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

Abstract

BACKGROUND

Patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) experience not only progressive respiratory impairment but also a significant psychological burden. The prevalence and impact of anxiety and depression and their intricate relationship with dyspnea severity and pulmonary function decline remain inadequately characterized in this population, hindering comprehensive care.

AIM

To explore the incidence of anxiety and depression in CTD-ILD and its relationship with dyspnea severity and pulmonary function index.

METHODS

Data of 100 patients with CTD-ILD (January 2022-June 2024) were retrospectively analyzed. Baseline demographic, pulmonary function [forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%)], modified medical research council (mMRC) score, and psychological scale [generalized anxiety disorder-7 (GAD-7) and patient health questionnaire-9 (PHQ-9)] were collected. Pulmonary function was reviewed every 3 months, and high-resolution computed tomography was performed every 6 months following standardized treatment (glucocorticoids + immunosuppressive + anti-fibrosis agents). Pearson/Spearman correlation analysis, linear mixed effect model, and Cox regression were used to analyze the correlation between anxiety and depression and physiological indicators as well as the prognosis.

RESULTS

Baseline prevalence of moderate-to-severe anxiety (GAD-7 ≥ 10) and depression (PHQ-9 ≥ 10) was 38% and 42%, respectively. Following 24 weeks of treatment, pulmonary function (FVC%: 72.11 ± 13.08 vs 67.89 ± 12.73; DLCO%: 60.67 ± 13.76 vs 55.32 ± 13.95, both P < 0.05), psychological scores (GAD-7 and PHQ-9, P < 0.05), and inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation, P < 0.05] significantly improved. The levels of inflammatory indicators were significantly decreased (P < 0.05). The GAD-7/PHQ-9 scores negatively correlated with FVC% and DLCO% (P < 0.05) and positively correlated with the mMRC scores and CRP (P < 0.05). The mixed model showed that for each one-point increase in GAD-7/PHQ-9, FVC% decreased by 0.412%/0.426% (P < 0.01). Cox regression analysis showed that for every liter of GAD-7 and PHQ-9, the risk of pulmonary function deterioration increased by 12.8% and 14.2%, respectively (hazard ratio = 1.128 and 1.142, P < 0.01).

CONCLUSION

Anxiety and depression in patients with CTD-ILD constituted a bidirectional negative feedback loop involving pulmonary function impairment, inflammatory activity, and dyspnea. Psychological disorders were identified as independent risk factors for deterioration of pulmonary function. Psychological evaluation and intervention should be integrated clinically to block brain–lung axis-mediated neuroendocrine–immune network imbalance and improve prognosis.

Keywords: Connective tissue disease-interstitial lung disease; Anxiety; Depression; Dyspnea; Pulmonary function; Prognosis

Core Tip: This retrospective study investigates the association between anxiety, depression, dyspnea severity, and pulmonary function in patients with Connective tissue disease-associated interstitial lung disease (CTD-ILD). Results revealed that higher anxiety (generalized anxiety disorder-7) and depression (patient health questionnaire-9) scores were significantly correlated with worse pulmonary function (forced vital capacity, diffusing capacity of the lungs for carbon monoxide), more severe dyspnea (modified medical research council score), and elevated systemic inflammation (C-reactive protein, erythrocyte sedimentation rate). Moreover, psychological distress emerged as an independent predictor of pulmonary function decline. These findings underscore the importance of routine psychological assessment and timely intervention in CTD-ILD management to prevent deterioration and improve prognosis.