Lung Function and Asthma Clinical Control in N-ERD Patients, Three-Year Follow-Up in the Context of Real-World Evidence

Figures & data

Figure 1 GINA-2014 guidelines.

Abbreviations: ICS, inhaled corticosteroids; OCS, oral corticosteroids; LTRA, leukotriene receptor antagonists; LABA, long-actingbeta₂-agonist; SABA, short-actingbeta₂-agonist; IgE, immunoglobulin E.

Figure 2 Design of the study.

Abbreviations: N-ERD G, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease group; AG, asthma group; NSAID, non-steroidal anti-inflammatory drugs; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second; REV, reversibility; OCS, oral corticosteroids; LTRA, leukotriene receptor antagonists; SABA, short-actingbeta₂-agonist; IgE, immunoglobulin E.

Table 1 Demographic Data

Variable	N-ERD	AG	p
n	75	68
Male n (%)	26 (34.7)	18 (26.5)
Female n (%)	49 (65.3)	50 (73.5)	NS
Age n (%)	51 (44–61)	52 (39–63)	NS
BMI	26.72	28.44	NS
Age at diagnosis of asthma	31	30	NS
Smoking rate	3	3.4	NS
Eosinophils (cells/mm^3)	400	200	0.05
SPT n (%)	50 (66.6)	47 (69)	NS

Abbreviations: N-ERD, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease; AG, asthma group; BMI, body mass index; SPT, skin prick test; NS, non-significative.

Table 2 Comparison Between the N-ERD Group and the AG

Variable	Time 0 (Baseline)					Time 1 (One Year)					Time 2 (Two Years)					Time 3 (Three Years)
	N-ERD	AG	p	OR	CI 95%	N-ERD	AG	p	OR	CI 95%	N-ERD	AG	p	OR	CI 95%	N-ERD	AG	p	OR	CI 95%
n	75	68				75	68				75	68				75	68
Eosinophils (cells/mm^3)	400 (200–700)	200 (12.1–600)	0.02			300 (225–400)	200 (100–325)	0.048			400 (300–800)	150 (40–600)	0.005			400 (200–500)	150 (15–375)	0.018
IgE (IU/mL)	129 (64.7–170)	432.5 (47.2–1388)	0.093			94.8 (46.8–232)	263 (21.4–1371)	0.37			114.5 (73.8–188.5)	197 (90.4–477.7)	0.16			96.1 (23–222.2)	55.1 (15.8–486)	0.713
SPTn (%)	50 (66.6)	47 (69)
FVC %	98 (90.7–104.5)	69 (58–83.5)	0.001			102 (92.5–110.2)	91 (73–98)	0.001			100 (88–109)	89 (73.7–95.2)	0.001			100 (90.5–105)	85 (72–94.7)	0.001
FVC L	3.7 (3.2–4.2)	2.5 (2–2.9)	0.001			3.8 (3.2–3.9)	3 (2.5–3.5)	0.001			3.5 (3–4.3)	2.6 (2.2–3.2)	0.001			3.5 (2.6–4)	2.4 (1.9–3.2)	0.001
FEV1%	87 (75.2–96.4)	50 (41.7–78.7)	0.001			90.5 (71.7–99)	83.5 (62.7–90.2)	0.01			89 (77–100)	76 (58.7–87.7)	0.001			85 (75–96)	73 (52.2–84)	0.001
FEV1 L	2.75 (2.3–3.1)	1.5 (1–2.1)	0.001			2.5 (2.1–2.9)	2.3 (1.6–2.7)	0.02			2.5 (1.9–3.2)	1.9 (1.3–2.4)	0.001			2.3 (1.6–2.6)	1.6 (1.1–2.2)	0.001
FVC/FEV1%	75 (67.7–78.8)	66.6 (55.7–74.2)	0.001			76.5 (70.5–79)	76 (70–80.5)	0.48			77 (66.7–83.2)	74 (64.7–79.7)	0.3			75.6 (66–82.5)	74 (57.2–89.7)	0.4
Reversibility %	11 (5–16)	10 (5–13)	0.41			7 (3–13)	7 (5–11)	0.7			8 (4–11)	8 (6–18)	0.61			8 (5–13)	8 (6–12)	0.56
Obstruction n (%)	24 (32)	41 (60.2)	0.001	0.30	(0.15–0.61)	8 (10.6)	11 (16.17)	0.469	0.61	(0.23–1.64)	14 (18.6)	13 (19.1)	1	0.97	(0.41–2.24)	17 (22.6)	17 (25)
High doses of ICS/LABA n (%)	23 (30.5)	36 (52.4)	0.011	0.39	(0.19–0.77)	19 (25)	22 (33)	0.358	0.66	(0.31–1.37)	32 (42.7)	20 (29.3)	0.141	1.78	(0.89–3.57)	25 (33.8)	21 (31)	0.893	1.11	(0.55–2.26)
OCS for 6 months n (%)	2 (2.7)	2 (2.9)	1	0.94	(0.12–6.6)	0 (0)	0 (0)	ND	ND	ND	2 (2.7)	0 (0)	ND	ND	ND	2 (2.7)	0 (0)	ND	ND	ND
Short-term OCS use n (%)	32 (42.6)	46 (67.7)	0.004	0.35	(0.17–0.70)	12 (16)	14 (20.6)	0.62	0.73	(0.31–1.72)	16 (21.3)	10 (14.5)	0.41	1.57	(0.69–3.75)	13 (17.3)	10 (14.7)	0.84	1.21	(0.49–2.98)
LTRA use n (%)	22 (29.3)	4 (5.9)	0.001	6.64	(2.15–20.47)	7 (9.3)	5 (7.4)	0.9	1.2	(0.39–4.29)	17 (22.7)	5 (7.4)	0.02	3.69	(1.28–10.64)	26 (34.7)	8 (11.8)	0.002	3.97	(1.65–9.57)
SABA use in the last year n (%)	21 (28)	27 (39.7)	0.19	0.59	(0.29–1.18)	7 (9.3)	6 (8.3)	1	1.06	(0.33–3.33)	12 (16)	6 (8.8)	0.29	1.96	(0.69–5.57)	9 (12)	6 (8.8)	0.72	1.4	(0.47–4.18)
GINA-Good Clinical control n (%)	47 (62.1)	23 (34.1)	0.001	3.28	(1.65–6.52)	44 (52)	24 (35)	0.008	2.6	(1.32–5.2)	48 (64.4)	35 (51.2)	0.178	1.67	(0.85–3.27)	50 (67)	39 (58)	0.329	1.48	(0.75–2.93)

