Relationship between anxiety and depression, dyspnea severity, and pulmonary function in connective tissue disease-associated interstitial lung disease

Table 1 General data of patients

Indicators	Data	χ2/t	P value
Age (years)	59.24 ± 10.51	1.733	0.086
BMI (kg/m2)	23.67 ± 3.18	1.294	0.199
Smoking history
Yes	42	2.763	0.096
No	58
Systemic sclerosis (n)	40	-	-
CRP (mg/L)	11.25 ± 6.34	2.184	0.031
ESR (mm/h)	29.17 ± 12.58	2.659	0.009
FVC (%)	67.89 ± 12.73	3.502	0.001
DLCO (%)	55.32 ± 13.95	3.761	< 0.001
mMRC (points)	1.87 ± 0.98	2.816	0.006
GAD-7 (points)	7.14 ± 4.03	3.945	< 0.001
PHQ-9 (points)	8.76 ± 4.85	4.118	< 0.001

P < 0.05 indicated significant difference. BMI: Body mass index; FVC: Forced vital capacity; DLCO: Diffusing capacity of the lungs for carbon monoxide; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; mMRC: Modified medical research council; GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9.

Table 2 Pulmonary function indicators

Indicators	At enrollment	Week 12	Week 24	F value	P value
FVC (%)	67.89 ± 12.73	70.48 ± 12.29	72.11 ± 13.08	8.742	0.001
DLCO (%)	55.32 ± 13.95	58.21 ± 14.10	60.67 ± 13.76	9.315	< 0.001
FEV1 (L)	1.81 ± 0.49	1.89 ± 0.51	1.93 ± 0.52	5.462	0.01
FEV1/FVC (%)	66.89 ± 7.41	67.35 ± 7.29	68.14 ± 7.25	2.374	0.112

P < 0.05 indicated significant difference. FVC: Forced vital capacity; DLCO: Diffusing capacity of the lungs for carbon monoxide; FEV₁: Forced expiratory volume in one second.

Table 3 High-resolution computed tomography imaging indicators

Indicators	At enrollment	Week 12	Week 24	χ2/t	P value
HRCT lesion score (%)	32.74 ± 10.29	29.65 ± 9.87	27.53 ± 9.34	7.813	0.001
Number of imaging progresses (n)	34	24	18	6.231	0.044

P < 0.05 indicated significant difference. HRCT: High-resolution computed tomography.

Table 4 Serological indicators

Indicators	At enrollment	Week 4	Week 12	Week 24	χ2/t	P value
CRP (mg/L)	11.25 ± 6.34	8.12 ± 4.27	6.45 ± 3.89	5.87 ± 3.12	8.423	< 0.001
ESR (mm/h)	29.17 ± 12.58	22.84 ± 10.76	18.32 ± 9.65	15.42 ± 9.73	7.125	< 0.001
ANA positive rate (%)	48	46	45	44	1.042	0.307
ENA positive rate (%)	32	30	29	28	0.789	0.446
RF positive rate (%)	35	33	32	31	0.654	0.521
Anti-CCP positive rate (%)	28	27	26	26	0.413	0.675

P < 0.05 indicated significant difference. CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; ANA: Antinuclear antibody; ENA: Extractable nuclear antibody; RF: Rheumatoid factor; anti-CCP: Anti-cyclic citrullinated peptide antibody.

Table 5 Psychological state indicators

Indicators	At enrollment	Week 4	Week 12	Week 24	F value	P value
GAD-7 (points)	7.14 ± 4.03	6.02 ± 3.58	5.23 ± 3.22	4.89 ± 3.11	12.753	< 0.001
PHQ-9 (points)	8.76 ± 4.85	6.98 ± 4.41	5.84 ± 3.93	5.12 ± 3.67	14.189	< 0.001
GAD-7 ≥ 10 (n)	38	28	22	19	8.429	0.038
PHQ-9 ≥ 10 (n)	42	31	25	21	7.165	0.047

P < 0.05 indicated significant difference. GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9.

Table 6 Indicators of oxygenation function

Indicators	At enrollment	Week 4	Week 12	Week 24	F value	P value
SpO2 (%)	88.74 ± 5.13	90.32 ± 4.88	91.45 ± 4.59	92.13 ± 4.21	15.238	< 0.001
PaO2 (mmHg)	58.96 ± 8.27	62.87 ± 7.56	65.23 ± 7.11	67.45 ± 6.85	18.427	< 0.001
PaCO2 (mmHg)	40.15 ± 5.42	39.82 ± 5.16	39.58 ± 5.21	39.34 ± 5.10	1.254	0.292
Hypoxemia cases	35	28	22	17	8.013	0.045

P < 0.05 indicated significant difference. SpO₂: Peripheral capillary oxygen saturation; PaO₂: Partial pressure of arterial oxygen; PaCO₂: Partial pressure of arterial carbon dioxide.

Table 7 Correlation matrix between psychological state scores and clinical indicators

Indicators	FVC (%)	DLCO (%)	CRP	ESR	mMRC	GAD-7	PHQ-9
FVC (%)	1
DLCO (%)	0.712b	1
CRP	-0.489b	-0.524b	1
ESR	-0.437b	-0.471b	0.586b	1
mMRC	-0.518b	-0.493b	0.442b	0.498b	1
GAD-7	-0.426b	-0.451b	0.372b	0.339a	0.534b	1
PHQ-9	-0.409b	-0.437b	0.356b	0.329a	0.519b	0.871b	1

^aP < 0.05.

^bP < 0.001.

P < 0.05 indicates significant differences. FVC: Forced vital capacity; DLCO: Diffusing capacity of the lungs for carbon monoxide; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; mMRC: Modified medical research council; GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9.

Table 8 Analysis of mixed-effect model

Fixed effect variable	FVC% (β)	FVC% (P)	DLCO% (β)	DLCO% (P)
Time	0.215	< 0.001	0.187	0.002
GAD-7	-0.412	0.003	-0.389	0.005
PHQ-9	-0.426	0.001	-0.411	0.002
Age	-0.038	0.217	-0.042	0.198
Sex (female = 1)	-0.074	0.532	-0.061	0.578
Systemic sclerosis (yes = 1)	-0.125	0.048	-0.109	0.061

P < 0.05 indicated significant difference. FVC: Forced vital capacity; DLCO: Diffusing capacity of the lungs for carbon monoxide; GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9.

Table 9 Cox regression analysis

Variable	Deterioration of pulmonary function HR (95%CI)	P value	HRCT progression HR (95%CI)	P value
GAD-7 (time-varying)	1.128 (1.042-1.221)	0.003	1.097 (1.015-1.186)	0.019
PHQ-9 (time-varying)	1.142 (1.053-1.238)	0.002	1.104 (1.017-1.198)	0.018
Age (years)	1.008 (0.976-1.041)	0.611	1.012 (0.982-1.043)	0.43
Sex (female = 1)	1.152 (0.752-1.764)	0.511	1.091 (0.698-1.707)	0.705
Systemic sclerosis (yes = 1)	1.324 (0.884-1.984)	0.176	1.287 (0.859-1.928)	0.221

P < 0.05 indicated significant difference. GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9; HRCT: High-resolution computed tomography.

Table 10 Receiver operating characteristic curve analysis

Indicators	Cut-off value	Sensitivity (%)	Specificity (%)	AUC	95%CI	Youden's index
GAD-7	7.5	76.2	68.4	0.762	0.675-0.849	0.446
PHQ-9	8	78.6	70.2	0.781	0.698-0.865	0.487

GAD-7: Generalized anxiety disorder-7; PHQ-9: Patient health questionnaire-9; AUC: Area under the curve.