The general objective is to elucidate the mechanisms whereby sex hormones may modulate the severity of respiratory disease. An important component of this proposal is a systematic and intensive approach to characterize how the cellular and cytokine components of airway inflammation respond to fluctuations in sex hormone levels. The effects of menstrual fluctuations in levels of sex hormones on inflammation and bacterial load in respiratory secretions of CF patients will also be determined.
Most CF patients die because of chronic lung infection with P. aeruginosa, chronic inflammation and progressive airway damage. Agents that reduce inflammation or enhance airway antibacterial defences hold potential therapeutic value. Therefore, there is considerable current interest in identifying and stimulating the activities of these agents. Although sex hormones are generally acknowledged to modulate respiratory inflammation, the downstream mechanism of such action remains incompletely understood. We have identified three antimicrobial peptides (AMPs), responsive to sex hormone in the CF human respiratory tract, including one (LTF) with known activity against P. aeruginosa biofilm formation. Our preliminary results show additive activity of LTF and STH against P. aeruginosa biofilm formation, and that LTF and STH also inhibit attachment of P. aeruginosa to airway epithelial cells. Taken together, these findings are consistent with the concept that female sex hormones exert their negative effect on the CF lung, in part, by reducing the levels of these AMPs in the airway. The next step is to determine if female sex hormones alter airway inflammation and infection or AMP levels in the respiratory secretions of CF patients.
Study Type
OBSERVATIONAL
Enrollment
28
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
The Hospital for Sick Children
Toronto, Ontario, Canada
Presence of inflammatory markers (cytokines, white blood cells), levels of LTF, STH and PIP. Serum levels of estrogen (E), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) will be determined in female human subjects
Time frame: For the female patients the visits will be timed so that one measure is taken in the luteal phase of their menstrual cycle and the other is taken during the follicular phase. Male patients will be asked to come to measure these levels two weeks apart.
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Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.