It has been observed that plasmatic concentrations of estrogens, progesterone, or both correlate with symptoms in asthmatic women. Fluctuations in female sex steroid concentrations during menstrual periods are closely related to asthma symptoms, while menopause induces severe physiological changes that might require hormonal replacement therapy (HRT), that could influence asthma symptoms in these women. Late-onset asthma (LOA) has been categorized as a specific asthmatic phenotype that includes menopausal women and novel research regarding therapeutic alternatives that might provide relief to asthmatic women suffering LOA warrants more thorough and comprehensive analysis. Therefore, the present review proposes phytoestrogens as a promising HRT that might provide these females with relief for both their menopause and asthma symptoms. Besides their well-recognized anti-inflammatory and antioxidant capacities, phytoestrogens activate estrogen receptors and promote mild hormone-like responses that benefit postmenopausal women, particularly asthmatics, constituting therefore a very attractive potential therapy largely due to their low toxicity and scarce side effects.

Sex differences in the anatomy and physiology of the respiratory system have been widely reported. These intrinsic sex differences have also been shown to modulate the pathophysiology, incidence, morbidity, and mortality of several lung diseases across the life span. In this chapter, we describe the epidemiology of sex differences in respiratory diseases including neonatal lung disease (respiratory distress syndrome, bronchopulmonary dysplasia) and pediatric and adult disease (including asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, lymphangioleiomyomatosis, obstructive sleep apnea, pulmonary arterial hypertension, and respiratory viral infections such as respiratory syncytial virus, influenza, and SARS-CoV-2). We also discuss the current state of research on the mechanisms underlying the observed sex differences in lung disease susceptibility and severity and the importance of considering both sex and gender variables in research studies' design and analysis.

Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.

There is an increasing amount of data regarding the influence of sex on dyspnea perception, however, the influence of sex has not been included in clinical guidelines for asthma and chronic obstructive pulmonary disease (COPD).

The study included 123 clinically stable subjects. Seventy five patients had COPD, of which 70.6% were men and 29.4% were women. Forty-eight subjects had asthma, comprised of 45.8% and 54.2%, men and women, respectively. Dyspnea was assessed with the use of modified Medical Research Council (mMRC) Visual Analogue Scale VAS, and BORG scale. All patients underwent spirometry with a broncho-reversibility test.

There were no differences in age for neither asthma patients, 56.5 ± 11.6 and 55.0 ± 12.7 (p = 0.5) for males and females, nor for COPD patients, 66.8 ± 9.0 and 66.8 ± 7.7 (p = 0.7) for males and females, respectively. Asthmatic females had more dyspnea than males when assessed with VAS, 1.85 ± 2.24 and 3.84 ± 2.80 (p = 0.01), for males and females, respectively. When assessed with BORGpre 6-MWT, dyspnea results were 0.86 ± 1.83 and 2.43 ± 2.31 (p = 0.005), for males and females, respectively. In the whole group, apart from FEV₁ (for mMRC, VAS, BORGpre) and BMI (BORGpost) the severity of dyspnea was related to female sex when assessed with mMRC (OR=2.83; 95%CI: 1.25-6.42) and VAS (OR = 2.17; 95%CI:1.00-4.73).

Although more apparent in asthma, it was revealed for the first time, that sex has a strong influence on the magnitude of dyspnea perception, both in asthma and COPD. Therefore, sex related dyspnea sensation should probably be included in clinical assessment and patient treatment.

Many asthmatic women of childbearing age experience cyclical aggravation of asthmatic symptoms during the perimenstrual period, or perimenstrual asthma (PMA). PMA is considered to be a difficult-to-treat asthma phenotype; conventional asthma therapies are not always effective against PMA.

We report a case of a 27-year-old female with PMA who had received standard asthma treatment since 2013.

The patient showed a dramatic response to therapeutic intervention of oral prednisone, taken for 7 days prior to menstruation each month, in a dose-dependent manner.

Premenstrual treatment with oral prednisone may be a successful new direction for the treatment of PMA, a troublesome type of asthma.

Studies show high comorbidity of mood disorders in asthma. As asthma is a highly heterogeneous disease with different phenotypes it can be expected that there is a difference in this association with different asthma phenotypes. The aim of our cross-sectional study was to assess the association of specific asthma phenotypes with anxiety and/or depression and their impact on asthma control.

A cross-sectional study in 201 consecutive adult outpatients with asthma (≥18 years of age) was conducted. Each patient underwent physical examination, detailed medical history, Hospital Anxiety and Depression Scale, Asthma Control Questionnaire, Asthma Control Test, together with measurements of lung function and fraction of exhaled nitric oxide. Phenotypes were assessed using cluster analysis, and a multivariate analysis was used to identify associations of mood disorders with different phenotypes.

Five asthma phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%), and respiratory infections associated asthma (RIAA, 5.5%). A multivariate analysis showed a significant association of anxiety with LOA and comorbid hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012), and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA, OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ, OR = 1.90; p < 0.001.

Mood disorders were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control.

Few studies have investigated the incidence of coronary heart disease (CHD) in patients with asthma, and their results remain inconclusive.

To conduct a meta-analysis to determine whether asthma increases the risk of CHD.

A systematic literature search of the PubMed and Embase databases from inception to August 2016, complemented with references screening of relevant articles and reviews, was performed to identify eligible studies. Only longitudinal cohort studies were included in our meta-analysis.

The retrieval process yielded 7 studies (12 asthma cohorts) with 495,024 patients. Data pooling across the cohorts revealed that asthma was associated with an increased risk of CHD (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.30-1.57; P < .001), without significant heterogeneity across the studies (I² = 26%, P = .19). This epidemiologic association was more pronounced in female than in male patients (female: HR, 1.50; 95% CI, 1.41-1.59; male: HR, 1.31; 95% CI, 1.16-1.47; P for interaction = .046). In addition, subgroup and sensitivity analyses supported the positive correlation between asthma and incident CHD.

Asthma is related to an increased incidence of CHD, particularly in women. Clinicians should be aware of this association when faced with a patient with asthma. Further investigations are required to examine how this excess risk should be managed in routine practice.

The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens' fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed.