Online Depository
Prevalence and Clinical Correlates of Bronchoreversibility in Severe Emphysema
MeiLan K. Han1, Robert Wise2, Jeanette Mumford3, Frank Sciurba4, Gerard J. Criner5,
Jeffrey L. Curtis1, Susan Murray6, Alice Sternberg2, Gail Weinman7, Ella Kazerooni8,
Alfred P. Fishman9, Barry Make10, Eric A. Hoffman11, Zab Mosenifar12,
Fernando J. Martinez1
for the NETT Research Group
1
Division of Pulmonary & Critical Care, University of Michigan Health System, Ann Arbor, MI
2
Department of Epidemiology and Department of Medicine, Johns Hopkins University,
Baltimore, MD
3
Department of Psychology, University of California, Los Angeles, CA
4
Division of Pulmonary and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA
5
Pulmonary and Critical Care Medicine, Temple University, Philadelphia, PA
6
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI
7
Division of Lung Diseases, National Heart, Lung and Blood Institute, Bethesda, MD
8
Department of Radiology, University of Michigan Health System, Ann Arbor, MI
9
Division of Pulmonary & Critical Care Medicine, University of Pennsylvania, Philadelphia, PA
10
Division of Pulmonary Sciences, National Jewish Health, Denver, CO
11
Department of Radiology, University of Iowa, Iowa City, IA
12
Division of Pulmonary Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
Funding acknowledgment:
The National Emphysema Treatment Trial (NETT) was supported by contracts with the
National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103,
N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108,
N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113,
N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119), the
Centers for Medicare and Medicaid Services (CMS; formerly the Health Care Financing
Administration); and the Agency for Healthcare Research and Quality (AHRQ).
Dr. Curtis is supported by funding from a Research Enhancement Award Program
(REAP) from the Biomedical Laboratory Research & Development Service,
Department of Veterans Affairs
1
Table E1. Pre-rehabilitation characteristics for 544 patients with severe emphysema.
Variable name
Mean
Standard
Deviation
Gender
345 Males
199 Females
Pack Years
66.1
31.8
Age
66.4
6.0
BMI
24.9
3.7
Difference in alpha between upper and lower lobe (-950
-0.09
0.5
12.8
17.7
% Upper lung emphysema (-950 HU)
22.3
16.7
% Lower lung emphysema (-950 HU)
9.5
9.8
%Whole lung emphysema (-950 HU)
15.9
10.5
Difference in percent emphysema between upper and
20.4
24.4
%Upper lung emphysema (-910 HU)
50.0
18.3
%Lower lung emphysema (-910 HU)
29.6
16.6
%Whole lung emphysema (-910 HU)
42.5
12.1
Pre-bronchodilator FEV1 (% predicted)
24.0
6.7
Pre-bronchodilator FVC (% predicted)
58.1
15.2
TLC (% predicted)
129.0
13.8
RV (% predicted)
224.5
47.1
DLCO (% predicted)
28.6
9.9
HU)
Difference in percent emphysema between upper and
lower lobe (-950 HU)
lower lobe (-910 HU)
Definition of Abbreviations: BMI - body mass index; FEV1 - forced expiratory volume in one
second; FVC - forced vital capacity, TLC - total lung capacity; RV – residual volume; DLCO diffusion capacity
2
3
Table E2. Number of patients who underwent measurement of spirometric bronchoreversibility
at each time point, the number that met or did not meet ATS/ERS criteria for
bronchoreversibility and the mean FEV1 at each time point.
Time point
Before
Total
Did not meet ATS/ERS
Met ATS/ERS
Pre-bronchodilator
(n)
BR criteria (%)
BR criteria (%)
mean FEV1 [L(SD)]
544
488 (89.7)
56 (10.3)
0.70 (0.22)
542
503 (92.8)
39 (7.2)
0.70 (0.22)
393
355 (90.3)
38 (9.7)
0.70 (0.24)
328
300 (91.5)
28 (8.5)
0.72 (0.26)
255
235 (92.2)
20 (7.8)
0.73 (0.29)
137
130 (94.9)
7 (5.1)
0.71 (0.28)
31
29 (93.6)
2 (6.5)
0.76 (0.28)
20
20 (100.0)
0 (0.0)
0.76 (0.39)
rehabilitation
After
rehabilitation
6 months after
randomization
12 months after
randomization
24 months after
randomization
36 months after
randomization
48 months after
randomization
60 months after
randomization
Definition of Abbreviations: BR - bronchodilator response
4
Table E3. Number of patients (out of 544) meeting various spirometric bronchoreversibility
criteria throughout the entire period of evaluation.
