Home High-Flow Nasal Cannula in Patients with Chronic Respiratory Failure: A Literature Review and Suggestions for Clinical Practice

Article information

Tuberc Respir Dis. 2025;88(2):264-277

Publication date (electronic) : 2025 February 18

doi : https://doi.org/10.4046/trd.2024.0196

¹Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea

²Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea

³Department of Pulmonary, Critical Care and Sleep Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

⁴Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

⁵Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inha University Hospital, Incheon, Republic of Korea

⁶Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea

⁷Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Republic of Korea

⁸Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

⁹Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea

Address for correspondence Sunghoon Park, M.D., Ph.D. Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, 22 Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang 14068, Republic of Korea Phone 82-31-380-3715 Fax 82-31-380-3973 E-mail f2000tj@gmail.com

Received 2024 December 22; Revised 2025 February 8; Accepted 2025 February 12.

Abstract

High-flow nasal cannula (HFNC) is a noninvasive respiratory support system that delivers air that is heated at 31°C−38°C, humidified 100%, and oxygen-enriched at a constant high flow rate of 15−60 L/min. Because of its numerous physiological benefits, convenience, and minimal side effects, HFNC has been increasingly used over the past decade in patients with acute hypoxemic respiratory failure, yet the clinical benefits of long-term HFNC remain uncertain. Several studies have suggested its potential use as an alternative home oxygen therapy for patients with chronic stable lung diseases, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, and bronchiectasis. The use of long-term home HFNC in patients with chronic respiratory failure is an emerging area with promising potential. Despite limited clinical research, this review aims to describe the physiology of HFNC use and summarize the current evidence on its long-term application, to provide healthcare providers with insights and perspectives on the potential role of long-term home HFNC.

Keywords: High-Flow Nasal Cannula; Home; Oxygen; Chronic Lung Disease

Key Figure

Introduction

Oxygen therapy has been a cornerstone in the management of hypoxemia, and in supporting patients at risk of this condition [1]. Conventional oxygen therapy (COT), involving the delivery of oxygen via nasal cannula or face mask, has been the traditional frontline treatment for both acute and chronic hypoxemia [2]. However, the inadequate heating and humidification of the gas mean that its capacity to deliver oxygen is limited to flow rates of up to 15 L/min, which as flow rates increase, can cause patient discomfort [2].

High-flow nasal cannula (HFNC) oxygen therapy represents an advanced approach that can deliver oxygen at higher flow rates (above 15 L/min), while ensuring adequate heating and humidification [3]. Since the publication in 2015 by the FLORALI study group of the landmark randomized controlled trial (RCT), HFNC has gained considerable attention as an innovative, noninvasive respiratory support method [3,4]. Compared to COT, HFNC offers greater comfort and improved efficiency [5], and recent guidelines have endorsed HFNC over COT to manage hypoxemic acute respiratory failure [6,7].

In contrast to established international guidelines for long-term oxygen therapy (LTOT) and noninvasive ventilation (NIV) [8,9], the evidence supporting the use of HFNC in long-term home settings, particularly for hypercapnic respiratory failure, remains limited. While some studies have reported that long-term HFNC reduces exacerbation rates in patients with chronic airway diseases, such as chronic obstructive pulmonary disease (COPD) [10-12], other studies, including systematic meta-analyses, have yielded inconsistent findings [13-15]. These discrepancies may stem from the inclusion of heterogeneous study populations, combining acute and chronic patients, as well as short-term and longterm treatment protocols.

Although the benefits of home HFNC may not apply uniformly across all chronic respiratory patients, there may be specific subgroups that stand to benefit more from HFNC, compared to LTOT or NIV. This article reviews the existing literature to evaluate the role of HFNC in home oxygen therapy (Tables 1, 2) [10,11,16-36], and proposes optimal settings for its long-term use at home, based on findings from previous research (Table 3) [9,34,37].

Table 1.

Clinical studies of home HFNC on patients with stable COPD

Table 2.

Clinical studies of home HFNC on patients with bronchiectasis and ILD

Table 3.

Suggestions for home (long-term) HFNC

Literature Search and Selection

The literature was searched in PubMed for relevant articles published in English up to June 2024. The indexing terms used were ‘high flow nasal cannula’ OR ‘high flow therapy’ OR ‘high flow oxygen therapy’ OR ‘high flow nasal oxygen’ OR ‘nasal high flow’ OR ‘HFNC.’ The terms ‘home’ OR ‘domiciliary’ OR ‘long-term’ were also used to retrieve publications that were focused on patients undergoing long-term HFNC therapy. Eligible studies included clinical research articles, reviews, meta-analyses, and case reports, while editorials were excluded. The full text of each searched article was reviewed by the authors, and finally, relevant articles were selected.

