Abstract
Objective
Short-acting β2 agonists (SABAs) are key drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD). A high-flow nasal cannula (HFNC) is widely used for respiratory failure. Recently, a consensus statement on inhalation therapy with HFNC has been published. However, information regarding the real-world state of inhalation therapy practices in Japan is lacking.
Methods
An anonymous online questionnaire survey endorsed by three Japanese associations (the Japanese Respiratory Society, Japanese Society of Intensive Care Medicine, and Japanese Society of Respiratory Care Medicine) was administered from October to November 2023. Responses were stratified into three questions: Question A, “Do you routinely treat patients with asthma and COPD?” Question B “Do you routinely perform high-flow therapy?”; and Question C “How do you provide inhaled SABAs during high-flow therapy in patients with asthma or COPD?”
Patients
This questionnaire was distributed to all members of the three societies.
Results
Of the 567 participants who completed the questionnaire, 387 responded to all 3 questions. When a nebulizer was included in high-flow devices, the frequencies of using an ultrasonic nebulizer, jet, vibrating mesh, other, or not performing nebulization were 49.1%, 30.8%, 5.4%, 0.5%, and 14.2%, respectively; when a nebulizer was included in high-flow devices, these frequencies were 24.0%, 11.1%, 16.0%, 0%, and 48.9%, respectively.
Conclusion
Various techniques for inhalation therapy are being employed, revealing a discrepancy between current practices in Japan and the recommendations outlined in the consensus statement.
Keywords: asthma, chronic obstructive pulmonary disease, high-flow nasal cannula, inhalation therapy, short-acting β2 agonist
Introduction
Asthma and chronic obstructive pulmonary disease (COPD) are obstructive ventilation disorders in which acute exacerbations can be triggered by respiratory infections (bacterial or viral), allergen exposure, food allergies, outdoor air pollution, or seasonal changes (1,2).
Short-acting β2 agonists (SABAs) are recommended as initial bronchodilators for treating acute exacerbations of asthma and COPD. SABAs increase cyclic adenosine monophosphate levels, inhibits contraction of bronchial smooth muscle, and promotes smooth muscle relaxation and bronchodilation (3). During exacerbations of asthma or COPD, methods of delivering oxygen, such as a nasal cannula, high-flow nasal cannula (HFNC), non-invasive positive-pressure ventilation, and endotracheal intubation, are considered. HFNCs have attracted particular attention owing to their high tolerability and have been widely used in recent years (4-8). Their usefulness in asthma and COPD has also been reported (9-18), and their use is expected to increase in the future. In 2023, a consensus statement (19) on aerosol administration strategies during HFNC was published, highlighting the usefulness of vibrating mesh nebulizers (VMNs) for inhalation therapy during HFNC use (20-35). However, awareness of such advances may be insufficient in Japan, and the real-world status of SABA inhalation therapy during HFNC use in Japan remains unclear.
We conducted a nationwide survey to elucidate the current practice of HFNC inhalation therapy in Japan.
Materials and Methods
Participants and methods
An internet-based questionnaire survey was designed using the Google Forms online survey platform. The survey (Supplementary material 1) included four main sections: common questions for all respondents, questions for doctors only, questions for clinical engineers (CEs) only, and questions for nurses only.
This study was approved by the Ethics Committee for Clinical Studies of the National Hospital Organization, Osaka Minami Medical Center (approval no. R5-18, June 8, 2023), and all participants were informed that by sending their responses, they were deemed to have agreed to the publication of the results. This research was conducted in accordance with the principles of the World Medical Association 2013 Declaration of Helsinki. With the cooperation of the Japanese Respiratory Society (JRS), the Japanese Society of Intensive Care Medicine (JSICM), and the Japanese Society of Respiratory Care Medicine (JSRCM), the survey was sent via e-mail to members of each society, and the response period was from October 19 to November 20, 2023. Society members who were sent duplicate survey requests were asked to respond only once and not to provide duplicate responses.
