Respiratory distress syndrome (RDS) is caused by
surfactant deficiency at birth. The risk of RDS decreases from the gestational age of 24 weeks to full-term. Genetic and acquired factors additionally influence the risk of RDS.
Surfactant deficiency in RDS is mainly caused by immaturity and a lack of differentiation of the alveolar epithelial cells involved in
surfactant synthesis and secretion. A network of
hormones and
growth factors regulate perinatal development. Host-related factors, including the levels of expression of
surfactant proteins (SP), modulate the responsiveness of
growth factors. SP-A has roles in surface activity and regulatory roles particularly in innate immunity; SP-B is essential for the processing of
surfactant and for the surface activity; SP-C has roles in
surfactant metabolism and function; the regulatory roles of
SP-D mainly pertain to innate immunity. The genetic variation of SP-A and SP-B genes and the risk of RDS have been studied. Both SP-A and SP-B associate with susceptibility to RDS. The association between the SP-A allele and genotypes and the risk of RDS is dependent on the SP-B genotype and significantly influenced by the degree of prematurity, antenatal
glucocorticoid therapy, multiple birth, and birth order. The alleles/genotypes of SP-A, SP-C, or
SP-D also associate with several other inflammatory lung and airway diseases. Rare mutations in SP-B or SP-C cause serious, often fatal
lung diseases. Genetic and post-genomic research is likely to eventually result in new diagnostic applications and specific
therapies for the prevention of
respiratory failure and inflammatory
lung diseases.