Diagnosis of COPD and clinical course in patients with unrecognized airflow limitation

Figures & data

Figure 1 Flow diagram of cohort analyzed using FR (FEV₁/FVC < 0.7) and LLN (FEV₁/FVC < LLN).

Notes: Three hundred twenty-five of the original 347 patients were eligible based on adequate spirometry. Patients were divided into subgroups based on spirometry and diagnosis of COPD recorded in the EMR problem list at time of recruitment. Patients with a COPD diagnosis in their medical record who did not have AFL based on spirometry were removed from analysis.
Abbreviations: AFL, airflow limitation; COPD, chronic obstructive pulmonary disease; EMR, electronic medical record; FEV₁, forced expiratory volume in 1 second; FR, fixed ratio; FVC, forced vital capacity; LLN, lower limit of normal.

Table 1 Comparisons of all subsets of diseased patients by age, BMI, baseline pulmonary data, and prescription medications, as well as clinical outcome data using health care utilization and mortality

	AFL definition
	FR						LLN
	COPD diagnosed	COPD not diagnosed	P-value	COPD subsequently diagnosed	COPD persistently undiagnosed	P-value	COPD diagnosed	COPD not diagnosed	P-value	COPD subsequently diagnosed	COPD persistently undiagnosed	P-value
n	45	92		16	76		36	67		12	55
Age (mean ± SEM)	66.1 ± 1.7	62.1 ± 1.16	0.05	58.9 ± 3	62.8 ± 1.25	0.2	64.9 ± 1.8	59.6 ± 1.3	0.02	56.6 ± 3	60.2 ± 1.4	0.28
Symptom score (mean ± SEM)	12.0 ± 0.9	7.15 ± 0.64	<0.001	10.2 ± 1.6	6.5 ± 0.7	0.03	12.5 ± 1.0	8.1 ± 0.8	0.001	11.1 ± 2.1	7.45 ± 0.8	0.07
BMI (mean ± SEM)	26.5 ± 1.0	28.3 ± 0.7	0.01	30.2 ± 2.4	27.9 ± 0.7	0.22	25.4 ± 1.1	28.9 ± 0.9	0.02	31.2 ± 3.1	27.9 ± 0.8	0.14
FEV1 (mean ± SEM)	1.7 ± 0.09	2.27 ± 0.06	<0.001	2.1 ± 0.16	2.3 ± 0.07	0.24	1.5 ± 0.09	2.2 ± 0.08	<0.001	2.0 ± 0.18	2.24 ± 0.08	0.9
Modified GOLD class (n [%])
1	3 (6)	22 (24)	0.017	2 (13)	20 (26)	0.34	1 (3)	14 (21)	0.02	2 (17)	12 (21)	1.0
2	22 (48)	57 (62)	0.2	8 (50)	49 (64)	0.40	15 (42)	42 (63)	0.06	5 (42)	37 (65)	0.11
3	14 (30)	12 (13)	0.02	6 (38)	6 (7.9)	0.006	13 (36)	10 (15)	0.02	5 (42)	5 (9)	0.01
4	7 (15)	1 (1)	0.002	0	1 (1.3)	1.0	7 (19)	1(1)	0.003	0	1 (2)	1.0
Cardiovascular disease	17 (37)	29 (32)	0.56	4 (25)	25 (33)	0.77	15 (42)	21 (31)	0.39	3 (25)	18 (32)	0.74
Medications (n [%])
SABA	35 (78)	21 (23)	<0.001	8 (50)	13 (17)	0.008	29 (81)	18 (27)	<0.001	7 (58)	11 (19)	0.01
LABA	15 (33)	6 (7)	<0.001	5 (31)	1 (1)	<0.001	13 (36)	6 (9)	0.001	5 (42)	1 (2)	<0.001
SA antichol	22 (49)	10 (11)	<0.001	3 (19)	7 (9)	0.37	18 (50)	8 (12)	<0.001	2 (17)	6 (11)	0.63
LA antichol	6 (13)	4 (4)	0.35	4 (25)	0	<0.001	5 (14)	4 (6)	0.27	4 (33)	0	<0.001
ICS	12 (27)	2 (3)	<0.001	0	2 (3)	1.0	12 (33)	2 (3)	<0.001	0	2 (4)	1.0
Health care utilization
ED visits/pt/yr (mean ± SEM)	0.26 ± 0.06	0.15 ± 0.03	0.07	0.33 ± 0.11	0.11 ± 0.05	0.009	0.21 ± 0.06	0.17 ± 0.04	0.57	0.31 ± 0.15	0.13 ± 0.04	0.11
Admissions/pt/yr (mean ± SEM)	0.2 ± 0.06	0.04 ± 0.01	<0.001	0.04 ± 0.04	0.04 ± 0.02	1.0	0.24 ± 0.07	0.05 ± 0.02	0.001	0.06 ± 0.05	0.04 ± 0.14	0.95
Annual mortality (% dead/yr ± SEM)	7.1 ± 2	2.4 ± 0.8	0.01	1.8 ± 2.4	2.6 ± 0.9	0.72	9.1 ± 2.3	1.9 ± 0.8	<0.001	2.1 ± 2	1.9 ± 0.9	0.93

Notes: AFL as defined by FR: FR = FEV₁/FVC < 0.70. AFL as defined by LLN: (FEV₁/FVC)/LLN < 1.0. Statistical analysis was performed using Fisher’s and Student’s t-test.

