Impact of depression and/or anxiety on accelerated lung function decline in patients with chronic obstructive pulmonary disease

Abstract

BACKGROUND

Irreversible airflow limitation is the hallmark of a progressive respiratory disorder known as chronic obstructive pulmonary disease (COPD). Depression and anxiety are common mental health problems that can happen with COPD and can make the disease worse. However, the extent to which they affect the rate of lung function decline is not yet known.

AIM

To examine how depression and/or anxiety, when present as comorbid conditions, affect the rate at which lung function declines each year in patients with COPD.

METHODS

From July 2022 to July 2025, 122 patients with stable COPD received continuous treatment and regular spirometric follow-up for up to three years at our hospital. We retrospectively analysed the data from these patients. Patients were assessed on two occasions, enabling the calculation of their yearly rate of lung function decline. Patients were divided into two groups. The first group was the control group. This included patients with COPD alone (n = 58). The second group was the comorbidity group. This included patients with COPD and depression and/or anxiety (n = 64). We used something called “linear mixed-effects models” to compare changes over time in something called “forced expiratory volume in one second (FEV1)”. We also used something called “multivariate linear regression analyses” to find out what causes a faster decline in lung function.

RESULTS

At the start of the study, patients with depression and/or anxiety as well as the disease had a lower FEV1, FEV1% predicted, and FEV1/forced vital capacity ratios, and had more acute exacerbations and inhaled corticosteroid use than the control group (all P < 0.05). After the study, the yearly decrease in lung function was a lot higher in the group with both conditions than in the control group (52.4 ± 10.8 mL/year vs 41.3 ± 9.5 mL/year, P < 0.001). After adjustment for age, sex, body mass index, smoking status, and baseline lung function, faster FEV1 decline was found to be independently associated with comorbid depression/anxiety (β = -10.92, 95% confidence interval: -17.35 to -4.49, P = 0.001). More detailed analysis showed that depression/anxiety was the biggest thing that made lung function get worse faster.

CONCLUSION

The rate of annual lung function decline in COPD was found to be independently accelerated by comorbidity, specifically depression and/or anxiety. This highlights the significance of incorporating psychological assessments and integrated management strategies during long-term follow-ups to decelerate disease progression.

Key Words: Lung function decline; Anxiety; Depression; Comorbidity; Chronic obstructive pulmonary disease

Core Tip: It has been demonstrated by this retrospective study that a significantly faster decline in forced expiratory volume in one second is experienced by patients with chronic obstructive pulmonary disease and comorbid depression and/or anxiety compared with those without psychological comorbidities. These findings highlight that psychological well-being is an independent hazard for the advancement of chronic obstructive pulmonary disease and should be incorporated into all-encompassing disease management tactics.

INTRODUCTION

It is both common and preventable, and it is treatable too. The condition is known as chronic obstructive pulmonary disease (COPD) and is characterised by ongoing respiratory symptoms and airflow limitation. This disease can cause serious illness, disability, and death, which can lead to financial problems and be very upsetting for patients[1,2]. A plethora of preceding studies have demonstrated that the predominance of psychological maladies, most notably depression and anxiety, is considerably elevated among COPD patients in comparison to the general populace[3,4]. The presence of these comorbidities can have a negative impact on both quality of life and disease progression.

Physiological processes associated with depression and anxiety may include increased tension in respiratory muscles, restricted thoracic expansion, impaired gas exchange, and accelerated pulmonary function decline. Furthermore, people who are in a constant state of psychological stress are more likely to suffer from respiratory infections and to experience exacerbated lung tissue damage because their immune systems are not functioning properly[5,6].

The impact of depression and/or anxiety on the core pathological feature of COPD -the rate of lung function decline - remains unclear, despite the increasing recognition of their coexistence in the condition[7]. The underlying mechanisms are not fully elucidated. Consequently, the present retrospective study endeavours to methodically analyse the effect of concomitant depression and/or anxiety on the annual rate of lung function deterioration in patients with COPD undergoing regular follow-up at our hospital. It is anticipated that these findings will furnish clinicians with exact, evidence-based indications for formulating exhaustive intervention strategies in the management of COPD.

