Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, particularly during acute exacerbations when respiratory failure and hypercapnia frequently occur. These episodes necessitate timely therapeutic interventions to stabilize respiratory function and reduce the risk of mortality (1). Over the years, non-invasive ventilation (NIV), particularly bilevel positive airway pressure (BiPAP), has become the standard treatment for acute exacerbations of COPD due to its efficacy in reducing CO₂ levels and improving respiratory function (2).

However, not all patients with COPD tolerate BiPAP well. Numerous patients experience discomfort from wearing the mask or face challenges with communication, which can reduce treatment effectiveness and patient compliance (3). To provide more flexible treatment options and enhance patient comfort, high-flow nasal cannula (HFNC) therapy has been increasingly adopted in recent years. HFNC delivers high-flow oxygen and generates positive pressure, improving blood oxygenation and reducing the risk of atelectasis without the discomfort often associated with BiPAP (4).

Recent international studies have demonstrated that HFNC can achieve comparable effectiveness to BiPAP in reducing blood CO₂ levels and improving oxygen saturation (SpO₂) in patients with acute COPD exacerbations. Cortegiani et al (5) reported that HFNC was as effective as BiPAP in decreasing the partial pressure of carbon dioxide in arterial blood (PaCO₂) and provided the added advantage of higher patient tolerance in numerous cases. Additionally, HFNC has been shown to enhance patient comfort and reduce the work of breathing, allowing patients to maintain a greater sense of ease during treatment (6,7).

In Vietnam, while BiPAP has been widely used in the management of acute exacerbations of COPD, the application of HFNC remains limited, necessitating further studies to evaluate its effectiveness in patients with COPD with respiratory failure. While previous studies have compared HFNC and BiPAP in patients with COPD, limited research has focused on Asian populations, particularly in Vietnam, where healthcare infrastructure, treatment availability and patient responses may differ. The present study aimed to provide novel insight by analyzing the real-world effectiveness of these interventions in a Vietnamese tertiary hospital setting. Unlike prior studies, which have mainly focused on short-term physiological improvements, the present study also evaluated patient comfort and treatment adherence as critical factors in therapy selection. The objective was to optimize treatment and improve the quality of life of patients with COPD, particularly those at risk of respiratory failure.

As demonstrated in Table I, the HFNC group exhibited a slightly lower mean age (70.76±10.18 vs. 73.48±8.83 years) and a lower percentage of male patients (55.68 vs. 68.18%) compared with the BiPAP group. Blood gas parameters, including blood pH, PaCO₂ and bicarbonate (HCO₃^-) levels, were similar in both groups. Oxygenation, measured by SpO₂, was slightly lower in the HFNC group (88.52±7.09 vs. 91.61±3.86%), while the FiO₂ levels were also lower (28.80±4.69 vs. 31.55±4.39%) in the HFNC group. Additionally, the respiratory rates were slightly higher in the HFNC group, whereas heart rates were comparable.

The longitudinal comparisons of FiO₂, PaCO₂ and SpO₂ between the HFNC and BiPAP groups are presented in Table II. The HFNC group consistently required lower FiO₂ across all time points (P<0.001), reflecting improved efficiency in oxygenation. Both groups exhibited progressive reductions in PaCO₂; however, the HFNC group exhibited significantly more significant reductions at T1 through T5, with differences ranging between -2.64 and -3.79 mmHg (P<0.05), except at T4 (P=0.0901). The SpO₂ levels were consistently higher in the BiPAP group, although the differences were minor, particularly after 12 h, with limited clinical relevance despite statistical significance (P<0.05). These results indicate a superior reduction in PaCO₂ in the HFNC group, while oxygenation was marginally better with BiPAP, albeit at the cost of higher FiO₂ requirements. Statistical significance was robust for FiO₂ and PaCO₂ changes.

The progression of respiratory and cardiovascular indices in the HFNC and BiPAP groups is presented in Table III, highlighting significant differences in respiratory rate, accessory muscle use and BP. The BiPAP group exhibited consistently lower respiratory rates at T0 and T3 (P<0.001), potentially indicating improved respiratory efficiency. Accessory muscle use was markedly lower in the HFNC group across all time points (P<0.001), reflecting reduced respiratory distress. BP remained similar between groups initially, although differences in systolic and diastolic BP emerged at a later stage, with lower values in the HFNC group at T4 and T5 (P<0.05). Heart rate trends were lower in the HFNC group; however, there were no statistically significant differences.

The patient comfort levels in the HFNC and BiPAP groups over time are presented in Table IV. The HFNC group consistently reported significantly higher comfort levels than the BiPAP group at all time points (P<0.001). At baseline (T0), the comfort scores were already notably improved in the HFNC group (1.92±0.57 vs. 3.20±0.91), with the difference widening as treatment progressed, particularly at T2 (12 h) and T4 (48 h). By the end of treatment (T5), the HFNC group maintained a low discomfort level (0.07±0.45) compared with the BiPAP group (1.36±1.77). These results suggest a substantial and consistent advantage of HFNC in enhancing patient-reported comfort during respiratory support, reinforcing its tolerability over prolonged treatment periods.

The present study extends previous research on HFNC and BiPAP by focusing on a Vietnamese population, an understudied demographic in COPD management. Unlike previous studies that primarily assessed short-term physiological responses (10,11), the present study incorporated patient comfort and treatment adherence as key outcome measures, which are crucial for the long-term management of COPD.

