Research Triangle Park,
- 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
- Nonsmoking adults age 18 - 60 who have moderate to severe asthma and are not pregnant or
- 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
- 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. Additionally, samples will be collected from the airways of
approximately 20 participants enrolled in a 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
- 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
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
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
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 L
- White blood cells count <3000 per L
- Absolute neutrophil count <1000 per L
- 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
- 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