Western Versus Prudent Diet Feeding Study in Adult Women With Asthma
Phase: NA
Conditions: Asthma
Sponsor: Johns Hopkins University

 
 
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Official Title: Western Versus Prudent Diet Feeding Study in Adult Women With Asthma 
 
NCT number: NCT03200522 
 
Document Date: August 10, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Date: September 27, 2018 
Principal Investigator: Dr. Emily Brigham  
Application Number: IRB00111434 
 
 
 
JHM IRB - eForm A – Protocol 
 
 
 
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1. 
ABSTRACT  
 
Background: In the U.S., increased intake of fast food and highly processed foods (a “Western-
style” diet) has been coincident with the dramatic rise in asthma. Observational studies demonstrate 
a link between a dietary pattern and asthma morbidity at the level of the individual, and limited 
trials of counselling for a healthier diet have shown promise in improving asthma health.  
 
Objectives: The objective of the study is to demonstrate the feasibility of a randomized, controlled 
trial of complete dietary replacement (feeding study) in a population of adults with asthma, and to 
provide measures of variability in the proposed outcomes (symptoms, lung function, markers of 
inflammation and oxidative stress) to inform sample size calculation for a larger, definitive trial.  
 
Methods: The study is a feasibility trial of a prudent (high in fruit and vegetables, whole grains, 
low-fat dairy) versus Western-style (high in processed foods, fast food, sweets) diet intervention in 
adults with asthma. Eight to twelve adult women (ages 18-55) who meet eligibility criteria will be 
enrolled. At baseline, demographic information, asthma symptom scores, usual dietary intake, 
anthropometric measures and DEXA, spirometry, FENO, blood, urine, nasal, and sputum samples 
will be collected. Participants will then be randomized to either the Western-style diet or a prudent 
diet. Prior to initiating the diet, they will have assessment of select biologic outcomes (FENO, 
spirometry, symptom assessment, biomarkers of oxidative stress and inflammation in urine and 
serum, and nasal swab). After 6 days of the randomized diet, they will repeat these assessments and 
undergo induced sputum for local (pulmonary) biomarkers of inflammation and oxidative stress. 
The participants will then have a 4-8 week washout period, and repeat the same order of 
assessments prior to and after receiving the alternate diet assignment. During each of the 6-day 
interventions, participants will record asthma-related symptoms via a standardized questionnaire. At 
the final session, participants will provide feedback on the acceptability and palatability of the 
dietary interventions and assessments. As this is a feasibility study, we will use results to assess the 
process and procedures necessary to scale the intervention to a larger study population.  
 
Implications: Study findings will provide insight into feasibility of a larger-scale clinical trial 
investigating the effect of these diet patterns on adult asthma. We expect to gain insights into the 

 
 
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acceptability of intervention duration, tolerability of study visits and participant flow, and sample 
size necessary for a larger, definitive clinical trial.  
 
2. 
OBJECTIVES  
 
The primary objective for this study is to determine the feasibility of a randomized, crossover trial 
of a Western-style compared to a prudent dietary intervention among Baltimore City adults with 
asthma. Our secondary objective is to gather preliminary data on markers of systemic and airway 
inflammation and oxidative stress, lung function, and changes in the microbiome induced by diet to 
inform sample size for a definitive trial. 
 
3. 
BACKGROUND  
 
The rising burden of asthma has trended in parallel with dramatic shifts of dietary habits towards a 
“Western” diet and away from a “prudent” diet (high in fruits, vegetables, whole grains, n3-PUFAs 
(found in fish, seafood, some plant-based oils), low fat dairy products, and overall antioxidant 
levels). These trends are particularly relevant to low-income, African American populations who, in 
addition to their particular vulnerability to asthma, tend to have poorer quality diets, lower in fiber, 
fruits, and vegetables, and higher in fat and sugar. These correlations have prompted further 
evaluation, though dietary investigations in asthma have primarily included a focus on individual 
micronutrients. These include “anti-inflammatory” and antioxidant vitamins (A, C, D, E), minerals 
(zinc, selenium), flavonoids, and unsaturated fatty acids. While each factor has demonstrated some 
positive association with improved asthma or wheeze, nearly all have conflicting evidence in the 
peer-reviewed literature and, disappointingly, randomized trials have shown inconsistent or 
negative results with single-micronutrient supplementation. The complexity of diet as an exposure 
variable may be difficult to accomplish by isolating nutrients. For example, while one medium 
grapefruit contains 200% daily value (DV) of vitamin C, it also contains 70% DV vitamin A, 8% 
DV calcium, and 16% DV fiber, and has a filling effect that may defer intake of other foods. 
Unanticipated correlations between nutrients may falsely diminish associations in controlled, 
statistical analyses, and fail to identify potentially synergistic effects. Because of these issues, there 
has been increased interest in evaluating whole foods and dietary patterns. To date, nutritional 
research studies examining dietary patterns have focused heavily on the relationship to other 
chronic diseases. Whole food intake and dietary patterns have been predictive of multiple disease 
states, including obesity, cardiovascular disease, and cancer, and there is evidence of an association 
between healthier, recommended dietary patterns and wellness in these examples. Indeed, evidence 
exists as to the success of this approach in asthma. A diet rich in antioxidants and low in saturated 
fats (the Mediterranean diet, similar to the prudent diet but typified by foods endemic to 
Mediterranean countries, i.e. olive oil, fish, wine) has been proposed as a “respiratory healthy” diet, 
possibly by attenuating the inflammatory response through high levels of antioxidant intake. Cross-
sectional studies suggest better symptom control with adherence to this diet and others similar in 
composition. Observational work outside of the U.S. demonstrates the positive effects of a 
“healthy” diet pattern and the negative effects of an “unhealthy” diet pattern on asthma morbidity 
and respiratory health.  
 
