Why do some children get sick with recurrent respiratory infections?

Abstract: Respiratory tract infections (RTI) represent a frequent condition, particularly among preschool children, with an important burden on the affected children and their families. It has been estimated that recurrent RTIs affect up to 25% of children during the first 4 years of life. Th- ese infections are mainly caused by viruses and are generally self-limiting. Social and environmen- tal factors have been studied in determining the incidence of recurrent RTIs and the mostly recog- nized are precocious day care attendance, tobacco exposure and pollution. Primary immune de- fects, local anatomical factors, and genetic disorders such as primary ciliary dyskinesia or cystic fi- brosis, may be also involved in recurrent RTIs of a subgroup of children, typically characterized by more severe and chronic symptoms. However, there is increasing awareness that RTIs have a com- plex pathophysiology and that some underrecognized factors, including genetic susceptibility to in- fections, low levels of some micronutrients, and respiratory microbiota might shape the probability for the child to develop RTIs. The sum (i.e. the number) of these factors may help in explaining why some children get sick for RTIs whilst other not. In some children iatrogenic factors, includ- ing improper use of antibiotics and NSAIDS or glucocorticoids might also aggravate this condi- tion, further weakening the host's immune response and the possibly of establishing a “vicious cir- cle”. The present review aims to focus on several possible factors involved in influencing RTIs and to propose a unifying hypothesis on pathophysiological mechanisms of unexplained recurrent RTIs in children.