* Inclusion Criteria
Participants must meet all of the following criteria for enrollment:
* Male or female, 18 to 60 years of age
* Must have clinical evidence of moderate-severe atopic asthma:
* self-reported symptoms suggestive of asthma (such as wheezing, chest tightness, shortness of breath, cough nocturnal symptoms)
within the past year, and
--\*a positive methacholine test confirming diagnosis \[provocative concentration causing a 20% fall in forced expiratory volume in 1 second (PC20 FEV1) \<16 mg/mL for participants on inhaled corticosteroids and \<8 mg/mL for participants not on inhaled corticosteroids\] or postbronchodilator FEV1 with at least 12% or 200 mL increase in FEV1 or forced volume vital capacity (FVC) on bronchodilator challenge, and
--no other diagnosis that could explain symptoms.
If there is documentation of a recent methacholine challenge, those results may be used in lieu of conducting a secondary methacholine challenge.
* Permanently resides within 50 miles of the CRU.
* Able to present a valid government issued form of identification for entry to the NIEHS campus
* Able to receive asthma treatment medication(s) via mail
* Willingness to comply with instructions regarding medication regimen, diet, and life style as directed by the investigator that are required per protocol
* Access to a vacuum cleaner with a detachable hose component
* If a woman is found to be pregnant or breastfeeding at the screening or baseline visit, they may continue their participation in the study but will be excluded from participation in the methacholine challenge and bronchoscopy procedures in this study while pregnant.
Bronchoscopy Visit Inclusion Criterion
In addition to the above inclusion criteria, participants must be able to fast for 6 hours (no food or drink, except a small amount of water if needed to take approved medications) prior to the bronchoscopy visit in order to be eligible for enrollment in the bronchoscopy visit.
Exclusion Criteria
Participants meeting any of the following criteria at screening will not be eligible for enrollment or to continue with study visits:
* Current smoker, significant second-hand smoke exposure (defined by urine cotinine \>200 ng/mL at screening), or a history of smoking greater than 5 pack years. Smoking encompasses all inhaled products, including e-cigarettes.
* piCO Smokealyzer value of \>11ppm
* History of the following comorbidities: chronic obstructive pulmonary disease, cystic fibrosis (CF), emphysema, non-CF bronchiectasis, pulmonary fibrosis, sarcoidosis, unstable angina, pulmonary hypertension
* Allergy or history of adverse reactions to methacholine
* Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with required study procedures
* Comorbid diseases that affect global health or survival- such as DVT, pulmonary embolism, class III - IV congestive heart failure, or a malignancy under treatment
Bronchoscopy Visit Exclusion Criteria
In addition to the above exclusion criteria, participants meeting any of the following criteria will not be eligible for enrollment into the bronchoscopy visit:
* Pregnancy, as indicated by urine pregnancy test, if of childbearing age and/or ability contraindication
* Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with bronchoscopy
* Bleeding disorders
* Facial deformity, major facial surgery
* Asthma exacerbation or respiratory infection less than or equal to 4 weeks prior to study visit
* Severe persistent asthma, defined as by ATS-ERS criteria.
* Allergy or history of adverse reactions to lidocaine
* Temperature \>37.6 (Infinite)C; blood pressure \<90/50 mm Hg or \>160/100 mm Hg; pulse rate \<50 or \>100 beats/minute
* Body weight \<50 kg (\<110 lbs)
* The following abnormal lab values (values obtained during clinical assessment):
* Platelet count \<100,000 per microliters
* White blood cells count \<3000 per microliters
* Absolute neutrophil count \<1000 per microliters
* Hematocrit \<35% for both female and male
* Prothrombin time (PT) / abnormal international normalized ratio (INR) and partial prothromboplastin time (PTT) based on reference laboratory established reference ranges
* Serum creatinine \>1.4 mg/dL
If a participant is recruited for the Bronchoscopy Visit but does not have current lab values (within 4 weeks), the participant may be asked to return to the CRU for an additional blood draw in order to run the requisite clinical assessments for safety purposes. The participant will be compensated for the additional visit. This is anticipated to be a rare occurrence, as the study team will make all efforts to schedule and complete the bronchoscopy procedure while the lab results are current.
Participants with active bronchospasm on the day of the bronchoscopy will not undergo bronchoscopy.