Criterion
Number meeting
Number not
Number of
criterion at least
meeting criterion
patients meeting
once (%)
at least once (%)
specific criterion
at all visits
ATS/ERS
FEV1 ≥ 400ml
FVC ≥ 400ml and
121 (22.2)
423 (77.8)
2
10 (1.8)
534 (98.2)
0
348 (64.0)
196 (36.0)
45
12% increase
Definition of Abbreviations; ATS - American Thoracic Society; ERS - European Respiratory
Society
1
Table E4. Comparison of characteristics between those who met and never met the criteria
defined by the ATS/ERS criteria.
Characteristics
pre-rehabilitation
ATS/ERS criteria
ATS/ERS criteria
Satisfied at least
never satisfied
once
mean (sd)
p value†
mean (sd)
Gender
21 Females
178 Females
100 Males
245 Males
Age
66.78 (6.16)
66.35 (5.89)
0.485
Pre-BD FEV1 % predicted
25.45 (6.32)
23.58 (6.70)
0.006
Pre-BD FVC % predicted
60.57 (15.11)
57.41 (15.18)
0.044
Post-BD TLC % predicted
125.78 (12.32)
129.91 (14.13)
0.004
DLCO % predicted
31.93 (9.92)
27.67 (9.64)
< 0.0001
 FEV1 (liter)
0.18 (0.09)
0.07 (0.07)
< 0.0001
Percent change FEV1
0.24 (0.14)
0.12 (0.11)
< 0.0001
Pack years
67.93 (30.93)
65.61 (32.06)
0.480
6 MWT (feet)
1445.65 (321.36)
1234.43 (294.42)
< 0.0001
UCSD SOBQ
63.85 (17.64)
66.56 (18.58)
0.153
SF-36 PCS
28.44 (7.78)
28.41 (7.64)
0.973
SF-36 MCS
54.17 (10.84)
51.77 (10.99)
0.035
QWB
0.54 (0.10)
0.52 (0.12)
0.135
SGRQ total score
55.94 (12.98)
56.38 (12.77)
0.740
1
< 0.0001
Whole lung emphysema % (-950
0.15 (0.10)
0.16 (0.11)
0.466
0.41 (0.12)
0.43 (0.12)
0.126
Alpha (-950 HU)
1.04 (0.20)
1.04 (0.22)
0.943
Alpha (-910 HU)
0.74 (0.13)
0.72 (0.13)
0.092
HU)
Whole lung emphysema % (-910
HU)
†P values calculated using a t-test, except categorical variables which used a chi-square test if
cell counts were greater than 5 and a Fisher’s exact test otherwise.
Definition of Abbreviations : BD- bronchodilator; TLC - total lung capacity; DLCO - diffusion
capacity; 6 MWT, - 6 minute walk test; UCSD SOBQ - University of California at San Diego
Shortness of Breath Questionnaire; SF-36 MCS, Short Form 36 mental component score; SF-36
PCS – Short Form 36 physical component score; QWB - quality of well being; SGRQ - St
George Respiratory Questionnaire
2
Table E5. Comparison of characteristics between those who met and never met the criteria defined by FEV1 ≥ 00ml and FVC ≥ 400
ml change.
