Characterization of Adults for Asthma Microbiome Research Studies

This is a prospective, observational, two-visit study in which approximately 200 subjects
will be enrolled, including healthy controls, atopic controls without asthma, and patients
with stable asthma (n = 150). Among asthmatics, 2/3 will be on regular inhaled corticosteroid
therapy and 1/3 will not be taking inhaled corticosteroids. Subjects who meet study criteria
will undergo phenotypic characterization in multiple domains, including evaluation of lung
function, assessments of asthma/allergy history, asthma triggers, asthma symptom control,
environmental microbial exposures and dietary intake. Oral rinse, sputum, stool, urine and
blood specimens will be collected for microbiome-related analyses, including molecular and
culture-based assays, metabolite studies, and to relate these to markers of inflammation and
immune function. The overall goal is to enroll a cohort of well-characterized asthmatic and
non-asthmatic control subjects to enable mechanism-oriented studies of how members of the
airway microbiota and possibly also gut microbiota influence phenotypes of adult asthma.

1. For all subjects:

Inclusion criteria:

- Men/Women, ages 18-75, with or without current asthma, are eligible to be screened.

Exclusion criteria:

- Cigarette smoking history of >30 total pack-years

- Current use of other smoked products or recreational drugs (e.g. pipes, cigars,
e-cigarettes, other illicit drugs)

- History of lung disease other than asthma

- Recent upper respiratory tract infection treated with antibiotics within 8 weeks
of visit 1

- Recent antibiotic use (except topical or ocular) within 8 weeks of visit 1
(chronic antibiotic use for asthma management allowed)

- Currently pregnant or breast-feeding

- Other medical conditions or treatments that may increase subject risk or affect
study results, based on study physician judgment. These include the following:
significant cardiovascular disease(+/- active symptoms), arrhythmia, or stroke,
active cancer, post-organ transplant

- Any other condition for which subject is taking immunosuppressive therapies
(except steroids for asthma)

- History of allergy to albuterol or methacholine

2. For asthma subjects only:

Note: Enrollment target is for 90 asthmatics already taking inhaled corticosteroids
prescribed by their physician (any formulation and dose) and 60 subjects who are not
currently using inhaled corticosteroid.

Additional inclusion criteria:

- History of asthma symptoms within the last 2 years (e.g. wheeze, shortness of
breath, etc.)

- Evidence of stable asthma as assessed by initial screening

- No changes in asthma medications within 30 days of visit 1

- Methacholine PC20 (dose at which there is a 20 percent change) ≤ 8 mg/ml (for
those asthmatics on inhaled steroids, PC20 ≤ 16 mg/ml), or change in FEV1 (forced
expiratory volume in first second of spirometry effort)≥ 12% after 4 puffs of
albuterol on reversibility testing (or PI discretion)

Additional exclusion criteria:

- An asthma exacerbation requiring treatment with oral or IV steroids within 1
month of visit 1

- No asthma symptoms within the last 2 years

3. For healthy control or atopic non-asthma subjects:

Additional exclusion criteria:

- Evidence of abnormal lung function by any of the following: FEV1/FVC ratio <0.70, FEV1 or
FVC (forced vital capacity on spirometry) < 80% predicted, methacholine PC20 < 16 mg/ml, or
FEV1 improvement > 12% in response to albuterol