Patient description: A 39-year-old man came to the clinic with cough and shortness of breath that was not relieved by his inhaler. He had these symptoms for 5 days during the past 2 weeks. He doubled his oral corticosteroids in the past week. He is a chef with a history of asthma for 3 years, suffering from frequent cough, wheezing, and shortness of breath and chest tightness. The symptoms become more bothersome within 1-2 hours of starting work every day and worsen throughout the work week. His symptoms improve within 1-2 hours outside the workplace. Spirometry was performed revealing a forced expiratory volume in the first second (FEV1) of 63% of the predicted. His past medical history is significant for seasonal allergic rhinitis in the summer. He doesn't smoke or use illicit drugs. His family history is significant for asthma in his father and sister. He currently uses inhaled corticosteroid (ICS) and fluticasone 500 mcg/salmeterol 50 mcg, one puff twice daily.

Clinical trial eligibility criteria: eligible ages (years): 18.0-70.0,  Asthma Participants must meet all of the following for enrollment: 1. Male or female, 18 to 60 years of age 2. 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. 3. Permanently resides within 50 miles of the CRU. 4. Able to present a valid government issued form of identification for entry to the NIEHS campus 5. Able to receive asthma treatment medication(s) via mail 6. Willingness to comply with instructions regarding medication regimen, diet, and life style as directed by the investigator that are required per protocol 7. Access to a vacuum cleaner with a detachable hose component Bronchoscopy Sub-Study Criterion In addition to the above 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 sub-study  Participants meeting any of the following at screening will not be eligible for enrollment or to continue with study visits: 1. Women who are pregnant or lactating at the time of screening will not be encouraged to enroll. However, if a woman is found to be pregnant at a screening or baseline visit, she may remain in the study but will not be eligible for the methacholine challenge or bronchoscopy sub-study until no longer pregnant or breastfeeding (this is in place because methacholine may pose an undue risk on the unborn fetus or nursing babies; women who become pregnant after completing the baseline visit will not be excluded from further participation but will also not be eligible for participation in the bronchoscopy sub-study). 2. 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. 3. piCO Smokealyzer value of >11ppm 4. History of the following comorbidities: chronic obstructive pulmonary disease, cystic fibrosis (CF), emphysema, non-CF bronchiectasis, pulmonary fibrosis, sarcoidosis, unstable angina, pulmonary hypertension 5. Allergy or history of adverse reactions to methacholine 6. Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with required study procedures 7. 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 Sub-Study In addition to the above  participants meeting any of the following will not be eligible for enrollment into the bronchoscopy sub-study: 1. Pregnant, as indicated by urine pregnancy test 2. Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with bronchoscopy 3. Bleeding disorders 4. Facial deformity, major facial surgery 5. Asthma exacerbation or respiratory infection less than or equal to 4 weeks prior to study visit 6. Severe persistent asthma, defined as by ATS-ERS criteria. 7. Allergy or history of adverse reactions to lidocaine 8. Temperature >37.6 (Infinite)C; blood pressure <90/50 mm Hg or >160/100 mm Hg; pulse rate <50 or >100 beats/minute 9. Body weight <50 kg (<110 lbs) 10. 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