Skip to main content
Download PDF

An efficacy and safety evaluation of montelukast + fluticasone propionate vs. fluticasone propionate in the treatment of cough variant asthma in children: a meta-analysis

BMC Pulmonary Medicine volume 23, Article number: 489 (2023) Cite this article

Abstract

Purpose

This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.

Methods

Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran’s Q test and I2 statistics, followed by sensitivity analysis and publication bias evaluation.

Results

Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group.

Conclusion

Mon + Flu is effective and safe for the treatment of CVA in children.

Peer Review reports

Introduction

Cough variant asthma (CVA), a phenotype of asthma that exhibits predominantly or solely airway hyperresponsiveness and cough but without wheezing or dyspnea [1, 2], is the most common cause of chronic cough [3]. Patients with CVA tend to experience hidden onsets, long courses, and repeated illnesses that directly affect their study, life, work, and sleep, and heavily affect their economic and mental well-being [4]. Induction therapy consisting of beta2-agonists, leukotriene receptor antagonists, and inhaled corticosteroids is considered useful for CVA [5]. However, resistance to therapy leads to a false-negative result, causing 30% of patients with CVA to develop typical bronchial asthma within a few years [6]. Therefore, it is of great significance to explore therapeutic methods with good curative effects and safety for the clinical intervention of CVA.

Inhaled glucocorticoids, such as fluticasone propionate (Flu) and oral leukotriene receptor antagonists, including montelukast (Mon), are commonly used for the clinical treatment of CVA [7]. Airway hyper-responsiveness due to chronic inflammation is believed to be the underlying mechanism of the disease. Leukotriene receptor antagonists are anti-asthma medications with anti-inflammatory and bronchodilatory properties [8]. A previous study showed that the leukotriene receptor antagonist Mon alone was effective for the treatment of CVA [9]. Furthermore, Takemura et al. indicated that the antitussive effect of Mon alone in CVA could be attributed to the attenuation of eosinophilic inflammation [10]. Moreover, a previous study showed that after two months of treatment, the Flu group had a significantly lower cough symptom score, which is a sample two-part questionnaire relating to cough symptoms [11] and significantly higher forced expiratory volume in 1 s (FEV1%) and percentage of predicted peak expiratory flow (PEF%) than the control group, indicating the effect of Flu treatment on CVA [12]. Ostrom et al. reported that Flu was significantly more effective than Mon in improving pulmonary function, asthma symptoms, and rescue albuterol use [13]. A recent randomized controlled trial (RCT)study explored the differences in the efficacy and safety of Mon combined with Flu or Flu alone in the treatment of CVA in children; however, the conclusions were inconsistent [12, 14, 15]. Therefore, it is necessary to comprehensively evaluate the efficacy and safety of Mon + Flu vs. Flu in the treatment of CVA in children based on a meta-analysis.

A meta-analysis is a statistical procedure that integrates the results of several independent studies that are considered combinable [16]. Although a meta-analysis has explored the relationship between Mon and Flu in CVA [17], some shortcomings cannot be ignored in previous studies, such as publication bias [18]. To obtain more comprehensive and objective results, current study has revealed the efficacy and safety of Mon + Flu vs. Flu in the treatment of CVA based on an updated meta-analysis. This study may provide novel insights into the clinical treatment of CVA.

Materials and methods

This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines (Table S1).

Data sources

Relevant studies were searched from electronic databases, including PubMed, Embase, WanFang, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CQVIP). The main searching keywords included: “Montelukast,” “fluticasone,” “fluticasone propionate,” “cough variant asthma,” and “CVA”. Keywords of the same category were combined with “or,” while keywords of different categories are combined with “and.” We combined subject words with free words to search and adjust the search mode according to the database characteristics. Additionally, the paper versions of the literature results were manually investigated, and relevant reviews and references were screened. The retrieval time for the present study was updated on July 3, 2022. No language restrictions were imposed on the meta-analysis.

