eISSN: 2299-0046
ISSN: 1642-395X
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
Current issue Archive Manuscripts accepted About the journal Editorial board Reviewers Abstracting and indexing Subscription Contact Instructions for authors Publication charge Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
6/2022
vol. 39
 
Share:
Share:
Original paper

The efficacy of high-flow oxygen versus conventional oxygen for asthma control: a meta-analysis of randomized controlled studies

Haoyue Deng
1, 2
,
Yongpeng He
3
,
Xiaoqin Fu
3
,
Zhiqiang Mei
2
,
Yi Li
4

  1. Department of Gastroenterology Suining First People's Hospital, Suining, Sichuan, China
  2. The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
  3. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
  4. Department of Thoracic Surgery Suining Central Hospital, Suining, Sichuan, China
Adv Dermatol Allergol 2022; XXXIX (6): 1077-1082
Online publish date: 2022/09/07
Article file
- The efficacy.pdf  [0.14 MB]
Get citation
 
 

Introduction

Asthma has the features of airway hyperresponsiveness and reversible airflow obstruction [15]. It has become one of the most common airway diseases in both children and adults [6]. The incidence of childhood asthma is estimated to range from 10% to 13%, and its incidence in adults is about 4% [79]. The exacerbation of asthma results in an acute obstruction of expiratory airflow due to airway inflammation, bronchospasm and hypersecretion [10, 11]. If the emergent and effective treatment is not conducted for asthma exacerbation, patients suffer from hypercapnia, severe hypoxemia and subsequent respiratory failure [12].

The Global Initiative for Asthma (GINA) guideline recommends early administration of supplemental oxygen and medications such as nebulized bronchodilators and systemic corticosteroid for the management of acute severe asthma [6]. The administration approaches of oxygen mainly include nasal cannula and nonrebreather mask which are promising for chronic obstructive pulmonary disease (COPD), but show limited success in acute severe asthma [13]. High-flow oxygen therapy is the oxygen-delivering method of inspired fraction (FiO2) up to 1.0 via a high-flow nasal cannula across a range of flows from 2 to 60 l/min. It also provides positive airway pressure and decreases rebreathing from anatomic dead space, which helps reduce the respiratory effort [14, 15]. Many studies reported the effectiveness of high-flow oxygen therapy for hypoxemic respiratory failure and cardiogenic pulmonary oedema [16, 17].

Current evidence is insufficient for routine clinical use of high-flow oxygen therapy for asthmatic patients. Recently, several studies have investigated the efficacy of high-flow oxygen versus conventional oxygen therapy for these patients, but the results are conflicting [12, 18, 19].

Aim

This systematic review and meta-analysis of RCTs aims to assess the efficacy of high-flow oxygen versus conventional oxygen therapy in asthmatic patients.

Material and methods

This systematic review and meta-analysis are performed based on the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and Cochrane Handbook for Systematic Reviews of Interventions [2022]. No ethical approval and patient consent are required because all analyses are based on previous published studies.

Literature search and selection criteria

We have systematically searched several databases including PubMed, Embase, Web of Science, EBSCO, and the Cochrane library from inception to May 2021 with the following key words: “high-flow oxygen” AND “asthma”. The reference lists of retrieved studies and relevant reviews are also hand-searched and the above process is performed repeatedly in order to include additional eligible studies.

The inclusion criteria are as follows: (1) study design is RCT, (2) patients are diagnosed with asthma, and (3) intervention treatments are high-flow oxygen versus conventional oxygen therapy.

Data extraction and outcome measures

Some baseline information is extracted from the original studies, and they include the first author, number of patients, age, female, medical history of asthma and detailed methods in two groups. Data are extracted independently by two investigators, and discrepancies are resolved by consensus. The primary outcomes are PaCO2 and PaO2. Secondary outcomes include the intubation rate, hospital length of stay and dyspnoea score.

Quality assessment in individual studies

The methodological quality of each RCT is assessed by the Jadad Scale which consists of three evaluation elements: randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points) [23]. One point would be allocated to each element if they are conducted and mentioned appropriately in the original article. The score of Jadad Scale varies from 0 to 5 points. An article with Jadad score ≤ 2 is considered to have low quality. The study is thought to have high quality if Jadad score ≥ 3 [22, 24].

