Effect of home noninvasive positive pressure ventilation combined with pulmonary rehabilitation on dyspnea severity and quality of life in patients with severe stable chronic obstructive pulmonary disease combined with chronic type II respiratory failure: a randomized controlled trial

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition that significantly affects patients' quality of life. Non-invasive positive pressure ventilation (NPPV) and pulmonary rehabilitation have both shown promise in improving symptoms and lung function in COPD patients. However, the combined effects of home-based pulmonary rehabilitation and NPPV on moderate to severe COPD patients remain unclear.

Objective

This study aimed to evaluate the efficacy of home pulmonary rehabilitation combined with non-invasive positive pressure ventilation (CPRNG group) compared to conventional treatment (CTG group) in patients with moderate to severe COPD.

Methods

A total of 269 patients with moderate to severe COPD were enrolled, with 137 patients in the CTG group and 132 in the CPRNG group. The primary outcome measures included the COPD assessment test (CAT) score, modified medical research council scale (mMRC) score, forced expiratory volume in one second (FEV₁) percentage, 6-min walk test, and arterial oxygen pressure (PaO₂). Secondary outcomes included various dimensions of quality of life (impact, symptoms, and activity) measured through patient-reported outcomes.

Results

Baseline comparisons between groups showed no significant differences in sociodemographic characteristics, disease duration, or symptoms. The CPRNG group showed significant improvements compared to the CTG group in the CAT score (p = 0.028), mMRC score (p = 0.015), FEV1% (p = 0.008), 6-min walk test (p = 0.001), and PaO₂ (p < 0.001). Additionally, improvements in impact, symptoms, activity, and overall scores were significantly better in the CPRNG group (p < 0.05).

Conclusions

Home pulmonary rehabilitation combined with non-invasive positive pressure ventilation significantly improves multiple dimensions of quality of life, particularly in controlling symptoms and enhancing daily activities in COPD patients. This combined therapy proves to be an effective treatment strategy, offering notable benefits in lung function, exercise capacity, and overall quality of life in COPD patients.

Trial registration

The clinical trial was registered retrospectively on the Chinese Clinical Trial Registry (ChiCTR, www.chictr.org.cn ID: ChiCTR2500096605) on 2025–01-26, as required by The Fourth Hospital of Institutional (Changsha Fourth Hospital, Hunan Province, China) Review Board guidelines. Ethics approval date: January 2023 to December 2025.

Introduction

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease characterized by irreversible airflow limitation and airway inflammation [9]. It is progressive and prone to recurrent acute exacerbations. COPD is one of the leading causes of death globally [10]. In the context of an aging population and worsening environmental pollution, the incidence and mortality rates of COPD continue to rise worldwide [1]. According to statistics, the prevalence of COPD among people over 40 years old is approximately 13.6%, severely impacting patients'quality of life and health burden [22].

Currently, the treatment of COPD is mainly divided into pharmacological and non-pharmacological approaches. Pharmacological treatment typically includes inhaled bronchodilators and corticosteroids, with the primary goals of alleviating symptoms, preventing acute exacerbations, and improving quality of life. However, studies have shown that pharmacological treatment is not effective in slowing the decline in lung function [19]. With the deepening of COPD management, non-drug therapy, especially respiratory rehabilitation therapy, has gradually become a key means of COPD management [12].

Current research in pulmonary rehabilitation focuses on personalized and home-based interventions, particularly for COPD patients. Evidence suggests that these interventions significantly improve perioperative recovery [15,20,23]. Additionally, individualized rehabilitation programs for elderly patients with chronic obstructive pulmonary disease (COPD) have attracted considerable attention, showing promising results in enhancing physical function and quality of life [15,20].