Physiology of HFNC

The HFNC system consists of a flow generator (e.g., air-oxygen blender with a flow meter), an active heated humidifier, a single-limb heated circuit, and a nasal cannula [38]. It can deliver flow rates of up to 60 L/min, and reliably achieve a fraction of inspired oxygen (FiO₂) of up to 100%. This system provides several physiological benefits that include improved mucociliary clearance, dead space washout, reduced work of breathing (WOB), and increased positive airway pressures [39,40].

1. Higher and more stable FiO₂

Alveolar oxygen delivery depends on the flow rate of supplemental oxygen, FiO₂, and the patient’s spontaneous inspiratory demand [41]. Low-flow oxygen devices, such as nasal cannula or masks, can deliver oxygen at a maximum of 15 L/min. In these systems, room air containing 21% FiO₂ dilutes the high FiO₂ provided by the oxygen device [42]. In contrast, HFNC devices can meet or exceed the patient’s inspiratory flow demand, which increases from 30 L/min at rest, to up to 100 L/min during respiratory failure [43]. By delivering flows higher than the patient’s inspiratory demand, HFNC minimizes room air entrainment, enabling the accurate delivery of high FiO₂.

2. Dead space washout

By effectively removing expired gas from the upper airways, HFNC reduces anatomical dead space [41]. This mechanism flushes out CO2, creates an oxygen reservoir, increases alveolar ventilation, and reduces CO2 rebreathing, leading to improved oxygenation [44]. The reduction of anatomical dead space is proportional to the increase in flow rate. Additionally, HFNC has been shown to improve thoraco-abdominal asynchrony in critically ill patients [45]. These effects collectively contribute to a reduction in dyspnea [46], and respiratory rate [47]. However, despite these advantages, robust evidence for CO2 elimination using HFNC remains limited [48].

3. Delivery of warmed and humidified gas

The active heated humidifier in the HFNC system, along with the connected heated circuit, delivers warmed and humidified gas, offering multiple physiological benefits. Mucus secretion and mucociliary transport are vital to maintain respiratory defenses. The cilia lining the respiratory epithelium propel mucus, which traps particles and pathogens [49]. Since airway mucus is 97% water, adequate hydration is essential to effectively mobilize secretion. Dry gas inhalation can lead to epithelial desiccation, damage, and impaired mucosal function [50,51]. Proper humidification enhances mucociliary clearance, maintains mucosal function, and potentially reduces WOB [52]. Optimal alveolar temperature is 37°C with 100% relative humidity [53], and inhaling warmed air at this level further supports mucociliary clearance [51].

4. Increased positive airway pressure

Although HFNC is not a closed system and allows air leaks, increased flow rates induce expiratory resistance, thereby increasing nasopharyngeal airway pressure [54]. HFNC at a flow rate of 35 L/min with the mouth closed generates approximately 2.7 cmH₂O of airway pressure [54]. When the mouth is open, this pressure can decrease to 1.2 cmH₂O, but overall, mean airway pressure rises in proportion to increased flow rate [55-57]. Parke and McGuinness [57] demonstrated that HFNC could produce a positive end-expiratory pressure (PEEP) of 3−5 cmH₂O at flow rates of 30−50 L/min with the mouth closed. PEEP offers several benefits that include prevention of alveolar collapse, improved oxygenation, enhanced lung compliance, and reduced respiratory effort, ultimately decreasing WOB [54].

Home HFNC for Chronic Lung Diseases

1. COPD with hypercapnia

Recent studies have investigated the potential benefits of home HFNC in patients with chronic stable hypercapnic COPD (Table 1). Although data remain limited, evidence suggests that home HFNC may provide effects that are comparable to home NIV, including improved ventilation and symptom management. Moreover, compared to LTOT (defined as supplemental oxygen use for over 15 hours daily), home HFNC has shown promise in improving quality of life, lowering partial pressure of carbon dioxide (PaCO₂) levels, and reducing the frequency of moderate to severe exacerbations [10,16-20]. These findings highlight its potential role as an adjunct therapy to manage chronic hypercapnic COPD.