A comparison between HFNC and BiPAP in improving blood gases and physiological parameters revealed that while HFNC reduced PaCO₂ more gradually than BiPAP, it remained effective in improving hypercapnia and alleviating respiratory symptoms. Specifically, in the HFNC group, PaCO₂ decreased from 55.97±10.50 to 50.31±7.32 mmHg, whereas in the BiPAP group, the reduction was more pronounced, from 54.14±10.40 to 47.06±5.99 mmHg. Despite the slower decrease in PaCO₂, HFNC was well-suited for patients requiring long-term treatment or those who found it challenging to tolerate BiPAP due to discomfort. Notably, the proportion of patients reporting comfort was significantly higher in the HFNC group compared with the BiPAP group (85 vs. 68%). This finding aligns with the findings of previous studies, such as the study by Storgaard et al (12), which documented the ability of HFNC to maintain stable SpO₂ and improve PaCO₂ in patients with COPD. On the whole, HFNC provides a practical and patient-friendly alternative to BiPAP, particularly for those requiring prolonged respiratory support or facing challenges in adhering to BiPAP therapy.

The comfort provided by HFNC promotes treatment adherence and reduces the frequency of requiring other supportive devices, as patients experience greater ease while using the equipment. In the study by Roca et al (13), HFNC was shown to cause less discomfort than BiPAP, resulting in a lower rate of hospital readmissions due to higher patient acceptance of the device. This also alleviates the burden on healthcare staff during patient management. In the present study, HFNC was found to effectively reduce the work of breathing, with the average respiratory rate decreasing from 27.02±1.36 to 22.45±7.80 breaths/min, thereby mitigating respiratory effort. These findings highlight the superior suitability of HFNC for patients requiring long-term therapy or those who encounter difficulties with BiPAP. This further reinforces the potential of HFNC as a patient-friendly and efficient option for managing respiratory distress, particularly in cases where comfort and adherence are critical for treatment success.

Pisani et al (14) reported that HFNC improved blood oxygenation, particularly in patients with chronic COPD. This highlights the effectiveness of HFNC in enhancing oxygen delivery and supporting respiratory function in this patient population, further underscoring its utility as a therapeutic option in managing chronic respiratory conditions. The results of the present study align with these findings, as SpO₂ levels in the HFNC group remained stable throughout the treatment period and showed significant improvement at time points T0 and T1 compared with the BiPAP group. The stability of SpO₂ is a critical factor in preventing prolonged hypoxemia, a high-risk condition for patients with COPD. This reinforces the role of HFNC in providing consistent oxygenation, which is essential for effectively managing COPD.

The safety profile of HFNC is a significant advantage, particularly for patients requiring long-term support. Pisani et al (14) demonstrated that prolonged use of BiPAP may lead to airway damage, whereas HFNC minimizes these complications by delivering a stable airflow with an appropriate FiO₂ level. This makes HFNC a safer and more sustainable option for chronic respiratory support in patients with COPD (14). The present study demonstrated that the complication rate in the HFNC group was significantly lower than that in the BiPAP group, emphasizing HFNC as a more sustainable and lower-risk supportive therapy. HFNC is easier to use and can be set up in a more timely manner without requiring complex adjustments, reducing the need for intensive monitoring by healthcare staff and allowing patients to adapt more rapidly. This highlights the practicality and suitability of HFNC, particularly in long-term treatment scenarios.

Regarding the ability to reduce PaCO₂, while BiPAP has the advantage of achieving a quicker and more effective reduction, HFNC also exhibits significant efficacy and is well-suited for patients with moderate COPD. Several studies have reported that HFNC is comparable to BiPAP in improving oxygenation and reducing hypercapnia (15-17). Storgaard et al (12) further highlighted the long-term effectiveness of HFNC in reducing PaCO₂ in patients with COPD, making it an appropriate option for those with poor tolerance to BiPAP. In the present study, HFNC contributed to a steady reduction in PaCO₂ and effectively alleviated respiratory burden, making it a suitable option for patients requiring long-term support without overloading the respiratory system. This reinforces the role of HFNC as a viable and patient-friendly alternative for managing chronic respiratory conditions.

The present study demonstrated that HFNC was a superior treatment option for patients with COPD with hypercapnia, particularly in cases requiring long-term support or when BiPAP causes discomfort or intolerance. HFNC improved blood gas parameters and enhanced patient comfort and safety, reducing the risk of treatment-related complications. These findings underscore the value of HFNC in optimizing COPD management, particularly in long-term treatment settings or healthcare facilities with limited staffing resources. However, further long-term studies are warranted to evaluate the efficacy of HFNC across varying severities of COPD and under diverse clinical conditions. This will provide more comprehensive insight into its potential and applicability in COPD management.

One key limitation of the present study was the absence of blinding in treatment allocation, which may have led to performance bias, particularly in subjective assessments such as patient comfort. Future research is required to incorporate independent, blinded evaluations of patient-reported outcomes to mitigate this. Additionally, as the present study was conducted in a single tertiary hospital in Vietnam, its findings may not be fully generalizable to healthcare systems with varying resources and patient demographics. Furthermore, the exclusion of patients with severe organ failure limits its applicability to critically ill patients with COPD. Multicenter studies in diverse clinical settings must confirm and extend these findings.

In conclusion, the present study evaluated the effectiveness of two respiratory support methods, HFNC and BiPAP, in the management of patients with COPD with moderate respiratory failure and hypercapnia. The results demonstrated that HFNC significantly improved SpO₂ and patient comfort compared with BiPAP, particularly during long-term treatment. HFNC can potentially enhance the quality of life of patients and treatment adherence due to its higher comfort level and reduced discomfort compared with BiPAP. Therefore, HFNC can be an essential and effective method in managing patients with COPD with hypercapnia, reducing the risk of post-extubation failure. These findings open avenues for further research into the broader applications of HFNC in chronic respiratory failure management.