Inclusion and exclusion criteria

The inclusion criteria for selected studies were as follows: i) patients with variant asthma under 18 years old; ii) study focused on the differences between Mon + Flu and Flu; iii) studies that were designed as RCTs; and iv) studies that included one or more of the following outcomes: treatment efficiency, cough recurrence rate, cough symptom score, cough remission time, cough disappearance time, FEV%, PEF%, and adverse reactions. In addition, the exclusion criteria were as follows: i) non-treatise literature, such as reviews, letters, and comments; ii) randomized controlled trials, such as cohort, case-control, and cross-sectional studies; and iii) duplicate publications or those that used the same data for multiple articles (only the one with the most complete data was retained).

Data extraction and quality assessment

Two investigators independently extracted available articles according to the selection criteria. Next, the following information was collected from each eligible study independently: first author, year of publication, recruitment time, treatment cycle and follow-up time, treatment plan and dose, basic information of subjects (sample size, age, sex, course of disease), and outcome. Both investigators reached a consensus on all items via discussion and re-examination.

The quality assessment of the included studies was based on the Cochrane guidelines [19], an official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions. If disputes arose during the data extraction and quality assessment, a panel discussion was held, and a third investigator was consulted to obtain consistent results.

Statistical analysis

Stata software (version 12.0) and RevMan (version 5.3) were used for statistical analysis. WMD (weighted mean difference) and 95% confidence interval (CI) were used to evaluate the continuous variables. The risk ratio (RR) and 95% CI were used to evaluate categorical variables. Heterogeneity analysis was performed using Cochran’s Q test and I2 statistics [20]. A random-effects model was used if heterogeneity was observed (P < 0.05, I2 > 50%); otherwise, a fixed-effects model was used (P ≥ 0.05, I2 ≤ 50%). Meta-regression was used to evaluate the effects of sample size and treatment cycle on heterogeneity. Moreover, a sensitivity analysis was performed to evaluate whether the combined outcomes were affected by the removal of a single study. Finally, publication bias was evaluated using a funnel plot and Egger’s test [21].

Results

Included studies

As shown in Fig. 1, the present meta-analysis initially retrieved 98 studies from all enrolled databases. After eliminating 38 duplicates, 60 studies were retained. After reading titles and abstracts, 47 articles were excluded because they did not meet the inclusion criteria. From the remaining 13 studies, four were filtered out after reading the full text. However, the manual search failed to identify studies that could be included in the current analysis. Finally, nine studies [14, 15, 22,23,24,25,26,27,28] with sufficient data were enrolled in the present meta-analysis.

Fig. 1
figure 1

Flow diagram of the screening process for eligible articles. 98 studies from all enrolled databases were initially retrieved. After eliminating 38 duplicates, 60 articles left. Then 47 articles were excluded after reading titles and abstracts, 4 were excluded after reading the full text. lefting nine studies included into meta-analysis

Full size image

Characteristics of the included studies

A total of 926 patients from the nine studies were enrolled, including 464 and 378 patients in the Mon + Flu and Flu groups, respectively (Table 1). There was no significant difference in sex composition (500 boys and 426 girls), age, and course of disease between the two groups. The study area was mainly located in China. The diagnostic criteria of the subjects were the same, and the children did not receive glucocorticoids, leukotriene antagonists, antihistamines, or other drugs within one month before the start of the study. With the exception of Wu et al. [28] and Zeng et al. [23], the dosages used in other studies were the same. The median treatment period of each study was 12 (8-24) weeks, and the follow-up time ranged from 3-6 months.

Table 1 Characteristics of 9 included studies in this meta-analysis
Full size table

The results of the literature quality evaluation showed that some of the included studies had moderate risk bias in the evaluation of selection bias, performance bias, and detection bias. Overall, the quality of the methodology used in this study was medium. The detailed characteristics and quality assessment of the eligible studies are shown in Fig. 2.