Several small trials of whole food and diet pattern intervention have shown promise. In Australia 
LG Wood, et al conducted a trial with 137 asthmatic adults who were asked to consume either <1 
serving fruit and 2 servings vegetables daily (low antioxidant, LAO) versus 2 servings fruit and 5 

 
 
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servings vegetables daily (high antioxidant, HAO). Percent predicted FEV1 and time to 
exacerbation were significantly reduced in the LAO compared to the HAO group. The same 
investigators found that a single high-fat/high-energy meal increased neutrophilic airway 
inflammation and reduced airway bronchodilator recovery in adult asthmatics. Two small, pilot 
trials of healthy diets in U.S. populations demonstrate encouraging improvements in asthma 
outcomes including symptoms, lung function, and serum inflammatory markers. Studies thus far 
have been limited by either scale-ability (due to duration and therefore cost of studied intervention) 
or underrepresentation of low-income, African-Americans who have the greatest burden of asthma 
prevalence and morbidity. Furthermore, the prevalence of adult asthma is 70% higher in females 
than males, females carry a higher rate of asthma attacks than males, and obesity is a greater risk 
factor for asthma among adult women compared to adult men. There is a need to define 
interventions in populations affected the most by asthma, in order to have the greatest impact.  
 
The current study is designed to assess the feasibility of a larger-scale intervention trial comparing a 
Western-style diet to a prudent diet intervention in an urban population disproportionately affected 
by asthma. Similarly, because females with obesity represent a high-risk group for asthma incidence 
and prevalence, and may represent a unique phenotype as compared to males and non-obese 
individuals, we propose to limit this small pilot to females with obesity.  
 
 
4.  
STUDY PROCEDURES 
 
a. Study design summary 
 
Figure 1. Study Design 
 
 
We will conduct a single-blinded (study staff only), randomized crossover pilot trial to evaluate the 
feasibility of a Western and prudent diet feeding study in Baltimore City adults with asthma (Figure 
1). The results from this study will provide data to inform a larger trial evaluating the differential 
effects of a Western-style (high in processed foods, fast food, sweets) diet and a prudent (high in 

 
 
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fruit and vegetables, whole grains, low-fat dairy) diet on symptoms, lung function, systemic 
inflammation, and local airway inflammation among adult asthmatics.  
 
Potential study subjects will undergo phone screening prior to invitation for initial clinic visit. 
Participants will be consented at initial clinic visit, after which they will complete additional 
eligibility testing (urine pregnancy testing, urinary cotinine measurement, induced sputum 
collection, and if eligible undergo baseline assessments (demographic information, baseline 
questionnaire, usual dietary intake evaluation, anthropometric measures, DEXA, spirometry, FeNO, 
blood, urine, and nasal sample collection). Participants will then be randomized to initiate a 
Western-style diet or prudent diet and scheduled a date to return for their first assessment (A1) prior 
to initiating the assigned intervention. FeNO, spirometry, symptoms/questionnaires, and nasal swab, 
urine, stool/fecal strip, and serum collection will occur at first assessment. Participants will then 
receive 3 days of meals to take home. Participants will return at day 3 to retrieve the last 3 days of 
meals (or alternatively, the last 3 days of meals will be delivered to their place of residence), and 
will return again at day 6 to repeat the assessments at A1 + sputum induction. During each of the 
Western and prudent intervention diet periods, participants will complete daily 
questionnaires/diaries on food consumed, symptoms, and other potential exposures that may affect 
asthma control. Participants will then have an approximately 4-8 week washout period during which 
they will be instructed to resume their regular diet before continuing with the alternate dietary 
intervention with mirrored assessments. At the second A2 visit, participants will be asked to answer 
questions regarding acceptability and tolerability of study schedule and participant flow, and to 
report comments on study acceptability ad libitum.  
 
i. Recruitment 
 
We will recruit 8-12 obese adult females with asthma, meeting the inclusion and exclusion criteria 
below. Participants will be recruited using a database of previous study participants in the Center 
for Childhood Asthma in the Urban Environment (which conducts research in child and adult 
population) and other Johns Hopkins asthma cohorts currently approved by the Johns Hopkins 
Institutional Review Board. All potential subjects in this database have consented to having their 
contact information maintained in a database and to be contacted about participating in research 
studies.  
 
We will also recruit patients from the Principal Investigator’s and Co-Investigator’s Pulmonary 
Clinics who have agreed to be contacted about research studies. In addition, we will recruit potential 
subjects who are referred from other physicians and have given permission to be contacted. These 
potential participants will not be approached by research staff or investigators unless they have 
given permission to their doctors and this permission has been documented in the medical record.  
All such potential subjects will be given information about the study by their doctor along with 
study team contact information. They may initiate contact with the study team unless they have 
given permission to be contacted by a study team member and it is documented in their medical 
record.   
 
