NHALES (Natural History of Asthma With Longitudinal Environmental Sampling)
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 and are not pregnant or
 breastfeeding.

 Design:

 -  Partaicipants 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.
This study will be a prospective, longitudinal, observational, single-center, exploratory,
 natural history study to collect samples and data that will enable prospective explorations
 of the interaction between environmental exposures and disease progression over time in
 moderate-severe atopic asthmatics with persistent disease, and facilitate the formation of
 mechanistic hypotheses. Environmental and body microbiome samples will be collected and
 stored from participants for future correlation to effects on asthma symptoms and control.

 Samples of blood, urine, DNA, saliva, sputum, stool, and household dust will be collected
 from approximately 200 participants, as well as quality of life information using asthma
 symptom questionnaires and, if consented, through the use of home devices. Additionally,
 samples will be collected from the airways of participants enrolled in the bronchoscopy
 sub-study. The samples and survey information collected may be used to explore the
 microbiological and genetic influences of atopic asthma. Data from the analyses of these
 samples and survey responses may be evaluated in the context of the environmental exposures,
 clinical outcomes (symptoms, exacerbations, and quality of life), and response to therapy.

 Male and female participants aged 18 to 60 years old with moderate-severe, symptomatic atopic
 asthma will be enrolled. Participants will be excluded from enrollment if they have a history
 of chronic obstructive pulmonary disease, cystic fibrosis, non-cystic fibrosis
 bronchiectasis, pulmonary fibrosis, pulmonary hypertension, emphysema, sarcoidosis, or
 unstable angina. Additionally, participants will be excluded if they have DVT, pulmonary
 embolism, class III - IV congestive heart failure, or a malignancy under treatment. Current
 smokers, and individuals who are allergic to methacholine will not be eligible to enroll.
 Women who are not pregnant or breastfeeding are preferred, however if a woman is found to be
 pregnant or breastfeeding at the screening or baseline visit (and has a good chance of being
 eligible), they may continue their participation in the study but will be excluded from
 participation in the methacholine challenge and bronchoscopy sub-study. Participants will be
 enrolled for five years and will receive standard of care asthma therapy as indicated. After
 the initial screening and baseline visits, participants will return for visits semi-annually
 and for sick visits as needed. Volunteers participating in the bronchoscopy sub-study will
 have an additional single visit after completing the baseline visit.

 This cohort of 200 participants will form the basis for future asthma study recruitment, and
 analysis of collected samples and data. Further expansion of the study beyond five years and
 200 participants will be desirable if logistically possible.
-  Inclusion Criteria

 Participants must meet all of the following criteria 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 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
 sub-study.

 Exclusion Criteria

 Participants meeting any of the following criteria 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 exclusion 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 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 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

 -  Serum creatinine >1.4 mg/dL

 If a participant is recruited for the Bronchoscopy Sub-Study 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.