribution and current smoking status. Figure E5. Comparison of COPD comorbidities networks using 3 cut-offs for statistical significance on Pearson’s correlation values between comorbidities. Figure E6. Degree’s distribution and tests for network characterization.

Chronic Obstructive Pulmonary Disease (COPD) Comorbidities Networkerj.ersjournals.com/content/erj/suppl/2015/07/09/09031936.00171614... · Chronic Obstructive Pulmonary Disease (COPD)

  • Upload
    ngotu

  • View
    217

  • Download
    3

Embed Size (px)

Citation preview

Chronic Obstructive Pulmonary Disease (COPD) Comorbidities Network

Miguel J. Divo MD, Ciro Casanova MD, Jose M. Marin MD, Victor M. Pinto-Plata MD, Juan P. de-Torres MD, Javier Zulueta MD, Carlos Cabrera

MD, Jorge Zagaceta MD, Pablo Sanchez-Salcedo MD, Juan Berto MD, Ana B. Alcaide MD, Claudia Cote MD, and Bartolome R. Celli MD

The BODE Collaborative Group

Online supplement

Table E1. Demographic and anthropometric characteristics comparing the Non-COPD controls with a randomly selected matched COPD subset.

Table E2. Comorbidities ranking by age category and group.

Table E3. Prevalence comparison between Females and Males in the COPD cohort.

Figure E1. Disease prevalence comparing COPD vs Control by age category.

Figure E2. Disease prevalence comparing COPD vs Control by gender.

Figure E3. Comorbidities network comparing COPD males and females.

Figure E4. Comorbidities network comparing COPD and controls matched by total number of subjects, age, gender distribution and current smoking

status.

Figure E5. Comparison of COPD comorbidities networks using 3 cut-offs for statistical significance on Pearson’s correlation values between

comorbidities.

Figure E6. Degree’s distribution and tests for network characterization.

Table E1. Demographic and anthropometric characteristics comparing the Non-COPD controls with a randomly selected matched COPD patients’

subset.

Demographic COPD Controls p-value

N 311 316

Age (mean±SD) 59 ± 8 58± 11 0.132

Male n (%) 152 (49%) 176 (56%) 0.093

Current smoker* n (%) 142* (49%) 142 (45%) 0.328

Spirometry

FEV1% predicted (mean±SD) 54 ± 21 100 ± 15 <0.0001

Body Mass Index (BMI)

BMI (mean± SD) 27.03± 5.9 27.8 ± 4.9 0.0630

Comorbidities (Median, IQR, Range)

Comorbidities (whole) 3, (2-6), 0-15 2, (0-3), 0-14 <0.0001

Number of comorbidities by Gender

Male 4, (2-7), 0-15 2, (1-3), 0-14 <0.0001

Female 2, (1-4), 0-14 1, (0-3), 0-8 <0.0001

*Data missing in 22 subjects.

Table E2. Top 20 comorbidities per group by age category.

Age ≤ 55

Age between 56 and 64

Age ≥ 65

Group Rank Disease Prevalence

(%) Disease

Prevalence

(%) Disease

Prevalence

(%)

CO

PD

1 Hyperlipidemia 38.5

Hypertension* 47.0

Hypertension 57.7

2 Hypertension 36.3

Hyperlipidemia 42.8

Hyperlipidemia 43.1

3 DJD 27.8

Coronary Artery Disease* 22.9

Coronary Artery Disease 30.0

4 Substance abuse 22.7

Diabetes Mellitus 22.0

DJD 28.4

5 Depression 21.8

DJD 21.8

Diabetes Mellitus 21.6

6 Coronary Artery Disease 19.7

BPH* 19.1

Peripheral Artery Disease 17.1

7 GORD 19.2

Depression* 18.4

Congestive Heart Failure 16.9

8 Anxiety 15.0

Substance abuse* 15.3

Chronic Renal Failure 16.4

9 Diabetes Mellitus 13.7

GORD 14.0

Atrial Fibrillation 15.9

10 Bipolar/Schizophrenia 13.7

Peripheral Artery Disease* 13.8

GORD 15.2

11 Hepatitis 11.5

Chronic Renal Failure* 13.5

CVA 12.0

12 Chronic Renal Failure 10.3

Anxiety 11.6

GORD 11.5

13 Obstructive Sleep Apnea 10.3

Erectile dysfunction* 11.6

Pulmonary Hypertension 9.7

14 BPH 8.6

Congestive Heart Failure* 10.8

Prostate CA 9.2

15 Gastro-Duodenal ulcers 8.1

Obstructive Sleep Apnoea 10.2

Osteoporosis 8.6

16 CVA 7.7

Gastro-Duodenal ulcers 9.5

Obstructive Sleep Apnoea 8.5

17 Peripheral Artery Disease 7.3

Bipolar/Schizophrenia* 9.3

Lung CA 8.2

18 Erectile dysfunction 6.4

Lung CA* 8.9

Pulmonary fibrosis 5.6

19 Congestive Heart Failure 6.0

Atrial Fibrillation* 8.0

Gout 3.9

20 Osteoporosis 6.0

Pulmonary Hypertension* 7.8

Bladder CA 3.9

Age ≤ 55

Age between 56 and 64

Age ≥ 65

Group Rank Disease Prevalence (%)