For patients with severe stable COPD and chronic type II respiratory failure, the treatment model combining home non-invasive positive pressure ventilation (NPPV) with home-based pulmonary rehabilitation has emerged as a novel therapeutic approach. This method not only effectively alleviates patients'breathing difficulties but also enhances lung function through continuous respiratory function exercises, thereby reducing the risk of acute exacerbations [3]). Advancements in telemedicine have enhanced patients'self-management and made home rehabilitation more convenient. Online platforms allow for frequent and timely interactions between doctors and patients, improving compliance and outcomes [7]. The goal of this study is to evaluate the effectiveness of combining NPPV with home-based pulmonary rehabilitation in improving the quality of life and disease prognosis for stable COPD patients.

Methods

Ethical consideration

The study was approved by the The Fourth Hospital of Institutional (Changsha Fourth Hospital, Hunan Province, China) Review Board, and written informed consent was obtained from all participants. Ethics Review Number: CSSDSYY-LLSC-KYXM- 2022–5–71. Ethics approval date: January 2023 to December 2025. Data were collected between January 2023 to December 2024. The data collection process followed a standardized protocol, and all participants signed written informed consent before the study began. The clinical trial was registered retrospectively on the Chinese Clinical Trial Registry(ChiCTR, www.chictr.org.cn ID: ChiCTR2500096605) on 2025–01–26 (Due to administrative delays, the registration could not be completed on time. Despite the late registration, the study was conducted in full compliance with ethical guidelines and institutional regulations.), as required by The Fourth Hospital of Institutional Review Board guidelines.

Randomization and participants

A randomized clinical trial of COPD patients was conducted from January 2023 to December 2023 from the Fourth Hospital. The study population consisted of all COPD patients who visited the chest diseases outpatient clinic of the hospital. Patients were selected from among volunteers who were being monitored by the collaborating physician, had applied to the same outpatient clinic, and met the inclusion criteria. The primary goal of assigning patients to groups was to minimize bias and prevent any potential influence between patients. To achieve this, a lottery method was used, with the draw conducted by an independent observer (Fig. 1). Specifically, all patients who met the inclusion criteria were randomly assigned to groups by an independent observer before enrollment, ensuring that each patient had an equal chance of being assigned to different groups. The randomization process was conducted by the researcher using sealed envelopes, ensuring the randomness and fairness of the allocation. The observer had no contact with the patients or researchers during the randomization process.

Fig. 1

Sample diagram

Inclusion criteria included patients diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [6], presenting with chronic type II respiratory failure characterized by elevated PaCO₂ and normal or reduced PaO₂ [16]. Participants were required to be in a stable phase of COPD, with no acute exacerbations in the past six months and without severe comorbidities that could affect the study. Eligible individuals were aged 40 years or older, with a baseline forced expiratory volume in one second (FEV1) ≤ 50% of the predicted value. Able to follow the home treatment protocol and attend regular follow-ups.

Exclusion criteria included a history of acute exacerbation or significant worsening of symptoms within the six weeks prior to screening, as well as patients with very severe COPD. Patients with severe comorbidities, such as heart failure, malignancy, or severe cardiovascular diseases that could impact study results, were excluded. Individuals with severe cognitive impairment or psychiatric disorders that could affect adherence to the treatment protocol were not eligible. Those unable to use the home NPPV device or follow the home-based pulmonary rehabilitation requirements were also excluded. Pregnant or breastfeeding women were not eligible for participation. Patients who recently participated in other clinical trials or used medications affecting lung function or respiratory treatment were excluded. Individuals with poor expected adherence to the study protocol were excluded.

Sample size calculating

In this study, the sample size calculation was based on the following assumptions: a significance level (α) of 0.05, statistical power (Power) of 0.8, an effect size (Δ) of 0.5 (medium effect), and a standard deviation (σ) assumed to be 1. The sample size was calculated using the following formula:

$$n=\frac{(\text{Z }\alpha/2 +\text{Z}\beta )^{2}\cdot 2\cdot\upsigma 2 }{\Delta ^{2}}$$

where$\text{Z}\alpha /2$ is the z-value corresponding to the significance level (1.96 for a two-tailed test with α = 0.05), $\text{Z}\beta$​ is the z-value corresponding to the statistical power (0.84 for 80% power), σ is the standard deviation (assumed to be 1), and Δ is the effect size (set to 0.5).