Data analyses
Participants were classified into three occupational categories and stratified according to three questions. The occupational categories were as follows: i) doctor, ii) CE, and iii) nurse. The three questions were Question A, “Do you routienly treat COPD and asthma patients?” (yes or no; Supplementary material 1 Q1); Question B “Do you routinely perform high-flow therapy?” (yes or no; Supplementary material 1 Q13/Q21/Q32); and Question C “How do you provide inhaled SABAs during high-flow therapy in patients with asthma or COPD?” (not provided or description of the method; Supplementary material 1 Q16/Q25/Q33). The chi-square test or Fisher's exact test was used to compare categorical variables, and the Mann-Whitney U test was used for continuous variables. A multivariate logistic regression analysis (forward selection: likelihood) was performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. All analyses were performed using the IBM SPSS software program, version 28 (IBM, Armonk, USA), and 2-sided p values of ＜0.05 were considered statistically significant.
Results
Overall results
A total of 567 participants returned the questionnaire (Fig. 1). Of these, 45 were excluded because consent was withdrawn (n=4) or they answered “no” to Question A (n=41). The remaining 522 responses were as follows: (i) 464 from doctors, (ii) 20 from CEs, and (iii) 26 from nurses, with 12 responses excluded because none of i)-iii) applied. Questions A and B were answered by 379 doctors, 19 CEs, and 23 nurses, and questions A, B, and C were answered by 354 doctors, 17 CEs, and 16 nurses.
Figure 1.
Flowchart of our questionnaire survey.
Questions for doctors
Basic characteristics
The questions in this section were answered by 464 doctors who responded to Question A. The basic characteristics of the patients are listed in Table 1. The chief departments with which the respondents were affiliated were respiratory medicine (342 doctors), emergency department (44), intensive-care medicine (43), anesthesiology (13), and others (22). With regard to specialty certification in Japan, 304 doctors were respiratory medicine specialists (certified by the JRS), 45 were intensivists (certified by the JSICM), 2 were respiratory therapists (certified by the JSRCM), 5 were double-boarded as respiratory medicine specialists and intensivists, 6 were respiratory medicine specialists and respiratory therapists, 26 were intensivists and respiratory therapists, 10 were specialists in all 3, and 66 were specialists in none of the 3.
Table 1.
Basic Characteristics of Each Category’s Participants.
| Overall n=522 | Doctor n=464 | Clinical engineer n=20 | Nurse n=26 | Others n=12 | |
|---|---|---|---|---|---|
| Hospital | |||||
| University | 170 | 151 | 6 | 8 | 5 |
| National | 38 | 34 | 2 | 1 | 1 |
| Community | 263 | 234 | 9 | 15 | 5 |
| Clinic | 45 | 43 | 1 | 0 | 1 |
| Others | 6 | 2 | 2 | 2 | 0 |
| Number of hospital beds | |||||
| ≥1,000 | 65 | 60 | 2 | 3 | 0 |
| 750-999 | 68 | 61 | 3 | 0 | 4 |
| 500-749 | 121 | 111 | 3 | 7 | 0 |
| 250-499 | 158 | 130 | 11 | 11 | 6 |
| ≤250 | 110 | 102 | 1 | 5 | 2 |
| Years of clinical experience | |||||
| ≥20 | 334 | 298 | 12 | 17 | 7 |
| 10-19 | 146 | 128 | 7 | 7 | 4 |
| ≤9 | 42 | 38 | 1 | 2 | 1 |
| Chief department | |||||
| Respiratory Medicine | - | 342 | - | - | - |
| Intensive Care Medicine | - | 43 | - | - | - |
| Anesthesiology | - | 13 | - | - | - |
| Emergency department | - | 44 | - | - | - |
| Others | - | 22 | - | - | - |
| Medical specialty qualifications | |||||
| Respiratory Medicine only | - | 304 | - | - | - |
| Intensivist only | - | 45 | - | - | - |
| Respiratory Therapy only | - | 2 | - | - | - |
| Respiratory Medicine and Intensivist | - | 5 | - | - | - |
| Respiratory Medicine and Respiratory Therapy | - | 6 | - | - | - |
| Intensivist and Respiratory Therapy | - | 26 | - | - | - |
| All of them | - | 10 | - | - | - |
| None of them | - | 66 | - | - | - |
| Main workplace | |||||
| Intensive Care Unit/Cardiac Care Unit | - | - | - | 7 | - |
| Emergency department | - | - | - | 4 | - |
| General ward | - | - | - | 10 | - |
| Others | - | - | - | 5 | - |
SABAs for asthma and COPD during treatment with or without an HFNC
Among Q11-12 and 14-15, the proportions of participants who answered ‘almost always’ for the use of inhaled SABA were as follows: asthma and non-HFNC (84.7%, n=393), asthma and HFNC (78.9%, n=299), COPD and non-HFNC (74.1%, n=344), and COPD and HFNC (72.3%, n=274) (Fig. 2).
