Development of a spirometry T-score in the general population

Figures & data

Figure 1 Probability of all-cause death (A–F), respiratory death (G), COPD death (H), and COPD-related health care utilization (I).

Notes: Probability of all-cause death after 10 years was shown according to FEV₁ expressed in T-score, Z-score, and % of predicted value (A–C) and according to the ratio of FEV₁/FVC expressed in T-score, Z-score, and the ratio itself (D–F) in the 9,101 US subjects. Probability of respiratory death and COPD death after 10 years was shown according to FEV₁ T-score (G and H) in the 9,101 US subjects. Probability of COPD-related health care utilization during 4 years of follow-up was shown according to FEV₁ T-score (I) in the 1,894 Korean subjects.
Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; F–U, follow-up.

Table 1 Baseline characteristics of subjects included in this study

	US subjects 9,101 (100%)	Korean subjects 1,894 (100%)
	Number of subjects (%)
Age (years)
17–39	4,092 (45.0%)	N/a
40–64	3,247 (35.7%)	1,618 (85.4%)
≥ 65	1,762 (19.4%)	276 (14.6%)
Sex
Male	4,460 (49.0%)	924 (48.8%)
Female	4,641 (51.0%)	970 (51.2%)
Smoking status
Never smoker	4,395 (48.3%)	1,112* (59.9%)
Current or ex-smoker	4,706 (51.7%)	745 (40.1%)
Comorbidity
Cancer	676 (7.4%)	N/a
Heart attack	334 (3.7%)	N/a
Heart failure	223 (2.5%)	N/a
Diabetes	605 (6.7%)	N/a
Hypertension	2,122 (23.5%)	N/a
	Mean ± standard deviation
Spirometry values
FEV1T-score	−1.52±1.76	−0.83±1.26
FEV1Z-score	−0.35±1.24	0.21±1.10
FEV1% of predicted value	89.0±16.8	95.0±14.6
FEV1/FVC T-score	−0.89±1.03	−0.67±0.79
FEV1/FVC Z-score	−0.21±0.97	−0.26±0.86
FEV1/FVC ratio	0.78±0.09	0.78±0.08

Notes: The US subjects and Korean subjects were the participants of the Third National Health and Nutrition Examination Survey (US NHANES III) and the Second Korean National Health and Nutritional Examination Survey (Korean NHANES II), respectively.

* The smoking history of 37 subjects was missing.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; N/a, not applicable.

Figure 2 Receiver operating characteristic (ROC) curves for the prediction of all-cause death (A and E), respiratory death (B and F), COPD death (C and G), and COPD-related health care utilization (D and H).

Notes: ROC curves for the prediction of death were shown according to FEV₁ expressed in T-score, Z-score, and % of predicted value (A–C) and according to the ratio of FEV₁/FVC expressed in T-score, Z-score, and the ratio itself (E–G) in the 9,101 US subjects. ROC curves for the prediction of COPD-related health care utilization were shown according to FEV₁ expressed in T-score, Z-score, and % of predicted value (D) and according to the ratio of FEV₁/FVC expressed in T-score, Z-score, and the ratio (H) in the 1,894 Korean subjects.
Abbreviations: AUC, area under curve; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; F–U, follow-up.

Table 2 Various criteria of abnormal spirometry for the prediction of all-cause death, respiratory death, COPD death, and COPD-related health care utilization

Criteria of abnormal spirometry	US subjects									Korean subjects
	All-cause death			Respiratory death			COPD death			COPD-related health care utilization
	Sensitivity	Specificity	Youden index*	Sensitivity	Specificity	Youden index	Sensitivity	Specificity	Youden index	Sensitivity	Specificity	Youden index
FEV1 T-score <−2.5#	0.78	0.78	0.56	0.92	0.72	0.64	0.93	0.72	0.65	0.23	0.92	0.15
FEV1 < LLN‡	0.31	0.89	0.20	0.58	0.87	0.45	0.72	0.87	0.59	0.14	0.96	0.10
FEV1 < 80% of predicted value	0.50	0.77	0.27	0.73	0.75	0.48	0.84	0.74	0.58	0.32	0.89	0.21
FEV1/FVC T-score <−1.5§	0.60	0.75	0.35	0.71	0.72	0.43	0.86	0.72	0.58	0.29	0.86	0.15
FEV1/FVC < LLN‡	0.17	0.94	0.11	0.41	0.93	0.34	0.63	0.93	0.56	0.16	0.94	0.10
FEV1/FVC <0.70	0.41	0.88	0.29	0.59	0.85	0.44	0.79	0.85	0.64	0.33	0.89	0.22

