Effect of inhaled drugs on anxiety and depression in patients with chronic obstructive pulmonary disease: a prospective observational study

Figures & data

Table 1 Demographic characteristics of the participants

Characteristics	Total (N=84)	ICS/LABA (N=35)	Non-ICS/LABA (N=49)	P-valuea	LAMA (N=31)	Non-LAMA (N=53)	P-valuea
	N (%)	N (%)	N (%)		N (%)	N (%)
Sex				0.965			0.030
Male	65 (77.38)	27 (77.14)	38 (77.55)		28 (90.32)	37 (69.81)
Female	19 (22.62)	8 (22.86)	11 (22.45)		3 (9.68)	16 (30.19)
Age (years)				0.807			0.329
Mean ± SD	63.67±13.20	64.09±12.13	63.37±14.03	0.467	65.52±11.44	62.58±14.12	0.608
<50	9 (10.71)	2 (5.71)	7 (14.29)		3 (9.68)	6 (11.32)
50–59	20 (23.81)	9 (25.71)	11 (22.45)		5 (16.13)	15 (28.30)
60–69	19 (22.62)	10 (28.57)	9 (18.37)		8 (25.81)	11 (20.75)
≥70	36 (42.86)	14 (40.00)	22 (44.90)		15 (48.39)	21 (39.62)
Marital status				0.112			0.365
Single	15 (17.86)	9 (25.71)	6 (12.24)		4 (12.90)	11 (20.75)
Married	69 (82.14)	26 (74.29)	43 (87.76)		27 (87.10)	42 (79.25)
Education				0.371			0.296
Less than middle school	36 (42.86)	17 (48.57)	19 (38.78)		11 (35.48)	25 (47.17)
High school or beyond	48 (57.14)	18 (51.43)	30 (61.22)		20 (64.52)	28 (52.83)
Job status				0.817			0.613
Employed	54 (64.29)	22 (62.86)	32 (65.31)		21 (67.74)	33 (62.26)
Unemployed	30 (35.71)	13 (37.14)	17 (34.69)		10 (32.26)	20 (37.74)
Income				0.768			0.311
≤2 million KRW/month	44 (52.38)	19 (54.29)	25 (51.02)		14 (45.16)	30 (56.60)
>2 million KRW/month	40 (47.62)	16 (45.71)	24 (48.98)		17 (54.84)	23 (43.40)

Note:

a χ² test.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Table 2 Clinical characteristics of the participants

Characteristics	Total (N=84)	ICS/LABA (N=35)	Non-ICS/LABA (N=49)	P-valuea	LAMA (N=31)	Non-LAMA (N=53)	P-valuea
	N (%)	N (%)	N (%)		N (%)	N (%)
BMI (n=82)
≤18.5	10 (12.20)	4 (11.76)	6 (12.50)	0.715	8 (3.33)	2 (3.92)	0.011
18.5–24.9	49 (59.76)	22 (64.71)	27 (56.25)		17 (73.33)	32 (62.75)
≥25.0	23 (28.05)	8 (23.53)	15 (31.25)		6 (20.00)	17 (33.33)
Pulmonary function test
FEV1 (n=81)
L, Mean ± SD	1.94±0.75	1.94±0.74	1.94±0.77	0.997	1.59±0.45	2.16±0.82	0.001
%, Mean ± SD	76.36±24.75	76.91±27.80	75.98±22.72	0.869	61.81±13.64	85.38±25.87	<0.0001
FVC (n=78)
L, Mean ± SD	3.33±0.91	3.31±0.92	3.34±0.92	0.862	3.11±0.74	3.48±0.99	0.082
%, Mean ± SD	92.72±22.29	91.35±20.89	93.62±23.35	0.664	87.48±26.01	96.17±18.97	0.092
Smoking
Never smoked	22 (26.19)	9 (25.71)	13 (26.53)	0.264	4 (12.90)	18 (33.96)	0.101
Past smoker	47 (55.95)	18 (48.57)	30 (61.22)		21 (67.74)	26 (49.06)
Currently smoking	15 (17.86)	9 (25.71)	6 (12.24)		6 (19.35)	9 (16.98)
Pack year (n=81)
Mean ± SD	28.13±29.36	24.46±20.17	30.64±34.27	0.312	32.94±21.50	25.14±33.18	0.203
Secondhand smoke (home)
No	57 (67.86)	21 (60.00)	36 (73.47)	0.344	23 (74.19)	34 (64.15)	0.636
Sometimes	17 (20.24)	8 (22.86)	9 (18.37)		5 (16.13)	12 (22.64)
Everyday	10 (11.90)	6 (17.14)	4 (8.16)		3 (9.68)	7 (13.21)
Secondhand smoke (office) (n=83)
No	53 (63.86)	22 (64.71)	31 (63.27)	0.980	19 (63.33)	34 (64.15)	0.462
Sometimes	18 (21.69)	7 (20.59)	11 (22.45)		5 (16.67)	13 (24.53)
Everyday	12 (14.46)	5 (14.71)	7 (14.29)		6 (20.00)	6 (11.32)
Period of secondhand smoke (years)
0–1	21 (25.00)	10 (28.57)	11 (22.45)	0.645	5 (16.13)	16 (30.19)	0.164
1–9	14 (16.67)	4 (11.43)	10 (20.41)		3 (9.68)	11 (20.75)
10–29	28 (33.33)	11 (31.43)	17 (34.69)		13 (41.94)	15 (28.30)
≥30	21 (25.00)	10 (28.57)	11 (22.45)		10 (32.26)	11 (20.75)
Past diagnosis of anxiety or depression
Yes	5 (5.95)	1 (2.86)	4 (8.16)	0.396b	2 (6.45)	3 (5.66)	1.000b
No	79 (94.05)	34 (97.14)	45 (91.84)		29 (93.55)	50 (94.34)
Current treatment of anxiety or depression
Yes	2 (2.38)	1 (2.86)	1 (2.04)	1.000b	1 (3.23)	1 (1.89)	1.000b
No	82 (97.62)	34 (97.14)	48 (97.96)		30 (96.77)	52 (98.11)