Substituting these values into the formula, the required sample size per group was approximately 63, with a total sample size of 126. To ensure sufficient statistical power and account for potential biases, a total of 300 patients were ultimately included in this study, which is adequate to support the research objectives and perform effective group comparisons.

Intervention protocol

Spirometry was performed using (Jaeger MasterScreen PFT) following ATS/ERS guidelines. The device was calibrated before each test. Participants refrained from using bronchodilators prior to the test. Each participant performed at least three acceptable maneuvers, and tests were repeated if they did not meet ATS/ERS standards. FEV1 (% predicted) was used to assess COPD severity, classified according to the GOLD guidelines as follows: GOLD 1: FEV1 ≥ 80% predicted; GOLD 2: 50% ≤ FEV1 < 80% predicted; GOLD 3: 30% ≤ FEV1 < 50% predicted; GOLD 4: FEV1 < 30% predicted.

The treatment follows the guidelines of the Global Initiative for GOLD and the European Respiratory Society (ERS). Treatment measures include long-term oxygen therapy (maintaining SpO2 between 88–92%), NPPV to alleviate respiratory failure, and the combined use of long-acting bronchodilators (LABA and LAMA) and inhaled corticosteroids (ICS) to improve airflow limitation. Pulmonary rehabilitation, nutritional support, respiratory muscle training, and regular follow-up are also recommended.

At the beginning of the study, on the first day of patient enrollment, a questionnaire (The Respiratory Questionnaire (RQ) version is the St. George's Respiratory Questionnaire (SGRQ)) was provided [11]. The intervention group received home-based pulmonary rehabilitation in addition to NPPV, with treatment monitored via internet technology. Patients in this group were added to a dedicated WeChat group, where daily check-ins were conducted by the research team. Each day, participants were required to report their symptoms, progress with exercises, and any concerns they may have had. The research team provided guidance, feedback, and motivational support through the WeChat group. Additionally, participants were given exercise schedules that included specific breathing exercises and physical activities designed to improve their lung function. The research team monitored the participants’ adherence to the prescribed exercises and offered virtual consultations when necessary.

The control group, on the other hand, did not receive the specific rehabilitation intervention being assessed, but continued to receive standard care as per clinical guidelines. This included pharmacological treatments, such as bronchodilators and corticosteroids, as well as other supportive measures and conventional pulmonary rehabilitation treatments, depending on their individual clinical conditions.

After 4 weeks of intervention, patients were invited to the hospital for reassessment, where follow-up was completed. During the initial interview, sociodemographic information was collected from the patients, and their COPD status, dyspnea, and quality of life were assessed. COPD assessment test: Developed by Jones et al. [13], this scale assesses the health status of COPD patients. It has 8 questions scored on a Likert scale from 0 to 5. St. George’s respiratory questionnaire: Created by Jones and Forde [8], this quality of life questionnaire for COPD patients contains 50 questions, also scored on a Likert scale from 0 to 5. modified medical research council scale: Developed by the British Medical Research Council, this scale evaluates the level of dyspnea in COPD patients based on their perception of the disease [2]. It has 5 questions, with scores ranging from 0 to 4.

Data analysis

Statistical analysis included the chi-square test for categorical variables to compare baseline characteristics between groups. Continuous variables were analyzed using non-parametric tests, such as the Mann–Whitney U test, for non-normally distributed data. Paired t-tests and one-way ANOVA were used to assess changes in clinical parameters, while independent t-tests were applied to compare outcome scores between groups. All statistical tests were two-sided, with a significance level set at p < 0.05.

