The Association Between Eosinophil Variability Patterns and the Efficacy of Inhaled Corticosteroids in Stable COPD Patients

Figures & data

Figure 1 Flowchart of participants.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; CBC, complete blood count; WBC, white blood cell count; CRP, C-reactive protein; AE, acute exacerbation; ICS, inhaled corticosteroid.

Figure 2 Correlation between blood eosinophil counts at baseline and 1-year follow-up. Dash line stands for 250/μL.

Abbreviation: R, intraclass coefficient.

Table 1 Baseline Characteristic of Study Population Classified with Eosinophil Variability

	Total (n=618)	CH Group (n=125)	CL Group (n=355)	VI Group (n=63)	VD Group (n=75)	p-value
Age, year	68.6±7.9	68.8±7.4	68.6±8.2	68.9±8.0	67.7±7.4	0.784
Sex, male (%)	600 (97)	123 (98)	345 (97)	60 (95)	72 (96)	0.604
Height, cm	165±6	165±5	165±6	165±7	165±6	0.989
Current smoker, n (%)	445 (72)	82 (66)	260 (73)	47 (74)	56 (75)	0.658
Smoking dosage, pack-year	46±27	46±24	45±27	40±23	51±32	0.173
Blood tests
White blood cell, x10^3/µL  Eosinophil counts,/µL  Eosinophil percentage, %  C-reactive protein, mg/dL	7.17±1.73 225±168 0.32±0.24 0.58±0.85	7.70±1.59 438±170 0.59±0.27 0.62±0.97	6.93±1.69 129±60 0.20±0.10 0.60±0.87	7.21±2.13 166±50 0.25±0.10 0.45±0.71	7.42±1.61 372±144 0.52±0.19 0.52±0.63	<0.001 <0.001 <0.001 0.714
LA inhalers use, n (%)						0.378
None  Single  Dual  Triple	168 (27) 150 (24) 139 (22) 161 (26)	34 (27) 39 (31) 24 (19) 28 (22)	96 (27) 75 (21) 85 (24) 99 (27)	17 (27) 15 (24) 18 (29) 13 (21)	21 (28) 21 (28) 12 (16) 21 (28)
ICS users, n (%)	250 (40)	43 (34)	154 (43)	24 (38)	29 (39)	0.333
Spirometry
Post-BD FEV1, L  Post-BD FEV1, % pred  Post-BD FEV1/FVC, %	1.60±0.53 61.9±19.2 48.9±11.5	1.63±0.52 62.5±17.6 49.7±11.7	1.61±0.55 62.1±20.0 48.4±11.5	1.57±0.47 61.7±18.5 49.5±11.2	1.59±0.53 60.5±19.0 49.0±11.6	0.931 0.915 0.695
Symptoms
mMRC dyspnea scale  CAT score  SGRQ score, total  6 minute walk distance, m	1.47±0.86 16.1±7.8 35.4±18.7 407±108	1.34±0.79 15.7±7.2 35.0±16.6 414±101	1.53±0.87 16.1±8.0 35.4±18.5 405±106	1.41±0.80 17.3±8.1 38.0±21.8 404±120	1.47±0.96 15.6±7.8 34.7±20.3 406±117	0.169 0.567 0.703 0.896
History of AE-COPD
AE rate, events/year  Incidence of AE, n (%)	0.55±1.66 141(23)	0.55±1.55 27 (22)	0.54±1.75 77 (22)	0.69±1.78 18 (29)	0.51±1.25 19 (26)	0.908 0.610
AE-COPD (during 1-year)
AE rate, events/year  Incidence of AE, n (%)	0.69±1.52 178 (29)	0.65±1.75 33 (27)	0.69±1.45 102 (29)	0.67±1.27 22 (35)	0.75±1.63 21 (28)	0.978 0.693

Note: Mean ± standard deviation.

Abbreviations: CH, consistently high; CL, consistently low; VI, variably increasing; VD, variably decreasing; BD, bronchodilator; LA inhaler, long-acting inhaler; ICS, inhaled corticosteroids; FEV₁, forced expiratory volume in 1 second; mMRC, the modified Medical Research Council; CAT score, COPD assessment test score; SGRQ score, St. George Respiratory Questionnaire score; AE, acute exacerbation.