Notes: The sensitivity and specificity for the prediction of all-cause death, respiratory death, and COPD death after 10 years of follow-up in the US subjects and for the prediction of COPD-related health care utilization during 4 years of follow-up in the Korean subjects.

* Defined as sensitivity + specificity −1.

# The cut-off values of the FEV₁ T-score that reached the maximum Youden index for the prediction of all-cause death were −2.5 in males and −2.4 in females.

‡ FEV1 or FEV₁/FVC < LLN (lower limit of normal, bottom 5% percentile) has the same meaning as “the Z-score of FEV₁ or FEV₁/FVC <−1.64”.

§ The cut-off values of the FEV₁/FVC T-scores that reached the maximum Youden index for the prediction of all-cause death were −1.1 in males and −1.6 in females. We arbitrarily chose the cut-off value of −1.5 between −1.1 and −1.6. The combined data of both males and females was presented here.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 3 Kaplan–Meier survival curves for all-cause death (A), respiratory death (B), and COPD death (C) and also for COPD-related health care utilization (D).

Notes: A total of 9,101 subjects in the US (A–C) and 1,894 subjects in South Korea (D) were stratified by FEV₁ T-score. All-cause death, respiratory death, COPD death, and COPD-related health care utilization differed significantly among the four groups (P<0.001 by the log-rank tests).
Abbreviation: FEV₁, forced expiratory volume in 1 second.

Figure S1 Flow of subjects’ selection from the US NHANES III.

Abbreviation: NHANES III, Third National Health and Nutrition Examination Survey.

Figure S2 Flow of subjects’ selection from the Korean NHANES II.

Abbreviation: NHANES II, Second National Health and Nutritional Examination Survey.

Table S1 Selection of “healthy” subjects for the development of spirometry reference values for Koreans

Reasons of exclusion	Number of subjects excluded	Number of subjects who remained
Total		4,927*
History of smoking ≥5 packs over whole life	2,038	2,889
Physician diagnosis of respiratory diseases
Asthma	111	2,778
COPD	10	2,768
Lung cancer	0	2,768
Pulmonary tuberculosis	118	2,650
Bronchiectasis	14	2,636
Respiratory symptoms or limitation
Wheezing during past year	132	2,504
Wheezing when exercise during past year	68	2,436
Phlegm more than 3 months during past year	3	2,433
Cough more than 3 months during past year	0	2,433
Activity limitation d/t respiratory problem	6	2,427
Occupational exposure to
Noxious chemicals	72	2,355
Environmental pollutants	95	2,260
Missing values
Height and weight	7	2,253
FEV1	1	2,252#

Notes:

* Total number of participants for spirometry.

# Final number of subjects for the development of spirometric reference equations.

Abbreviations: FEV₁, forced expiratory volume in 1 second; d/t, due to.

Table S2 Various criteria of abnormal spirometry for the prediction of COPD-related health care utilization (COPD utilization)

Criteria* of abnormal spirometry	COPD-related health care utilization in the Korean subjects
	Sensitivity	Specificity	Youden index#
FEV1 T-score <−1.5*	0.50	0.74	0.24
FEV1 Z-score <−1.0*	0.31	0.90	0.20
FEV1 % of predicted value <79	0.31	0.90	0.21
FEV1/FVC T-score <−1.8*	0.24	0.92	0.16
FEV1/FVC Z-score <−1.4*	0.21	0.92	0.12
FEV1/FVC <0.71*	0.37	0.87	0.24

Notes: The sensitivity and specificity for the prediction of COPD utilization during 4 years of follow-up in the Korean subjects.

* The cut-off values were chosen where their Youden indices were the maximum.

# Defined as sensitivity + specificity −1.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.