The appeal of shock wave therapy rests on well-documented mechanobiologic activity outside the lung. In wound-healing models, shock waves promote the efflux of adenosine triphosphate, activate extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase, and modulate proliferation, migration, and repair responses. In human mesenchymal stem cells, the P2X7 purinergic receptor participates in shock-wave-induced osteogenic differentiation. Low-intensity shock waves can also improve macrophage functions associated with chronic wound healing, alter fibrosis-related molecules, and modulate fibroblast activation through a transient proinflammatory milieu. Across these systems, the therapy appears to influence inflammatory tone, stromal activation, and repair timing rather than acting through a single dominant pathway.

Adult clinical studies reinforce the picture of biologic responsiveness, but with important caveats. The Cochrane review of erectile dysfunction judged much of the evidence to be low or very low certainty, with limited long-term confidence. Peyronie’s disease studies show more consistent pain improvement than structural change. Musculoskeletal evidence is heterogeneous across disorders and endpoints, chronic wound data support adjunctive benefit rather than replacement of standard care, and neurorehabilitation evidence is strongest for spasticity without supporting claims of neural regeneration. Effect sizes vary and durability is often undemonstrated, a pattern the review authors warn against importing into respiratory medicine, where symptom relief could easily be mistaken for tissue reversal.

Direct pulmonary evidence is far thinner. Di Stefano and colleagues exposed the 16HBE bronchial epithelial cell line and primary bronchial fibroblasts from three COPD donors and three smoking controls to focused piezoelectric shock waves in culture, using a nominal energy flux density of 0.3 millijoules per square millimeter, 500 pulses, and 4 hertz. Although described as low-energy in the abstract, the Methods label this setting medium-high energy, exceeding the approximate low-energy range used operationally in the review. Proliferation-related indices increased after exposure, TGF-beta1 protein rose at 72 hours in control-smoker fibroblasts without a corresponding significant increase in COPD fibroblasts, and procollagen-I increased early in COPD fibroblasts and declined later. The authors did not exclude a modest profibrotic effect, and no intact lung was treated.

Two animal studies extend the signal to injured lung tissue. Lin and colleagues treated rats after hyperoxia-induced acute respiratory distress syndrome with focused shock waves at a nominal 0.15 millijoules per square millimeter, 200 impulses at 6 hertz per lung field in a single session, and found improved injury and fibrosis-related readouts including TGF-beta, phosphorylated Smad3, and collagen deposition, with combined mitochondrial treatment producing greater improvements than either intervention alone. Guo and colleagues reported chest treatment at 0.09 millijoules per square millimeter, 200 impulses, and 10 hertz in an LPS-induced mouse lung-injury model, linking improved injury readouts with mitochondrial and pyroptosis-related changes. Critically, however, the healthy shock-wave-exposed group in that study showed minor alveolar atrophy, occasional alveolar fusion, and scant perivascular fibrosis and inflammatory cells, providing limited short-term safety information rather than evidence of an injury-free exposure.

The physics of the lung is the deepest barrier. Shock waves propagate very differently across air-liquid interfaces than through solid tissue, so energy transfer across the chest wall, pleura, and parenchyma is likely to be heterogeneous and difficult to predict. Experimental lung-injury studies and blast-lung literature both document that rapidly transmitted pressure phenomena can injure air-containing tissue, and device studies indicate that cavitation and interface effects may further amplify local stress. The operative question is not whether shock waves can reach the lung in a general sense, but whether a device- and parameter-specific window exists in which biologic signaling is achieved without causing injury. Interface reflections, inflation-dependent energy scatter, and uncertain lesion depth collectively mean that energy deposition in lung tissue remains poorly characterized.