MATERIALS AND METHODS

Study population

Clinical data of 122 patients with COPD who received treatment and regular follow-up at our hospital between July 2022 and July 2025 were retrospectively collected. The study protocol was approved by the Institutional Medical Ethics Committee of Wuxi No. 2 People’s Hospital (Approval No. WXEY-2026-21).

Inclusion criteria were as follows: (1) Diagnosis consistent with the Guidelines for the Diagnosis and Treatment of COPD (2021 revised edition)[8]; (2) Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.70; (3) Age ≥ 40 years; (4) Complete clinical and spirometry data; and (5) Ability to comply with follow-up and related assessments.

Exclusion criteria included concomitant respiratory conditions causing airflow limitation (e.g., bronchiectasis, pulmonary tuberculosis sequelae, interstitial lung disease, lung cancer); diagnosed asthma or allergic bronchopulmonary aspergillosis; comorbid neuropsychiatric disorders (e.g., Alzheimer’s disease, schizophrenia, severe stroke sequelae, cognitive impairment); and incomplete medical records or missing key data.

Data collection

Data were obtained through the hospital’s electronic medical record system and supplemented by follow-up interviews. The following information was collected: (1) General information: Age, sex, body mass index (BMI), smoking history, and current smoking status; (2) Clinical data: Duration of COPD, frequency of acute exacerbations (defined as the number of emergency visits or hospitalizations due to COPD exacerbations in the past year), comorbidities (e.g., hypertension, diabetes, coronary heart disease), and medication use, including inhaled corticosteroids, long-acting β₂-agonists, and long-acting muscarinic antagonists; (3) Psychological assessment: Depressive and anxiety symptoms were evaluated at baseline during patients’ stable clinical condition using validated clinician-administered scales. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), which evaluates mood, guilt, suicidal ideation, insomnia, work and activities, psychomotor changes, anxiety, and somatic symptoms. Most items are scored on a 5-point scale (0 = absent to 4 = severe), while several items use a 3-point scale (0-2). Total HAMD-17 scores range from 0 to 52, with higher scores indicating more severe depressive symptoms. The severity of anxiety was evaluated using the Hamilton Anxiety Rating Scale (HAMA), a 14-item instrument that encompasses both psychic and somatic anxiety symptoms. We ask them to score each item on a 5-point Likert scale (0 = not present to 4 = severe), and then we calculate the total score, which can range from 0 to 56. The higher the score, the more anxious they are. All psychological tests were done in person by trained doctors who specialise in breathing problems. To make sure that the results were consistent, the patients were asked to respond to questions about their symptoms from the previous week in a quiet outpatient consultation room or inpatient ward setting without being interrupted. Lung function parameters: The lung function parameters of the subjects were measured using a MasterScreen spirometer (Jaeger, Germany). The parameters measured included FEV1, FVC, the FEV1/FVC ratio, and FEV1% predicted.

Grouping

Patients were split into two groups based on their HAMD-17 and HAMA scores at the start of the study[9]. The control group comprised patients with COPD who did not have depression or anxiety (n = 58), while the comorbidity group included patients with COPD who had depression and/or anxiety (HAMD-17 ≥ 17 and/or HAMA ≥ 14; n = 64).

Assessment of lung function decline rate

For each patient, FEV1 measurements at all follow-up time points were treated as dependent variables, and time (in years) was used as the independent variable. For each patient, a linear regression equation was fitted, with the regression line’s slope (β) representing the annual decline in FEV1 (mL/year).

Statistical analysis

The data were analysed using SPSS version 26.0. Continuous variables that were normally distributed were expressed as the mean ± SD and compared using a t-test. The Mann-Whitney U test was used to compare data that was not normally distributed. This data was presented as the median (interquartile range). We expressed categorical variables as n (%) and compared them using the χ² test or Fisher’s exact test.

A linear mixed-effects model (LMM) was utilised to analyse the disparities in the rate of lung function decline between the groups, with the annual decline rate in FEV1 serving as the dependent variable and potential influential factors as independent variables. Categorical variables were dummy coded. These included comorbidity status, sex and current smoking. Continuous variables were analysed on their original scales. These included age, BMI and smoking pack-years. To identify independent predictors, stepwise multivariate linear regression analysis was performed. Statistical significance was set at P < 0.05.