We will also recruit patients at community events and with IRB-approved fliers.  
 

 
 
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We will also send letters regarding the study to the families of children who have enrolled in our 
pediatric asthma studies within the Center for Childhood Asthma in the Urban Environment. These 
families have demonstrated an active interest in research and a high proportion of family members 
of these children also have asthma. The letter will provide an “opt-out” option where female adult 
family members may choose not to be contacted by phone. If no “opt-out” letter is returned, we will 
contact the families to assess interest.  
 
ii. Participant eligibility, baseline visit, and randomization 
 
Participant eligibility is determined by an initial telephone screening call and in an in-person 
screening visit.  
 
Phone Screening: Potential participants will be asked brief questions on major eligibility criteria 
(see Section 5), including age, sex, medical history, medications, smoking history and status, food 
storage and preparation equipment available to the potential participant, and willingness to consume 
foods planned for the study. 
 
Screening/Baseline exam: All potential participants who pass the phone screen will be invited to 
consent and complete the in-person screening, which includes an assessment of asthma symptoms 
via the Asthma Control Test (ACT), measurement of body mass index (BMI), a urine cotinine 
test and, for women of childbearing potential, a urine pregnancy test. Individuals with a negative 
urine cotinine who are not pregnant will complete initial spirometry and sputum induction.  
Spirometry and Induced Sputum Details: 
1) Spirometry will be performed according to American Thoracic Society guidelines using a 
KOKO (Pulmonary Data Services, Inc., Louisville, CO) pneumotachometer to obtain FEV1, 
FVC, FEF25-75, and PEF. After spirometry is obtained, participants will be administered 2 puffs 
of albuterol via a spacer.  After 15-45 minutes, spirometry will be repeated. With each 
spirometry session, 3 sets of FEV1 values will be obtained. The highest FEV1 measurement post 
albuterol administration will be used to determine eligibility for induced sputum (must be >60% 
of predicted value based on standard reference equations adjusted for age, race, gender, and 
height).  
2) Sputum induction: Participants will be instructed through an induced sputum procedure via 
hypertonic saline nebulization. Sputum inductions and processing will be performed following 
published protocols.  Briefly, after baseline spirometry, an ultrasonic nebulizer will be used to 
deliver hypertonic saline for at most a total of 20 minutes. The subject will be asked to 
expectorate sputum into a specimen cup placed on ice. Lung function will be monitored to 
ensure participant safety. If there is a fall in FEV1 of ≥ 20% compared baseline FEV1 prior to 
sputum induction at any point or if the patient is unwilling or unable to continue, sputum 
induction will be terminated and albuterol administered as needed. 
 
 
Those who are able to successfully produce an adequate sputum sample will be enrolled in the full 
trial and asked to complete the baseline evaluation on the same day.  
 
The baseline evaluation will include the following:  
 

 
 
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1) Collection of demographic information, including name, address, date of birth, and medical 
history 
2) Baseline questionnaire, including questions on common exposures known or hypothesized to 
exacerbate asthma (i.e. cleaning products, home environment, etc).  
3) Symptom report via questionnaires. These include the Asthma Quality of Life Questionnaire 
(AQLQ), Asthma Symptom Utility Index (ASUI), and Asthma Control Test (ACT). The AQLQ 
has been validated for individuals 15 and older and is designed to measure daily impact of 
asthma in patients’ lives. The ASUI is a validated 2-week recall questionnaire that addresses 
issues of asthma control weighted by impact on functional status. The ACT is a validated 4-
week recall of symptoms and functioning.  
4) Other questionnaires aimed at assessing self-efficacy in disease management, including the 
validated PROMIS-29 and EQ-5D-5L.  
5) Instruction for evaluation of usual diet via a 3-day food diary, to be completed at home over 
the ensuing 3 days.  
6) Assessment of daily caloric needs by a registered dietician, on which to base calories provided 
during 6-day feeding intervention.  
7) Dual Energy X-ray Absorptiometry (DEXA) Scan at the Johns Hopkins Hospital Broadway 
Adult Outpatient CRU.  
8) Anthropometric measures of height, weight, waist circumference, chest circumference, and 
neck circumference 
9) Fractional exhaled nitric oxide (FeNO) measurement: Exhaled nitric oxide is a known 
marker of pulmonary inflammation and will provide a means of assessing pulmonary oxidative 
stress and inflammation. Measurement of exhaled nitric oxide will be obtained according to 
ATS guidelines and prior to lung function whenever possible. Nitric oxide concentrations will 
be measured using a chemiluminescent analyzer (NIOX Mino, Aerocrine, Sweden). This 
equipment is FDA-approved for clinical use in asthma management.  
10) Serum collection: Serum will be collected via phlebotomy, a routine clinical procedure 
performed by drawing blood from a vein in the forearm, in order to investigate serum 
biomarkers indicating inflammation and oxidative stress, such as IL-5, IL-13, RANTES, 
superoxide anion, and lipid peroxides. Any excess serum will be stored for future analyses. 
11) Urine collection: Prior to enrollment, all participants will submit a urine sample for pregnancy 
testing, and urine will also be collected for analysis at each assessment visit. Urine biomarkers, 
including LTE4 and F-isoprostane, will be measured to assess oxidative stress and inflammation. 
We will also measure other markers of inflammation/chemical exposure that may affect asthma 
control. Any excess urine will be stored for future analyses.  
12) Nasal swab collection: Nasal swab (and optionally, oropharyngeal and skin swab) collection 
will occur at each assessment visit, before and after each dietary intervention, to obtain a sample 
for cellular examination. Analysis of biomarkers in nasal specimens will include (1) cell count 
and differential, (2) cytokines, (3) chemokines, and other markers of inflammation, (4) 
microbial assessment.  
 