1) Physiologic study

A study involving 14 patients with stable hypercapnic COPD demonstrated that using HFNC at flow rates of 20–30 L/min reduced intrinsic PEEP, prolonged expiratory time, and decreased the trans-diaphragmatic pressure–time product [21]. These physiological changes improved lung mechanics, reduced diaphragm fatigue, and alleviated WOB, ultimately ameliorating hypercapnia. Notably, when patients kept their mouths closed, these effects were more pronounced, likely due to better pressure maintenance and reduced air leakage. Another study of 36 patients with stable hypercapnic COPD (PaCO₂ >45 mm Hg), using varying flow rates and degrees of air leakages, also showed significant reductions in hypercapnia across all participants [22]. However, those with higher flow rates (40 L/min) and higher air leakage (i.e., two prongs with one outside the nostril) experienced the greatest reductions in PaCO₂, particularly those with baseline PaCO₂ >55 mm Hg. This indicates airway washout and reduction of functional dead space, rather than increased mean airway pressure, as important mechanisms of HFNC therapy in this patient group.

2) Randomized controlled trials

Braunlich et al. [23] compared HFNC and NIV in COPD patients with baseline PaCO₂ levels of 50 mm Hg or higher. In this study, 94 patients alternated between HFNC and NIV treatments every 6 weeks. Although the NIV group showed a slightly greater reduction in PaCO₂ (−7.1% vs. −4.7% for HFNC), the difference was not statistically significant. These findings suggest that HFNC may offer comparable CO2 reduction, with potentially greater comfort and ease of use.

A crossover RCT by Nagata et al. [16] studied COPD patients at Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2–4 with hypercapnia. Participants alternated between two 6-week periods: HFNC/LTOT (HFNC at night, and LTOT during waking hours), and LTOT alone. During the HFNC/LTOT phase, patients used HFNC at 30−40 L/min for at least 4 hours during sleep. The results showed significant improvements in St. George’s Respiratory Questionnaire (SGRQ) scores, PaCO₂ levels, nocturnal transcutaneous pCO2, and exacerbation rates (0% vs. 19% for HFNC/LTOT vs. LTOT alone). A follow-up RCT also demonstrated that adding HFNC to LTOT reduced moderate to severe exacerbation rates, compared to LTOT alone over 52 weeks, with an adjusted exacerbation ratio of 2.85 (95% confidence interval, 1.48 to 5.47) [17]. Although most benefits were observed in moderate exacerbations, limiting conclusions about severe exacerbations or mortality, this marked the first RCT to demonstrate that home HFNC reduces exacerbations.

3) Non-randomized controlled trials

Studies that focus exclusively on hypercapnic COPD patients are limited. In 2015, Braunlich et al. [24] reported the results of a crossover study, which served as a precursor to their multicenter crossover RCT [23]. This earlier study involved stable hypercapnic COPD patients with PaCO₂ ≥50 mm Hg, who alternated between HFNC and NIV for at least 5 hours per day over a 6-week period. At the end of each intervention, no statistically significant differences between the two groups were found in the changes in PaCO₂. Although the NIV settings in this study were not explicitly described, HFNC was administered at a maximum flow rate of 20 L/min. Subsequent research by the same group included a post hoc analysis from an RCT originally conducted on COPD patients with chronic hypoxemic respiratory failure, focusing on those with hypercapnic respiratory failure [19]. This analysis demonstrated that over a 12-month period, patients receiving HFNC with LTOT showed reductions in PaCO₂ levels, exacerbation rates, and hospital admissions, compared to the LTOT-only group. A more recent retrospective study by Weinreich and Storgaard [25] compared long-term HFNC and longterm NIV as secondary add-on therapies for patients already on LTOT. Both groups showed reduced hospitalization rates over 12 months (HFNC: from 2.5 to 1.5 admissions, p=0.022; NIV: from 2.9 to 1.6 admissions, p=0.014).

2. COPD with hypoxemia

LTOT is known to prolong survival in COPD patients with severe resting hypoxemia [58-60]. Additionally, LTOT improves exercise capacity [61], neuropsychiatric function [62], health-related quality of life [63], and pulmonary hemodynamics [64]. HFNC therapy, which was originally designed for hospital use, is also gradually being introduced as a home-based treatment for patients with chronic respiratory diseases [26,44,65]. Short-term studies of patients with stable, advanced COPD and chronic hypoxemic respiratory failure showed HFNC therapy to be associated with reductions in respiratory rate and PaCO₂, as well as improved exercise performance [26,44,65].