Figure 2.
Frequency of short-acting β2 agonists for asthma and COPD during treatment, with or without the use of a high-flow nasal cannula. A) Asthma and non-HFNC. B) COPD and non-HFNC groups. C) Asthma and HFNC groups. D) COPD and HFNC. COPD: chronic obstructive pulmonary disease, HFNC: high-flow nasal cannula
Methods for using SABAs with an HFNC
Among the doctors who used SABAs with HFNCs, 137 mainly used a metered dose inhaler (MDI), 151 mainly used a nebulizer with a mask, and 52 mainly used a nebulizer within the high-flow device circuit (Table 2). Among the 354 doctors who responded to Questions A, B, and C, ultrasonic nebulizers (USNs) (50.0%, n=177) were most commonly used when a nebulizer was not placed in the high-flow therapy circuit (Table 3). When a nebulizer was placed within the high-flow device circuit, doctors reported that they used a jet nebulizer (JN) (11.6%, n=41), USN (24.0%, n=85), VMN (13.0%, n=46), or unknown (51.4%, n=182).
Table 2.
Participants Who Met the Questions A, and B. How Do You Perform SABA Inhalation during High-flow Nasal Cannula Oxygen Therapy in Patients with Asthma or COPD?
| Overall n=421 | Doctor n=379 | Clinical engineer n=19 | Nurse n=23 | |||
|---|---|---|---|---|---|---|
| Metered-dose inhaler | Discontinued HFNC | 36 (8.6%) | 31 (8.2%) | 3 (15.8%) | 2 (8.7%) | |
| Continued HFNC | Reduce the flow | 10 (2.4%) | 10 (2.6%) | 0 | 0 | |
| Do not reduce the flow | 103 (24.5%) | 96 (25.3%) | 0 | 7 (30.4%) | ||
| Sub-total | 149 (35.4%) | 137 (36.1%) | 3 (15.8%) | 9 (39.1%) | ||
| Nebulizer with a mask | Discontinued HFNC | 29 (6.9%) | 23 (6.1%) | 4 (21.1%) | 2 (8.7%)) | |
| Continued HFNC | Reduce the flow | 21 (5.0%) | 21 (5.5%) | 0 | 0 | |
| Do not reduce the flow | 109 (25.9%) | 107 (28.2%) | 2 (10.5%) | 0 | ||
| Sub-total | 159 (37.8%) | 151 (39.8%) | 6 (31.6%) | 2 (8.7%) | ||
| Nebulizer placed within the high-flow device circuit | Continued HFNC | Reduce the flow | 8 (1.9%) | 6 (1.6%) | 2 (10.5%) | 0 |
| Do not reduce the flow | 52 (12.4%) | 46 (12.1%) | 2 (10.5%) | 4 (17.4%) | ||
| Sub-total | 60 (14.3%) | 52 (13.7%) | 4 (21.1%) | 4 (17.4%) | ||
| Not done | 34 (8.1%) | 25 (6.6%) | 2 (10.5%) | 7 (30.4%) | ||
| Unknown | 19 (4.5%) | 14 (3.7%) | 4 (21.1%) | 1 (4.3%) |
Due to rounding to two decimal place, the sum of individual percentages may not exactly match the subtotal or total percentages.
HFNC: high-flow nasal cannula
Table 3.
