Inhaled corticosteroids, blood eosinophils, and FEV₁ decline in patients with COPD in a large UK primary health care setting

Figures & data

Figure 1 Study design.

Abbreviations: GP, general practice; EOS, eosinophil; ICS, inhaled corticosteroids.

Table 1 Reference and comparison patient groups

Reference group	Comparison group
High blood eosinophils and ICS	High blood eosinophils and no ICS
	Low blood eosinophils and ICS
Low blood eosinophils and ICS	Low blood eosinophils and no ICS
	High blood eosinophils and ICS

Abbreviation: ICS, inhaled corticosteroids.

Table 2 Sample size needed to detect a difference in rates of change of FEV₁ between ICS and non-ICS groups of patients

	Initial sample size		Sample size after Bonferonni correction
∆ (mL/year)	Total sample (N)	Patients on ICS	Total sample (N)	Patients on ICS
2	55,293	13,016	64,275	17,021
3	24,575	5,785	28,567	7,565
4	13,824	3,254	16,069	4,255
5	8,847	2,082	10,284	2,723
7	4,514	1,063	5,247	1,389
10	2,212	521	2,571	681

Abbreviation: ICS, inhaled corticosteroids.

Table 3 Baseline characteristics for all included patients (N=26,675). Values are n (%) or median (IQR)

Variables	All patients (N=26,675)	Blood eosinophil and ICS group
		Higher blood eosinophils & ICS (N=11,461)	Higher blood eosinophils & no ICS (N=6,716)	Lower blood eosinophils & ICS (N=5,140)	Lower blood eosinophils & no ICS (N=3,358)
Female gender	12,379 (46.4)	5,206 (45.4)	2,574 (38.3)	2,920 (56.8)	1,679 (50.0)
Age (years)	69 (62–89)	69 (62–76)	69 (62–76)	70 (62–77)	69 (62–77)
Current smoking status	12,825 (48.1)	5,195 (45.3)	3,564 (53.1)	2,361 (45.9)	1,705 (50.8)
History of MI	2,415 (9.1)	1,105 (9.6)	687 (10.2)	380 (7.4)	243 (7.2)
History of stroke	401 (1.5)	165 (1.4)	104 (1.6)	76 (1.5)	56 (1.7)
History of heart failure	1,802 (6.8)	786 (6.9)	428 (6.4)	380 (7.4)	208 (6.2)
History of lung cancer	171 (0.6)	56 (0.5)	42 (0.6)	43 (0.8)	30 (0.9)
History of bronchiectasis	616 (2.3)	317 (2.8)	91 (1.4)	154 (3.0)	54 (1.6)
History of GORD	1,761 (6.6)	780 (6.8)	371 (5.5)	378 (7.4)	232 (6.9)
History of anxiety	2,133 (8.0)	919 (8.0)	453 (6.8)	466 (9.1)	295 (8.8)
History of depression	2,343 (8.8)	1,028 (9.0)	545 (8.1)	488 (9.5)	282 (8.4)
History of asthma	9,623 (36.1)	5,839 (51.0)	574 (8.6)	2,540 (49.4)	279 (8.3)
BMI (kg/m^2) (N=25,528)	26.8 (23.3–30.8)	27.3 (23.7–31.3)	26.9 (23.4–30.8)	26.5 (23.0–30.7)	25.7 (22.3–29.7)
White blood cell count (cells/µL)	7.6 (6.4–9.1)	7.9 (6.6–9.3)	7.8 (6.6–9.2)	7.2 (6.0–8.7)	7.1 (5.9–8.5)
Neutrophil count (cells/µL) (N=26,585)	4.5 (3.6–5.7)	4.7 (3.7–5.8)	4.5 (3.6–5.6)	4.5 (3.5–5.8)	4.3 (3.4–5.5)
Airflow obstruction (N=26,518) Mild (≥80% FEV1 predicted) Moderate (50–80% FEV1 predicted) Severe (30–50% FEV1 predicted) Very severe (≤30% FEV1 predicted)	5,550 (20.9) 13,834 (52.2) 5,988 (22.6) 1,146 (4.3)	2,185 (19.2) 5,640 (49.5) 2,935 (25.8) 633 (5.6)	1,556 (23.3) 3,879 (58.1) 1,092 (16.3) 154 (2.3)	957 (18.8) 2,469 (48.4) 1,407 (27.6) 270 (5.3)	852 (25.5) 1,846 (55.3) 554 (16.6) 89 (2.7)
AECOPD frequency 0 1 ≥2	11,105 (41.6) 6,593 (24.7) 8,977 (33.7)	4,000 (34.9) 2,788 (24.3) 4,673 (40.8)	3,501 (52.1) 1,688 (25.1) 1,527 (22.7)	1,828 (35.6) 1,212 (23.6) 2,100 (40.9)	1,776 (52.9) 905 (27.0) 677 (20.2)
MRC dyspnoea score (N=18,090) 1 2 3 4 5	3,749 (20.7) 7,457 (41.2) 4,435 (24.5) 2,066 (11.4) 383 (2.1)	1,313 (17.6) 2,911 (39.0) 2,030 (27.2) 998 (13.4) 215 (2.9)	1,287 (26.2) 2,177 (44.3) 986 (20.1) 396 (8.1) 66 (1.3)	531 (15.8) 1,315 (39.2) 945 (28.2) 493 (14.7) 68 (2.0)	618 (26.2) 1,054 (44.7) 474 (20.1) 179 (7.6) 34 (1.4)