Table 1 includes clinical studies of patients with COPD and chronic hypoxemic respiratory failure. In an RCT by Storgaard et al. [18] (the Aalborg study), 200 patients with COPD and chronic hypoxemic respiratory failure were randomized to receive usual care with or without HFNC. The HFNC group, who used the device for an average of 6 hours daily, demonstrated significantly fewer acute exacerbations (3.12/patient/year vs. 4.95/patient/year, p=0.001) and hospital admissions, along with improvements in modified Medical Research Council and SGRQ scores [18]. However, no significant difference between the two groups in all-cause mortality was observed. Post hoc analysis revealed that HFNC showed the greatest benefit in patients with two or more exacerbations in the year prior to the study, significantly reducing both exacerbation rates and hospitalization days [27]. Similarly, an RCT by Rea et al. [10] studied 108 patients with COPD or bronchiectasis who in the previous 12 months had experienced at least two exacerbations. Compared to the usual care, patients using humidification therapy over 12 months experienced fewer exacerbation days (18.2 days vs. 33.5 days, p=0.045), longer time to first exacerbation (52 days vs. 27 days, p=0.049), and improvements in quality of life and lung function [10]. However, the Aalborg study interestingly observed a significant reduction in exacerbation rates with a longer duration of HFNC use, i.e., 6−7 hr/day, which underscores the importance of consistent usage [18].

HFNC appears to be more effective than usual care or other home respiratory therapies as a long-term strategy to reduce exacerbations and enhance quality of life in patients with stable COPD. However, it does not improve all-cause mortality. Further real-world studies are required to clarify its effectiveness, and to determine optimal settings and usage durations, especially during sleep, to maximize its benefits.

3. Bronchiectasis

Bronchiectasis is a chronic condition that is characterized by persistent airway inflammation, leading to excessive production of purulent secretions and impaired secretion clearance due to reduced mucociliary function [66]. The accumulation of secretions can provide a nutrient-rich environment for bacterial overgrowth and obstruct the bronchial airways, which potentially results in respiratory failure [67]. HFNC delivers warm, humidified gas that enhances mucociliary function and facilitates secretion clearance through sufficient liquefaction. This therapy improves gas exchange by reducing airway resistance, while also decreasing the risk of pneumonia [68]. Despite these potential benefits, research on the long-term use of HFNC in bronchiectasis remains limited. A post hoc analysis of the study by Rea et al. [10] and Good et al. [28] followed patients with bronchiectasis over 12 months, comparing outcomes between those treated with HFNC (humidified air at 37°C, 20−25 L/min for at least 2 hr/day), and those receiving usual care. Among 45 patients, the 26 who adhered to HFNC therapy experienced a significant reduction in acute exacerbation rates (2.39 exacerbations/patient/year vs. 3.48 exacerbations/patient/year) in the usual care group, and demonstrated notable improvements in lung function and SGRQ scores at 12 months [28]. Similarly, a retrospective case-control study involving 40 patients with bronchiectasis reported that when HFNC was used over a 12-month period for more than 6 hours daily, significant reductions in acute exacerbations and hospitalizations occurred, along with improved lung function [29]. Given the physiological benefits of HFNC and the encouraging findings from small clinical studies, long-term home HFNC therapy appears to offer promise for patients with bronchiectasis.

4. Interstitial lung diseases

In patients with interstitial lung disease (ILD), tidal volume decreases when increased lung elasticity cannot be adequately compensated by the strength of the respiratory muscles [69]. This reduction in tidal volume often results in progressive dyspnea, which worsens during exercise, and is frequently accompanied by hypoxemia and hypercapnia [70]. As a modality for respiratory support, HFNC can alleviate dyspnea in patients with ILD by increasing airway pressure and reducing functional dead space, thereby decreasing the WOB [52].

In a crossover retrospective study, 10 patients with ILD underwent alternating 6-week periods of home HFNC therapy (flow rate of 30 L/min, average usage of 6.5 hr/day) and standard oxygen therapy. While no significant improvements were observed in SGRQ scores or sleep quality, home HFNC therapy resulted in reduced dyspnea severity and improved exercise capacity [30]. Another recent study evaluated 25 patients with ILD using a 6 minutes walk test under three different conditions in a crossover design: room air (flow 0 L/min, FiO₂ 0.21), HFNC (flow 40 L/min, FiO₂ 0.21), and HFNC with oxygen supplementation (flow 40 L/min, FiO₂ 0.6). Compared to the other two modalities, HFNC therapy with oxygen supplementation significantly improved exercise duration and resting saturation of partial pressure oxygen (SpO2) [31]. Currently, data on the long-term use of home HFNC in ILD patients remains scarce. The benefits of HFNC in improving exercise capacity may depend on the severity of ILD. Future studies should investigate the potential role of home HFNC to enhance quality of life and prevent acute exacerbations in this patient population.

