Skip to main content
Top
Published in:

Open Access 01-12-2023 | Pneumonia | Study protocol

Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial

Authors: Xiao Li, Wen Li, Lianjie Sun, Junyi Ren, Ying Xu, Yuanyi Zheng, Wenkun Bai

Published in: Trials | Issue 1/2023

Login to get access

Abstract

Background

Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia.

Methods

Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded.

Discussion

This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body’s self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia.

Trial registration

ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.
Appendix
Available only for authorised users
Literature
1.
go back to reference Pagliano P, Sellitto C, Conti V, Ascione T, Esposito S. Characteristics of viral pneumonia in the COVID-19 era: an update. Infection. 2021;49:607–16.CrossRefPubMedPubMedCentral Pagliano P, Sellitto C, Conti V, Ascione T, Esposito S. Characteristics of viral pneumonia in the COVID-19 era: an update. Infection. 2021;49:607–16.CrossRefPubMedPubMedCentral
2.
go back to reference Uddin SMZ, Komatsu DE, Motyka T, Petterson S. Low-intensity continuous ultrasound therapies—a systematic review of current state-of-the-art and future perspectives. J Clin Med. 2021;10:2698.CrossRefPubMedPubMedCentral Uddin SMZ, Komatsu DE, Motyka T, Petterson S. Low-intensity continuous ultrasound therapies—a systematic review of current state-of-the-art and future perspectives. J Clin Med. 2021;10:2698.CrossRefPubMedPubMedCentral
3.
go back to reference Best TM, Wilk KE, Moorman CT, Draper DO. Low intensity ultrasound for promoting soft tissue healing: a systematic review of the literature and medical technology. Intern Med Rev (Wash D C). 2016;2:271.PubMed Best TM, Wilk KE, Moorman CT, Draper DO. Low intensity ultrasound for promoting soft tissue healing: a systematic review of the literature and medical technology. Intern Med Rev (Wash D C). 2016;2:271.PubMed
4.
go back to reference Schandelmaier S, Kaushal A, Lytvyn L, Heels-Ansdell D, Siemieniuk R, Agoritsas T, et al. Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials. BMJ. 2017;356:j656.CrossRefPubMedPubMedCentral Schandelmaier S, Kaushal A, Lytvyn L, Heels-Ansdell D, Siemieniuk R, Agoritsas T, et al. Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials. BMJ. 2017;356:j656.CrossRefPubMedPubMedCentral
5.
go back to reference Poolman R, Agoritsas T, Siemieniuk R, Harris I, Schipper I, Mollon B, et al. Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline. BMJ. 2017;356:j576.CrossRefPubMed Poolman R, Agoritsas T, Siemieniuk R, Harris I, Schipper I, Mollon B, et al. Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline. BMJ. 2017;356:j576.CrossRefPubMed
6.
go back to reference Zura R, Mehta S, Della Rocca GJ, Jones J, Steen RG. A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients. BMC Musculoskelet Disord. 2015;16:45.CrossRefPubMedPubMedCentral Zura R, Mehta S, Della Rocca GJ, Jones J, Steen RG. A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients. BMC Musculoskelet Disord. 2015;16:45.CrossRefPubMedPubMedCentral
7.
go back to reference Jiang X, Savchenko O, Li Y, Qi S, Yang T, Zhang W, et al. A review of low-intensity pulsed ultrasound for therapeutic applications. IEEE Trans Biomed Eng. 2019;66:2704–18.CrossRefPubMed Jiang X, Savchenko O, Li Y, Qi S, Yang T, Zhang W, et al. A review of low-intensity pulsed ultrasound for therapeutic applications. IEEE Trans Biomed Eng. 2019;66:2704–18.CrossRefPubMed
8.
go back to reference de Lucas B, Pérez LM, Bernal A, Gálvez BG. Application of low-intensity pulsed therapeutic ultrasound on mesenchymal precursors does not affect their cell properties. PLoS One. 2021;16:e0246261.CrossRefPubMedPubMedCentral de Lucas B, Pérez LM, Bernal A, Gálvez BG. Application of low-intensity pulsed therapeutic ultrasound on mesenchymal precursors does not affect their cell properties. PLoS One. 2021;16:e0246261.CrossRefPubMedPubMedCentral
9.
go back to reference Xin Z, Lin G, Lei H, Lue TF, Guo Y. Clinical applications of low-intensity pulsed ultrasound and its potential role in urology. Transl Androl Urol. 2016;5:255–66.CrossRefPubMedPubMedCentral Xin Z, Lin G, Lei H, Lue TF, Guo Y. Clinical applications of low-intensity pulsed ultrasound and its potential role in urology. Transl Androl Urol. 2016;5:255–66.CrossRefPubMedPubMedCentral
10.