Randomization: Randomization will occur within approximately one to two weeks of enrollment. 
Participants will be randomized using a computerized random assignment table with permuted 
blocks. Participants will be aware of their assignment as the study cannot be blinded.  
 
iii. Intervention  

 
 
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Participants will be provided with all meals for 6 days through the Nutrition Core at the ICTR. 
Meals will be calorically balanced such that the “prudent” versus “Western-style” intervention will 
contain similar caloric counts.  
 
Participants will be instructed not to consume meals or snacks outside of those provided and will be 
asked to visit the research clinic at most twice to pick up their meals: once at initial assessment, and 
mid-way through the intervention period, they may either return to the clinic to pick up the 
remainder of their meals or their meals will be delivered to their home. For each day of this 
controlled feeding, participants will also complete a daily diary. The daily diary asks about study 
foods not eaten, non-study foods eaten, and beverages consumed over the past day. Participants will 
also report daily symptom assessment with validated symptom scales and rescue inhaler use daily 
during the 6-day dietary intervention, as well as exposures that may affect asthma control. 
 
A washout period of approximately 4-8 weeks separates each intervention period; the washout 
period allows ad libitum food intake. 
 
Description of Diets: 
Energy values and macronutrient distribution (as percent of kilocalories) will be similar for the 
prudent and Western diet with a goal of 35-37% Fat, 45-47% Carbohydrate, and 16-18% Protein. 
Differences between the diets are defined in the table below.  
 
Nutrient or Food Pattern 
Western Diet 
Prudent Diet 
Saturated fat (% of kcals) 
≥10 
<8 
Omega-6:Omega-3 ratio 
≥13:1 
≤5:1 
Whole grains (% of grain servings) 
0 
100 
Fruit (servings/day) 
≤1 
≥3 
Vegetable, not potato (servings/day) 
≤1 
≥3 
Nuts (1 oz. serving/day) 
0 
≥1 
Fish (3 ounce serving 4/6 days) 
0 
2 
Processed meat (ounces/day)  
≥3 
0 
Sweets (30-125 gram serving/day) 
≥1 
0 
Sugar sweetened beverages (fluid 
ounces/day) 
≥8 
0 
 
Food Production and Distribution: 
Meals will be prepared and distributed in the research kitchen of the Nutrition Core at the ICTR.  
The research kitchen is inspected annually by the Baltimore City Health Department. Managers and 
staff of the ICTR research kitchen are certified through ServeSafe. Participants will be instructed in 
food safety. 
 
Promotion of Adherence: Efforts to promote adherence begin at the earliest stages of the study. 
During the phone and in-person screenings, participants are repeatedly provided with information 
about key features of the study. During the phone screening, participants will complete the Diet 
Screening Form, which includes a detailed list of foods provided. Individuals must be willing to eat 

 
 
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each of these foods; otherwise, they are excluded. Key contacts with nutrition staff include an in-
person evaluation by a dietitian. The intent of these efforts is to identify and exclude, prior to 
randomization, participants who are unwilling or unable to comply with the feeding protocol.  
 
Efforts to promote adherence center on making the foods palatable and convenient to the participant 
lifestyles; maintaining easy access to staff; and providing available, daily, supportive contacts.  
Acceptance of the controlled feeding protocol is increased by allowing participants to consume pre- 
approved selected beverages, as well as an unlimited amount of water and artificially sweetened soft 
drinks. 
 
Assessment of Adherence 
Adherence assessment includes both self-reported and objective measures. The subjective measures 
are used to determine suitability for randomization and subsequently to counsel participants and 
promote adherence during the trial. Self-reported measures are obtained from information provided 
on a daily diary and from subjective judgment by clinic personnel. Each day, an overall compliance 
score (0=compliant; 1, 2, or 3 for various degrees of non-compliance) is calculated based on staff 
observation and information from the daily diary. Adherence will also be assessed at each post-
intervention assessment via objective measures, including serum biomarkers (lipids, carotenoids, 
and free fatty acids), and on-site meal consumption of the first meals within each intervention. 
Comparison pre- and post-intervention will provide objective measures of adherence to provided 
intervention.    
 
iv. Assessments  
 
Assessments will include the following (refer to Figure 1):  
 
 
Assessment 1 (before the dietary intervention period) 
 
