Relationship Between the Response to Antibody Therapy and Symptoms of Depression and Anxiety Disorders in Patients with Severe Asthma

Figures & data

Table 1 Characteristics of the Patients at Baseline

	All Patients n=82	No MDD or GAD n=44	MDD or GAD n=38	p-value
Age (years) – Median (IQR)	57 (50–63)	55 (49–64)	57 (50–62)	0.964
Female Sex – n (%)	49 (60%)	26 (59%)	23 (61%)	0.895*
BMI (kg/m^2) – Median (IQR)	27.4 (24.2–32.5)	26.7 (23.9–31.1)	28.9 (24.8–34.9)	0.139
HADS-A – n (%)
— Suspect	15 (18%)	0 (0%)	15 (40%)
— Probable	15 (18%)	0 (0%)	15 (40%)
— Unsuspicious	52 (63%)	44 (100%)	8 (21%)
HADS-D – n (%)
— Suspect	10 (12%)	0 (0%)	10 (26%)
— Probable	21 (26%)	0 (0%)	21 (55%)
— Unsuspicious	51 (62%)	44 (100%)	7 (18%)
Smoking status – n (%)				0.496*
— Never	40 (49%)	23 (52%)	17 (45%)
— Former	42 (51%)	22 (48%)	21 (55%)
Pack years – Median (IQR)	14.5 (7.5–30)	10 (5.5–29)	19 (9–36)	0.281
Alcohol (Audit-C-Score Points) –Median (IQR)	2 (0–3.0)	2 (0–3.0)	1 (0–2.3)	0.374
Alcohol abuse - n (%)	7 (9%)	5 (11%)	2 (5%)	0.324*
Responder status – n (%)				0.030*
— Responder	61 (74%)	37 (84%)	24 (63%)
— Non-Responder	21 (26%)	7 (16%)	14 (37%)
Therapy – n (%):				0.051*
— Benralizumab	26 (32%)	14 (32%)	12 (32%)
— Dupilumab	16 (20%)	9 (21%)	7 (18%)
— Mepolizumab	33 (40%)	14 (32%)	19 (50%)
— Omalizumab	7 (9%)	7 (16%)	0 (0%)
Allergies – n (%)	54 (66%)	32 (59%)	22 (41%)	0.158*
Education category – n (%)^a				0.483*
— low	13 (16%)	5 (11%)	8 (21%)
— moderate	58 (71%)	33 (75%)	25 (66%)
— high	11 (13%)	6 (14%)	5 (13%)
Family status – n (%)				0.088*
— Divorced	14 (17%)	4 (9%)	10 (26%)
— Single	16 (20%)	12 (27%)	4 (11%)
— Married	42 (51%)	23 (52%)	19 (50%)
— Widowed	10 (12%)	5 (11%)	5 (13%)
Comorbidities– n (%)
— Obesity	28 (34%)	13 (30%)	15 (40%)	0.344*
— Atopic dermatitis	8 (10%)	5 (11%)	3 (8%)	0.598*
— Chronic sinusitis	9 (11%)	5 (11%)	4 (11%)	0.904*
— Diabetes	8 (10%)	4 (9%)	4 (11%)	0.827*

Notes: ^aIow, no vocational education; moderate, non-academic vocational education; high, academic degree. Continuous variables are stated as median and interquartile ranges (IQR) and categorical variables are stated as n and percent (%); * = x²-Test. Statistically significant values in bold.

Abbreviations: MDD, Major Depression Disorder; GAD, General Anxiety Disorder; BMI, body mass index; HADS-A, Hospital Anxiety and Depression Scale—Anxiety; HADS-D, Hospital Anxiety and Depression Scale—Depression; IQR, interquartile range.

Figure 1 Flowchart of patient inclusion with consecutive subdivision in patients with and without signs of MDD/GAD and their respective responder-status.

Figure 2 Comparison between baseline (BL) and follow-up (F/U) for (A) Asthma-Control Test (ACT), (B) Generalized Anxiety Disorder (GAD)-2 score, (C) Patients Health Questionnaire (PHQ)-2 score, (D) Quality of Life on Visual Analogue Scale (QoL-VAS), (E) Exacerbation counts and (F) Forced expiratory volume in one second (FEV₁) subdivided in Responder and Non-Responder. Data are presented as boxplots. The bars show the median value, the lower and upper ends correspond to the first and third quantiles (25th and 75th percentiles). The upper whisker extends from the upper edge of the boxplot to the highest value, the lower whisker extends from the lower edge of the boxplot to the smallest value.