go back to reference Harrison A, Alt V. Low-intensity pulsed ultrasound (LIPUS) for stimulation of bone healing - a narrative review. Injury. 2021;52:S91–6.CrossRefPubMed Harrison A, Alt V. Low-intensity pulsed ultrasound (LIPUS) for stimulation of bone healing - a narrative review. Injury. 2021;52:S91–6.CrossRefPubMed
11.
go back to reference Bian N, Yuan Y, Li Y, Liu M, Li X. Low-intensity pulsed ultrasound stimulation inhibits cortical spreading depression. Cereb Cortex. 2021;31:3872–80.CrossRefPubMed Bian N, Yuan Y, Li Y, Liu M, Li X. Low-intensity pulsed ultrasound stimulation inhibits cortical spreading depression. Cereb Cortex. 2021;31:3872–80.CrossRefPubMed
12.
go back to reference Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.CrossRefPubMedPubMedCentral Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.CrossRefPubMedPubMedCentral
13.
go back to reference Ji P, Zhu J, Zhong Z, Li H, Pang J, Li B, et al. Association of elevated inflammatory markers and severe COVID-19: a meta-analysis. Medicine (Baltimore). 2020;99:e23315.CrossRefPubMed Ji P, Zhu J, Zhong Z, Li H, Pang J, Li B, et al. Association of elevated inflammatory markers and severe COVID-19: a meta-analysis. Medicine (Baltimore). 2020;99:e23315.CrossRefPubMed
14.
go back to reference Yang Q, Nanayakkara G, Drummer C, Sun Y, Johnson C, Cueto R, et al. Low-intensity ultrasound-induced anti-inflammatory effects are mediated by several new mechanisms including gene induction, immunosuppressor cell promotion, and enhancement of exosome biogenesis and docking. Front Physiol. 2017;8:818.CrossRefPubMedPubMedCentral Yang Q, Nanayakkara G, Drummer C, Sun Y, Johnson C, Cueto R, et al. Low-intensity ultrasound-induced anti-inflammatory effects are mediated by several new mechanisms including gene induction, immunosuppressor cell promotion, and enhancement of exosome biogenesis and docking. Front Physiol. 2017;8:818.CrossRefPubMedPubMedCentral
15.
go back to reference Khanna A, Nelmes RT, Gougoulias N, Maffulli N, Gray J. The effects of LIPUS on soft-tissue healing: a review of literature. Br Med Bull. 2009;89:169–82.CrossRefPubMed Khanna A, Nelmes RT, Gougoulias N, Maffulli N, Gray J. The effects of LIPUS on soft-tissue healing: a review of literature. Br Med Bull. 2009;89:169–82.CrossRefPubMed
16.
go back to reference Lin G, Reed-Maldonado AB, Lin M, Xin Z, Lue TF. Effects and mechanisms of low-intensity pulsed ultrasound for chronic prostatitis and chronic pelvic pain syndrome. Int J Mol Sci. 2016;17:1057.CrossRefPubMedPubMedCentral Lin G, Reed-Maldonado AB, Lin M, Xin Z, Lue TF. Effects and mechanisms of low-intensity pulsed ultrasound for chronic prostatitis and chronic pelvic pain syndrome. Int J Mol Sci. 2016;17:1057.CrossRefPubMedPubMedCentral
17.
go back to reference Chernysh IN, Everbach CE, Purohit PK, Weisel JW. Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots. J Thromb Haemost. 2015;13:601–9.CrossRefPubMedPubMedCentral Chernysh IN, Everbach CE, Purohit PK, Weisel JW. Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots. J Thromb Haemost. 2015;13:601–9.CrossRefPubMedPubMedCentral
18.
go back to reference Nouvenne A, Zani M, Milanese G, Parise A, Baciarello M, Bignami E, et al. Lung ultrasound in COVID-19 pneumonia: correlations with chest CT on hospital admission. Respiration. 2020;99:617–24.CrossRefPubMed Nouvenne A, Zani M, Milanese G, Parise A, Baciarello M, Bignami E, et al. Lung ultrasound in COVID-19 pneumonia: correlations with chest CT on hospital admission. Respiration. 2020;99:617–24.CrossRefPubMed
19.
go back to reference Soldati G, Smargiassi A, Inchingolo R, Buonsenso D, Perrone T, Briganti D, et al. Proposal for international standardization of the use of lung ultrasound for patients with COVID-19: a simple, quantitative, reproducible method. J Ultrasound Med. 2020;39:1413–9.CrossRefPubMedPubMedCentral Soldati G, Smargiassi A, Inchingolo R, Buonsenso D, Perrone T, Briganti D, et al. Proposal for international standardization of the use of lung ultrasound for patients with COVID-19: a simple, quantitative, reproducible method. J Ultrasound Med. 2020;39:1413–9.CrossRefPubMedPubMedCentral
20.
go back to reference Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50.CrossRefPubMed Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50.CrossRefPubMed
21.