1) Spirometry: Spirometry will be performed according to ATS guidelines to obtain FEV1, FVC, 
FEF25-75, and PEF. After spirometry is obtained, participants will be administered 2 puffs of 
albuterol via a spacer.  After 15-45 minutes, spirometry will be repeated. At each examination, 3 
sets of FEV1 values will be obtained, and the highest FEV1 measurement will be used as the 
baseline measurement for FEV1 recovery.  
2) Fractional exhaled nitric oxide (FeNO) measurement: Exhaled nitric oxide is a known 
marker of pulmonary inflammation and will provide a means of assessing pulmonary oxidative 
stress and inflammation. Measurement of exhaled nitric oxide will be obtained according to 
ATS guidelines and prior to lung function whenever possible. Nitric oxide concentrations will 
be measured using a chemiluminescent analyzer (NIOX Mino, Aerocrine, Sweden). This 
equipment is FDA-approved for clinical use in asthma management.  
3) Serum collection: Serum will be collected via phlebotomy, a routine clinical procedure 
performed by drawing blood from a vein in the forearm, in order to investigate serum 
biomarkers indicating inflammation and oxidative stress. Any excess serum will be stored for 
future analyses. 
4) Urine collection: Prior to enrollment, all participants will submit a urine sample for pregnancy 
testing, and urine will also be collected for analysis at each assessment visit. Urine biomarkers, 
including LTE4 and F-isoprostane, will be measured to assess oxidative stress and inflammation. 

 
 
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We will also measure other markers of inflammation/chemical exposure that may affect asthma 
control. Any excess urine will be stored for future analyses. 
5) Stool/Fecal strip sample: One sample will be collected to analyze gut microbiome at baseline 
and during each follow-up visit. Sample will be stored at -80°C until further analysis of gut 
microbiome. 
6) Symptom report via questionnaires including the Asthma Quality of Life Questionnaire 
(AQLQ), Asthma Symptom Utility Index (ASUI), and the Asthma Control Test (ACT). The 
AQLQ has been validated for individuals 15 and older and is designed to measure daily impact 
of asthma in patients’ lives. The ASUI is a validated 2-week recall questionnaire that addresses 
issues of asthma control weighted by impact on functional status. Participants will also complete 
daily symptom diaries during the 6 days of intervention. The ACT is a validated 4-week recall 
of symptoms and functioning.  
 
7) Nasal swab collection: Nasal swab (and optionally, oropharyngeal and skin swab) collection 
will occur at each assessment visit, before and after each dietary intervention, to obtain a sample 
for cellular examination. Analysis of biomarkers in nasal specimens will include (1) cell count 
and differential, (2) cytokines, (3) chemokines, and other markers of inflammation, (4) 
microbial assessment.  
 
Daily Diaries: 
During the course of each feeding period, participants will complete daily diaries (questions and 
format supplied) to document data such as adherence to the diet, use of cleaning products, 
symptoms and albuterol use. Participants will be contacted daily with reminders to complete the 
diaries and to allow for any participant questions or concerns. Telephone calls or text messages will 
be used for this purpose.  
 
Assessment 2 (after the dietary intervention period) will include all of the above assessments,  
plus:  
8) Sputum induction: Participants will be instructed through an induced sputum procedure via 
hypertonic saline nebulization. Sputum inductions and processing will be performed following 
published protocols.  Briefly, after baseline spirometry, an ultrasonic nebulizer will be used to 
deliver hypertonic saline for at most a total of 20 minutes. The subject will be asked to 
expectorate sputum into a specimen cup placed on ice.  Lung function will be monitored to 
ensure participant safety. If there is a fall in FEV1 of ≥ 20% compared baseline FEV1 prior to 
sputum induction at any point or if the patient is unwilling or unable to continue, sputum 
induction will be terminated and albuterol administered as needed. 
9) Feedback session: We will solicit feedback on acceptability of intervention and satisfaction 
with study structure, including study instruments administered to optimize participant 
experience and retention for an anticipated, larger-scale trial.  
 
b. Study duration and number of study visits required of research participants 
 
Each study participant will be enrolled for a maximum of approximately 16 weeks, and with rolling 
enrollment we anticipate completion of all study visits within 1 year. Each research participant will 
be required to attend a baseline clinic visit and four assessment clinic visits. In addition, during each 
of the Western and prudent intervention periods, the participants will be required to pick up their 
meals at most twice: once at initial assessment, and mid-way through the intervention period, they 

 
 
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may either return to the clinic to pick up the remainder of their meals or their meals will be 
delivered to their home. In total, each research participant will be required to make five to seven 
study-related visits.  
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. 
 
It is not possible to blind participants to this protocol, as they will be aware which diet they have 
been assigned. Participants will be randomized using a computerized random assignment table with 
permuted blocks to receive either the “Western” or “prudent” diet first, and they will receive the 
alternate diet after the washout period. We will blind investigators and all study staff outside of the 
nutrition CRU staff to diet assignment.  
 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped. 
 
All patients enrolled in this study will continue to have their usual care for asthma as determined by 
their primary care provider or their usual asthma caregiver. The study protocol will not interfere 
with participants receiving their previous routine medical care. A copy of all complete blood count 
results along with a copy of all pulmonary function test results obtained during their visits will be 
given to the participants at the end of the study accompanied by a letter for their PCP.  
 
e. Justification for inclusion of a placebo or non-treatment group. 
 