Fig. 2
figure 2

The results of the quality evaluation for the current analysis. Green indicates low risk of bias; yellow indicates unclear risk of bias and red indicates high risk of bias. Overall, the quality of the methodology used in this study was medium

Full size image

Results of meta-analysis

The forest plot of the total effective rate and cough recurrence rate between the Mon + Flu and Flu groups is shown in Fig. 3A-B. Because the heterogeneity among these studies was not significant (I2 < 50%, P > 0.05), based on the heterogeneity test, the fixed-effect model was used to merge the results. The pooled results showed that Flu + Mon significantly improved the total efficacy rate (RR (95% CI) = 1.30 (1.19, 1.43), P < 0.001) and reduced cough recurrence (RR (95% CI) = 0.51 (0.31, 0.86), P = 0.01).

Fig. 3
figure 3

The result of the forest plot analysis for the total effective rate and cough recurrence rate between the montelukast (Mon) + fluticasone propionate (Flu) group and the Flu group. A The result of the forest plot analysis for total effective rate between the Mon + Flu group and the Flu group. A fixed-effect model was used since the I2=15%. The pooled results showed that Flu + Mon significantly improved the total efficacy rate. B The result of the forest plot analysis for cough recurrence rate between the Mon + Flu group and the Flu group. A fixed-effect model was used since the I2=0%. The pooled results showed that Flu + Mon significantly reduced cough recurrence

Full size image

A forest plot of cough symptom score, cough relief time, and cough disappearance time between the Mon + Flu and Flu groups is shown in Fig. 4A-C. Because the heterogeneity among these studies was significant (I2 > 50%, P < 0.05), the random-effect model was used to merge the results. The pooled results showed that the cough symptom score (WMD (95% CI) = -0.33 (-0.67, 0.00), P = 0.05), the cough relief time (WMD (95% CI) = -2.72 (-3.54, -1.89) days, P < 0.001) and cough disappearance time (WMD (95% CI) = -4.40 (-6.00, -2.79) days, P < 0.001) in Mon + Flu group were significantly lower than those in the Flu group.

Fig. 4
figure 4

The result of the forest plot analysis for the cough symptom score, cough relief time, and cough disappearance time between the Mon + Flu group and the Flu group. A The result of the forest plot analysis for the cough symptom score between the Mon + Flu group and the Flu group. A random-effect model was used since the I2=92%. The pooled results showed that Flu + Mon significantly reduced the cough remission time. B The result of the forest plot analysis for cough relief time between the Mon + Flu group and the Flu group. A random-effect model was used since the I2=65%. The pooled results showed that Flu + Mon significantly reduced the cough relief time. C The result of the forest plot analysis for cough disappearance time between the Mon + Flu group and the Flu group. A random-effect model was used since the I2=78%. The pooled results showed that Flu + Mon significantly reduced the cough disappearance time

Full size image

A forest plot of FEV1% and PEF% between the Mon + Flu and Flu groups is shown in Fig. 5A-B. Since the heterogeneity among these studies associated with FEV1% was not significant (I2 = 35%, P = 0.20), the pooled results showed that, based on the fixed-effect model, the FEV1% recovery in Mon + Flu group was significantly better than that of the Flu group (WMD (95%CI) = 2.65 (0.78, 4.52) %, P = 0.006). The pooled results by a random-effect (I2=84%) showed that, the PEF% in Mon + Flu group was improved than that of the Flu group but without statistical significance (WMD (95%CI) = 3.64 (-0.59, 7.87) %, P = 0.09).

Fig. 5
figure 5

The result of the forest plot analysis for percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%) between the Mon + Flu group and the Flu group. A The result of the forest plot analysis for FEV1% between the Mon + Flu group and the Flu group. A fixed-effect model was used since the I2=35%. The pooled results showed that Flu + Mon significantly improved the FEV1%. B The result of the forest plot analysis for PEF% between the Mon + Flu group and the Flu group. A random-effect model was used since the I2=84%. The pooled results showed that the PEF% in Mon + Flu group was improved than that of the Flu group but without statistical significance

Full size image

The forest plot of headache, dizziness, hoarseness, abdominal pain, and total complications between the Mon + Flu and Flu groups showed no significant heterogeneity among these studies (I2 = 0%, P > 0.05), and the pooled result differences were not statistically significant, indicating the incidence of headache, dizziness, hoarseness, abdominal pain and total complications were not significantly different between groups (P > 0.05) (Fig. 6).