Statistical analysis

We assess standard mean difference (SMD) with 95% confidence intervals (CIs) for continuous outcomes and odd ratio (OR) with 95% CI for dichotomous outcome. Heterogeneity is evaluated using the I 2 statistic, and I 2 > 50% indicates significant heterogeneity [25]. The random-effects model is used for all meta-analyses. We search for potential sources of heterogeneity when encountering significant heterogeneity. Sensitivity analysis is performed to detect the influence of a single study on the overall estimate via omitting one study in turn or performing the subgroup analysis. Owing to the limited number (< 10) of included studies, publication bias is not assessed. Results with p < 0.05 are considered to be significant. All statistical analyses are performed using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK).

Results

Literature search, study characteristics and quality assessment

Figure 1 shows the detail flowchart of the search and selection results. 152 potentially relevant articles are identified initially and four RCTs are finally included in the meta-analysis [12, 18, 19, 26].

Figure 1

Flow diagram of the study searching and selection process

/f/fulltexts/PDIA/47714/PDIA-39-47714-g001_min.jpg

The baseline characteristics of four included RCTs are shown in Table 1. These studies are published between 2018 and 2021, and the total sample size is 175. The flows of high-flow oxygen range from 2 to 60 l/min. One RCT involves children with asthma [26], while the other three RCTs involve adult patients [12, 18, 19].

Table 1

Characteristics of included studies

No.AuthorHigh flow groupControl groupJada scores
NumberAge [years]Female (n)Duration of asthma [year]MethodsNumberAge [years]Female (n)Duration of asthma [year]Methods
1Ruangsomboon 20211963.7 ±16.91635 l/min, adjusted from 30 to 60 l/min according to the participant’s level of comfort1863.2 ±21.815Standard oxygen nasal cannula3
2Geng 20201643.3 ±10.6106.38 ±1.28Initial gas flow of 30–40 l/min, to maintain pulse oxygen saturation at 92–96%2037.5 ±8.4125.95 ±1.36Standard oxygen nasal cannula4
3Raeisi 20192050.75 ±10.7155.3 ±2.7Flow range 15–35 l/min2044.4 ±11.6136.4 ±3.4Standard oxygen nasal cannula4
4Ballestero 2018303.0 (1.7–6.0), median (range)15Fow range 2–25 l/min323.0 (2.0–6.0)14Standard oxygen nasal cannula3

Two studies report dyspnoea score, PaCO2, PaO2 and intubation rate [12, 18], three studies report hospital length of stay [12, 18, 26], and two studies report dyspnoea score [12, 19]. Jadad scores of the four included studies vary from 3 to 4, and all four studies have high quality based on the quality assessment.

Primary outcomes: PaCO2 and PaO2

The random-effect model is used for the analysis of primary outcomes. The results find that compared to conventional oxygen therapy for asthma, high-flow oxygen has no obvious influence on PaCO2 (SMD = 0.28; 95% CI: –0.22 to 0.77; p = 0.28) with no heterogeneity among the studies (I 2 = 0%, heterogeneity p = 0.37, Figure 2) or PaO2 (SMD = 0.44; 95% CI: –1.34 to 2.22; p = 0.63) with significant heterogeneity among the studies (I 2 = 91%, heterogeneity p = 0.0008, Figure 3).

Figure 2

Forest plot for the meta-analysis of PaCO2

/f/fulltexts/PDIA/47714/PDIA-39-47714-g002_min.jpg
Figure 3

Forest plot for the meta-analysis of PaO2

/f/fulltexts/PDIA/47714/PDIA-39-47714-g003_min.jpg

Sensitivity analysis

Significant heterogeneity remains for PaO2. There are just two RCTs, and thus we do not perform sensitivity analysis by omitting one study in each turn to detect the source of heterogeneity.

Secondary outcomes

In comparison with conventional oxygen therapy for asthma, high-flow oxygen shows no obvious impact on intubation rate (OR = 1.09; 95% CI: 0.15 to 8.21; p = 0.93; Figure 4) or hospital length of stay (SMD = –0.07; 95% CI: –0.41 to 0.27; p = 0.67; Figure 5), but is associated with significantly lower dyspnoea score (SMD = –0.63; 95% CI: –1.08 to –0.17; p = 0.008; Figure 6).