Each participant will receive both dietary interventions, the “Western” diet and the “prudent” diet. 
 
f. Definition of treatment failure or participant removal criteria. 
 
 
We do not anticipate that participants will experience any significant side effects from ingestion of 
the study diets.  
 
At any time, the subject’s participation will stop if he/she requests not to proceed with the study or 
at the determination of the Principal Investigator.  
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. 
 
 
If a participant’s participation in the study ends prematurely, no additional dietary measures will be  
taken. Participants will resume their typical diet once the study concludes or when the participant 
exits the study.  
 
5.  
INCLUSION/EXCLUSION CRITERIA  
 
Inclusion criteria:  
1) Age 18-55 
2) Female 
3) Obese (BMI>30kg/m2) 
4) Not breastfeeding 
5) Diagnosis of asthma, defined as  

 
 
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• Physician diagnosis of asthma, and  
• Current treatment for asthma by a healthcare provider within the preceding twelve months. 
(Current asthma treatment defined as regular use of asthma medications. Asthma 
medications include short and long acting adrenergic bronchodilators, bronchodilator 
combinations, inhaled anticholinergics, inhaled corticosteroids, cromolyn sodium and 
nedocromil, leukotriene modifiers and methylxanthines.) 
6)  Stable asthma, defined by no asthma exacerbation (ED visit, course of increased systemic 
steroids, or urgent health care visit for asthma) during the prior four weeks.  
7) Symptomatic asthma (Asthma Control Test <20 at baseline screening visit) 
8)  Non-smoker, defined by no cigarettes in the past year and a negative urine cotinine 
9)  No other major pulmonary disease such as cystic fibrosis or COPD 
10)  Willing to eat study diet and nothing else for each of the 6 days of controlled feeding 
 
Exclusion criteria:  
1) Chronic oral steroid therapy (daily) 
2) Oral corticosteroid use within the past 4 weeks  
3) Respiratory tract infection within the past 4 weeks 
4) Significant medical issues such as heart disease or poorly controlled hypertension, type 1 
diabetes, poorly controlled type 2 diabetes, or hypothyroidism that would interfere with 
collection of outcome measures or present safety issues in the opinion of the Principal 
Investigator  
5) Pregnancy (self-report), planning a pregnancy, or nursing/breastfeeding mothers 
6) Food allergy that interferes with ability to complete the study 
7) Food preferences, intolerances, or dietary requirements that would interfere with diet adherence 
8) Taking vitamin supplements 
9) Planned dietary changes during the study period 
10) Use of coumadin  
11) Consumption of more than 14 alcoholic drinks per week, or consumption of 6 or more drinks on 
an occasion, one or more occasions per week  
12) FEV1<1.5L or <60% predicted post bronchodilator administration 
13) Inability to perform acceptable spirometry 
14) Any condition or compliance issue which in the opinion of the investigator might interfere with 
participation in the study  
15) Lack of appropriate food refrigeration and preparation equipment (oven or microwave) 
16) Inability to produce adequate sputum following induction with hypertonic saline neb 
 
6.  
DRUGS/SUBSTANCES/DEVICES 
 
a. The rationale for choosing the drug and dose or for choosing the device to be used. 
 
Albuterol is a commercially available, FDA approved drug. We will administer albuterol according 
to ATS guidelines and as described elsewhere on this form.  
 
b. Justification and safety information if FDA approved drugs will be administered for non-
FDA approved indications or if doses or routes of administration or participant 
populations are changed. 
 

 
 
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 Not applicable.  
 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.  
 
Not applicable.  
 
7.  
STUDY STATISTICS 
 
a. Primary outcome variable 
 
Primary Outcome: Feasibility of intervention and study procedures. We will measure this via 
qualitative interviews at the feedback sessions.  
 
     b. Secondary outcome variables 
 
Secondary Outcomes: We will also assess compliance with the dietary intervention via change in 
dietary markers; examples include serum lipids, serum fatty acids, and serum carotenoids. We will 
assess success of the study procedures based on success at obtaining serial induced sputum at 
follow-up visits. Based on previous findings that have demonstrated increases in inflammation (both 
Th1 and Th2) and oxidative stress among individuals with asthma or in response to diet exposure, 
we have selected a panel of biomarkers to be measured in study participants utilizing the resources 
and staff of the CCAUE. We will measure markers of Th1 inflammation (including sputum 
neutrophil %, neutrophil elastase, IL-8, and IL-6; serum TNF-alpha and IFN-gamma), markers of 
Th2 inflammation (including sputum eosinophil %, IL-5, and IL-13; FeNO; serum eosinophil %), 
and markers of oxidative stress (including sputum 8-isoprostane, serum RANTES, and urine 8-
isoprostane). We will also evaluate stool samples, nasal swab samples, and sputum samples for 
microbiome and changes with each dietary intervention. We will also look at change in reported 
symptoms, self-efficacy in managing disease, and lung function between the Western and prudent 
diets. Lastly, we will also evaluate temporal variability in exposures (such as cleaning agents) that 
could be linked to respiratory effects and/or to other related health outcomes, including oxidative 
stress. 
 
     c. 
Statistical plan including sample size justification and interim data analysis 
 
