Understanding hydrogen sulfide signaling in neonatal airway disease

ABSTRACT

Introduction

Airway dysfunction leading to chronic lung disease is a common consequence of premature birth and mechanisms responsible for early and progressive airway remodeling are not completely understood. Current therapeutic options are only partially effective in reducing the burden of neonatal airway disease and premature decline of lung function. Gasotransmitter hydrogen sulfide (H₂S) has been recently recognized for its therapeutic potential in lung diseases.

Areas covered

Contradictory to its well-known toxicity at high concentrations, H₂S has been characterized to have anti-inflammatory, antioxidant, and antiapoptotic properties at physiological concentrations. In the respiratory system, endogenous H₂S production participates in late lung development and exogenous H₂S administration has a protective role in a variety of diseases such as acute lung injury and chronic pulmonary hypertension and fibrosis. Literature searches performed using NCBI PubMed without publication date limitations were used to construct this review, which highlights the dichotomous role of H₂S in the lung, and explores its promising beneficial effects in lung diseases.

Expert opinion

The emerging role of H₂S in pathways involved in chronic lung disease of prematurity along with its recent use in animal models of BPD highlight H₂S as a potential novel candidate in protecting lung function following preterm birth.

KEYWORDS:

• Bronchopulmonary dysplasia
• neonatal airway disease
• hydrogen sulfide
• lung development
• prematurity

Article highlights

• Chronic airway and pulmonary dysfunction remain major concerns following premature birth and account for significant respiratory morbidity throughout life. Early interventions (e.g. oxygen therapy, ventilation) can further impact airway pathophysiology and treatments to protect lung function are lacking.

• Hydrogen sulfide (H₂S) is an endogenous anti-inflammatory agent with proangiogenic and pro-alveolarization properties in the lung. Its exogenous administration using H₂S donors has shown promising protective roles in acute and chronic respiratory conditions.

• Research on targets of H₂S and its physiological effects - using both in vitro and in vivo models - make it a strong candidate to address BPD pathophysiology with particular regard to airway remodeling and dysfunction.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

C Pabelick is supported by grants from the Mayo Clinic Center for Biomedical Discovery and [R01 HL 138402], and C Bartman is supported by grants from the American Heart Association [20POST35210002] and [NIH T32 HL105355].