Figure 4

Forest plot for the meta-analysis of intubation

/f/fulltexts/PDIA/47714/PDIA-39-47714-g004_min.jpg
Figure 5

Forest plot for the meta-analysis of hospital length of stay.

/f/fulltexts/PDIA/47714/PDIA-39-47714-g005_min.jpg
Figure 6

Forest plot for the meta-analysis of dyspnoea score

/f/fulltexts/PDIA/47714/PDIA-39-47714-g006_min.jpg

Discussion

Several studies demonstrated the benefit of high-flow oxygen therapy in decreasing the arterial partial pressure of carbon dioxide in patients with hypercapnic respiratory failure [2729]. In patients with severe asthma, high-flow oxygen therapy also showed favourable benefit in decreasing the respiratory rate and increasing their expiratory time which thereby help decrease dynamic hyperinflation. In addition, heated and humidified air could increase the comfort and reduce bronchoconstriction induced by cold air [12].

Our meta-analysis included four RCTs and 175 patients, and the results revealed that high-flow oxygen therapy was associated with a significantly lower dyspnoea score than conventional oxygen therapy for asthma, but PaCO2, PaO2, intubation rate and hospital length of stay were found to be similar between two groups. In paediatric patients with acute severe asthma, high-flow oxygen therapy was approved to improve clinical severity compared with conventional oxygen therapy [26, 30]. Its benefit in decreasing PaCO2 is confirmed in both children and adolescents [31].

In Figure 3, only adults patients are included for the meta-analysis of PaCO2 after pooling the results of two RCTs [12, 18]. These suggest that high-flow oxygen therapy may provide better efficacy to decrease PaCO2 and improve clinical severity in paediatric patients than that in adult patients. Regarding the sensitivity analysis, there is significant heterogeneity, which may be caused by different flow range and detail methods of high-flow oxygen therapy as well as various severity of asthma.

Several limitations exist in this meta-analysis. Firstly, our analysis is based on only four RCTs, and more RCTs with a larger sample size should be conducted to explore this issue. Next, there is significant heterogeneity, which may be caused by different flow range and severity of asthma. Children and adult patients are both included in this meta-analysis, which may affect the evaluation of efficacy such as the decrease in PaCO2. Finally, it is not feasible to perform the analysis of some outcomes such as modified Borg scale and respiratory rate.

Conclusions

High-flow oxygen therapy may be beneficial in decreasing the dyspnoea score compared to conventional oxygen therapy in asthmatic patients, but results in no improvement in PaCO2, PaO2, intubation or hospital length of stay. More studies should be conducted to confirm this issue.

Acknowledgments

Haoyue Deng, Yongpeng He, Xiaoqin Fu contributed equally to this work.

Conflict of interest

The authors declare no conflict of interest.

References

1 

Papi A, Brightling C, Pedersen SE. Asthma. Lancet 2018; 391: 783-800.

2 

Barnes PJ. Cellular and molecular mechanisms of asthma and COPD. Clin Sci 2017; 131: 1541-58.

3 

Padem N, Saltoun C. Classification of asthma. Allergy Asthma Proc 2019; 40: 385-8.

4 

Fehrenbach H, Wagner C, Wegmann M. Airway remodeling in asthma: what really matters. Cell Tissue Res 2017; 367: 551-69.

5 

Ramsahai JM, Hansbro PM, Wark PAB. Mechanisms and management of asthma exacerbations. Am J Respir Crit Care Med 2019; 199: 423-32.

6 

Boulet LP, Reddel HK, Bateman E, et al. The global initiative for asthma (GINA): 25 years later. Eur Respir J 2019; 54: 1900598.

7 

Teeratakulpisarn J, Pairojkul S, Heng S. Survey of the prevalence of asthma, allergic rhinitis and eczema in schoolchildren from Khon Kaen, Northeast Thailand. an ISAAC study. International Study of Asthma and Allergies in Childhood. Asian Pac J Allergy Immunol 2000; 18: 187-94.