Table 2 Characteristics of Study Population Between ICS Users and Nonusers Before and After Propensity Score Matching

	Overall Patients			After Propensity Score Matching
	ICS User (n=250)	ICS Nonuser (n=368)	p-value	ICS User (n=239)	ICS Nonuser (n=239)	p-value
Age, year	69.0±8.4	68.3±7.5	0.272	69.0±8.3	69.1±7.1	0.827
Sex, Male (%)	242 (97)	358 (97)	0.915	231 (97)	232 (97)	1.000
Height, cm	164±6	165±5	0.224	165±6	164±6	0.927
Current smoker (%)	187 (75)	258 (70)	0.336	176 (74)	175 (73)	1.000
Eosinophil,/µL	212±156	234±175	0.108	213±158	226±166	0.352
LA inhalers use, n (%)			–			–
None  Single  Dual  Triple	0 (%) 3 (1%) 86 (34%) 161 (64%)	168 (46%) 147 (40%) 53 (14%) 0 (0%)		0 (%) 3 (1%) 85 (35%) 151 (63%)	106 (44%) 98 (41%) 35 (15%) 0 (0%)
Spirometry
Post-BD FEV1, L  Post-BD FEV1, % pred	1.47±0.53 57.0±19.6	1.70±0.52 65.2±18.3	<0.001* <0.001*	1.48±0.53 57.4±19.7	1.54±0.46 60.5 ±17.6	0.190 0.066
Symptom
mMRC dyspnea scale	1.68±0.86	1.33±0.83	<0.001*	1.67±0.87	1.55±0.82	0.131
History of AE-COPD
AE rate, events/year  Incidence of AE, n (%)	0.65±1.55 67 (27)	0.48±1.73 74 (20)	0.225 0.059	0.66±1.57 65 (27)	0.56±1.96 53 (22)	0.520 0.243

Notes: *Matching variables: post-BD FEV₁(L), mMRC dyspnea scale, AECOPD. Mean ± standard deviation, p-value < 0.05.

Abbreviations: BD, bronchodilator; LA inhaler, long-acting inhaler; ICS, inhaled corticosteroids; FEV₁, forced expiratory volume in 1 second; mMRC, the modified Medical Research Council; AE, acute exacerbation.

Table 3 The Acute Exacerbation Rates of COPD in ICS Users and Nonusers According to Eosinophil Cutoffs

Cutoff (/µL)	ICS Users				ICS Nonusers
	CH	CL	VI	VD	CH	CL	VI	VD
100	0.60±1.25	0.97±1.27	0.94±1.78	1.46±2.28	0.70±1.51	0.83±1.69	0.67±1.24	0.80±1.35
150	0.58±1.33	1.01±1.58	0.67±1.18	0.98±1.85	0.79±1.68	0.80±1.51	0.43±1.03	0.59±1.13
200	0.33±0.82	0.93±1.58	0.84±1.37	0.98±1.90	0.76±1.64	0.67±1.33	0.74±1.42	0.85±1.64
250	0.33±0.89	0.89±1.51	0.45±0.66	1.21±2.27	0.79±1.78	0.63±1.36	1.00±1.65	0.71±1.19
300	0.25±0.52	0.88±1.52	0.37±0.58	1.18±2.28	0.39±1.00	0.65±1.44	1.07±1.72	1.10±1.79

Note: Mean ± standard deviation.

Abbreviations: CH, consistently high; CL, consistently low; VI, variably increasing; VD, variably decreasing.

Figure 3 Eosinophil variability and the effect of ICS on acute exacerbation rate.

Abbreviation: CI, confidence interval.

Figure 4 Comparison of eosinophil change between ICS user and nonusers.

Table 4 Changes of Eosinophil Variability According to Eosinophil Cutoffs

Cutoff (/µL)	Consistently High (A)	Consistently Low (B)	Variably Increasing (C)	Variably Decreasing (D)	D/(A+D)*	C/(B+C)**	(C+D)/(A+B+C+D)^┼
100	414	69	55	80	80/494 (16%)	55/124 (44%)	135/618 (22%)
150	267	168	82	101	101/368 (27%)	82/250 (33%)	183/618 (30%)
200	178	274	73	93	93/271 (34%)	73/347 (21%)	166/618 (27%)
250	125	355	63	75	75/200 (38%)	63/418 (15%)	138/618 (22%)
300	86	412	53	67	67/153 (44%)	53/465 (11%)	120/618 (19%)

Notes: *The proportion of patients who showed high eosinophil initially, but changed to low eosinophil count after a year. **The proportion of patients who showed low eosinophil initially, but changed to high eosinophil count after a year. ^┼The proportion of patients who showed inconsistent levels of eosinophil in serial examination.