Cost-Effectiveness of Home HFNC

Three clinical studies have assessed the cost-effectiveness of long-term home HFNC therapy, particularly in patients with severe COPD. A New Zealand study demonstrated significant healthcare cost savings in patients receiving home HFNC, compared to those on LTOT alone [32]. Similarly, a Danish RCT found that adding HFNC to usual care was highly cost-effective, with an incremental cost-effectiveness ratio of £3,605 per quality-adjusted life-year (QALY) gained [11]. An American study reported that incorporating HFNC into standard treatment for severe COPD patients on LTOT resulted in both health benefits (incremental QALYs of 0.058) and cost savings (incremental total costs of −$3,939). These cost savings were attributed to reductions in exacerbation rates, which more than offset the higher device costs [33].

Safety Issues for Home HFNC

To date, RCTs have not identified significant safety concerns associated with the use of HFNC. Nagata et al. [16] in 2018 found the most common HFNC-related adverse event to be nighttime sweating, reported in six of 32 patients in the HFNC group, and one patient in the LTOT group; this was classified as a mild adverse event, and no cases resulted in the discontinuation of HFNC therapy. Similarly, an RCT by Nagata et al. [17] in 2022 found no HFNC-related safety issues. Braunlich et al. [23] in 2019 compared HFNC with NIV, observing non-lethal serious adverse events to be more frequent in the NIV group. While panic attacks were more commonly associated with NIV, HFNC was linked to a higher incidence of epistaxis, nasal dryness, and nasal irritation. Although rare, a case report described HFNC-induced tension pneumocephalus in a patient with head trauma, highlighting the need for caution when applying HFNC to individuals with suspected skull base or paranasal sinus fractures, particularly at higher flow rates [71].

Discussion

Long-term HFNC therapy has been increasingly adopted recently as a home-based respiratory treatment for various chronic lung diseases. Compared to traditional home oxygen therapy, HFNC provides superior humidification, which supports mucociliary clearance [72,73], while offering physiological benefits [41,74], with added convenience and minimal side effects [12,75,76]. While the clinical efficacy of HFNC in hospital settings is well-documented, research on its long-term use at home for patients with chronic lung diseases remains limited. Nevertheless, home HFNC therapy has attracted growing attention from clinicians, with the publication of the first guidelines on long-term HFNC therapy by the Danish Respiratory Society [77].

Most studies on home HFNC therapy have focused on patients with COPD, with limited research on other chronic lung diseases, such as bronchiectasis and ILD. Much of the evidence among COPD patients pertains to those with persistent hypoxemic failure, where when added to LTOT, home HFNC therapy has been associated with significant reductions in exacerbation and hospitalization rates, as well as improvements in quality of life and exercise tolerance [16,18,46,78,79]. While data on stable hypercapnic COPD are more limited, home HFNC therapy has demonstrated benefits in these patients in reducing PaCO₂ levels and exacerbation rates [17,20,23,29,46]. Recent meta-analysis also reported a reduction in exacerbation rates and improved quality of life among COPD patients with chronic hypercapnia, compared to those who received COT [15,48].

NIV is well-established in reducing PaCO₂ levels in hypercapnic COPD patients, and is indicated for those with persistent hypercapnia following acute exacerbation of COPD [8], though discomfort and intolerance to NIV often hinder its long-term use at home. In contrast, HFNC is simpler, more comfortable, and hence a viable alternative for long-term therapy. Studies have shown no significant differences in reducing PaCO₂ or hospitalization rates between home HFNC and NIV [23-25]. In cases where home NIV is not tolerated or indicated, home HFNC may thus serve as an alternative for COPD patients with mild to moderate hypercapnia. However, clinicians need to be aware that as flow rates increase, adherence to HFNC therapy may decline [80], while in some patients with chronic hypercapnia, higher FiO₂ levels could exacerbate hypercapnia [9,81].