Disease Prevalence

(%) Disease

Prevalence

(%)

Non-

COPD

Controls

1 Hyperlipidemia 20.1

Hyperlipidemia 44.1

Hyperlipidemia 49.0

2 Hypertension 11.4

Hypertension* 29.8

Hypertension 48.0

3 Anxiety 7.4

Diabetes Mellitus 16.7

DJD 31.0

4 DJD 6.0

DJD 16.7

Diabetes Mellitus 24.0

5 Asthma 6.0

GORD 13.1

GORD 18.0

6 CTD 6.0

Obstructive Sleep Apnea 11.9

Osteoporosis 14.0

7 Depression 5.4

Osteoporosis 10.7

Obstructive Sleep Apnoea 11.0

8 GORD 5.4

Anxiety 8.3

Prostate CA 6.0

9 Diabetes Mellitus 5.4

Coronary Artery Disease* 7.1

Lung CA 6.0

10 Obstructive Sleep Apnea 4.7

BPH* 6.0

Atrial Fibrillation 5.0

11 Coronary Artery Disease 2.7

Cataract 6.0

Gout 5.0

12 Gastro-Duodenal ulcers 2.7

Nephrolithiasis 4.8

CAD 4.0

13 Nephrolithiasis 2.7

Ventricular Arrhythmias 4.8

PAD 4.0

14 BPH 2.0

HIV* 4.8

Gastro-Duodenal ulcers 4.0

15 Thyroid CA 2.0

Depression* 3.6

Bladder CA 4.0

16 Peripheral Artery Disease 1.3

Gastro-Duodenal ulcers 3.6

CTD 4.0

17 Hypothyroidism 1.3

Hypothyroidism 3.6

Pulmonary embolism 4.0

18 Deep Vein Thrombosis 1.3

Chronic Renal Failure* 2.4

Asthma 4.0

19 Ventricular arrhythmias 1.3

Pulmonary fibrosis 2.4

Congestive Heart Failure 3.0

20 Venous insuficiency 1.3

Prostate CA 2.4

Hepatitis 3.0

Abbreviations:

AAA= Abdominal Aortic Aneurism, BPH= Benign Prostatic Hypertrophy, CAD = Coronary Artery Disease, CHF=Congestive Heart Failure,

CRF=Chronic Renal Failure, CVA=Cerebro-Vascular Accident, DM= Diabetes Mellitus, DVT= Deep Venous Thrombosis, GORD= Gastro-

Oesophageal Reflux Disease, HTN= Systemic Hypertension, OSA= Obstructive Sleep Apnoea, PAD: peripheral artery disease, Pulmonary HTN=

Pulmonary Hypertension.

Table E3. Comorbidity prevalence and comparison between COPD females and males.

Comorbidity Females (n=219) Males (n=1750) P

Fem

ale

pre

dom

inan

t Osteoporosis 20.1 6.3 <. 0001

Hypothyroidism 11.9 5.7 0.0011

Venous insufficiency 6.9 3.7 0.0417

Asthma 4.1 1.5 0.0141

Breast cancer 6.9

HTN 38.4 54.1 <. 0001

Mal

e pre

dom

inan

t

CAD 13.2 28.5 <. 0001

DM 15.5 21.6 0.0423

GERD 7.8 16.2 0.0007

Peripheral arterial disease 3.2 15.9 0.0069

CHF 6.8 14.9 0.0009

Substance abuse 3.7 12.7 <. 0001

Atrial Fibrillation/Flutter 5 12.4 0.0004

Gastric/Duodenal Ulcer 4.6 11.4 0.0011

CVA 6.4 10.7 0.0447

OSA 0.5 10.2 <. 0001

Cataract 3.2 9.3 0.0013

Pulmonary HTN 4.6 9.1 0.0212

Lung Cancer 3.7 8.7 0.0082

AAA 2.3 6.2 0.0139

Ventricular arrhythmia 2.3 5.7 0.0359

Pulmonary fibrosis 0.9 5.5 0.0358

Hepatitis 0.9 3.7 0.0279

DM w/ Neuropathy 0.5 3.7 0.008

Bladder and tract urinary cancer 0 3.2 0.002

Pancreatitis 0.5 2.2 0.0422

Hypogonadism 0 0.9 0.2432

BPH 29.2

Erectile dysfunction 9.9

Prostate cancer 8.1

Testicular cancer 0.2

Abbreviations:

AAA= Abdominal Aortic Aneurism, BPH= Benign Prostatic Hypertrophy, CAD = Coronary Artery Disease, CHF=Congestive Heart Failure,

CRF=Chronic Renal Failure, CVA=Cerebro-Vascular Accident, DM= Diabetes Mellitus, DVT= Deep Venous Thrombosis, GERD= Gastro-

Oesophageal Reflux Disease, HTN= Systemic Hypertension, OSA= Obstructive Sleep Apnoea, PAD: peripheral artery disease, Pulmonary HTN=

Pulmonary Hypertension, TB= tuberculosis.

