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Prescribing Information

Prescribing Information

 
 

What is surfactant? 

What is surfactant? 

 

Surfactants are a combination of fats, proteins, and sugars made by specific lung cells that lower surface tension at the air-water interface in the alveoli, preventing their collapse.1 While surfactant and its surface-active properties were first identified in the 1920s, its components and how it works were only understood in the 1950s.1 Key research connected surfactant deficiency to infant deaths from RDS, leading to the development of surfactant replacement therapy, which has transformed the treatment of RDS.1

 

About the development
of CUROSURF?

 
 
 

CUROSURF has a natural composition closely resembling human surfactant, contains almost exclusively polar lipids, in particular phosphatidylcholine (about 70% of the total phospholipid content), and about 1% of SP-B and SP-C.2

 

About CUROSURF

 

How is surfactant made?

 

Surfactant production starts at approximately 24 weeks of gestation, but sufficient levels to prevent alveolar collapse (atelectasis) are typically not reached until around 32 weeks.3 As a result, infants born before 32 weeks are at an increased risk for disorders linked to surfactant deficiency, with RDS being the most well-known.1 

 
 
 

Terminal bronchioles contain several specialised cells that are important for gas exchange, including alveolar Type I and Type II cells:

 
 

Flat epithelial cells that facilitate gas exchange between the alveolar space and the capillaries surrounding each alveolus

 

Specialised cells that produce, store and secrete surfactant. The amount and composition of the surfactant, as well as functional ability, changes with foetal maturity

 

* Produces surfactant ** Lining cell

How is surfactant made
 

Lung development during the embryonic and foetal periods

 

The development of functional alveoli:1,9

 
 

The development of the lung is divided into five stages during embryonic and foetal development, with surfactant production occurring at the stage of alveoli formation.6

 
 

Adapted from Bancalari E. In: The Newborn Lung. 2nd ed. Netherlands, NL: Elsevier Saunders; 2012.

 

Surfactant lifecycle

 

After synthesis, surfactant molecules go through cycles of storage, use, and recycling, forming various highly organised structures.7,8 

Surfactant’s lipid components and proteins are secreted together as lamellar bodies into the fluid layer around the alveoli. Once the lamellar bodies fuse to form a film at the air–liquid interface, Type II alveolar cells recycle the lipid components. These cells can either recycle the lipids into new lamellar bodies or break them down for energy.7,8 

 
 

See LaPlace’s law in action

 

Clinical effects of surfactant

 
 

The ability of a lung to stretch and expand is known as ‘compliance,’ and surfactant plays a key role in this function.1,9 

 

In healthy lungs, inspiration creates a certain level of pressure (opening pressure) that allows the alveoli to expand and for surfactant phospholipids to quickly enter the surface layer. During expiration, the alveoli shrink, compressing the monolayer and expelling some surfactant proteins, leaving mainly phosphatidylcholine to reduce surface tension and prevent collapse.7,8 

 

In surfactant-deficient RDS lungs, poor lung compliance means more pressure is needed to open the alveoli and increasing the work of breathing. Higher surface tension causes alveoli to collapse at the end of expiration, reducing lung volume for the next breath.8,9

 

An important insight into how pressure affects the opening pressure of alveoli may be explained by Laplace’s law. It states that the pressure inside a spherical structure, like an alveolus, increases with surface tension and decreases with the radius. For lung compliance, this means smaller alveoli need higher pressure to stay inflated because of their greater surface tension, affecting how easily the lungs expand and contract.8  

 
 

See process of LaPlace’s law

 
 
 

Lung inflation in the normal lung9

 

Adapted from Lissauer T et al. Neonatology at a Glance. 2016

 

Figure 1:

 

The volume pressure curve for a healthy newborn9.

 

The pressure required to initiate inflation (opening pressure) is reached

 

In the healthy lung there is a large change in volume for any given change in airway pressure

 

Air is retained until lower pressures are reached (hysteresis)

 

Lungs do not collapse at the end of expiration

 
 

Lung Inflation in the surfactant deficient lung9

 

Adapted from Lissauer T et al. Neonatology at a Glance. 2016

 

Figure 2:

 

The volume pressure curve for a newborn with surfactant deficiency9.

 

In surfactant deficiency the lung has a lower compliance and requires a greater opening pressure

 

The change in lung volume for any given change in airway pressure is much less compared to the healthy lung

 

During deflation, the change in pressure follows a pattern similar to that seen during inflation

 

In the surfactant-deficient lung, the alveoli collapse at end expiration and the next breath starts from a reduced lung volume

 
 

Want to learn about how CUROSURF
is used in clinical practice?

 
 

Abbreviations

 

RDS, respiratory distress syndrome; SP, surfactant protein. 

 
 

References

  1. Han S and Mallampalli RK. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Ann Am Thorac Soc 2015;12(5):765–774.
  2. CUROSURF SmPC. Available at https://www.medicines.org.uk/emc/product/6450/smpc. Accessed September 2024.
  3. Rehman S and Bacha D. Embryology, Pulmonary. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available at https://www.ncbi.nlm.nih.gov/books/NBK544372. Accessed September 2024.
  4. Wang Y, et al. Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate. Proc Natl Acad Sci USA 2018;115 (10):2407–2412.
  5. Nkadi PO, et al. An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab. 2009;97(2):95–101.
  6. Bancalari E. In: The Newborn Lung. 2nd Ed. Netherlands, NL: Elsevier Saunders; 2012.
  7. Carnielli VP, et al. Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes. J Perinatol. 2009;29:S29–37.
  8. Ainsworth SB. Pathophysiology of neonatal respiratory distress syndrome: implications for early treatment strategies. Treat Respir Med. 2005;4(6):423–37.
  9. Lissauer T, Fanaroff AA, Miall L, Fanaroff J. In: Neonatology at a Glance. 3rd ed. New Jersey, NJ: Wiley Blackwell; 2016
 
 

IE-CUR-2400044 | December 2024

 

Adverse event reporting

For the UK: Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Chiesi Limited on 0800 0092329 (UK) or PV.UK@Chiesi.com.

For Ireland: Adverse events should be reported to HPRA Pharmacovigilance – www.hpra.ie. Adverse events should also be reported to Chiesi Limited on 1800 817459 (IE) or PV.UK@Chiesi.com.