In this review, we provide suggestions for the clinical use of home (long-term) HFNC (Table 3). While data remain insufficient, we believe offering preliminary guidance for healthcare providers is necessary. First, we outline potential indications for home HFNC based on previous study populations, including stable COPD with hypoxemic or hypercapnic respiratory failure, bronchiectasis with exacerbations in the previous year, and ILD with persistent hypoxemia. We further propose optimal HFNC settings derived primarily from expert opinions and manufacturers’ instructions, rather than clinical trials, in the hope that these suggestions will assist clinicians in prescribing home HFNC, and support medical staff in managing these patients.

However, this review has several limitations that need to be acknowledged. First, the referenced studies used diverse designs and HFNC settings, which might affect the generalizability of their findings; also, both trials and participants included were relatively small in number, with significant variability in follow-up durations across studies. Second, most studies focused on stable patients, leaving uncertainty about whether patients with more severe conditions would experience similar benefits. Third, this review does not comprehensively address the potential limitations of home HFNC. Notably, the cost of home HFNC devices and their operation is higher than that of LTOT; this may pose a barrier to widespread long-term use. Also, current HFNC systems are less portable than LTOT, potentially restricting patient mobility and affecting quality of life. Hence, given the limited evidence that is available, home HFNC should be considered only for selected patient populations. Finally, a significant gap in the literature exists regarding data from Korea, while the absence of insurance coverage for home HFNC poses a substantial barrier to its broader application. Addressing these challenges will require strategies such as the development of more cost-effective HFNC devices, the conducting of cost-effectiveness and longterm effectiveness studies to inform policy decisions, and advocacy for insurance reimbursement policies.

In conclusion, the efficacy of home HFNC therapy has been demonstrated in managing chronic lung diseases, such as COPD, ILD, and bronchiectasis, with the potential for broader clinical adoption. Further largescale studies are needed to identify target populations, refine application methods, and establish comprehensive management strategies. In particular, comparative studies between home HFNC and COTs, as well as subgroup analyses for specific patient populations— such as those with severe chronic respiratory failure— are essential to better define its role in clinical practice. These efforts will provide the evidence required for the development of definitive practice guidelines and supportive insurance policies.

Notes

Authors’ Contributions

Conceptualization: Chang Y, Kim JW, Cho JH, Park S. Methodology: Chang Y, Baek MS, Kim SW, Lee SH, Kim JS, Park SY, Park S. Formal analysis: Chang Y, Park S. Data curation: Chang Y, Baek MS, Kim SW, Lee SH, Kim JS, Park SY, Park S. Project administration: Chang Y, Park S. Visualization: Chang Y, Park S. Software: Chang Y, Park S. Validation: Kim JW, Cho JH, Park S. Investigation: Chang Y, Baek MS, Kim SW, Lee SH, Kim JS, Park SY, Park S. Writing - original draft preparation: Chang Y, Baek MS, Kim SW, Lee SH, Kim JS, Park SY, Park S. Writing - review and editing: Chang Y, Park S. Approval of final manuscript: all authors.

Conflicts of Interest

Jae Hwa Cho is a deputy editor of the journal, but he was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Funding

No funding to declare.

Acknowledgements

We wish to thank Tai Sun Park (Hanyang University Guri Hospital), Ae-Rin Baek (Soonchunhyang University Bucheon Hospital), Jick Hwan Ha (Incheon St. Mary’s Hospital), and Hyonsoo Joo (Uijeongbu St. Mary’s Hospital) for their assistance in data collection and interpretation.