Participants Who Met the Questions A, B, and C. If You Use a Nebulizer with/without Placed It into a High-flow Therapy Circuit, Which Type of Nebulizer Would You Use? Please Answer Assuming a Patient with Asthma or COPD.
| Overall n=387 | Doctor n=354 | Clinical Engineer n=17 | Nurse n=16 | ||
|---|---|---|---|---|---|
| Nebulizer not placed within the high-flow device circuit | Jet nebulizer | 119 (30.7%) | 107 (30.2%) | 5 (29.4%) | 7 (43.8%) |
| Ultrasonic nebulizers | 190 (49.1%) | 177 (50.0%) | 7 (41.2%) | 6 (37.5%) | |
| Vibrating mesh nebulizers | 21 (5.4%) | 16 (4.5%) | 5 (29.4%) | 0 | |
| Not done | 2 (0.5%) | 0 | 0 | 2 (12.5%) | |
| Unknown | 55 (14.2%) | 54 (15.3%) | 0 | 1 (6.3%) | |
| Nebulizer placed within the high-flow device circuit | Jet nebulizer | 43 (11.1%) | 41 (11.6%) | 1 (5.9%) | 1 (6.3%) |
| Ultrasonic nebulizers | 93 (24.0%) | 85 (24.0%) | 3 (17.6%) | 5 (31.3%) | |
| Vibrating mesh nebulizers | 62 (16.0%) | 46 (13.0%) | 13 (76.5%) | 3 (18.8%) | |
| Unknown | 189 (48.8%) | 182 (51.4%) | 0 | 7 (43.8%) |
Due to rounding to two decimal place, the sum of individual percentages may not exactly match the subtotal or total percentages.
We conducted a multivariate logistic regression analysis to examine the factors influencing nebulizer placement in high-flow device circuits. The dependent variable was whether or not a nebulizer was placed in the high-flow device circuit among doctors answering Questions A and B. The basic characteristics of the doctors were used as independent variables. The respondents were divided into two groups: ‘in-circuit’ and ‘out-of-circuit.’ We compared the results of the questionnaire items between groups. For variable selection, we initially considered factors with a risk rate of ＜0.1. However, due to the 5 main medical departments being considered, Bonferroni correction was applied, resulting in a more stringent criterion of p＜0.02. We then performed a multivariate logistic regression analysis using forward selection (likelihood ratio method). Variables meeting the corrected criteria were included as independent variables in this analysis. ORs with 95% CIs were calculated for each significant factor. A univariate analysis revealed that respiratory physicians exhibited a lower implementation rate than others, whereas intensivists demonstrated a tendency towards higher implementation rates (Supplementary material 2). No significant difference was observed between the size of the affiliated hospital or years of experience as a doctor and the rate of nebulizer placement in the high-flow circuit (Supplementary material 3). A logistic regression analysis was performed for the categorical variables Q7-10. The stepwise method was employed for variable selection in the logistic regression, with an entry criterion of p＜0.05 and a removal criterion of p＞0.10. The logistic regression analysis demonstrated a lower implementation rate among respiratory and emergency physicians than physicians from other specialties (Table 4).
Table 4.
Multivariate Logistic Regression Analysis Was Performed with Only the Factors Remaining in the Univariate Analysis.
| Chief department | Odds ratio | 95%CI | p vaule |
|---|---|---|---|
| Respiratory Medicine | 0.195 | 0.099-0.384 | <0.001 |
| Emergency department | 0.317 | 0.114-0.878 | 0.027 |
Reasons for not using SABAs during HFNC use
The 85 doctors who answered affirmatively to Question A, but not Question B, were asked why they did not use inhaled SABA during HFNC (Supplementary material 4). The main responses were that they did not know the rationale for SABA inhalation during HFNC (n=50, 58.8%), the method of SABA administration was not simple enough (n=48, 56.5%), the cost was problematic (n=16, 18.8%), there were concerns about infection (n=8, 9.4%), or unknown (n=25, 29.4%).
Questions for CEs
Basic characteristics
The questions in this section were answered by 20 CEs. The basic characteristics of the CEs are presented in Table 1. Eleven worked in hospitals with 250-499 beds, and 12 had more than 20 years of clinical experience.