Abbreviations: N-ERD, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease; AG, asthma group; OR, odds ratio; CI, confidence interval; IgE, immunoglobulin E; SPT, skin prick test; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second; ICS, inhaled corticosteroids; IU, international units; OCS, oral corticosteroids; LABA, long-acting beta₂-agonist; LTRA, leukotriene receptor antagonists; SABA, short-acting beta₂-agonist.

Table 3 Comparison Between the N-ERD Group

Variable	Time 0	Time 1	Time 2	Time 3	p
n	75	75	75	75
Eosinophils (cells/mm^3)	400 (200–700)	300 (225–400)	400 (300–800)	400 (200–500)
IgE (kU/mL)	129 (64.7–170)	94.8 (46.8–232)	114.5 (73.8–188.5)	96.1 (23–222.2)
FVC %	98 (90.7–104.5)	102 (92.5–110.2)	100 (88–109)	100 (90–105)
FVC L	3.7 (3.2–4.2)	3.8 (3.2–3.9)	3.5 (3–4.3)	3.5 (2.6–4)	<0.05^‡,≠
FEV1%	87 (75.2–96.4)	90.5 (71.7–99)	89 (77–100)	85 (75–96)	<0.05^‡
FEV1 L	2.75 (2.3–3.1)	2.5 (2.1–2.9)	2.5 (1.9–3.2)	2.3 (1.6–2.6)	<0.01^‡,≠,Ᵹ
FVC/FEV1%	75 (67.7–78.8)	76.5 (70.5–79)	77 (66.7–83.2)	75.6 (66–82.5)	<0.01*
Reversibility %	11 (5–16)	7 (3–13)	8 (4–11)	8 (5–13)	<0.05*
Obstruction n (%)	24 (32)	8 (10.6)	14 (18.6)	17 (22.6)	0.002*
High doses of ICS n (%)	23 (30.5)	19 (25)	32 (42.7)	25 (33.8)	<0.05^±
OCS for 6 months n (%)	2 (2.7)	0 (0)	2 (2.7)	2 (2.7)
Short-term OCS use n (%)	32 (42.6)	12 (16)	16 (21.3)	13 (17.3)	<0.01^*,†,‡
LTRA use n (%)	22 (29.3)	7 (9.3)	17 (22.7)	26 (34.7)	<0.05^*,±,≠
SABA use in the last year n (%)	21 (28)	7 (9.3)	12 (16)	9 (12)	<0.05^*,‡
Clinical control n (%)	47 (62.1)	44 (52)	48 (64.6)	50 (67)

Notes: *Comparison between Time 0 and Time 1; ^†Comparison between Time 0 and Time 2; ^‡Comparison between Time 0 and Time 3; ^±Comparison between Time 1 and Time 2; ^≠Comparison between Time 1 and Time 3; ^ꝽComparison between Time 2 and Time 3.

