Background
Methods
Identification cohort, sample collection and processing
Data normalization, preprocessing and analysis
Comparison of COPD-associated gene expression changes in the nasal and bronchial epithelium
-
Comparator cohort 1 was a previously published dataset of bronchial airway gene expression in current and former smokers with and without moderate-to-severe COPD (GSE37147) [4].
-
Comparator cohort 2 was an independent cohort of current and former smokers with and without moderate-to-severe COPD who participated in a previous study in the UMCG [12, 13]. COPD was defined as FEV1/FVC ≤ 0.7. Bronchial brushes were taken during bronchoscopy and RNA was isolated and processed as described in the online supplement.
Pathway analysis
Results
Study populations
Identification cohort
|
Comparator cohorts
| ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Nasal brushes
|
Bronchial brushes (cohort 1)
| Bronchial brushes (cohort 2) | |||||||||||||
COPD
(
n = 31)
|
Control
(n = 22) |
p
|
COPD
(
n = 87)
|
Control
(
n = 151)
|
p
|
COPD
(
n = 10)
|
Control
(n = 20)
|
p
| |||||||
Age, years
|
61
|
(8)
|
52
|
(8)
| <0.01 |
65
|
(6)
|
64
|
(6)
|
0.25
|
67
|
(5)
|
55
|
(10)
| <0.01 |
Male gender, n (%) |
21
|
(68%)
|
14
|
(64%)
|
0.76
|
52
|
(60%)
|
83
|
(55%)
|
0.50
|
10
|
(100%)
|
17
|
(85%)
|
0.20
|
Smoking status
| |||||||||||||||
Current smoking, n (%) |
31
|
(100%)
|
22
|
(100%)
|
1
|
30
|
(35%)
|
69
|
(46%)
|
0.10
|
8
|
(80%)
|
19
|
(95%)
|
0.20
|
Ex smoking, n (%) |
0
|
(0%)
|
0
|
(0%)
|
57
|
(66%)
|
82
|
(54%)
|
2
|
(20%)
|
1
|
(5%)
| |||
Packyears
|
39
|
(18)
|
29
|
(12)
| 0.03 |
51
a
|
(25)
|
47
a
|
(19)
|
0.11
|
31
b
|
(22-45)
|
26
b
|
(24-36)
|
0.57
|
ICS use, n (%) |
27
|
(87%)
|
–
| <0.01 |
18
|
(21%)
|
7
|
(5%)
| <0.01 |
8
|
(80%)
|
0
|
(0%)
| <0.01 | |
FEV
1
c
, % predicted
|
31
|
(6)
|
102
|
(11)
| <0.01 |
60
|
(14)
|
93
|
(13)
| <0.01 |
62
b
|
(52-68)
|
102
b
|
(97-114)
| <0.01 |
FEV
1
/FVC, %
|
34
|
(8)
|
75
|
(4)
| <0.01 |
56
|
(9)
|
75
|
(6)
| <0.01 |
50
b
|
(42-56)
|
73
b
|
(71-83)
| <0.01 |
GOLD classification
c
| |||||||||||||||
GOLD 1, n (%) |
0
|
(0%)
|
–
|
–
|
0
|
(0%)
|
–
|
–
|
1
|
(10%)
|
–
|
–
| |||
GOLD 2, n (%) |
2
|
(6%)
|
–
|
–
|
68
|
(78%)
|
–
|
–
|
8
|
(80%)
|
–
|
–
| |||
GOLD 3, n (%) |
22
|
(71%)
|
–
|
–
|
17
|
(20%)
|
–
|
–
|
1
|
(10%)
|
–
|
–
| |||
GOLD 4, n (%) |
7
|
(23%)
|
–
|
–
|
2
|
(2%)
|
–
|
–
|
0
|
(0%)
|
–
|
–
| |||
TLC, % predicted
|
132
|
(17)
|
105
|
(10)
| <0.01 |
n/a
|
n/a
| – |
n/a
|
n/a
| – | ||||
RV/TLC, %
|
62
|
(7)
|
30
|
(3)
| <0.01 |
n/a
|
n/a
| – |
n/a
|
n/a
| – | ||||
CCQ
|
2.4
|
(0.9)
|
0.4
|
(0.3)
| <0.01 |
n/a
|
n/a
| – |
n/a
|
n/a
| – | ||||
Allergic rhinitis, n (%) |
1
|
(3%)
|
5
|
(23%)
|
0.07
|
n/a
|
n/a
| – |
n/a
|
n/a
| – | ||||
Nasal CS use, n (%) |
2
|
(7%)
|
1
|
(5%)
|
0.99
|
n/a
|
n/a
| – |
n/a
|
n/a
| – |
COPD-associated genes in nasal epithelium
Comparison of COPD-associated gene expression in the nasal and bronchial epithelium
Similarities in pathway enrichment among COPD-associated gene expression in nasal and bronchial epithelium
Nasal | Bronchial (cohort 1) | Bronchial (cohort 2) | ||||
---|---|---|---|---|---|---|
t-value |
p value‡
| t-value | FDR p value | t-value |
p value‡
| |
Enriched pathways for genes upregulated in COPD | ||||||
O-glycan biosynthesis (KEGG) | 0.01#
| <0.01#
| 0.02#
| |||
GALNT6
| 3.00 | <0.01 | 3.21 | 0.02 | 1.57 | 0.13 |
GALNT12
| 3.25 | <0.01 | 3.32 | 0.01 | 3.83 | <0.01 |
B3GNT6
| 2.51 | 0.02 | 3.55 | <0.01 | 2.92 | <0.01 |
ST6GALNAC1
| 2.65 | 0.01 | 3.44 | <0.01 | 1.91 | 0.07 |
Glycosphingolipid biosynthesis (KEGG)a
| 0.04#
| <0.01#
| 0.11#
| |||
FUT3
| 2.13 | 0.04 | 6.76 | <0.01 | 2.68 | 0.01 |
FUT6
| 2.72 | 0.01 | 6.22 | <0.01 | 2.77 | 0.01 |
B4GALT4
| 2.11 | 0.04 | 4.15 | <0.01 | 0.12 | 0.90 |
B3GNT3
| 3.32 | <0.01 | 5.06 | <0.01 | 1.36 | 0.19 |
Enriched pathways for genes downregulated in COPD | ||||||
DNA replication (KEGG) | <0.01#
| 0.09#
| 0.19#
| |||
RFC3
| −2.36 | 0.02 | −3.82 | <0.01 | −2.43 | 0.02 |
RNA degradation (KEGG) | <0.01#
| 0.06#
| 0.06#
| |||
Propanoate metabolism (KEGG) | 0.13#
| 0.20#
| 0.09#
| |||
LDHB
| −3.93 | <0.01 | −3.88 | <0.01 | −1.12 | 0.28 |
ACADM
| −2.71 | 0.01 | −6.06 | <0.01 | −2.14 | 0.04 |
ALDH3A2
| −2.53 | 0.02 | −4.57 | <0.01 | −1.15 | 0.26 |
Tight junction (KEGG) | 0.13#
| 0.21#
| 0.24#
| |||
CLDN16
| −2.33 | 0.02 | −3.56 | <0.01 | −2.76 | 0.01 |
CTNNB1
| −3.33 | <0.01 | −3.18 | 0.02 | −1.65 | 0.11 |
EPB41L2
| −2.64 | 0.01 | −6.03 | <0.01 | −1.67 | 0.11 |