NHALES (Natural History of Asthma With Longitudinal Environmental Sampling)

Background: \- Asthma is a serious clinical and public health problem. Researchers want to collect data to better understand how bacteria and other things in the environment can affect people's asthma. Eligibility: \- Nonsmoking adults age 18 - 60 who have moderate to severe asthma. Design: * Participants will complete a medical history form before the first visit. * Study visits will include collecting medical history, and conducting physical exam, lung and smoking tests. Participants will give blood, urine, stool, dust, saliva, and sputum samples. * Participants will take tests that measure their breathing abilities. They will give saliva samples for DNA study. They will get kits to collect stool and dust samples at home. They will fill out surveys. * Participants will have visits every 6 months for 5 years. They can schedule sick visits, if needed, at no cost to the participant. For all visits, they will have asthma check-ups and get treatment, at no cost to the participant. * Some participants may take part in a sub-study that includes one 4-hour visit. They will have medical history, physical exam, and lung tests. They will have urine tests to check for pregnancy and tobacco exposure. Then they will have bronchoscopy. For this, an intravenous line will be placed in an arm vein. The nose and throat will be numbed. A flexible fiber-optic tube will be inserted into their airways through the nose. Their airways will be examined and areas of their lung will be washed. A small sample of cells will be taken.

* 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) \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 \160/100 mm Hg; pulse rate \100 beats/minute * Body weight \