Figure E1. Disease prevalence by age distribution.

Diseases with a statistically significant difference in proportion are indicated with an *.

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

Pre

vale

nce

(%

)

Age Goup ! 55 years

COPD (n=231)

Non-COPD Control (n=159)

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

45.0

50.0

Pre

vale

nce

(%

)

Age Goup between 56 and 64 years

COPD (n=528)

Non-COPD Control (n=159)

0

10

20

30

40

50

60

Pre

vale

nce

(%

)

Age Goup " 65 years

COPD (n=1191) Non-COPD Controls (n=100)

Figure E2. Disease prevalence by gender.

Diseases with a statistically significant difference in proportion are indicated with an *.

0

5

10

15

20

25

30

35

40

45

50

55

Pre

va

len

ce (

%)

Males

COPD n=1794

Non-COPD Control n=194

0

5

10

15

20

25

30

35

40

45

Pre

vale

nce

(%

)

Females

COPD n=216

Non-COPD Control n=146

Figure E3. Comorbidities network comparing COPD males and females.

The network layout is based on a force directed algorithm of attractions and repulsions called Fruchterman-Reingold algorithm1. Note that 1. The

network is denser in the male cohort, 2. There are more current smoker, more individuals younger than 55 years, higher prevalence of psychiatric

(depression and anxiety), osteoporosis and more perception of dyspnoea in the female cohort, while the male cohort has higher prevalence and

influence of cardiovascular diseases.

1. Fruchterman T, Reingold E, Graph Drawing by Force-directed Placement. Graph Drawing by Force-directed Placement. SOFTWARE—PRACTICE AND EXPERIENCE,

VOL. 21(1 1), 1129-1164 (NOVEMBER 1991)

COPD Females

o! 68 nodes

o! 206 edges

COPD Males

o! 87 nodes

o! 548 edges

Figure E4. Comorbidities network comparing matched COPD and controls by total number of subject, age, gender distribution and current smoking

status.

Note that 1. The network is denser in the Matched COPD cohort, the prevalence of common diseases in both groups is higher for COPD and there is

a higher influence (by prevalence and connections) of psychiatric, behavioural and cardiovascular comorbidities.

Matched COPD Cohort

Nodes=69

Edges= 214

Non-COPD Controls

Nodes=56

Edges= 149

Figure E5. Comparison of COPD comorbidities network using 3 cut-offs for statistical significance on Pearson’s correlation values between

comorbidities and clinical variables.

Panel A.

p≤ 0.01 p≤ 0.001 p≤ 0.0001

Panel B.

Combination of plot chart and histogram demonstrating the distribution of p-values at the following cut-off point (doted lines): ≤0.01 (520

correlations), ≤0.001 (357 correlations) and ≤0.0001 (265 correlations). Correlations are positive or negative with values ranging from 0.06 to 0.42

and -0.05 to -0.16.

-0.2

-0.1

0

0.1

0.2

0.3

0.4

Rh

o

0.01 0.009 0.008 0.007 0.006 0.005 0.004 0.003 0.002 0.001 0

p-value

! "##$%&' " ( )*+, -#+. / ' " ( ). 0)123&%/$)&( *)45" )

Pea

rson’s

co

rrel

atio

n (

!)

Figure E6. Degree’s distribution and tests for network characterization.

Panel A. Histogram of the distribution of links per nodes (degree), superimposed with a fitted Poisson’s (red), normal (blue) and exponential

(green) distribution curves. Note that the distribution better approximate an exponential distribution (long rightward tail)

Panel B. Fitted plot to test how distribution better fit the degree distribution in the cohort of COPD individuals.

P

ois

son

Qu

an

tile

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30 35

Degree

No

rmal

Pro

bab

ilit

y

0.015

0.05

0.09

0.16

0.3

0.5

0.7

0.84

0.91

0.95

0 5 10 15 20 25 30 35

Degree

Ex

po

nen

tial

Pro

bab

ilit

y

0.05

0.250.350.450.55

0.65

0.75

0.85

0.91

0.93

0.95

0.97

0 5 10 15 20 25 30 35

Degree

Fitted Poisson Fitted Exponential Fitted Normal

Pearson’s ChiSquared

p< 0.0001

H0= The data is from the

Poisson distribution

Small p-values reject H0

Kolmogorov’s D

P=0.0785

H0= The data is from the

Exponential distribution

Small p-values reject H0

Shapiro-Wilk W test

p< 0.0001

H0= The data is from the

Normal distribution

Small p-values reject H0