Prostaglandin E2 as a Critical Mediator of Sex Disparities in Asthma

Inclusion Criteria:

- Subject must be able to understand and provide informed consent

- Age 18-50

- A history of physician-diagnosed asthma well controlled as assessed by ACQ-6 <1.5 and
FEV1>70% of predicted and FEV1 >1.5 liters.

- Asthma must be persistent, defined by the requirement of a daily controller agent.

- Use of a stable dose of daily inhaled corticosteroids for the prior 3 months.

- Female subjects of childbearing potential must have a negative pregnancy test upon
study entry and at each study visit.

Exclusion Criteria:

- Inability or unwillingness of a participant to give written informed consent or comply
with study protocol.

- Hypogonadism, irregular menstrual cycles, polycystic ovarian syndrome (PCOS),
exogenous hormonal supplements or contraception.

- Any chronic lung condition outside of asthma including chronic obstructive pulmonary
disease (COPD), interstitial lung disease, eosinophilic granulomatosis with
polyangiitis, allergic bronchopulmonary aspergillosis.

- Inability or unwillingness to hold the following medications prior to mannitol and
methacholine inhalational challenge(s): Short-Acting Beta 2 Agonists >8 hours, Inhaled
Corticosteroids and Anticholinergic Bronchodilators >12 hours, Phosphodiesterase
Inhibitors or Adenosine Receptors >24 hours, Long-acting Beta 2 Agonists >36 hours,
Long-acting Anticholinergics or Short-Acting Antihistamines >48 hours, Long-Acting
Antihistamines >72 hours, and Leukotriene-Receptor Antagonist or 5-Lipooxygenase
Inhibitors >4 days.

- For males, a screening morning serum total testosterone level (obtained between 8-10
AM) below the normal reference lab value.

- Current pregnancy, breast-feeding, or plans to become pregnant during the study
period.

- Oral or systemic corticosteroid use or biologic agent for asthma in the previous 3
months or ED/Hospitalization for asthma within 6 months.

- Use of investigational drugs within 12 weeks of participation.

- Known hypersensitivity or allergy to mannitol, gelatin or methacholine.

- Upper or lower respiratory tract infection within the proceeding 6 weeks.

- A history of uncontrolled hypertension, coronary artery disease, stroke, epilepsy,
urinary tract obstruction, untreated thyroid disease, or a chronic lung disease other
than asthma.

- Daily use of a beta-blocker.

- Intolerance to anticholinergic medications.

- Inability to produce an adequate sputum sample.

- Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may pose
additional risks from participation in the study, may interfere with the participant's
ability to comply with study requirements or that may impact the quality or
interpretation of the data obtained from the study.