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Study	Patient groups	No. of patients	Study design	HFNC setting	Results
Rea et al. (2010) [10]	Stable COPD or bronchiectasis	108	Randomized, open-labeled, controlled trial: HFNC+usual care vs. usual care (12 mo)	Flow 20−25 L/min	↓ Exacerbation rate
				HFNC use 1.6±0.67 hr/day	↑ Time to first exacerbation
				Temperature 37°C	↑ QoL and lung function
Braunlich et al. (2015) [24]	Stable COPD with daytime hypercapnia (PaCO₂ ≥50 mm Hg)	11	Prospective cross-over study: HFNC vs. NIV (6/6 wk, at least 5 hr/day)	Flow 20 L/min (HFNC group)	Both HFNC and NIV reduced PaCO₂
Braunlich et al. (2015) [24]	Stable COPD with daytime hypercapnia (PaCO₂ ≥50 mm Hg)	11		Device use >5 hr/day	Both HFNC and NIV reduced PaCO₂
Fraser et al. (2016) [26]	Stable COPD in LTOT	30	Randomized cross-over study: HFNC vs. LTOT (20 min for each)	Flow 30 L/min	↓ TcO₂, TcCO₂, RR, I:E ratio
Fraser et al. (2016) [26]	Stable COPD in LTOT	30		Flow 30 L/min	↑ Vt and EELV
Pisani et al. (2017) [21]	Stable hypercapnic COPD	14	Randomized cross-over study	HFNC 20 L/min vs. 30 L/min vs. NIV (for every 30 min)	↓ RR, intrinsic PEEP and PTPdi
Pisani et al. (2017) [21]	Stable hypercapnic COPD	14	Randomized cross-over study	HFNC 20 L/min vs. 30 L/min vs. NIV (for every 30 min)	More pronounced effects with mouth closed
Braunlich et al. (2018) [22]	Stable hypercapnic COPD (PaCO₂ >45 mm Hg)	36	Comparison between four conditions (different flow rates and nasal prong positions)	A: 20 L/min (two prongs inside)	Greater reductions in PaCO₂ with higher flow rates and air leakages (D > C > B > A)
				B: 40 L/min (two prongs inside)
				C: 40 L/min (one outside, open)
				D: 40 L/min (one outside, closed)
Nagata et al. (2018) [16]	Stable hypercapnic COPD	32	Randomized, cross-over study (9 hospitals): HFNC+LTOT vs. LTOT (6 wk for each)	Flow 29.2±1.9 L/min (A)	Improved PaCO₂, pH, and nocturnal PtcCO₂
				Flow 30.3±4.6 L/min (B)	↑ QoL
				HFNC use 7.1±1.3 hr/day (A)
				HFNC use 8.6±2.9 hr/day (B)
Storgaard et al. (2018) [18]	COPD with hypoxemic respiratory failure in LTOT	200	Randomized clinical trial: HFNC+LTOT vs. LTOT (12 mo)	Flow 20 L/min	↓ AECOPD, hospital admission, and PaCO₂
				HFNC use 6 hr/day	↑ mMRC, QoL, and 6MWT
				HFNC use 6 hr/day	Similar mortality rates
Braunlich et al. (2019) [23]	Stable COPD with daytime hypercapnia (PaCO₂ ≥50 mm Hg)	94	Randomized, cross-over study (13 hospitals): HFNC vs. NIV (6 wk for each)	Flow 19.8±0.6 L/min	Both HFNC and NIV reduced PaCO₂ and improved QoL
				HFNC use 5.2±3.3 hr/day
				NIV use 3.9±2.5 hr/ day
Weinreich et al. (2019) [27]	Advanced COPD patients with chronic hypoxic failure	100	Post hoc analysis from an RCT [18]: patients with 0 or 1 exacerbation vs. those with ≥2 exacerbations in the preceding year	HFNC use 6.1 vs. 6.0 hr/day	↓ Exacerbation & hospitalization rates in those with ≥2 exacerbations in the preceding year
Storgaard et al. (2020) [19]	COPD with hypoxemic and hypercapnic failure (PaCO₂ >45 mm Hg)	74	Post hoc analysis from an RCT [18]: 31 HFNC plus LTOT vs. 43 LTOT for 12 mo	Flow 20 L/min	↓ PaCO₂ (more effective for those with higher baseline PaCO₂)
				HFNC use 8 hr/day	↓ Exacerbation rate
				HFNC use 8 hr/day	↓ Hospital admission rate
Pisani et al. (2020) [20]	COPD (±OSA) with hypercapnia who recovered from AECOPD	50	One-arm study with patients with pH >7.35 and PaCO₂ >45 mm Hg	Temp 31°C, up to 37°C	↓ PaCO₂ for 72 hr (in pure COPD not in overlap [COPD/OSA])
				FiO₂ for SpO₂ target 92%−94%	More effective in those with lower baseline pH
				Flow 33.5±3.2 L/min
				HFNC use >8 hr/day (day and night)
Nagata et al. (2022) [17]	Stable COPD (GOLD 2−4; PaCO₂ >45 mm Hg and pH >7.35)	104	Multicenter RCT: 49 HFNC+LTOT vs. 60 LTOT for 12 mo	Temperature 37°C	↓ AECOPD (moderate/severe)
				Flow 28.5±4.57 L/min	↑ QoL (SGRQ)
				HFNC use 7.3±3.0 hr/day	↑ SpO₂
Weinreich et al. (2023) [25]	COPD with hypoxic or hypercapnic respiratory failure or both	33	LTOT plus HFNC vs. LTOT plus NIV for 12 mo	Not described	Both HFNC and NIV reduced hospitalization rates
Weinreich et al. (2023) [25]		33	LTOT plus HFNC vs. LTOT plus NIV for 12 mo	Not described	HFNC is more tolerable than NIV at the very end of COPD.
Milne et al. (2022) [32]	COPD on LTOT (cost-effectiveness study)	99	55 HFNC+LTOT vs. 44 LTOT	Not described	↑ Cost saving
Sorenssen et al. (2021) [11]	COPD with chronic hypoxic failure (cost-effectiveness study)	200	HFNC+usual care (LTOT) vs. usual care	Not described	↑ Health-related QoL
Sorenssen et al. (2021) [11]		200	HFNC+usual care (LTOT) vs. usual care	Not described	ICER of £3,605 per QALY gained
Groessl et al. (2023) [33]	COPD on LTOT (cost-effectiveness study)	200 (data from an RCT [18])	QALYs using health utility values associated with acute exacerbations	Not described	↑ Healthcare benefit
Groessl et al. (2023) [33]	COPD on LTOT (cost-effectiveness study)	200 (data from an RCT [18])		Not described	↑ Cost saving