Results

Patients Characteristics: There were no statistically significant differences between the CTG and CPRNG groups in terms of sociodemographic characteristics, disease duration, and symptoms (Table 1). In terms of pharmacological treatment, there were no significant differences between the CTG and CPRNG groups in the use of long-acting muscarinic antagonists (LAMA), long-acting β2 agonists (LABA), and inhaled corticosteroids (ICS). Additionally, the proportion of patients using combined therapies such as LAMA + LABA, LAMA + ICS, and LABA + ICS was similar between the two groups. The proportion of patients using triple therapy (LAMA + LABA + ICS) also showed no significant difference between the groups. This indicates that the baseline pharmacological treatments were balanced between the two groups, minimizing potential confounding factors.

Table 1 Comparison of general data between the two groups

In terms of the CAT score, the CPRNG group showed a significant improvement in the median score at the last follow-up, which was 23.0, compared to the CTG group's median score of 27.0. The difference between the two groups was statistically significant (p = 0.028). The score difference for the CPRNG group was 11.0, with a p-value of 0.001, indicating a clear therapeutic effect. For the mMRC score, the CPRNG group's median score at the last follow-up was 2.0, while the CTG group remained at 3.0. The difference between the two groups was significant (p = 0.015), suggesting that the CPRNG group was effective in treatment, with an improvement of 2.0 and a p-value of 0.010 (Table 2). In summary, the CPRNG group demonstrated significant improvement in both CAT and mMRC scores, highlighting the positive impact of combined home pulmonary rehabilitation and non-invasive positive pressure ventilation on patients.

Table 2 The distribution of differences in CAT and mMRC scores, used to assess the condition of COPD patients, between the CTG and CPRNG groups at the first and last follow-up

Significant improvements were observed in both groups across various indicators (Table 3), with the CPRNG group showing more pronounced changes. Notably, the CPRNG group demonstrated a significant increase in FEV1%, FEV1 (L), FVC (L), FEV1/FVC ratio, 6MWT, PaO₂, and a substantial reduction in PaCO₂. During the 6MWT, 42 participants (30.7%) in the CTG group (n = 137) experienced a ≥ 4% drop in SpO₂, whereas 19 participants (14.4%) in the CPRNG group (n = 132) had a similar decline. Compared to the CTG group, the CPRNG group had a significantly lower proportion of patients with SpO₂ desaturation, suggesting that the intervention may improve exercise tolerance and reduce exercise-induced hypoxemia. In contrast, the CTG group showed more modest improvements, with only minor changes in the same parameters. Furthermore, the CPRNG group had a significant reduction in mean PAP, while the CTG group showed no significant change. Overall, the CPRNG group exhibited superior treatment outcomes in comparison to the CTG group.

Table 3 Impact of different treatment approaches on key respiratory indicators across groups

The results showed that at the first follow-up, the effect, symptom, activity, and total scores were similar between the two groups, with no significant differences. However, at the last follow-up, the CPRNG group had significantly better scores in terms of effect (28.90 ± 3.50 vs. 34.75 ± 3.67, p = 0.012), symptoms (56.75 ± 2.77 vs. 61.50 ± 2.91, p = 0.021), activity (53.39 ± 3.17 vs. 58.75 ± 3.32, p = 0.015), and total score (40.15 ± 2.87 vs. 45.87 ± 3.01, p = 0.028) compared to the CTG group (Table 4). These results suggest that home pulmonary rehabilitation combined with non-invasive ventilation has a significant advantage in improving the overall outcomes and quality of life of patients.

Table 4 Effect of different treatment methods on quality of life in COPD patients

Discussion

This study demonstrates that home pulmonary rehabilitation combined with non-invasive positive pressure ventilation (CPRNG) significantly improves pulmonary function, exercise tolerance, and quality of life compared to conventional treatment (CTG). The two groups had comparable baseline characteristics, including pharmacological treatments, ensuring that the observed differences were mainly attributed to the intervention rather than confounding factors.