RESULTS

Baseline characteristics

No significant differences were observed between the two groups in age, sex, BMI, smoking history, proportion of current smokers, COPD duration, or presence of comorbid hypertension, diabetes, or coronary heart disease (all P > 0.05).

However, the comorbidity group had significantly lower baseline FEV1, FEV1% predicted, and FEV1/FVC ratios, as well as higher acute exacerbation frequency, inhaled corticosteroids use rate, and HAMD-17 and HAMA scores compared with the control group (P < 0.05; Table 1).

Table 1 Comparison of baseline characteristics between the two groups, mean ± SD/n (%)/median (interquartile range).

Variable	Control group (n = 58)	Comorbidity group (n = 64)	Statistic	P value
Age (years)	68.4 ± 7.2	69.8 ± 6.9	t = 1.123	0.264
Male	42 (72.4)	45 (70.3)	χ2 = 0.072	0.788
BMI (kg/m2)	23.1 ± 3.4	22.5 ± 3.8	t = 0.921	0.359
Smoking (pack-years)	40.5 (30.0-55.0)	45.0 (32.8-58.3)	Z = 1.402	0.161
Current smokers	18 (31.0)	22 (34.4)	χ2 = 0.160	0.689
Duration of COPD (years)	7.5 ± 3.8	8.4 ± 4.1	t = 1.273	0.206
Baseline FEV1 (L)	1.52 ± 0.41	1.38 ± 0.39	t = 2.012	0.046
Baseline FEV1% predicted	62.5 ± 13.2	56.8 ± 14.5	t = 2.287	0.024
Baseline FVC (L)	2.88 ± 0.65	2.79 ± 0.71	t = 0.734	0.465
Baseline FEV1/FVC (%)	52.8 ± 7.1	49.5 ± 8.3	t = 2.363	0.020
Acute exacerbation frequency (times/year)	1.0 (0.0-2.0)	2.0 (1.0-3.0)	Z = 3.125	0.002
Hypertension	25 (43.1)	32 (50.0)	χ2 = 0.592	0.442
Diabetes mellitus	11 (19.0)	15 (23.4)	χ2 = 0.367	0.545
Coronary heart disease	9 (15.5)	13 (20.3)	χ2 = 0.489	0.484
Use of inhaled corticosteroids	28 (48.3)	43 (67.2)	χ2 = 4.654	0.031
Use of long-acting β2-agonists	50 (86.2)	58 (90.6)	χ2 = 0.587	0.444
Use of long-acting muscarinic antagonists	52 (89.7)	59 (92.2)	χ2 = 0.256	0.613
HAMD-17 score	8.5 ± 3.2	20.1 ± 4.5	t = 16.543	< 0.001
HAMA score	7.8 ± 2.9	18.9 ± 3.8	t = 18.772	< 0.001

BMI: Body mass index; COPD: Chronic obstructive pulmonary disease; FEV1: Forced expiratory volume in one second; FVC: Forced vital capacity; HAMD-17: 17-item Hamilton Depression Rating Scale; HAMA: Hamilton Anxiety Rating Scale.

Comparison of lung function decline rate

The annual decline in FEV1 was significantly greater in the comorbidity group (52.4 ± 10.8 mL/year) than in the control group (41.3 ± 9.5 mL/year; t = 6.174, P < 0.001). In the LMM, after adjusting for age, sex, baseline BMI, current smoking status, and baseline FEV1% predicted, the interaction between group and time remained significant (β = -10.92, 95% confidence interval: -17.35 to -4.49, P = 0.001; Figure 1).

Figure 1 Trajectory of forced expiratory volume in one second changes over time in the two groups. Based on predicted values from the linear mixed-effects model, shaded areas represent 95% confidence intervals. FEV1: Forced expiratory volume in one second; COPD: Chronic obstructive pulmonary disease.

Multivariate linear regression analysis of factors associated with annual FEV1 decline

Thirteen potential influencing variables were included in a stepwise multiple linear regression model. The results identified comorbid depression/anxiety, current smoking, lower baseline FEV1% predicted, and higher acute exacerbation frequency as independent predictors of accelerated FEV1 decline (P < 0.05). Among these factors, comorbid depression/anxiety had the largest standardized regression coefficient (β = 0.312). The final model had an adjusted R² of 0.402, indicating a statistically significant fit (F = 8.734, P < 0.001; Table 2; Figure 2).