go back to reference Pugin J, Auckenthaler R, Mili N, Janssens J, Lew P, Suter P. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;143:1121–9.CrossRefPubMed Pugin J, Auckenthaler R, Mili N, Janssens J, Lew P, Suter P. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;143:1121–9.CrossRefPubMed
22.
go back to reference Sedgwick P. Intention to treat analysis versus per protocol analysis of trial data. BMJ. 2015;350:h681.CrossRefPubMed Sedgwick P. Intention to treat analysis versus per protocol analysis of trial data. BMJ. 2015;350:h681.CrossRefPubMed
23.
go back to reference Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020;92:491–4.CrossRefPubMedPubMedCentral Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020;92:491–4.CrossRefPubMedPubMedCentral
24.
go back to reference Wu Y, Huang X, Sun J, Xie T, Lei Y, Muhammad J, et al. Clinical characteristics and immune injury mechanisms in 71 patients with COVID-19. mSphere. 2020;5:e00362-20.CrossRefPubMedPubMedCentral Wu Y, Huang X, Sun J, Xie T, Lei Y, Muhammad J, et al. Clinical characteristics and immune injury mechanisms in 71 patients with COVID-19. mSphere. 2020;5:e00362-20.CrossRefPubMedPubMedCentral
25.
go back to reference Zhang B, Chen H, Ouyang J, Xie Y, Chen L, Tan Q, et al. SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated antiinflammatory effect. Autophagy. 2020;16:1262–78.CrossRefPubMed Zhang B, Chen H, Ouyang J, Xie Y, Chen L, Tan Q, et al. SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated antiinflammatory effect. Autophagy. 2020;16:1262–78.CrossRefPubMed
26.
go back to reference Song J, Li N, Xia Y, Gao Z, Zou S, Yan Y, et al. Arctigenin confers neuroprotection against mechanical trauma injury in human neuroblastoma SH-SY5Y cells by regulating miRNA-16 and miRNA-199a expression to alleviate inflammation. J Mol Neurosci. 2016;60:115–29.CrossRefPubMed Song J, Li N, Xia Y, Gao Z, Zou S, Yan Y, et al. Arctigenin confers neuroprotection against mechanical trauma injury in human neuroblastoma SH-SY5Y cells by regulating miRNA-16 and miRNA-199a expression to alleviate inflammation. J Mol Neurosci. 2016;60:115–29.CrossRefPubMed
27.
go back to reference Da Silva Junior E, Mesquita-Ferrari R, França C, Andreo L, Bussadori S, Fernandes K. Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells. Biomed Pharmacother. 2017;96:1147–53.CrossRefPubMed Da Silva Junior E, Mesquita-Ferrari R, França C, Andreo L, Bussadori S, Fernandes K. Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells. Biomed Pharmacother. 2017;96:1147–53.CrossRefPubMed
28.
go back to reference Zhang Z, Yang Y, Li B, Hu X, Xu S, Wang F, et al. Low-intensity pulsed ultrasound promotes spinal fusion by regulating macrophage polarization. Biomed Pharmacother. 2019;120:109499.CrossRefPubMed Zhang Z, Yang Y, Li B, Hu X, Xu S, Wang F, et al. Low-intensity pulsed ultrasound promotes spinal fusion by regulating macrophage polarization. Biomed Pharmacother. 2019;120:109499.CrossRefPubMed
29.
go back to reference Farkash U, Bain O, Gam A, Nyska M, Sagiv P. Low-intensity pulsed ultrasound for treating delayed union scaphoid fractures: case series. J Orthop Surg Res. 2015;10:72.CrossRefPubMedPubMedCentral Farkash U, Bain O, Gam A, Nyska M, Sagiv P. Low-intensity pulsed ultrasound for treating delayed union scaphoid fractures: case series. J Orthop Surg Res. 2015;10:72.CrossRefPubMedPubMedCentral
30.
go back to reference Tan Y, Guo Y, Reed-Maldonado A, Li Z, Lin G, Xia S, et al. Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications. Asian J Androl. 2021;23:602–10.CrossRefPubMedPubMedCentral Tan Y, Guo Y, Reed-Maldonado A, Li Z, Lin G, Xia S, et al. Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications. Asian J Androl. 2021;23:602–10.CrossRefPubMedPubMedCentral
31.
go back to reference Tanaka E, Liu Y, Xia L, Ogasawara N, Sakamaki T, Kano F, et al. Effectiveness of low-intensity pulsed ultrasound on osteoarthritis of the temporomandibular joint: a review. Ann Biomed Eng. 2020;48:2158–70.CrossRefPubMed Tanaka E, Liu Y, Xia L, Ogasawara N, Sakamaki T, Kano F, et al. Effectiveness of low-intensity pulsed ultrasound on osteoarthritis of the temporomandibular joint: a review. Ann Biomed Eng. 2020;48:2158–70.CrossRefPubMed
Metadata
Title
Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial
Authors
Xiao Li
Wen Li
Lianjie Sun
Junyi Ren
Ying Xu
Yuanyi Zheng
Wenkun Bai
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07382-1

Other articles of this Issue 1/2023

Trials 1/2023 Go to the issue