# Sex-Based Differences in Bronchial Asthma: What Are the Mechanisms behind Them?
## 4 Sex-Based Differences in Different Life Periods
### Childhood  
Sex-based differences in the development of asthma or wheeze in childhood are probably linked to several contributing factors, including prenatal stress, preterm birth, low birth weight, maternal smoking, maternal obesity during pregnancy, no or shorter period of breastfeeding, repetitive respiratory tract infections, use of antibiotics or corticosteroids, and/or genetic susceptibility [51].  
Prematurity, low birth weight, and/or prenatal maternal stress have been confirmed as factors increasing the risk of asthma and impaired lung function in early childhood, which may persist up to adulthood [52; 53], while reduced expiratory flow and higher vulnerability are more strongly associated with male sex [54]. Greater occurrences of preterm births with worse response to prenatal corticosteroids and worse prognosis in boys than girls [55; 56; 57] are likely caused by sex hormones. Female neonates exhibit decreased susceptibility to infection and accelerated lung maturation under the stimulatory action of estrogen on the transition from the terminal saccular stage to the alveolar stage and the production of pulmonary surfactant, while testosterone has the opposite effects [58]. Dysanaptic lung development, characterized by retarded growth in the large airways in comparison to the lung parenchyma in boys, leading to narrower airways, is an additional factor resulting in sexual disparity in children [59]. A relation between low birth weight and decreased lung function or risk of asthma later in childhood and/or in adulthood has been demonstrated in several studies [60; 61], with some of them finding a higher risk of asthma in males [62; 63].  
Higher risk of asthma or wheeze during childhood is also associated with other factors [64], such as maternal smoking during pregnancy [65; 66; 67], maternal obesity in pregnancy [68], maternal use of antibiotics during pregnancy [69], exposure to allergens and endotoxins [70], and low vitamin D status during pregnancy [71]. However, while the lung functions of male fetuses exposed to smoking in utero may be more adversely affected than those of females [72], no convincing sex-specific associations between the other mentioned risk factors and the development of wheeze in children have been found [65; 73].  
The higher prevalence of asthma--mainly allergic asthma--in boys of prepubertal age is linked to two times more frequent admissions to hospital due to asthma exacerbation [74; 75; 76; 77]. In addition, boys have increased serum immunoglobulin (Ig)E levels and interferon (IFN)-\(\gamma\) levels, and positive skin trick tests for allergens are more frequent [78; 79]. In both sexes, higher incidences of asthma were found in overweight or obese children; however, respiratory symptoms of asthma (wheezing, shortness of breath) were more frequently reported in obese boys than in obese girls [80].  
\begin{table}
\begin{tabular}{l c} \hline \hline
**Classified Drugs** & **Examples of Drugs Used** & **References** \\ \hline
**Paucigranulocytic asthma** & \\ Prospective treatments: & \\ \hline Bronchial thermoplasty & [45; 46] \\ Bronchodilators (LAMA) & [35; 36] \\ Mast-cell directed therapy & [47; 48] \\ \hline \hline \end{tabular} Abbreviations: CXCR: chemokine (C-X-C motif) receptor, ICS: inhaled corticosteroids, IgE: immunoglobulin E, IL: interleukin, IL-4R: interleukin-4 receptor, IL-5R: interleukin-5 receptor, LABA: long-acting \(\beta\)-agonist, LAMA: long-acting muscarinic antagonist, OCSs: oral corticosteroids, PDE: phosphodiesterase, PGD2: prostaglandinD2, SABA: short-acting \(\beta\)2-agonist, SAMA: short-acting muscarinic antagonist, TNF: tumor necrosis factor alpha, TSLP: thymic stromal lymphopoietin.  
\end{table}
Table 3: Cont.