Abbreviations: AECOPD, exacerbations of COPD; BMI, body mass index; ICS, inhaled corticosteroids; MI, myocardial infarction; GORD, gastro-oesophageal reflux disease.

Table 4 Medication prescribed in the year prior to start of follow-up by baseline ICS use. Values are n (%)

COPD medications	ICS combinations at baseline (n=16,601)		No ICS at baseline (n=10,074)
	ICS (n=6,515 (40%))	ICS/LABA (n=10,086 (60%))
LABA	1,764 (27)	n/a	658 (7)
LAMA	1,061 (16)	4,110 (41)	1,728 (17)
LABA and LAMA	288 (4)	286 (3)	154 (2)

Abbreviations: ICS, inhaled corticosteroids; LAMA, long-acting muscarinic antagonist; LABA, long active beta agonist.

Figure 2 Flow diagram of included patients.

Abbreviation: ICS, inhaled corticosteroids.

Table 5 Rates of change of FEV₁ by blood eosinophil/ICS group in prevalent ICS cohort

	Crude rate of FEV1 change ml/year (95% CI) (N=26,675)	P-value for significant differences between rates		Adjusted* rate of FEV1 change ml/year (95% CI) (N=17,557)	P-value for significant differences between rates
High blood eosinophil level & ICS (crude n=11,461, adjusted n=7,255)	−16.8 (−18.9 to −14.8)	Ref		−13.7 (−16.8 to −10.5)	Ref
High blood eosinophil level & no ICS (crude n=6,716, adjusted n=4,783)	−24.3 (−30.5 to −18.2)	<0.001		−20.8 (−29.8 to −11.9)	0.016
Low blood eosinophil level & ICS (crude n=5,140, adjusted n=3,238)	−15.5 (−21.2 to −9.7)	0.479	Ref	−10.2 (−19.0 to −1.3)	0.229	Ref
Low blood eosinophil level & no ICS (crude n=3,358, adjusted n=2,281)	−28.4 (−35.8 to −21.0)	<0.001	<0.001	−21.7 (−32.7 to −10.8)	0.043	0.008

Notes: *Adjusted for: gender, age, smoking status, MI, stroke, HF, lung cancer, bronchiectasis, GORD, anxiety, depression, BMI, WBC count, neutrophil count, airflow obstruction, AECOPD frequency, and MRC dyspnea.

Abbreviations: BMI, body mass index; HF, heart failure; ICS, inhaled corticosteroids; AECOPD, exacerbations of COPD; MI, myocardial infarction; MRC, Medical Research Council; GORD, gastro-oesophageal reflux disease; WBC, white blood cell.

Table 6 Rates of change of FEV₁ by blood eosinophil/ICS group in incident ICS cohort

	Crude rate of FEV1 change ml/year (95% CI) (N=12,469)	P-value for significant differences between rates		Adjusted* rate of FEV1 change ml/year (95% CI) (N=6,402)	P-value for significant differences between rates
High blood eosinophil level & ICS (crude n=2,336, adjusted n=315)	−10.7 (−15.5 to −5.9)	Ref		12.2 (−25.0 to 27.0)	Ref
High blood eosinophil level & no ICS (crude n=5,984, adjusted n=4,006)	−25.9 (−36.9 to −15.0)	<0.001		−20.8 (−51.1 to 9.5)	<0.001
Low blood eosinophil level & ICS (crude n=1,081, adjusted n=148)	−15.5 (−29.0 to −1.9)	0.284	Ref	−15.7 (−56.7 to 25.2)	0.037	Ref
Low blood eosinophil level & no ICS (crude n=3,068, adjusted n=1,933)	−29.7 (−41.6 to −17.9)	<0.001	0.002	−21.3 (−52.5 to 9.8)	<0.001	0.632

Note: *Adjusted for: gender, age, smoking status, history of MI, history of stroke, history of HF, history of lung cancer, history of bronchiectasis, history of GORD, history of anxiety, history of depression, BMI, WBC count, neutrophil count, airflow obstruction, AECOPD frequency, and MRC dyspnea.

Abbreviations: BMI, body mass index; HF, heart failure; ICS, inhaled corticosteroids; AECOPD, exacerbations of COPD; MI, myocardial infarction; MRC, Medical Research Council; GORD, gastro-oesophageal reflux disease; WBC, white blood cell.