Abbreviations: N-ERD, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease; IgE, immunoglobulin E; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second; ICS, inhaled corticosteroids; OCS, oral corticosteroids; LTRA, leukotriene receptor antagonists; SABA, short-acting beta₂-agonist.

Table 4 Logistic Regression in N-ERD Group

Variable*	Time	Sig.	Exp (B)	95% C.I. EXP (B)
				Low	Upper
High dose of ICS	t0	0.572	0.713	0.221	2.305
Short term of OCS		0.846	0.908	0.342	2.409
LTRA use		0.528	1.510	0.419	5.439
High dose of ICS	t1	0.617	1.414	0.364	5.490
Short term of OCS		0.771	0.820	0.216	3.115
LTRA use		0.718	1.465	0.185	11.610
High dose of ICS	t2	0.003	6.094	1.835	20.242
Short term of OCS		0.225	0.426	0.107	1.691
LTRA use		0.147	3.063	0.675	13.890
High dose of ICS	t3	0.636	1.551	0.252	9.561
Short term of OCS		0.623	1.447	0.332	6.307
LTRA use		0.186	4.462	0.487	40.916

Note: *Results adjusted by gender.

Abbreviations: ICS, Inhaled corticosteroids; OCS, Oral Corticosteroid; LTRA, LTRA, leukotriene receptor antagonists.

Figure 3 Forced Expiratory Volume in the First Second (FEV₁) in N-ERD and Asthma groups. *Indicates p-value <0.05.

Abbreviations: AG, Asthma group; N-ERD, Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

Figure 4 Frequency of good clinical control of asthma and high doses of inhaled corticosteroids in N-ERD and asthma groups. Basal time (t0), 12 months-time 1 (t1), 2 years-time 2 (t2), and 3 years-time 3 (t3). *Indicates p-value <0.05.

Abbreviations: AG, Asthma group (RED); N-ERD, Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (BLUE).

Figure 5 N-ERD patients in step 4 of the GINA 2014 guidelines.

Table 5 Comparison Between the AG

Variable	Time 0	Time 1	Time 2	Time 3	p
n	68	68	68	68
Eosinophils (cells/mm^3)	200 (12.1–600)	200 (100–325)	150 (40–600)	150 (15–375)
IgE (kU/mL)	432.5 (47.2–1388)	263 (21.4–1371)	197 (90.6–477.7)	55.1 (15.8–486)
FVC %	69 (58–83.5)	91 (73–98)	89 (73.7–95.2)	85 (72–94.7)	<0.01^*,†,‡
FVC L	2.5 (2–2.9)	3 (2.5–3.5)	2.6 (2.2–3.2)	2.4 (1.9–3.2)	<0.05^*,≠
FEV1%	50 (41.7–78.7)	83.5 (62.7–90.2)	76 (58.7–87.7)	73 (52.2–84)	<0.01^*,†,‡
FEV1 L	1.5 (1–2.1)	2.3 (1.6–2.7)	1.9 (1.3–2.4)	1.6 (1.1–2.2)	<0.01^*,≠
FVC/FEV1%	66.6 (55.7–74.2)	76 (70–80.5)	74 (64.7–79.7)	74 (57.2–89.7)	<0.05^*,†
Reversibility %	10 (5–13)	7 (5–11)	8 (6–18)	8 (6–12)
Obstruction n (%)	41 (60.2)	11 (16.1)	13 (19.1)	17 (25)	0.001^*,†,‡
High doses of ICS n (%)	36 (52.4)	22 (33)	20 (29.3)	21 (31)	<0.05^*,†,‡
OCS for 6 months n (%)	2 (2.9)	0 (0)	0 (0)	0 (0)
Short-term OCS use n (%)	46 (67.6)	14 (20.6)	10 (14.7)	10 (14.7)	0.001^*,†,‡
LTRA use n (%)	4 (5.9)	5 (7.4)	5 (7.4)	8 (11.8)
SABA use in the last year n (%)	27 (39.8)	6 (8.8)	6 (8.8)	6 (8.8)	0.001^*,†,‡
Clinical control n (%)	23 (34.1)	24 (35)	35 (51.2)	39 (58)	<0.01^‡,≠,Ᵹ

Notes: *Comparison between Time 0 and Time 1; ^†Comparison between Time 0 and Time 2; ^‡Comparison between Time 0 and Time 3; ^≠Comparison between Time 1 and Time 3; ^ꝽComparison between Time 2 and Time 3.

Abbreviations: AG, asthma group; IgE, immunoglobulin E; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second; ICS, inhaled corticosteroids; OCS, oral corticosteroids; LTRA, leukotriene receptor antagonists; SABA, short-acting beta₂-agonist.