Characteristic
Pre-rehabilitation
FEV1 ≥ 400 ml
FEV1 ≥ 400 ml
Satisfied at least
once
p value†
FVC ≥ 400 ml and
FVC ≥ 400 ml
never satisfied
12% satisfied
and 12% never
mean (sd)
mean (sd)
satisfied
mean (sd)
Gender
p value†
mean (sd)
0 Females
199 Females
10 Males
335 Males
Age
65.30 (6.41)
66.46 (5.95)
Pre-BD FEV1 % predicted
27.60 (5.34)
Pre-BD FVC % predicted
82 Females
117 Females
266 Males
79 Males
0.540
66.15 (6.20)
66.97 (5.46)
0.109
23.93 (6.67)
0.084
23.29 (6.28)
25.24 (7.13)
0.001
66.30 (9.01)
57.96 (15.27)
0.086
57.05 (14.80)
60.01 (15.78)
0.029
Post-BD TLC % predicted
125.60 (6.75)
129.06 (13.93)
0.149
128.56 (13.66)
129.77 (14.15)
0.327
DLCO % predicted
40.60 (9.29)
28.40 (9.73)
<0.0001
29.44 (10.16)
27.16 (9.11)
0.010
 FEV1 (liter)
0.29 (0.11)
0.09 (0.08)
<0.0001
0.12 (0.08)
0.05 (0.07)
<0.0001
Percent change FEV1
0.32 (0.16)
0.14 (0.13)
<0.0001
0.18 (0.13)
0.09 (0.11)
<0.0001
1
0.02
<0.0001
Pack years
73.93 (42.33)
65.98 (31.60)
0.434
69.41 (33.22)
60.20 (28.18)
0.0012
6 MWT (feet)
1627.30 (265.09)
1274.93 (310.29)
<0.0001
1336.55 (302.70)
1183.52 (307.51)
<0.0001
UCSD SOBQ
63.10 (20.07)
66.01 (18.37)
0.621
65.60 (17.89)
66.58 (19.27)
0.551
SF-36 PCS
30.10 (6.54)
28.39 (7.68)
0.486
28.09 (7.28)
29.01 (8.29)
0.196
SF-36 MCS
48.49 (11.58)
52.37 (10.98)
0.269
52.95 (10.87)
51.15 (11.14)
0.067
QWB
0.54 (0.09)
0.53 (0.12)
0.835
0.53 (0.12)
0.52 (0.12)
0.365
SGRQ total score
53.67 (16.31)
56.33 (12.74)
0.514
56.23 (12.97)
56.38 (12.53)
0.902
Whole lung emphysema % (-950
0.15 (0.05)
0.16 (0.11)
0.548
0.15 (0.11)
0.17 (0.10)
0.153
0.42 (0.08)
0.43 (0.12)
0.827
0.42 (0.12)
0.43 (0.12)
0.199
Alpha (-950 HU)
1.01 (0.13)
1.04 (0.22)
0.667
1.05 (0.22)
1.01 (0.20)
0.022
Alpha (-910 HU)
0.71 (0.09)
0.72 (0.13)
0.787
0.73 (0.13)
0.70 (0.12)
0.003
HU)
Whole lung emphysema % (-910
HU)
†P values calculated using a t-test, except categorical variables which used a chi square test if cell counts were greater than 5 and a
Fisher’s exact test otherwise.
2
Definition of Abbreviations : BD- bronchodilator; TLC - total lung capacity; DLCO - diffusion capacity; 6 MWT, - 6 minute walk test;
UCSD SOBQ - University of California at San Diego Shortness of Breath Questionnaire; SF-36 MCS, Short Form 36 mental
component score; SF-36 PCS – Short Form 36 physical component score; QWB - quality of well being; SGRQ - St George
Respiratory Questionnaire
3
Table E6. Multivariate logistic models where the outcome has a value of 1 if the patient ever
met the bronchoreversibility criterion (n=544).
A. 12% change in FVC as well as a 400ml increase
Predictor
Odds Ratio
95% CI
P-Value
0.80
(0.67, 0.96)
0.01
Male gender
5.83
(3.75, 9.07)
<0.0001
Age (10 year increase)
0.60
(0.43, 0.84)
0.003
0.1 L increase in absolute FEV1
0.99
(0.90, 1.09)
0.87
Odds Ratio
95% CI
P-Value
0.88
(0.72, 1.08)
0.23
Male gender
2.37
(1.37, 4.12)
0.002
Age (10 year increase)
0.96
(0.67, 1.37)
0.81
0.1 L increase in absolute FEV1
1.25
(1.13, 1.38)
<0.0001
10% increase in whole lung
emphysema (-950 HU )
B. ATS/ERS criteria
Predictor
10% increase in whole lung
emphysema (-950 HU )
4