Fig. 6
figure 6

The result of the forest plot analysis for headache, dizzy, hoarseness, abdominal pain, and total complications between the Mon + Flu group and the Flu group. A fixed-effect model was used since the I2=0%. The pooled result indicates the incidence of headache, dizziness, hoarseness, abdominal pain and total complications were not significantly different between groups

Full size image

Meta-regression

In order to explore the source of heterogeneity, regression analysis was used to evaluate the outcome with obvious heterogeneity. Except for cough symptom score, the number of included literatures for other indicators (cough remission time, cough disappearance time, and PEF%) was 5 or less, which was not suitable for meta regression. Therefore, meta-regression was only performed to identify the heterogeneity source on cough symptom score. The effects of sample size and treatment cycle on the heterogeneity of cough symptom score were evaluated. It was found that neither sample size (P=0.757) nor treatment cycle (P= 0.587) was significant factors influencing heterogeneity. The heterogeneity source is unclear.

Sensitivity and publication bias analyses

Since cough appearance time was reported in only two studies, sensitivity and publication bias analyses were not available for this outcome. As shown in Table 2, the results of the sensitivity analysis suggest that the meta-analysis results of relaxation rate, cough score, FEV1%, and PEF% were unstable, and the combined results of other outcome indicators were stable. The symmetric funnel plot demonstrated no apparent publication bias (Figure S1), and Egger's tests found there was no significant publication bias in the included literature for any of the indicators (P > 0.05).

Table 2 Outcomes of the sensitivity analysis and test of publication bias
Full size table

Discussion

CVA is a relatively common respiratory disease in pediatrics, which is a special type of asthma. After the onset of the disease, children can appear repeated cough symptoms, if the condition is not controlled in time, it is easy to progress into typical bronchial asthma [29]. Flu is a well-established inhaled steroid used as a preventative agent in controlling asthma symptoms [18]. A previous study showed that Flu, which suppresses eosinophilic airway inflammation, is an effective therapy for CVA, since eosinophilic airway inflammation plays an important role in CVA [30]. Chervinsky et al. showed that FEV1%, forced vital capacity, and forced expiratory flow measurements at the mid-expiratory phase at weekly visits throughout the study revealed that Flu was more efficacious than placebo in maintaining asthma control [31]. However, Kawai et al. indicated that after two weeks of Mon treatment, cough symptoms did not improve in 14 patients but disappeared two weeks after additional treatment with Flu, which further indicated the value of Mon + Flu in CVA [32]. Mon is a potent leukotriene receptor antagonist that allows dose-related asthma improvement [33]. It has been proven that both Mon and Flu can prevent recurrent wheezing CVA, but the combined effect of Mon + Flu is more effective [34]. Although Flu alone or Flu + Mon are commonly used for the clinical treatment of CVA, the efficacy and safety of Mon + Flu vs. Flu in the treatment of CVA remain controversial [12, 14, 15]. Therefore, this study compared the efficacy and safety of Mon+Flu with Flu in the treatment of CVA based on a meta-analysis, with a view to providing new insights into the clinical treatment of CVA.

One of the most important inflammatory mediators in the pathogenesis of CVA is leukotriene, which plays an important role in the airway inflammatory cascade [35]. It was found that the amount of leukotriene and its receptor in CVA patients was significantly higher than that in normal people [36]. Leukotriene can not only promote airway smooth muscle contraction, but also increase airway vascular permeability and aggravate mucosal edema [37]. Mon is a potent leukotriene receptor antagonist, which can effectively inhibit the binding of leukotriene to the receptor and block its biological effect, thereby relaxing airway smooth muscle, repairing swollen mucosa, reducing airway hyperresponsiveness, improving lung function and relieving cough [38]. In this study, we included nine articles from our online database search. The meta-analysis showed that, compared with Flu alone, Flu + Mon significantly improved the treatment efficiency, improved FEV1%, and reduced the recurrence rate, cough remission time, and cough disappearance time in CVA. Moreover, the risk of adverse reactions did not significantly increase. Thus, we speculated that Flu + Mon was more effective and safer for CVA treatment than Flu alone.

