# Sex-Based Differences in Bronchial Asthma: What Are the Mechanisms behind Them?
## 7 Future Directions  
The differences between the sexes may be primarily caused by the different actions of female and male sex hormones in the lungs. The influence of changing levels of sex hormones on the production of pro- and anti-inflammatory cytokines, airway reactivity, and the production of mucus in the airways represents an important factor in the pathogenesis of asthma. This should be considered in the diagnostics, especially in complex therapy for asthma. However, there are additional factors that may contribute to the sex-related differences in asthma, such as anatomical and physiological differences in the lungs of males and females; differences in genetically conditioned factors; obesity and lifestyle; and exposure to environmental factors, including smoking, chronic stress, etc. Although experimental and clinical research in recent decades has gathered the principal information necessary for differentiation of asthma into several endotypes and phenotypes, resulting in the introduction of more appropriate treatment, there are many questions that should be answered in the future. In particular, large clinical studies should be carried out on the \begin{table}
\begin{tabular}{l c c} \hline \hline  & **Males** & **Females** \\ \hline Lung maturation in neonates & Delayed compared to female neonates & \\ \hline Lung dysanapsis & Retarded AW growth in boys & Smaller AWs vs. lungs in adult women \\ \hline Excitability for cough & \(\downarrow\) & \(\uparrow\) \\ \hline Clinical course of asthma & & \(\uparrow\) severity and hospital admissions \\ \hline Type 2 inflammation & \(\downarrow\) & \(\uparrow\) \\ \hline Non-type 2 inflammation & \(\downarrow\) & \(\uparrow\) \\ \hline General immune response & \(\downarrow\) & \(\uparrow\) \\ \hline Effectiveness of response to viral infections, including COVID-19 & \(\downarrow\) & \(\uparrow\) \\ \hline Effectiveness of response to bacterial infections & \(\downarrow\) & \(\uparrow\) \\ \hline Relation to smoking & \(\uparrow\) exposure to smoke & \(\uparrow\) vulnerability to smoke \\ \hline Occupation-associated asthma & \(\uparrow\) exposure to organic dust, diesel, flour/bakery products, & \(\uparrow\) exposure to inorganic dust, hair \\  & wood/wood-component dust & products, ozone \\ \hline Obesity-associated asthma & \(\uparrow\) risk in boys & \(\uparrow\) risk in adolescent and adult women \\ \hline Stress-associated asthma & \(\uparrow\) risk & \(\uparrow\) risk \\ \hline Sex-specific genes associated with asthma & \(\uparrow\)_FBXL7, ITPR3, ALOX15; \(\downarrow\)_RAD51B_ & \(\downarrow\)_HLA_DQA1_ \\ \hline Sex-specific alleles associated with asthma risk & _5q31.1, 10q26.1_ & _2q23.3, 2q34, 6q27, 17213.3_ \\ \hline Response to corticosteroids & \(\uparrow\) & \(\downarrow\) \\ \hline Response to bronchodilators & \(\downarrow\) & \(\uparrow\) \\ \hline Response to anti-leukotrienes & \(\downarrow\) & \(\uparrow\) \\ \hline Response to anti-IgE & \(\uparrow\) & \(\downarrow\) \\ \hline Response to anti-IL-5 & \(\downarrow\) & \(\uparrow\) \\ \hline \hline \end{tabular} Abbreviations: AW; airway, IgE; immunoglobulin E, IL; interleukin, \(\uparrow\); increase, \(\downarrow\); decrease.  
\end{table} 
Table 4: Sex-based differences in lung-related features and asthma. For more details, see the text above. evaluation of sex-related differences in the response to the asthma therapy given. In female patients with asthma, the effects of hormonal contraceptive pills in pre-menopausal women, as well as the effects of HRT in menopause/post-menopause, should also be thoroughly investigated in relation to asthma endotypes/phenotypes. Searches for novel biomarkers should continue in order to find more sensitive and specific indicators for precise diagnoses of asthma endotypes/phenotypes. Further analysis of genetic, epigenetic, and other factors may reveal higher susceptibilities for asthma in selected groups of patients, which may be of importance for early screening of asthma.