Analysis Plan: Participant feedback will be analyzed via a deductive approach for content analysis. 
We will examine for themes within the interview data which either support the current approach or 
suggest that procedure modification could improve feasibility and participant experience in a future 
trial.  The distributions of all quantitative variables will be examined for outliers and missing data 
points. Next, the distributions of serum lipids, carotenoids, fatty acids, FEV1, FeNO, and sputum 
neutrophil % will be summarized and displayed for each time point. Post-challenge levels of these 
outcome variables will be compared between prudent and Western diet interventions using paired t-
tests, displaying the calculated differences as percentages and absolute differences. Group 1 will be 
defined as the group randomized first to the Western diet, and Group 2 will be defined as the group 
randomized first to the prudent diet. We will also evaluate for evidence of carryover effect 
(measurable effect from order of intervention), although the washout period has been carefully 
selected to prevent this. We will examine differences in the outcome variables by order of 
intervention occurrence and apply the t-test. If the outcomes do not appear normally distributed, we 

 
 
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will transform them so that they meet assumptions of normality. In addition, we will calculate the 
intraclass correlation coefficient (ICC) using mixed effects models to assess the temporal variability 
of target biomarkers. The ICC is a measure of reproducibility and commonly used to assess the 
suitability of biomarkers to properly characterize exposures.  
 
Power Calculations: Power calculations cannot be completed for the primary, qualitative outcome 
of feasibility.  
 
Sample Size:  We propose a small study as a feasibility trial to generate preliminary data for a 
future, larger intervention that will be powered to detect clinical endpoints.  
 
Study Duration: The duration of intervention, 6 days, is shorter than most other diet intervention 
studies to date. Our prior intervention was of one-month duration, with outcomes similar at two 
weeks and one month. Other trials of diet intervention in asthma have also been at least two weeks 
in duration, though this duration of meal replacement is costly and difficult to scale. Importantly, 
just four hours after a high-fat diet challenge, meaningful changes in lung function and 
inflammatory markers have been detected, suggesting the presence of short-term effects on asthma 
health. We intend to further evaluate these short-term effects, both a novel and important aspect of 
the proposal that will inform duration and timing of outcome assessment in the planned, future trial. 
Based on variability of the secondary outcomes assessed in this trial and degree and directionality of 
change seen, we anticipate that this pilot will inform both feasibility as well as necessary duration of 
a future, definitive trial.  
 
As this is a pilot study, we do not intend to complete interim analyses.  
 
     d. Early stopping rules 
 
 
As this is a pilot study, there will be no formal criteria for stopping the study early, however 
participants may choose to leave the study early or may leave the study early at the determination of 
the Principal Investigator.  
 
8. RISKS 
 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency, 
and 
b. Steps taken to minimize the risks. 
 
 
Urine collection: Urine collection is considered a very low risk procedure. Urine will be collected 
the morning of the in-person screening visit and the morning of each of the four assessment visits. 
 
Questionnaires: The only risk involved in completing the questionnaires is the potential for breach 
of confidentiality. Unique identifiers will be assigned to participants and these will be used to label 
all paperwork, including questionnaires. Some participants may also feel uncomfortable answering 
personal questions, but all participants will be offered the opportunity to refrain from answering any 
questions they do not want to answer. Participants will answer questionnaires/logs at the baseline 
visit, and during each of the intervention periods. 
 

 
 
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Dual Energy X-ray Absorptiometry (DEXA) scan: The DEXA scan is considered a safe test and is 
widely used in clinical practice for estimation of bone mineral density in screening for osteoporosis, 
and it is also widely used in research studies including the National Health and Nutrition 
Examination Survey as conducted by the Centers for Disease Control and Prevention. The risks of 
this scan are directly related to the radiation dose received by the participant. We estimate that the 
dose of radiation received during a DEXA total body scan is around 0.001 rem per DEXA scan, a 
miniscule dose compared to the dose of 0.04 rem for an abdominal x-ray (Huda, 1996). Women 
capable of bearing children will receive a urine pregnancy test prior to the DEXA scan to exclude 
pregnant women from this procedure. The DEXA scan will only be performed once per participant, 
at the baseline visit.  
 
Spirometry: Spirometry is a routine clinical procedure that entails little risk. One minor risk is the 
slight discomfort of forceful exhalation, but this will be minimized by effective coaching and 
administration by trained study personnel. Spirometry will be performed at the baseline visit and 
during each of the four assessment visits. 
 
The drug albuterol will be administered during spirometry and can lead to tremor, nervousness, 
tachycardia, palpitations, and headache. These reactions are transient and rare (< 5%) with the 
proposed doses used for this study, and if they occur, we will monitor the patient until they return to 
baseline. High dose albuterol may cause arrhythmias and hypokalemia. However, these reactions 
are very unlikely with the doses used for this study.  
 
Induced sputum: Hypertonic saline nebulization can cause bronchospasm; to prevent this, albuterol 
will be administered prior to the procedure, hypertonic saline will be administered in escalating 
doses, and lung function will be measured throughout the protocol to prevent excessive responses. 
If there is a fall in post-bronchodilator FEV1 of ≥ 20% compared to FEV1 prior to sputum induction 
at any point or if the patient is unwilling or unable to continue, sputum induction will be terminated 
and albuterol administered as needed. Sputum induction will not be performed or will be terminated 
in subjects with post-bronchodilator FEV1 < 60% predicted. Risks are minimized by conducting the 
test in a medically supervised environment with trained personnel, and a physician will be available 
in the clinic during the procedure. Oxygen and albuterol via metered dose inhaler will be available 
and additional therapy will be administered as deemed appropriate depending on the circumstance. 
In the event of an emergency, the JHH Adult Code team will be called to respond. Induced sputum 
will be conducted at the baseline visit and during each of the two assessment visits following each 
dietary intervention. 
 
 Stool/fecal strip collection: Stool/fecal strip collection is considered a very low risk procedure. 
Samples will be collected during each of the four assessment visits. 
 
FeNO measurement: FeNO measurement is considered a very low risk procedure. Measurement of 
exhaled nitric oxide will be obtained according to ATS guidelines at each of the four assessment 
visits.  
 
Serum collection via venipuncture: Phlebotomy is a routine clinical procedure. There is a risk of 
minor discomfort or bruising at the site of the blood draw.  In addition, some people experience 
lightheadedness.  Very rarely, an infection can develop at the venipuncture site. In order to reduce 

 
 
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risks, a trained staff member who is experienced in phlebotomy will perform the venipuncture. 
Phlebotomy will be performed at each of the four assessment visits.  
 
Nasal swab collection: The main risk of cell sampling is minor discomfort while the sample is 
being collected, though the discomfort should subside immediately after the sample is taken. There 
is a slight risk of some nasal bleeding during or just after the sample is collected, and rarely, an 
infection may occur at the sampling site. In order to minimize these risks, a staff member who is 
experienced and trained in nasal sample collection will perform the procedure. Nasal swab 
collection will be performed at each of the four assessment visits.  
 
Dietary intervention: The two periods of dietary interventions pose minimal risk. Participants may 
experience some bloating and other minor gastrointestinal (GI) discomforts related to the high fruit, 
dairy, and fiber content of the intervention diets. Our experience suggests that GI discomfort is 
generally minor and subsides quickly, and GI problems often resolve soon after changes in diet. 
Participants are monitored for reactions to the diets and, if necessary, the diet can be modified or 
terminated. 
 
c. Plan for reporting unanticipated problems or study deviations 
 
Any serious or unexpected adverse event will be reported to the IRB according to institutional 
reporting requirements; other adverse events will be reported to the IRB at the time of continuing 
review. Protocol deviations will be reported to the IRB according to institutional reporting 
requirements: minor or administrative deviations to the protocol will be reported with the 
continuing review; major, non-emergent deviations will be submitted for review; and emergent 
deviations will be reported as soon as possible and at least within 5 days to the IRB.  
 
d.   Legal risks such as the risks that would be associated with breach of confidentiality 
 
The risk of breach of confidentiality will be minimized by using unique identifiers for participants 
and keeping the record that links the identifier to the participant in a locked file cabinet or office 
and/or password protected database accessible only to the investigators and study staff.   
 
e.   Financial risks to the participants. 
 
 
In the rare event that a participant has a reaction to diet intervention and he/she seeks medical care,  
he/she will be responsible for payment of those services.  The subject will not be charged for any of  
the proposed procedures and will be compensated for time spent in the study. 
      
 
9. BENEFITS 
 
a. 
Description of the probable benefits for the participant and for society. 
 
The potential benefits of this study for the participant include the introduction of healthy meals into 
their diet and a broader understanding of the relationship between their diet and asthma symptoms. 
Benefits for society include the identification of important relationships between dietary patterns 

 
 
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and asthma morbidity, and the potential future implementation of scalable dietary interventions for 
asthma. 
 
10. 
PAYMENT AND RENUMERATION 
 
a. 
Detail compensation for participants including possible total compensation, proposed 
bonus, and any proposed reductions or penalties for not completing the protocol. 
 
Participants can earn up to $380 total:  
● $50 after completing the in-person screening and all subsequent baseline measurements and 
questionnaires ($15 for completing urine pregnancy test and urine cotinine only, $20 for 
completing urine pregnancy test, urine cotinine, and spirometry only, $25 for completing 
urine pregnancy test, urine cotinine, spirometry, and induced sputum only) 
● $70 after completing the first period of dietary intervention (+ $10 bonus for completing all 
surveys) 
● $70 after completing the second period of dietary intervention (+ $10 bonus for completing 
all surveys) 
● $25 for every stool sample you’re able to provide at the 4 Assessment visits (+ $50 bonus 
for providing a stool sample at all 4 visits) 
● $20 bonus after completing the entire study including the feedback session 
 
 
Participants will receive Compensation to cover any travel-related expenses; this may include cab 
fare, bus fare, or cost of parking garage ticket.  
Participants will receive all of their meals during the dietary intervention periods. We will provide a 
meal of the participants choosing from the hospital cafeteria following the baseline visit and each of 
the assessment 2 visits.  
There are no penalties for not completing the protocol.  
 
11. 
COSTS 
 
a. 
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them. 
 
All costs that are associated with the study procedures are covered by the investigators.