Study	Patient groups	No. of patients	Study design	HFNC setting	Results
Hasani et al. (2008) [34]	Bronchiectasis	10	Physiology study: mucociliary clearance of (99 m)Tc-labelled polystyrene tracer particles	Flow 20−25 L/min	High flow via humidification system improved mucociliary clearance
				HFNC use >3 hr/day
				Temperature 37°C
Good et al. (2021) [28]	Bronchiectasis with 2 or more exacerbations in the previous year and daily sputum production	45	A post hoc analysis of a previous RCT (by Rea et al. [10]): HFNC vs. usual care (12 mo)	Temperature 37°C	↓ Exacerbation rate
				Flow 20−25 L/min	↑ Pulmonary function
				HFNC use 1.7 hr/day	↑ QoL (SGRQ)
Crimi et al. (2022) [29]	Bronchiectasis with a severe exacerbation in the previous year	40	Retrospective study: HFNC vs. optimized medical treatment (12 mo)	Temperature 34°C or 37°C	↓ Exacerbation rate
				Flow 20 (initial)–40 L/min	↓ Hospitalization
				HFNC use >6 hr/day (night)	↑ Pulmonary function
				SpO₂ ≥92%
Hui et al. (2020) [35]	Cancer involving the lungs without hypoxemia	44	Patients with SpO₂ >90% at rest:	High-flow air ~70 L/min	↓ Exertional dyspnea (Borg dyspnea intensity)
			High-flow oxygen vs. high-flow air vs. low-flow oxygen vs. low-low air	High-flow oxygen 100%	↑ Exercise capacity
			Symptom-limited cycle ergometry	Low-flow oxygen and air 2 L/min
			Symptom-limited cycle ergometry	Temp 35°C and 37°C
Weinreich et al. (2022) [30]	ILD on AOT or LTOT	10	A retrospective, cross-over study: HFNC (6 wk) vs. observation (6 wk)	Temperature 37°C	↑ Walking distance
				Flow 30 L/min	↓ Dyspnea (mMRC)
				HFNC use 6.5 hr/day (night)	↑ Minimum SpO₂ during 6MWT
Harada et al. (2022) [36]	Stable IPF with desaturation during 6MWT (not home setting)	24	Randomized, open-labeled, cross-over study (a single center): 12 HFNC vs. 12 VM	HFNC 37°C, 60 L/min (flow), 50% (FiO₂)	↑ Exercise duration
				HFNC 37°C, 60 L/min (flow), 50% (FiO₂)	↑ Minimum SpO₂
			Symptom-limited cycle ergometry	VM: 12 L/min and 50%	↓ Leg fatigue
Yanagita et al. (2024) [31]	Stable ILD (not home setting)	25	Three-treatment cross-over study: room air vs. HFNC (FiO₂ 0.21) vs. HFNC with oxygen (FiO₂ 0.60)	Temp 34°C	↑ Exercise duration
				Humidification 100%	↑ SpO₂
			Constant-load cycle ergometry.	Flow 40 L/min	↑ SpO₂