Figure 2 Forest plot of multiple linear regression analysis of factors influencing the annual decline rate of forced expiratory volume in one second. COPD: Chronic obstructive pulmonary disease; ICS: Inhaled corticosteroids; FEV1: Forced expiratory volume in one second.

Table 2 Multiple linear regression analysis of factors influencing the annual decline rate of forced expiratory volume in one second.

Independent Variable	Unstandardized coefficient (B)	SE	Standardized coefficient (β)	Variance inflation factor	t	P value
Constant	18.735	10.246			1.828	0.070
Comorbid depression/anxiety (yes vs no)	10.892	2.138	0.312	1.168	5.094	< 0.001
Current smoking status (yes vs no)	9.521	2.931	0.284	1.325	3.248	0.002
Baseline FEV1% predicted	-0.295	0.108	-0.230	1.289	-2.731	0.007
Frequency of acute exacerbations (times/year)	2.874	1.235	0.251	1.467	2.327	0.022
Use of ICS (yes vs no)	3.128	1.876	0.142	1.412	1.667	0.098
Age (years)	0.148	0.195	0.055	1.102	0.759	0.450
Sex (male vs female)	-1.198	2.857	-0.031	1.115	-0.419	0.676
BMI (kg/m2)	-0.284	0.402	-0.052	1.087	-0.706	0.482
Smoking (pack-years)	0.041	0.057	0.061	1.435	0.719	0.474
Duration of COPD (years)	0.328	0.387	0.064	1.218	0.848	0.398
Hypertension (yes vs no)	1.025	1.894	0.041	1.194	0.541	0.590
Diabetes mellitus (yes vs no)	1.873	2.145	0.065	1.176	0.873	0.385
Coronary heart disease (yes vs no)	2.016	2.378	0.063	1.152	0.848	0.398

Dependent variable: Annual rate of decline in forced expiratory volume in one second (mL/year). FEV1: Forced expiratory volume in one second; ICS: Inhaled corticosteroids; BMI: Body mass index; COPD: Chronic obstructive pulmonary disease.

DISCUSSION

The World Health Organization has reported that COPD is the third biggest cause of death around the world. This means that it imposes a significant disease burden and substantially affects patients’ quality of life and their socioeconomic development[10,11]. Evidence is growing that COPD is not just a localised pulmonary disorder, but a systemic disease with marked heterogeneity and multiple extrapulmonary manifestations[12,13]. Depression and anxiety are particularly prevalent among these manifestations.

Psychological comorbidities are primarily caused by a number of factors, including dyspnea, limited activity, social isolation and feelings of uncertainty about the future. Furthermore, the central nervous system may be directly affected by chronic hypoxia and systemic inflammation, two key pathophysiological features of COPD. This disruption can lead to impaired emotional regulation and an increased risk of negative affective states in patients[14,15]. On the other hand, depression and anxiety can cause problems with treatment. They can change how people behave when it comes to their health. They can also make inflammation in the body worse[16]. This can lead to more lung tissue damage. The connection between COPD and psychological comorbidities is intricate and goes in both directions. This creates a cycle that makes things worse and negatively impacts the prognosis of the disease.

Consistent with this understanding, our study demonstrated that patients with comorbid depression and/or anxiety had poorer baseline pulmonary function (FEV1, FEV1% predicted, FEV1/FVC) and a higher frequency of acute exacerbations than those without such comorbidities (P < 0.05). Similarly, Karlsen et al[17] and Hernández-Pérez et al[18] reported that patients with COPD who had emotional comorbidities experienced a greater respiratory symptom burden and more severe impairment in lung function.