Dosimetry compounds the problem. The cited pulmonary experiments report nominal device settings and biological responses, not a calibrated spatial distribution of pressure or energy within aerated lung tissue. Exposing cells in a liquid-filled tube bypasses the chest wall, pleura, and air-containing parenchyma entirely, and a bar setting in cell experiments is not interchangeable with energy flux density in animal treatment. Device-reported energy flux density and pulse counts cannot be equated with the dose received by a particular lung region, since coupling, thoracic geometry, focal depth, inflation state, and air-tissue interfaces all affect transmission. No existing study demonstrates a lung-tissue dose that is both biologically effective and established as safe. Notably, no clinical Li-ESWT study in adult asthma, interstitial lung disease, or pulmonary fibrosis was identified in the literature the review examined.

Children add layers of uncertainty that adults do not present. Ongoing alveolarization, age-dependent chest-wall mechanics, and the absence of pediatric device data all sharpen the risk. Preterm infants and term neonates have highly compliant chest walls, immature alveolar structures, limited ability to cooperate, and a high likelihood of requiring sedation or anesthesia for any repeatable device-based study. Adult-oriented focal geometry may overshoot a thin neonatal or infant chest wall, while radial delivery sacrifices spatial control. YAP/TAZ activity during alveolar morphogenesis raises the possibility that external pressure-wave exposure could disturb normal growth programs, and continuous positive airway pressure or mechanical ventilation would change the mechanical conditions of exposure. The review also notes that within pediatric asthma, type 2-low or steroid-resistant subtypes show greater matrix change and would be a more plausible mechanobiologic target, but these subgroups are less prevalent in children and their mechanical drivers are incompletely characterized.

The ethical analysis is equally sobering. The authors’ framework judges the scientific premise limited but real, supporting more preclinical work rather than pediatric research; the risk category is poorly bounded and more consistent with above-minimal risk; the prospect of direct benefit is not established; no unified adverse-event monitoring framework or stopping rules exist; the pediatric device evidence base is not mature enough; and current long-term follow-up frameworks are insufficient to assess lung growth and function. Sedation and follow-up are independent sources of risk, since cumulative exposure to repeated device sessions and their anesthetic context creates a burden qualitatively different from a single adult procedure. Any meaningful pediatric study would need a prespecified sedation protocol, defined cumulative exposure limits, neurodevelopmental monitoring thresholds, and prospective follow-up covering lung function, growth, rehospitalization, imaging, and quality of life.

The review’s conclusion is that pediatric pulmonary clinical trials are not yet justified. The key gaps are device-specific lung exposure measurements, pulmonary injury thresholds, adult pulmonary safety data, and developmental risk assessment. The proposed research agenda calls for spatial exposure measurements linked with epithelial injury, microvascular leakage, inflammatory resolution, and delayed remodeling in the same model; ex vivo and phantom measurements followed by small- and large-animal injury-threshold studies; and cell-specific experiments on YAP/TAZ activity, integrin alphavbeta6-TGF-beta signaling, fibroblast activation, and collagen accumulation to distinguish organized repair from persistent profibrotic response. Future studies would also require standardized reporting of wave source, energy flux density, pulse number, treatment frequency, estimated target depth, imaging guidance, sedation strategy, and adverse-event definitions. Until lung-specific dosimetry and preclinical safety characterization are followed by adult safety evidence, the authors argue, pediatric enrollment cannot be responsibly reconsidered.

Subject of Research: Translational barriers to applying low-intensity extracorporeal shock wave therapy to pediatric respiratory diseases

Article Title: Low-intensity extracorporeal shock wave therapy for pediatric respiratory diseases: current evidence and translational barriers

Article References: Su, X., Liu, D., Liu, J., Lv, D., Guo, J., Hui, Q., Ye, F., Chen, Y., Wang, C., Tang, L., Xia, M., & Zhang, Q. (2026). Low-intensity extracorporeal shock wave therapy for pediatric respiratory diseases: current evidence and translational barriers. Frontiers in Pediatrics, 14, Article 1876906. https://doi.org/10.3389/fped.2026.1876906

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1876906

Keywords: shock wave therapy, Li-ESWT, pediatric pulmonology, lung dosimetry, bronchopulmonary dysplasia, airway remodeling, acute lung injury, mechanotransduction, research ethics, translational research, device governance, Frontiers in Pediatrics