Notes:

a χ² test;

b Fisher’s exact test.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Table 3 HADS questionnaire scores

HADS scores	Baseline	4 weeks	Change from baseline		P-valueb	12 weeks	Change from baseline		P-valueb
	Mean ± SD	Mean ± SD	Mean ± SD	P-valuea		Mean ± SD	Mean ± SD	P-valuea
	Median (q1,q3)	Median (q1,q3)	Median (q1,q3)			Median (q1,q3)	Median (q1,q3)
Total	(N=84)	(N=67)	(N=67)			(N=55)	(N=54)
Total score	9.75±5.30	10.72±6.68	1.24±4.67	0.065		10.95±6.25	1.63±5.34	0.058
	9.00 (6,13)	10.00 (7,14)	0.00 (−1,3)			10.00 (7,15)	1.50 (−2,5)
Anxiety	3.92±2.79	4.63±3.76	0.73±2.56	0.038		4.51±3.35	0.72±2.84	0.100
	3.50 (2,6)	4.00 (2,7)	0.00 (−1,1)			4.00 (2,7)	0.00 (−1,3)
Depression	5.83±3.13	6.09±3.41	0.51±2.71	0.171		6.44±3.56	0.91±3.26	0.061
	6.00 (3,8)	6.00 (4,8)	0.00 (−1,2)			6.00 (4,9)	0.50 (–1,2)
ICS/LABA	(N=35)	(N=28)	(N=28)			(N=20)	(N=19)
Total score	10.14±5.30	10.00±6.46	0.14±4.30	0.878	0.055	11.05±4.63	1.26±5.43	0.504	0.723
	10.00 (7,14)	8.50 (7,12.5)	0.00 (−2,2)			10.50 (8,14.5)	1.00 (−3,3)
Anxiety	4.26±2.94	4.54±3.95	0.32±2.70	0.809	0.125	4.55±2.65	0.42±3.10	0.735	0.465
	5.00 (1,6)	4.50 (2,7)	0.00 (−1,1)			4.00 (2,6.5)	−0.50 (3,9)
Depression	5.89±3.12	5.46±3.14	−0.18±2.36	0.656	0.098	6.50±3.22	0.84±3.37	0.366	0.993
	5.00 (3,9)	5.00 (3,7)	0.00 (−1.5,0.5)			6.50 (4,9)	1.00 (−2,3)
Non-ICS/LABA	(N=49)	(N=39)	(N=39)			(N=35)	(N=35)
Total score	9.47±5.34	11.23±6.86	2.03±4.82	0.008		10.89±7.08	1.83±5.35	0.073
	9.00 (5,13)	10.00 (7,15)	1.00 (0,4)			9.00 (6,15)	2.00 (−2,5)
Anxiety	3.67±2.68	4.69±3.67	1.03±2.44	0.013		4.49±3.74	0.89±2.72	0.067
	3.00 (2,5)	4.00 (2,7)	1.00 (0,2)			5.00 (1,7)	0.00 (–1,3)
Depression	5.80±3.18	6.54±3.56	1.00±2.87	0.031		6.40±3.78	0.94±3.24	0.087
	6.00 (3,8)	6.00 (5,8)	0.00 (0,2)			6.00 (4,9)	0.00 (−1,2)
LAMA	(N=31)	(N=27)	(N=27)			(N=24)	(N=24)
Total score	8.58±5.57	10.19±7.93	1.63±5.13	0.112	0.597	10.88±7.48	1.83±4.86	0.064	0.523
	8.00 (3,12)	9.00 (3,14)	1.00 (−1,3)			9.50 (6,15)	2.00 (−1.5,5)
Anxiety	3.32±2.59	4.26±4.07	1.00±2.75	0.124	0.654	4.58±4.10	1.12±2.76	0.065	0.334
	3.00 (2,5)	3.00 (1,7)	1.00 (−1,1)			4.50 (1.5,7)	1.00 (−1,3)
Depression	5.26±3.30	5.93±4.10	0.63±2.76	0.212	0.636	6.29±3.83	0.71±2.44	0.105	0.806
	5.00 (3,8)	6.00 (2.8)	0.00 (−1,2)			6.00 (3,8)	1.00 (−1,2)
Non-LAMA	(N=53)	(N=40)	(N=40)			(N=23)	(N=23)
Total score	10.43±5.07	11.08±5.76	0.98±4.39	0.279		11.00±5.24	1.47±5.77	0.349
	10.00 (7,14)	10.00 (7,14.5)	0.00 (−2,2)			10.00 (8,14)	0.50 (−3,3)
Anxiety	4.26±2.87	4.88±3.57	0.55±2.43	0.194		4.45±2.72	0.40±2.91	0.513
	4.00 (2,6)	4.50 (2,7)	0.00 (−0.5,1.5)			4.00 (2,7)	0.00 (−1,2)
Depression	6.17±3.01	6.20±2.90	0.43±2.71	0.433		6.55±3.39	1.07±3.82	0.253
	6.00 (4,9)	6.00 (4,7.5)	0.00 (−1,1)			6.00 (4,9)	0.00 (−1,2)