There were some advantages to our study analysis: i) all enrolled studies were RCTs with low methodological heterogeneity and medium risk level of bias; ii) the differences in research design, clinical information, and statistical heterogeneity of outcomes among the included studies were small; and iii) the results were highly reliable, because there was no significant publication bias among the studies.

However, the current study had some limitations. Specifically, i) small sample size; ii) no quantitative methods such as meta-regression or subgroup analysis were used to identify the source of heterogeneity; and iii) the enrolled studies were all from China, and the extrapolation of meta-analysis results was affected.

Conclusions

In conclusion, by integrating 9 studies, we obtained a more comprehensive and objective results that Mon + Flu is relatively effective and safe regimen for treating CVA in children. This study may provide novel insights into the clinical treatment of CVA. Further prospective cohort studies with high quality and large samples are needed to verify the authenticity of the results.

Availability of data and materials

All data generated or analysed during this study are included in this published article (and its supplementary information files).

References

  1. Corrao WM, Braman SS, Irwin RS. Chronic cough as the sole presenting manifestation of bronchial asthma. N Engl J Med. 1979;300(12):633–7.

    Article  CAS  PubMed  Google Scholar 

  2. Yi F, Zhan C, Liu B, Li H, Zhou J, Tang J, Peng W, Luo W, Chen Q, Lai K. Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma. Respir Res. 2022;23(1):279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wang J, Sun R, Wang R, Han J, Zhang S, Yin Z, Han Z, Nong Y, Lin J. A traditional Chinese patent medicine—Suhuang zhike capsule for cough variant asthma in adults: A protocol of systematic review and meta-analysis of randomized controlled trials. Medicine. 2019;98(50):e18335.

  4. Xiong J, Qi W, Yang H, Zou S, Kong J, Wang C, Zhou Y, Liang F. Acupuncture Treatment for Cough-Variant Asthma: A Meta-Analysis. Evid Based Complement Altern Med. 2021;2021:6694936.

    Article  Google Scholar 

  5. Rayees S, Din I. Current Asthma Treatments. In: Asthma: Pathophysiology, Herbal and Modern Therapeutic Interventions. SpringerBriefs in Immunology. Berlin (Germany): Springer, Cham; 2021. p. 19–25.

  6. Fujimura M. Pathophysiology, diagnosis and treatment of cough variant asthma. Rinsho Byori. 2014;62(5):464–70.

    PubMed  Google Scholar 

  7. Akin O, Yavuz ST. Effects of Inhaled Corticosteroids and Montelukast on Growth and BMI in Children with Asthma. ESPE Abstracts. 2018;89:P-P2-278.

  8. Wei H, Li W, Jiang Z, Xi X, Qi G. Clinical efficacy of montelukast sodium combined with budesonide or combined with loratadine in treating children with cough variant asthma and influence on inflammatory factors in the serum. Exp Ther Med. 2019;18(1):411–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Spector SL, Tan RA. Effectiveness of montelukast in the treatment of cough variant asthma. Ann Allergy Asthma Immunol. 2004;93(3):232–6.

    Article  CAS  PubMed  Google Scholar 

  10. Takemura M, Niimi A, Matsumoto H, Ueda T, Matsuoka H, Yamaguchi M, Jinnai M, Chin K, Mishima M. Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma. Respiration. 2012;83(4):308–15.