Use of SABAs with HFNC
Among the 17 CEs responding to Questions A, B, and C, the site at which the nebulizer was attached to the circuit was the prong side (just before the nasal cannula) in 7, the dry side (just before the humidifier) in 6, the wet side (after the humidifier) in 3, and unknown in 1 (Supplementary material 5). A USN (41.2%, n=7) was most commonly used when a nebulizer was not placed in the high-flow device circuit, while a VMN was most commonly used (76.5%, n=13) when a nebulizer was placed within the high-flow device circuit (Table 3).
Questions for nurses
Basic characteristics
Twenty-six nurses answered the questions in this section. The nurses’ basic characteristics are listed in Table 1. Ten worked in general wards, seven in intensive- or cardiac-care units, four in emergency departments, and five in other areas.
Use of SABAs with HFNC
Among the 16 nurses who answered Questions A, B, and C, a JN (43.8%, n=7) was most commonly used when a nebulizer was not placed in a high-flow therapy circuit, and “unknown” (43.8%, n=7) was the most common answer when a nebulizer was placed within the high-flow device circuit (Table 3). All of the responses are presented in Supplementary material 6.
Discussion
To our knowledge, this is the first nationwide questionnaire survey on SABA inhalation during HFNC therapy in Japan. Responses were obtained from 464 doctors, 20 CEs, and 26 nurses. SABA inhalation tended to be performed less frequently with HFNC than without HFNC for both asthma and COPD. Furthermore, a high proportion of SABA inhalation under HFNC was performed using a nebulizer over the nasal cannula or MDI via the mouth, without placing the nebulizer into the high-flow circuit. Our survey results suggest that even doctors specializing in respiratory care in Japan frequently employ treatment methods that deviate from consensus statement recommendations (19).
Comparisons with consensus statement
According to the consensus statement regarding aerosol administration, during aerosol delivery via an HFNC, rather than administering medications using a JN or USN over the nasal cannula or through the mouth, a VMN or MDI with a spacer should be placed in the high-flow device circuit. It is recommended that the VMN be placed at the inlet of the humidifier and the MDI with a spacer be placed in the circuit, close to the nasal cannula. Discontinuing the use of the HFNC to use a nebulizer with a mask or mouthpiece is not recommended.
Studies evaluating USN implementation in non-invasive ventilation circuits are limited. Using an in vitro bilevel positive airway pressure model, Michotte et al. demonstrated that USN delivered significantly lower inhaled doses than VMN and JN (33). Several comparative studies conducted between JN and VMN, studies using single-photon emission computed tomography for analyzing pulmonary deposition patterns, and in vitro assessments of drug delivery efficiency have consistently shown superior performance with VMNs (34,35). In addition, while a JN requires compressed oxygen or air, which can affect the flow and fraction of inspiratory oxygen delivery during HFNC treatment, a VMN does not interfere with circuit parameters such as humidification, oxygen concentration, or flow rate.
Placing a nebulizer or MDI with a mask or mouthpiece with a concurrent HFNC should be avoided because patients inhale and exhale gases supplied by the HFNC through the nasal cavity; as such, when attempting to administer inhalation therapy using a nebulizer or MDI via the mouth of the patient, inspiratory gases from HFNC are likely to leak. The use of a nebulizer or MDI via the mouth of the patient is considered inappropriate as inhalation therapy during HFNC.
In our survey, some participants indicated that they would reduce their flow rate when performing inhalation therapy. Recommendation (19) does not mention whether or not to reduce flow via HFNC, but reducing flow during inhalation therapy seems to be a reasonable choice. Alcoforado et al. pointed out that a higher flow causes turbulence, leading to more particle impaction in high-flow devices and airways. This reduces the amount of aerosols available for inhalation (20). Furthermore, when the gas flow exceeds the inspiratory flow, the aerosol is diluted. This lowers the concentration of inhaled aerosols and decreases the amount reaching the lungs.