Abbreviations: AFL, airflow limitation; BMI, body mass index; COPD, chronic obstructive pulmonary disease; ED, emergency department; FEV₁, forced expiratory volume in 1 second; FR, fixed ratio; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LA antichol, long acting anticholinergic; LABA, long acting beta agonist; LLN, lower limit of normal; pt, patient; SA antichol, short acting anticholinergic; SABA, short acting beta agonist; SEM, standard error of the mean; yr, year.

Figure 2 Mean symptom scores of study subjects showing spirometric classification, and diagnostic status.

Abbreviations: COPD, chronic obstructive pulmonary disease; LLN, lower limit of normal.

Table 2 Comparisons of diseased patients without a documented diagnosis of COPD and patients with normal spirometry

	Definition of AFL
	FR			LLN
	Normal	COPD persistently undiagnosed	P-value	Normal	COPD persistently undiagnosed	P-value
n	92	76		104	55
Age (mean ± SEM)	55.1 ± 1.22	62.8 ± 1.25	<0.001	56.6 ± 1.2	60.2 ± 1.4	0.07
Symptom score (mean ± SEM)	4.9 ± 0.55	6.5 ± 0.7	0.07	4.8 ± 0.54	7.45 ± 0.8	0.006
BMI (mean ± SEM)	30.4 ± 0.67	27.9 ± 0.7	0.01	30 ± 0.6	27.9 ± 0.8	0.04
FEV1 (mean ± SEM)	3.3 ± 0.06	2.3 ± 0.07	<0.001	3.24 ± 0.06	2.24 ± 0.08	<0.001
Cardiovascular disease	15 (16)	25 (33)	0.02	16 (15)	18 (32)	0.015
Health care utilization
ED visits/year (mean ± SEM)	0.09 ± 0.04	0.11 ± 0.05	0.75	0.09 ± 0.03	0.13 ± 0.04	0.43
Hospitalizations/year (mean ± SEM)	0.03 ± 0.02	0.04 ± 0.02	0.73	0.03 ± 0.02	0.04 ± 0.14	0.92
Annual mortality (% dead/year ± SEM)	1.7 ± 0.7	2.6 ± 0.9	0.42	2.2 ± 0.8	1.9 ± 0.9	0.82

Notes: AFL as defined by FR: FR = FEV₁/FVC < 0.70. AFL as defined by LLN: (FEV₁/FVC)/LLN < 1.0.

Abbreviations: AFL, airflow limitation; BMI, body mass index; COPD, chronic obstructive pulmonary disease; ED, emergency department; FEV₁, forced expiratory volume in 1 second; FR, fixed ratio; FVC, forced vital capacity; LLN, lower limit of normal; SEM, standard error of the mean.

Figure 3 Mean number of annual emergency department visits per patient.

Abbreviations: COPD, chronic obstructive pulmonary disease; ED, emergency department; LLN, lower limit of normal; VAMC, Veterans Administration Medical Center.

Figure 4 Mean number of annual hospitalizations per patient.

Notes: *One patient had four admissions during the 6 months after the recruitment period prior to his death, contributing half of all admissions for the entire group. Data presented for completeness; without this outlier the restricted population values are similar to that of the normal population.

Abbreviations: COPD, chronic obstructive pulmonary disease; LLN, lower limit of normal; VAMC, Veterans Administration Medical Center.

Figure 5 Annual mortality rate during study period.

Abbreviations: COPD, chronic obstructive pulmonary disease; LLN, lower limit of normal.

Table 3 Comparisons of patients with decreased FVC (restricted) and normal spirometry

	Definition of AFL
	FR			LLN
	Normal	Restriction	P-value	Normal	Restriction	P-value
n	92	68		104	77
Age (mean ± SEM)	55.1 ± 1.22	64.1 ± 1.4	<0.001	56.6 ± 1.2	64.9 ± 1.3	<0.001
Symptom score (mean ± SEM)	4.9 ± 0.55	6.4 ± 0.7	0.09	4.8 ± 0.54	6.1 ± 0.64	0.12
BMI (mean ± SEM)	30.4 ± 0.67	31 ± 0.9	0.6	30 ± 0.6	30.9 ± 0.82	0.37
FVC (mean ± SEM)	4.3 ± 0.08	3.0 ± 0.07	<0.001	4.3 ± 0.08	3.0 ± 0.07	<0.001
FEV1 (mean ± SEM)	3.3 ± 0.06	2.3 ± 0.06	<0.001	3.24 ± 0.06	2.29 ± 0.06	<0.001
Cardiovascular disease	15 (16)	29 (43)	<0.001	16 (15)	35 (45)	<0.001
Health care utilization
ED visits/year (mean ± SEM)	0.09 ± 0.04	0.13 ± 0.03	0.45	0.09 ± 0.03	0.12 ± 0.03	0.49
Hospitalizations/year (mean ± SEM)	0.03 ± 0.02	0.16 ± 0.12	0.22	0.03 ± 0.02	0.15 ± 0.11	0.22
Annual mortality (% dead/year ± SEM)	1.7 ± 0.7	2.8 ± 1	0.35	2.2 ± 0.8	2.89 ± 1	0.59

Notes: AFL as defined by FR: FR = FEV₁/FVC < 0.70. AFL as defined by LLN: (FEV₁/FVC)/LLN < 1.0.

Abbreviations: AFL, airflow limitation; BMI, body mass index; ED, emergency department; FEV₁, forced expiratory volume in 1 second; FR, fixed ratio; FVC, forced vital capacity; LLN, lower limit of normal; SEM, standard error of the mean.