    Article  CAS  PubMed  Google Scholar 

  11. Zhan W, Zhang L, Jiang M, Chen M, Yuan X, Sun J, Xu P, Wu F, Zhang C, Luo W, et al. A new simple score of chronic cough: cough evaluation test. BMC Pulm Med. 2020;20(1):68.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhu X-H, Tu J-W, Dai J-H. Clinical effect of fluticasone propionate, montelukast sodium and ketotifen in treatment of cough variant asthma in children. Zhongguo Dang Dai Er Ke Za Zhi. 2019;21(4):393–8.

    PubMed  Google Scholar 

  13. Ostrom NK, Decotiis BA, Lincourt WR, Edwards LD, Hanson KM, Rosenzweig JRC, Crim C. Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma. J Pediatrics. 2005;147(2):213–20.

    Article  CAS  Google Scholar 

  14. Lai M, Xie C. The efficacy of fluticasone propionate combined with montelukast sodium in the treatment of cough variant asthma in children and its effects on lung function, FeNO and airway inflammation. Hainan Med J. 2021;32:7.

    Google Scholar 

  15. Xu Q. Regulatory effect of montelukast sodium combined with fluticasone propionate on peripheral blood immunoglobulin 4 and intercellular adhesion molecule-1 in children with cough variant asthma. J Clin Pulmonary Med. 2018;23(5):898–901.

  16. Borenstein M, Hedges LV, Higgins JP, Rothstein HR: Introduction to meta-analysis. 2nd Edition. Chichester (UK): John Wiley & Sons; 2021.

  17. Feng W, YI H, Yuan H. Efficacy and Safety of Salmeterol/fluticasone Combined with Montelukast versus Salmeterol/fluticasone in the Treatment of Cough Variant Asthma: A Meta-analysis. China Pharmacy. 2018;29(5):699–703.

  18. Szefler SJ, Phillips BR, Martinez FD, Chinchilli VM, Lemanske RF Jr, Strunk RC, Zeiger RS, Larsen G, Spahn JD, Bacharier LB. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233–42.

    Article  CAS  PubMed  Google Scholar 

  19. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors): Cochrane handbook for systematic reviews of interventions. 2nd Edition. Chichester, UK: John Wiley & Sons; 2008.

  20. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clinical research ed). 2003;327(7414):557–60.

    Article  PubMed  Google Scholar 

  21. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed). 1997;315(7109):629–34.

    Article  CAS  PubMed  Google Scholar 

  22. Zhu X, Tu J, Dai J. Clinical observation of fluticasone propionate, montelukast sodium and ketotifen in the treatment of cough variant asthma in children. Chin J Contemp Pediatr. 2019;21(4):393–8.

  23. Zeng J. Fluticasone propionate aerosol plus montelukast sodium chewable tablets in the treatment of cough variant asthma with mite allergy. Chin Pediatr Integr Tradit Western Med. 2016;8(6):616–8.

    Google Scholar 

  24. Chen J, Pan F, Yu S, Dai J. Clinical study of montelukast sodium combined with fluticasone propionate in the treatment of cough variant asthma in children. Chin J Gen Pract. 2016;15(8):608–13.

    Google Scholar 

  25. Dong J, Yang M, Li B. Clinical comparison of fluticasone propionate, montelukast sodium and ketotifen in the treatment of cough variant asthma in children. J Pediatr Pharm. 2020;26(3):18–21.

  26. Hu H, Liu Y, Jia X. Effect of fluticasone propionate combined with montelukast sodium in the treatment of cough variant asthma in children. J Front Med. 2021;11(17):62–3.

    Google Scholar 

  27. Li R. Observation on the efficacy of fluticasone propionate combined with montelukast sodium in the treatment of children with CVA. Pract Clin J Integrated Trad Chin Western Med. 2018;18(5):149–50.

  28. Wu J, Liu Y, Xu P. Effect of montelukast on cough variant asthma in children. Chin J Woman Child Health Res. 2011;22(2):208–9.

    Google Scholar 

  29. Enseki M, Nukaga M, Tadaki H, Tabata H, Hirai K, Kato M, Mochizuki H. A breath sound analysis in children with cough variant asthma. Allergol Int. 2019;68(1):33–8.