Notes: Change =4 weeks – baseline or 12 weeks – baseline.

a Wilcoxon signed-rank test for the change in scores from baseline to 4 and 12 weeks.

b Wilcoxon signed-rank test for the change in score from baseline to 4 and 12 weeks in the ICS/LABA vs non-ICS/LABA as well as LAMA vs non-LAMA. Anxiety: item-1,3,5,7,9,11,13; depression: item-2,4,6,8,10,12,14.

Abbreviations: HADS, Hospital Anxiety and Depression Scale; ICS, inhaled corticosteroid; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Figure 1 The mean changes in HADS scores from baseline to (A) 4 weeks and (B) 12 weeks.

Abbreviations: HADS, Hospital Anxiety and Depression Scale; ICS, inhaled corticosteroid; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist.

Table 4 GLMM model to evaluate the association between treatment and changes in HADS, anxiety, and depression scores

Time	HADS score	Estimates	SE	df	t-value	P-value
ICS/LABA usea
4 weeks	Total score	−0.163	0.522	144	−0.31	0.755
	Anxiety	−0.081	0.287	144	−0.28	0.778
	Depression	−0.123	0.298	144	−0.41	0.681
12 weeks	Total score	−0.083	0.587	131	−0.14	0.888
	Anxiety	−0.008	0.311	131	−0.03	0.980
	Depression	−0.081	0.358	131	−0.23	0.820
LAMA useb
4 weeks	Total score	0.772	0.598	129	1.29	0.199
	Anxiety	0.419	0.319	129	1.32	0.191
	Depression	0.365	0.352	129	1.04	0.301
12 weeks	Total score	0.587	0.678	117	0.87	0.389
	Anxiety	0.591	0.355	117	1.67	0.098
	Depression	0.010	0.410	117	0.02	0.980

Notes:

a Adjusted for marriage status and initial scores.

b Adjusted for sex, BMI, FEV₁, smoking status, period of secondhand smoke exposure (year), and initial scores.

Abbreviations: FEV₁, forced expiratory volume in 1 second; GLMM, general linear mixed model; HADS, Hospital Anxiety and Depression Scale; ICS, inhaled corticosteroid; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; SE, standard error; BMI, body mass index; df, degrees of freedom.