Comparisons with the previous global survey
Li et al. conducted a worldwide anonymous online questionnaire survey on HFNCs and concomitant aerosol therapy among adult critical care patients (36). The number of participants varied from section to section, and approximately 1,000 responses were received from 60 countries/regions. The routes of administration for aerosol treatment during HFNC were as follows: 40% applied the nebulizer via a mask or mouthpiece while continuing HFNC usage, 30% used the aerosol device conventionally while discontinuing HFNC usage, and 24% placed the nebulizer within the high-flow device circuit. When those who reported placing a nebulizer within the high-flow device circuit were surveyed about the methods of administration, 40% used a VMN, 30% used a USN, and 28% used a small-volume JN. Compared with the report by Li et al., a higher percentage of participants in our survey applied the nebulizer via a mask or used MDI while continuing HFNC usage, and the placement of a nebulizer within the high-flow device circuit was done less frequently. Li et al. reported that among those who did not provide aerosol therapy via a high-flow device, 54% had never heard of this delivery route, 27% considered evidence supporting its utilization to be insufficient, and 17% believed that aerosol deposition in the lungs was inadequate (36). Our survey showed that a high percentage of respondents cited a lack of evidence as the main reason for not administering SABAs during HFNC use. Further practical clinical studies and educational activities in Japan are vital to improve the implementation of aerosol therapy during HFNC use.
Involvement of Japanese CEs and nurses in inhalation therapy
Among CEs, practices regarding nebulizer placement in high-flow circuits often diverge from the consensus recommendations. The site of the nebulizer attachment to the circuit was most commonly reported as the prong-side in our survey. This contrasts with the consensus statement that recommended dry-side placement of the VMN into the high-flow circuit and prong-side placement of the MDI with a spacer. These findings suggest that consensus statements may not be sufficiently recognized or implemented by CEs in Japan. Among Japanese nurses, JN and USN are recognized as the most convenient and easy-to-use inhalation methods during asthma or COPD exacerbation, regardless of the use of an HFNC. Since we found that nurses were unaware that consensus statement recommendations differ depending on whether or not an HFNC is being used, closing this knowledge gap appears important.
Limitations
Several limitations of this study should be considered when interpreting the results. While this study sought responses from a range of Japanese professionals, most were doctors, and relatively few CEs or nurses responded. Furthermore, the participants were assumed to be only those usually interested in HFNCs and inhalation therapy, which does not necessarily reflect the actual situation in Japan.
Conclusion
This anonymous online questionnaire survey confirmed that SABA inhalation therapy is not consistently performed during HFNC usage in Japan, even among specialists, and that the method is far from standardized. This applies not only to doctors but also to CEs and nurses. Further educational initiatives and clinical trials are essential to enhance the awareness and understanding of this critical issue among healthcare professionals.
Author’s disclosure of potential Conflicts of Interest (COI).
TO received lecture fees from GlaxoSmithKline, Nippon Boehringer Ingelheim, AstraZeneca, Novartis Pharma, and Teijin Healthcare. The other authors declare no conflicts of interest.
Supplementary Material
List of questions in the questionnaire survey.
Statistical analysis with "whether the nebulizer is placed in a high-flow device circuit" as the dependent variable and doctors' basic characteristics as the independent variable.
Number of hospital beds and years of clinical experience by "whether the nebulizer is placed in a high-flow device circuit".
Reasons for not using short-acting β2 agonist during high-flow nasal cannula (Multiple responses allowed).
List of answers in the clinical engineering section.
List of answers in the nurse section.
Acknowledgments
We thank all the participants for completing the survey. This study was approved by the Japanese Respiratory Society, Japanese Society of Intensive Care Medicine, and Japanese Society of Respiratory Care Medicine. We also thank the Japanese Respiratory Society, Japanese Society of Intensive Care Medicine, and Japanese Society of Respiratory Care Medicine for allowing us to survey their members.