Table 2 Psychological Disorder Prevalence Rates in Patient with Severe Asthma Compared to German Population

	Severe Asthma n=82	DEGS1-MH n=5318	p-value	Risk Ratio
Any current mental disorder	52.5% (41.2–63.5)	27.7% (26.3–29.2)	<0.001	1.90
Alcohol abuse	8.5% (3.8–17.4)	1.8% (1.4–2.3)	<0.001	4.72
Major Depressive Disorder	37.8% (27.5–49.2)	7.7% (6.9–8.6)	<0.001	4.91
Generalized Anxiety Disorder	36.6% (26.4–48.0)	2.2% (1.8–2.8)	<0.001	16.6

Notes: Any current mental disorder is defined by a positive AUDIT-C-Score or a probable or suspect HADS-D or HADS-A Score. Statistically significant values in bold. Data are shown as percent (%) and 95% confidence intervals (CI) and risk ratios.

Abbreviations: CI, confidence interval; DEGS1-MH, Studie zur Gesundheit Erwachsener in Deutschland (German study of health status in adults) – Mental Health.

Table 3 Comparison Between Responders and Non-Responders

	Non-Responder n = 21	Responder n = 61	p-value
Age (years) – Median (IQR)	56 (51–67)	57 (49–63)	0.504
Female Sex – n (%)	13 (62%)	36 (59%)	0.816
BMI (kg/m^2) – Median (IQR)	27.1 (24.1–37.1)	27.6 (24.1–32)	0.862
HADS-A – n (%)			0.336*
Suspect	4 (19%)	11 (18%)
Probable	11 (52%)	41 (67%)
Unsuspicious	6 (29%)	9 (15%)
HADS-A Score – Median (IQR)	7 (3–12)	5 (2–9)	0.063
HADS-D – n (%)			0.018*
Suspect	3 (14%)	7 (12%)
Probable	8 (38%)	43 (71%)
Unsuspicious	10 (48%)	11 (18%)
HADS-D-Score – Median (IQR)	10 (6–13)	4 (2–9)	0.002
Smoking status – n (%)			0.902*
Never	10 (48%)	31 (51%)
Former	11 (52%)	30 (49%)
Pack years – Median (IQR)	15 (9–38)	14 (6–30)	0.361
Alcohol (Audit-C-Score Points) –Median (IQR)	1 (0–2)	2 (1–3)	0.035
Alcohol abuse - n (%)	0 (0%)	1 (12%)	0.105
BL PHQ2 – Median (IQR)	3 (2–4)	2 (1–3)	0.028
FU PHQ2 – Median (IQR)	2 (2–4)	1 (0–2)	0.003
BL GAD2 – Median (IQR)	2 (1–5)	2 (0–2)	0.045
FU GAD2 – Median (IQR)	2 (1–3)	1 (0–2)	0.191

Notes: Continuous variables are stated as median and interquartile ranges (IQR), Statistically significant values in bold. * = x²-Test.

Abbreviations: PHQ-2, Patient Health Questionnaire-2; GAD-2, General Anxiety Disorder-2; BL, Baseline; FU, Follow-Up; BMI, body mass index; HADS-A, Hospital Anxiety and Depression Scale—Anxiety; HADS-D, Hospital Anxiety and Depression Scale—Depression.

Table 4 Multivariate Analysis of Impact on Non-Responding to mAb-Therapy

	Univariate OR (95% CI)	p-value	Multivariate OR (95% CI)	p-value
HADS-A	1.11 (0.99–1.24)	0.068
HADS-D	1.19 (1.06–1.33)	0.004	1.23 (1.07–1.42)	0.004
Male Sex	0.89 (0.23–2.45)	0.816
Pollutants exposure, any	0.87 (0.27–2.81)	0.812
Education category	0.90 (0.36–2.25)	0.819
Audit-C-Score	0.67 (0.46–0.98)	0.040	0.65 (0.43–0.99)	0.043
BMI	1.0 (0.93–1.09)	0.86
Age	1.02 (0.97–1.06)	0.499
Smoking status	1.07 (0.40–2.87)	0.902
Allergies, any	0.95 (0.33–2.72)	0.927
FEV1	0.99 (0.96–1.02)	0.406
Marital status	0.37 (0.13–1.05)	0.062

Note: Statistically significant values in bold.

Abbreviations: CI, confidence interval; OR, Odds-ratio; HADS-A, Hospital Anxiety and Depression Scale—Anxiety; HADS-D, Hospital Anxiety and Depression Scale – Depression: Audit-C, Alcohol Use Disorders Identification Test; BMI, Body mass index; FEV₁, Forced expiratory volume.