    Article  PubMed  Google Scholar 

  30. Kirishi S, Tagaya E, Ishii M, Takeyama K, Isono K, Kondo M, Shinya F, Tamaoki J. Comparable effectiveness of budesonide/formoterol combination and fluticasone for the treatment of cough variant asthma. Eur Respir J. 2013;42(Suppl 57):P3399.

  31. Chervinsky P, Van As A, Bronsky E, Dockhorn R, Noonan M, La Force C, Pleskow W. Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. J Allergy Clin Immunol. 1994;94(4):676–83.

    Article  CAS  PubMed  Google Scholar 

  32. Kawai S, Baba K, Matsubara A, Shiono H, Okada T, Yamaguchi E. The efficacy of montelukast and airway mast cell profiles in patients with cough variant asthma. J Asthma. 2008;45(3):243–50.

    Article  CAS  PubMed  Google Scholar 

  33. Castro-Rodriguez JA, Rodriguez-Martinez CE, Ducharme FM. Daily inhaled corticosteroids or montelukast for preschoolers with asthma or recurrent wheezing: A systematic review. Pediatric Pulmonol. 2018;53(12):1670–7.

    Article  Google Scholar 

  34. Ding B, Lu Y, Li Y, Zhou W, Qin F. Efficacy of treatment with montelukast, fluticasone propionate and budesonide liquid suspension for the prevention of recurrent asthma paroxysms in children with wheezing disorders. Experiment Therapeut Med. 2019;18(4):3090–4.

    CAS  Google Scholar 

  35. Morina N, Haliti A, Iljazi A, Islami D, Bexheti S, Bozalija A, Islami H. Comparison of Effect of Leukotriene Biosynthesis Blockers and Inhibitors of Phosphodiesterase Enzyme in Patients with Bronchial Hyperreactivity. Open Access Maced J Med Sci. 2018;6(5):777–81.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang Y. The clinical effect of Montelukast and chlorpheniramine in treatment of children with cough variant asthma. Jilin Med J. 2018;39(6):1085–7.

    Google Scholar 

  37. Liu M, Yokomizo T. The role of leukotrienes in allergic diseases. Allergol Int. 2015;64(1):17–26.

    Article  CAS  PubMed  Google Scholar 

  38. Li S. Effect of montelukast sodium combined with salbutamol on children with cough variant asthma. Qingdao Med J. 2020;52(5):332–4.

    Google Scholar 

Download references

Acknowledgements

None.

Funding

This work was supported by the Medical Science and Technology Development Project of Yancheng [grant number YK2021051] and Key Research and Development Plan Project of Yangcheng [grant number YCBE202205].

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Affiliated Yancheng Maternity&Child Health Hospital of Yangzhou University Medical School, No. 31, Century Avenue East Road, Economic Development Area, Yancheng, Jiang Su Province, 224002, China

    Zhengbo Wei & Sheng Li

Authors
  1. Zhengbo Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of the research: SL; Acquisition of data: ZW; Data analysis and interpretation: ZW; Statistical analysis: ZW; Drafting the manuscript: ZW; Revision of manuscript for important intellectual content: SL. Obtaining funding: SL. All authors reviewed the manuscript.

Corresponding author

Correspondence to Sheng Li.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Figure S1.

Funnel plot. A, the total effective rate. B, cough recurrence rate. C, the cough symptom score. D, cough relief time. E, cough disappearance time. F, percentage of forced expiratory volume in 1 second (FEV1%). G, percentage of predicted peak expiratory flow (PEF%). H, headache. I, dizzy. J, hoarseness. K, abdominal pain. L, total complications.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, Z., Li, S. An efficacy and safety evaluation of montelukast + fluticasone propionate vs. fluticasone propionate in the treatment of cough variant asthma in children: a meta-analysis. BMC Pulm Med 23, 489 (2023). https://doi.org/10.1186/s12890-023-02721-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12890-023-02721-z

Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

Contact us