The CPRNG group showed substantial improvements in FEV1%, FEV1 (L), FVC (L), and FEV1/FVC ratio, indicating enhanced airway function and gas exchange. Additionally, the increase in 6MWT distance and reduction in PaCO₂ reflect better exercise capacity and ventilation efficiency, supporting the benefits of combining pulmonary rehabilitation with ventilatory support in chronic respiratory disease management.

The significant reduction in SpO₂ desaturation events during the 6MWT in the CPRNG group further confirms the efficacy of this combined approach in reducing exercise-induced hypoxemia. The proportion of patients with a ≥ 4% drop in SpO₂ was significantly lower in the CPRNG group (14.4%) compared to the CTG group (30.7%), suggesting improved oxygenation and endurance during physical activity. This improvement may be attributed to better respiratory muscle function and enhanced alveolar ventilation, reducing hypoxic stress during exertion.

Furthermore, the CPRNG group showed more pronounced improvements in patient-reported outcomes, including CAT and mMRC scores, reflecting better symptom control and reduced disease burden. The significant improvement in effect, symptom, activity, and total scores at the final follow-up further emphasizes the positive impact of this intervention on health-related quality of life.

The large number of COPD patients imposes a heavy economic burden. Although pulmonary rehabilitation is considered an effective management strategy for COPD with significant cost-effectiveness compared to drug therapy, it has not yet been widely implemented in developing countries [17]. The management of COPD in primary healthcare institutions is weak, and the lack of policy support and guidelines for pulmonary rehabilitation, insufficient knowledge among healthcare professionals, and limited patient awareness of pulmonary rehabilitation all hinder its promotion in primary healthcare settings.

With the widespread adoption of internet technology, telemedicine has become a new research direction, but it currently focuses primarily on exercise training, lacking comprehensive guidance and interactive education [21]. Therefore, research on the application of home non-invasive positive pressure ventilation combined with home-based pulmonary rehabilitation for patients with severe stable chronic type II respiratory failure in COPD is still in the early stages. Nevertheless, with advancements in telemedicine technology, the potential for home-based pulmonary rehabilitation and home non-invasive positive pressure ventilation in patients with severe stable chronic type II respiratory failure in COPD is gradually being recognized.

The results of our study are consistent with previous research showing the benefits of combining home pulmonary rehabilitation with non-invasive positive pressure ventilation for patients with COPD and chronic respiratory failure [5]. Our findings, including improvements in lung function (FEV1%, FEV1, FVC) and a reduction in exercise-induced hypoxemia, are in line with previous research that has demonstrated similar benefits of pulmonary rehabilitation on these outcomes [18]. Additionally, the significant reduction in SpO₂ desaturation during the 6-min walk test in the CPRNG group is supported by other studies [14], which demonstrated that non-invasive ventilation can reduce hypoxemia and improve exercise tolerance in COPD patients.

Moreover, our findings on the improvements in patient-reported outcomes (CAT and mMRC scores) are in line with studies by other Studies [4], which reported enhanced symptom control and reduced disease burden with pulmonary rehabilitation and NIPPV. However, while telemedicine offers potential for expanding pulmonary rehabilitation programs, it often focuses primarily on exercise training and lacks comprehensive education and interactive support. Future research should examine long-term effects, patient adherence, and cost-effectiveness to further support the broader adoption of this combined approach in clinical practice.

One limitation of the present study is the relatively short follow-up period, which may not fully capture the long-term benefits and sustainability of home pulmonary rehabilitation combined with non-invasive positive pressure ventilation (CPRNG). A longer follow-up would provide more insight into the lasting effects of this intervention on both physiological outcomes and quality of life. Additionally, while the study demonstrated improvements in various parameters, the sample size, though adequate, may still limit the generalizability of the findings, particularly in different healthcare settings or populations. Another limitation is the lack of a detailed assessment of patient adherence to the home-based intervention, which is crucial for understanding the real-world applicability of the treatment. Furthermore, the study did not evaluate the potential cost-effectiveness of the combined intervention, which is a key consideration for widespread implementation, especially in resource-limited settings.