Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough.

Nasal and ocular responses after specific and nonspecific nasal challenges in seasonal allergic rhinitis.

BACKGROUND: Different nasal challenges induce neural and immune response leading to nasal and ocular symptoms in patients with seasonal allergic rhinitis (SAR). The release of neural mediators from nasal mucosa and conjunctiva after no-specific challenges in patients with SAR remains unknown. OBJECTIVES: To compare the release of mediators from the nose and conjunctiva with symptoms after different nasal challenges in patients with SAR. METHODS: Three types of consecutive nasal challenges were performed outside the pollen season in 25 patients with SAR. Challenges consisted of 500 biological units (BU) of allergen, 80 µg of histamine, and 1 mL of 2% hypertonic saline per nostril, within 24-hour and 72-hour intervals, respectively. Before and 15 minutes after challenges, evaluation of symptoms was performed with a visual analog scale. Concentrations of tryptase, eosinophil cationic protein in nasal lavages after 15 minutes, and substance P in tears after 5 minutes were measured with enzyme immunoassays. RESULTS: Concentrations of substance P in tears were significantly higher after nonspecific challenges. Substance P concentration in tears significantly correlated with eye itchiness after histamine and hypertonic saline and with tearing after allergen. Ocular symptoms correlated significantly with tryptase concentration in nasal lavage collected 15 minutes after allergen challenge. There is a significant correlation in tear volume comparing different nasal challenges. CONCLUSIONS: Nasal challenges with allergen, histamine, or irritants outside the pollen season induce a significant increase in nasal and ocular symptoms in patients with SAR. Interaction of the early-phase response and neurogenic inflammation define the pattern and severity of eye symptoms.