References
- 1. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2024 [Internet]. [cited 2024 Jul 2]. http://www.ginasthma.org/
- 2. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, 2024 [Internet]. [cited 2024 Jul 2]. https://goldcopd.org/2024-gold-report/
- 3.Marques L, Vale N. Salbutamol in the management of asthma: a review. Int J Mol Sci 23: 14207, 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lewis SR, Baker PE, Parker R, Smith AF. High-flow nasal cannulae for respiratory support in adult intensive care patients. Cochrane Database Syst Rev 3: CD010172, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Takase E, Akamatsu H, Teraoka S, et al. A phase II study of high-flow nasal cannula for relieving dyspnea in advanced cancer patients. J Pain Symptom Manage 67: 204-211.e1, 2024. [DOI] [PubMed] [Google Scholar]
- 6.Sharma VK, Singh PK, Govindagoudar MB, et al. Efficacy of different respiratory supports to prevent hypoxia during flexible bronchoscopy in patients of COPD: a triple-arm, randomised controlled trial. BMJ Open Respir Res 10: e001524, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Nagata K, Horie T, Chohnabayashi N, et al. Home high-flow nasal cannula oxygen therapy for stable hypercapnic COPD: a randomized clinical trial. Am J Respir Crit Care Med 206: 1326-1335, 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Li Y, Li C, Chang W, Liu L. High-flow nasal cannula reduces intubation rate in patients with COVID-19 with acute respiratory failure: a meta-analysis and systematic review. BMJ Open 13: e067879, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Cortegiani A, Longhini F, Madotto F, et al.; the H. F. -AECOPD study investigators . High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial. Crit Care 24: 692, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Pisani L, Betti S, Biglia C, et al. Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study. BMC Pulm Med 20: 12, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Rezaei A, Fakharian A, Ghorbani F, Idani E, Abedini A, Jamaati H. Comparison of high-flow oxygenation with noninvasive ventilation in COPD exacerbation: a crossover clinical trial. Clin Respir J 15: 420-429, 2021. [DOI] [PubMed] [Google Scholar]
- 12.Cortegiani A, Longhini F, Madotto F, et al. High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial. Crit Care 24: 692, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sun J, Li Y, Ling B, et al. High flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: an observational cohort study. Int J Chron Obstruct Pulmon Dis 14: 1229-1237, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Piquilloud L, Olivier PY, Richard JC, et al. High flow nasal cannula improves breathing efficiency and ventilatory ratio in COPD patients recovering from an exacerbation. J Crit Care 69: 154023, 2022. [DOI] [PubMed] [Google Scholar]
- 15.Pilcher J, Eastlake L, Richards M, et al. Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: a randomized controlled cross-over trial. Respirology 22: 1149-1155, 2017. [DOI] [PubMed] [Google Scholar]
- 16.Geng W, Batu W, You S, Tong Z, He H. High-flow nasal cannula: a promising oxygen therapy for patients with severe bronchial asthma complicated with respiratory failure. Can Respir J 2020: 2301712, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Raeisi S, Fakharian A, Ghorbani F, Jamaati HR, Mirenayat MS. Value and safety of high flow oxygenation in the treatment of inpatient asthma: a randomized, double-blind, pilot study. Iran J Allergy Asthma Immunol 18: 615-623, 2019. [DOI] [PubMed] [Google Scholar]
- 18.Ruangsomboon O, Limsuwat C, Praphruetkit N, Monsomboon A, Chakorn T. Nasal high-flow oxygen versus conventional oxygen therapy for acute severe asthma patients: a pilot randomized controlled trial. Acad Emerg Med 28: 530-541, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Li J, Liu K, Lyu S, et al. Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support. Ann Intensive Care 13: 63, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Alcoforado L, Ari A, Barcelar JM, Brandão SCS, Fink JB, deAndrade AD. Impact of gas flow and humidity on trans-nasal aerosol deposition via nasal cannula in adults: a randomized cross-over study. Pharmaceutics 11: 320, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Li J, Chen Y, Ehrmann S, Wu J, Xie L, Fink JB. Bronchodilator delivery via high-flow nasal cannula: a randomized controlled trial to compare the effects of gas flows. Pharmaceutics 13: 1655, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Li J, Zhao M, Hadeer M, Luo J, Fink JB. Dose response to transnasal pulmonary administration of bronchodilator aerosols via nasal high-flow therapy in adults with stable chronic obstructive pulmonary disease and asthma. Respiration 98: 401-409, 2019. [DOI] [PubMed] [Google Scholar]
- 23.Bennett G, Joyce M, Fernández EF, MacLoughlin R. Comparison of aerosol delivery across combinations of drug delivery interfaces with and without concurrent high-flow nasal therapy. Intensive Care Med Exp 7: 20, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Colaianni-Alfonso N, MacLoughlin R, Espada A, et al. Delivery of aerosolized bronchodilators by high-flow nasal cannula during COPD exacerbation. Respir Care 68: 721-726, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Arunsurat I, Rittayamai N, Chuaychoo B, et al. Bronchodilator efficacy of high-flow nasal cannula in COPD: vibrating mesh nebulizer versus jet nebulizer. Respir Care 69: 157-165, 2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Beuvon C, Coudroy R, Bardin J, et al. β Agonist delivery by high-flow nasal cannula during COPD exacerbation. Respir Care 67: 9-15, 2022. [DOI] [PubMed] [Google Scholar]
- 27.Reminiac F, Vecellio L, Bodet-Contentin L, et al. Nasal high-flow bronchodilator nebulization: a randomized cross-over study. Ann Intensive Care 8: 128, 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Bräunlich J, Wirtz H. Oral versus nasal high-flow bronchodilator inhalation in chronic obstructive pulmonary disease. J Aerosol Med Pulm Drug Deliv 31: 248-254, 2018. [DOI] [PubMed] [Google Scholar]
- 29.Li J, Williams L, Fink JB. The impact of high-flow nasal cannula device, nebulizer type, and placement on trans-nasal aerosol drug delivery. Respir Care 67: 1-8, 2022. [DOI] [PubMed] [Google Scholar]
- 30.Dugernier J, Hesse M, Jumetz T, et al. Aerosol delivery with two nebulizers through high-flow nasal cannula: a randomized cross-over single-photon emission computed tomography-computed tomography study. J Aerosol Med Pulm Drug Deliv 30: 349-358, 2017. [DOI] [PubMed] [Google Scholar]
- 31.Madney YM, Fathy M, Elberry AA, Rabea H, Abdelrahim ME. Aerosol delivery through an adult high-flow nasal cannula circuit using low-flow oxygen. Respir Care 64: 453-461, 2019. [DOI] [PubMed] [Google Scholar]
- 32.Szychowiak P, Gensburger S, Bocar T, et al. Pressurized metered dose inhaler aerosol delivery within nasal high-flow circuits: a bench study. J Aerosol Med Pulm Drug Deliv 34: 303-310, 2021. [DOI] [PubMed] [Google Scholar]
- 33.Michotte JB, Jossen E, Roeseler J, Liistro G, Reychler G. In vitro comparison of five nebulizers during noninvasive ventilation: analysis of inhaled and lost doses. J Aerosol Med Pulm Drug Deliv 27: 430-440, 2014. [DOI] [PubMed] [Google Scholar]
- 34.Dugernier J, Hesse M, Vanbever R, et al. SPECT-CT comparison of lung deposition using a system combining a vibrating-mesh nebulizer with a valved holding chamber and a conventional jet nebulizer: a randomized cross-over study. Pharm Res 34: 290-300, 2017. [DOI] [PubMed] [Google Scholar]
- 35.Réminiac F, Vecellio L, Heuzé-Vourc'h N, et al. Aerosol therapy in adults receiving high flow nasal cannula oxygen therapy. J Aerosol Med Pulm Drug Deliv 29: 134-141, 2016. [DOI] [PubMed] [Google Scholar]
- 36.Li J, Tu M, Yang L, et al. Worldwide clinical practice of high-flow nasal cannula and concomitant aerosol therapy in the adult ICU setting. Respir Care 66: 1416-1124, 2021. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
List of questions in the questionnaire survey.
Statistical analysis with "whether the nebulizer is placed in a high-flow device circuit" as the dependent variable and doctors' basic characteristics as the independent variable.
Number of hospital beds and years of clinical experience by "whether the nebulizer is placed in a high-flow device circuit".
Reasons for not using short-acting β2 agonist during high-flow nasal cannula (Multiple responses allowed).
List of answers in the clinical engineering section.
List of answers in the nurse section.