Opportunistic etiological agents causing lung infections: emerging need to transform lung-targeted delivery

New Research In Pulmonary Fibrosis Could Reverse Lung Scarring

PULMONARY fibrosis (PF), a severe form of lung disease, often leads to irreversible lung damage, and macrophages play a critical role in its progression. New research sheds light on the significant role of YAP and TAZ, two proteins activated in macrophages in PF patients and in animal models. This study uncovers the pivotal function of YAP/TAZ signaling in the inflammatory and fibrotic processes within PF.

Researchers focused on the effects of YAP/TAZ in macrophages after bleomycin-induced PF. Their findings revealed that deleting YAP/TAZ specifically in macrophages led to reduced inflammation and fibrosis, providing insight into how YAP/TAZ activation accelerates the condition. Interestingly, a constitutively active form of YAP (YAP5SA) made PF worse by enhancing macrophage recruitment, promoting inflammation, and impairing cell regeneration. In contrast, blocking key signaling pathways in this process prevented the exacerbation of PF.

The study also highlighted a crucial signaling axis involving YAP/TAZ, CCL2, and TGFβ1. This axis regulates macrophage polarization and their interaction with lung fibroblasts, driving the transition from fibroblasts to myofibroblasts—a key process in fibrosis. These findings suggest that targeting YAP/TAZ activity may be an effective approach for PF treatment, potentially halting or even reversing its progression.

With these discoveries, YAP/TAZ emerge as promising targets in the development of therapies aimed at managing pulmonary fibrosis, offering hope for improved patient outcomes.

Reference: Mia MM et al. YAP/TAZ are Crucial Regulator of Macrophage-mediated Pulmonary Inflammation and Fibrosis after Bleomycin-induced Injury. Eur Respir J. 2025. Doi:10.1183/13993003.01544-2023.

Anaya MalikAMJ

Data Backs Lungpacer Medical's Diaphragm Neurostim

Lungpacer Medical today announced positive results from a Phase 1 clinical study evaluating its neurostimulation technology platform.

The STIMULUS trial investigated the application of diaphragm neurostimulation to improve hemodynamic performance in patients on invasive mechanical ventilation. Results demonstrated improvement in hemodynamic performance, according to a news release. Investigators presented findings at the 2025 Transcatheter Heart Therapies (THT) conference.

Exton, Pennsylvania-based Lungpacer Medical's trial evaluated its investigational AeroNova system. The company already offers the FDA-approved AeroPace system that delivers neurostimulation via an electrode-containing cardiovascular catheter and a software-controlled system. It delivers periodic phrenic nerve stimulation through the venous catheter. The system contracts and strengthens the diaphragm in patients on mechanical ventilation.

The investigational AeroNova system comprises a cardiovascular catheter embedded with stimulating electrodes. It features a software-controlled system that contracts the diaphragm through transvenous prenic nerve neurostimulation. The company designed AeroNova to achieve ventilation using lower positive pressures from the ventilator. This mitigates ventilator-induced injury to the lung, diaphragm, heart and brain of patients on mechanical ventilation.

LungPacer said STIMULUS marks a significant milestone in advancing medtech designed to optimize patient care in the ICU. The single-center study aimed to evaluate AeroNova's safety and effectiveness in patients with acute hypoxemic respiratory failure or post-thoracic surgery respiratory failure.

A key outcome focused on measuring how diaphragm activation, when synchronized with mechanical ventilation, could improve cardiovascular function and mitigate the negative hemodynamic effects commonly seen with invasive mechanical ventilation.

A look at the Lungpacer study results

Lungpacer's study enrolled 19 patients. Of those, 16 underwent a stimulation titration procedure. The majority of patients (12/16, 75%) had pre-existing cardiac dysfunction and exhibited a high incidence of right ventricular dysfunction and/or pulmonary hypertension.

Using the AeroPace catheter, investigators safely delivered transvenous bilateral neurostimulation. They used stimulation levels titrated to achieve diaphragm activation, resulting in increasing levels of expiratory occlusion pressure. The study evaluated a range of cardiac outcomes at baseline compared to after treatment.

Increasing levels of diaphragm neurostimulation led to a significant increase in cardiac index and stroke volume. Lungpacer said this indicates better heart performance and enhanced blood flow. The company also reported overall hemodynamic stability and decreased pulmonary artery pressure.

"The study results indicate that diaphragm neurostimulation merits further exploration as a novel therapy to counteract the harmful cardiovascular effects associated with positive pressure ventilation by improving cardiac function and pulmonary hemodynamics," Lungpacer said. "The study suggests a dose-response relationship, where increasing stimulation correlates with further improvements in cardiac and pulmonary parameters, providing a strong foundation for future investigation."

---