8 

Boonsawat W, Charoenphan P, Kiatboonsri S, et al. Survey of asthma control in Thailand. Respirology 2004; 9: 373-8.

9 

Boonsawat W, Thompson PJ, Zaeoui U, et al. Survey of asthma management in Thailand – the asthma insight and management study. Asian Pac J Allergy Immunol 2015; 33: 14-20.

10 

Castillo JR, Peters SP, Busse WW. Asthma exacerbations: pathogenesis, prevention, and treatment. J Allergy Clin Immunol Practice 2017; 5: 918-27.

11 

Peters MC, Mauger D, Ross KR, et al. Evidence for exacerbation-prone asthma and predictive biomarkers of exacerbation frequency. Am J Respir Crit Care Med 2020; 202: 973-82.

12 

Ruangsomboon O, Limsuwat C, Praphruetkit N, et al. Nasal high-flow oxygen versus conventional oxygen therapy for acute severe asthma patients: a pilot randomized controlled trial. Acad Emerg Med 2021; 28: 530-41.

13 

Ram FS, Picot J, Lightowler J, Wedzicha JA. Non‐invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2004; 1: CD004104.

14 

Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care 2010; 55: 408-13.

15 

Gotera C, Díaz Lobato S, Pinto T, Winck JC. Clinical evidence on high flow oxygen therapy and active humidification in adults. Rev Portug Pneumol 2013; 19: 217-27.

16 

Rittayamai N, Tscheikuna J, Praphruetkit N, Kijpinyochai S. Use of high-flow nasal cannula for acute dyspnea and hypoxemia in the emergency department. Respir Care 2015; 60: 1377-82.

17 

Ruangsomboon O, Dorongthom T, Chakorn T, et al. High-flow nasal cannula versus conventional oxygen therapy in relieving dyspnea in emergency palliative patients with do-not-intubate status: a randomized crossover study. Ann Emerg Med 2020; 75: 615-26.

18 

Geng W, Batu W, You S, et al. High-flow nasal cannula: a promising oxygen therapy for patients with severe bronchial asthma complicated with respiratory failure. Canad Respir J 2020; 2020: 2301712.

19 

Raeisi S, Fakharian A, Ghorbani F, et al. Value and safety of high flow oxygenation in the treatment of inpatient asthma: a randomized, double-blind, pilot study. Iran J Allergy Asthma Immunol 2019; 18: 615-23.

20 

Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.

21 

Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1. 0 [updated March 2011], The Cochrane Collaboration (2011).

22 

Zhao J, Huang W, Zhang S, et al. Efficacy of glutathione for patients with cystic fibrosis: a meta-analysis of randomized-controlled studies. Am J Rhinol Allergy 2019; 34: 115-21.

23 

Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1-12.

24 

Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135: 982-9.

25 

Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics Med 2002; 21: 1539-58.

26 

Ballestero Y, De Pedro J, Portillo N, et al. Pilot clinical trial of high-flow oxygen therapy in children with asthma in the emergency service. J Pediatr 2018; 194: 204-10.

27 

Lee HW, Choi SM, Lee J, et al. Reduction of PaCO(2) by high-flow nasal cannula in acute hypercapnic respiratory failure patients receiving conventional oxygen therapy. Acute Crit Care 2019; 34: 202-11.

28 

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 Pulmon Med 2020; 20: 12.

29 

Rittayamai N, Phuangchoei P, Tscheikuna J, et al. Effects of high-flow nasal cannula and non-invasive ventilation on inspiratory effort in hypercapnic patients with chronic obstructive pulmonary disease: a preliminary study. Ann Intens Care 2019; 9: 122.

30 

Baudin F, Buisson A, Vanel B, et al. Nasal high flow in management of children with status asthmaticus: a retrospective observational study. Ann Intensive Care 2017; 7: 55.

31 

David MMC, Gomes EL, Cavassin CL, et al. Clinical impact of the high flow nasal cannula in the treatment of asthma crisis in children and adolescents. A pilot study. Eur Respiratory Soc 2019; 54 Suppl 63: PA1228.

Copyright: © 2022 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
Quick links
© 2024 Termedia Sp. z o.o.
Developed by Bentus.