Multivariate linear regression analysis in our study further identified comorbid depression/anxiety, current smoking, lower baseline FEV1% predicted, and higher acute exacerbation frequency as independent risk factors for accelerated FEV1 decline (P < 0.05), with comorbid depression/anxiety having the largest standardized regression coefficient (β = 0.312). Furthermore, the LMM demonstrated that, after adjusting for multiple confounders, the interaction between group and time remained statistically significant (P < 0.05). These findings indicate that psychological comorbidities play a crucial and independent role in the progression of COPD. There are several potential mechanisms that may explain this association: (1) Pathophysiological mechanisms: The hypothalamic-pituitary-adrenal axis can become dysregulated due to chronic psychological stress, e.g. depression and anxiety, which leads to elevated cortisol and other stress hormone levels. These, in turn, promote systemic inflammation. The combination of this “psychoneurogenic inflammation” and pre-existing pulmonary inflammation has been shown to lead to an acceleration of parenchymal destruction and airway remodelling, which in turn results in a faster decline in lung function[19,20]. Depression and anxiety are often accompanied by problems with the body’s autonomic nervous system. This is when the body’s fight-or-flight response is not working properly. It can cause the muscles in the airways to tighten, making it harder to breathe. It can also lead to the production of more mucus, which can make breathing even more difficult[21,22]. A link between anxiety, depression and impaired lung function has also been demonstrated in an exploratory study of patients with mild asthma by Lehrer et al[23]; (2) Behavioural mechanisms: It is vital for patients with COPD to engage in regular physical activity if they are to maintain their respiratory muscle strength, skeletal muscle mass and overall functional capacity. Nevertheless, symptoms of depression and anxiety frequently result in anhedonia, fatigue and feelings of worthlessness. This significantly hinders patients’ motivation and their capacity to maintain healthy behaviours. This can accelerate functional decline, creating a vicious cycle of ‘dyspnoea-reduced activity-functional deterioration-worsened mood’[24,25]. Psychological distress also adversely affects treatment adherence, which is why it is important to consider psychological well-being alongside medical treatment. Complex inhalation regimens and pulmonary rehabilitation programmes may not be adhered to or participated in by patients with depression or anxiety due to their cognitive impairment or feelings of hopelessness[26,27]. Inadequate compliance gives rise to inadequate disease management, a greater frequency of exacerbations, and thus accelerated lung function deterioration; and (3) Social support mechanisms: Depression and anxiety can reduce patients’ contact with family, friends and society. This can gradually weaken the support they have from others and increase their psychological burden. This then affects how well they can cope and how they engage with their treatment. Lee et al[28] identified social support as a key determinant of life satisfaction among elderly patients with COPD. Similarly, Panjwani et al[29] introduced the concept of “invisible support”, indicating that subtle, nonperceived forms of support may exert an indirect influence on lung function among patients with COPD.

This study has several limitations. Although the two groups had comparable demographic characteristics, patients in the comorbidity group demonstrated worse baseline lung function and more frequent acute exacerbations, indicating more advanced disease at study enrollment. While these factors were adjusted for in multivariate and LMMs, residual confounding related to baseline disease severity cannot be excluded and should be considered when interpreting the findings. In addition, the comorbidity group was heterogeneous, including patients with depression alone, anxiety alone, and both, which may have attenuated the disorder-specific effects on lung function decline. Subgroup analyses could not be performed because of the limited sample size; future prospective studies with larger cohorts are warranted to further clarify these relationships. Despite these limitations, several important clinical implications are presented by this study. It is vital that clinicians closely monitor the psychological well-being of COPD patients, with a particular focus on those experiencing dyspnoea or activity limitations. Early identification of depressive and anxious symptoms, combined with comprehensive management strategies - including patient education, psychological counselling, optimised pharmacotherapy, and enhanced social support - may improve psychological well-being and treatment adherence. These benefits may also include a reduction in exacerbation frequency, slowed lung function decline, and ultimately an improvement in long-term prognosis and quality of life in patients with COPD.

This study looked at past data, but it has some problems. This includes problems with the data, problems with the causes of the problems, and problems with how well it can show cause and effect. In the future, we should do more research to see if depression and anxiety can really make it hard for people with COPD to breathe.

CONCLUSION

To sum up, feeling sad and/or worried a lot can make COPD patients’ lungs work even faster. These mental health problems are important risk factors for disease getting worse. To improve long-term outcomes, enhance overall quality of life and delay lung function deterioration, it is vital that psychological screening and timely intervention be integrated into the management.