Utilizing Real-time Technology to Assess the Impact of Home Environmental Exposures on Asthma Symptoms: Protocol for an Observational Pilot Study

Background It is estimated that over 60% of adults with asthma have uncontrolled symptoms, representing a substantial health and economic impact. The effects of the home environment and exposure to volatile organic compounds (VOCs) and fine particulate matter (PM2.5) on adults with asthma remain unknown. In addition, methods currently used to assess the home environment do not capture real-time data on potentially modifiable environmental exposures or their effect on asthma symptoms. Objective The aims of this study are to (1) determine the feasibility and usability of ecological momentary assessment (EMA) to assess self-report residential environmental exposures and asthma symptoms, home monitoring of objective environmental exposures (total VOCs and PM2.5), and lung function in terms of forced expiratory volume in 1 second (FEV1%); (2) assess the frequency and level of residential environmental exposures (eg, disinfectants/cleaners, secondhand smoke) via self-reported data and home monitoring objective measures; (3) assess the level of asthma control as indicated by self-reported asthma symptoms and lung function; and (4) explore associations of self-reported and objective measures of residential environmental exposures with self-reported and objective measures of asthma control. Methods We will recruit 50 adults with asthma who have completed our online Global COVID-19 Asthma Study, indicated willingness to be contacted for future studies, reported high use of disinfectant/cleaning products, and have asthma that is not well controlled. Participants will receive an indoor air quality monitor and a home spirometer to measure VOCs, PM2.5, and FEV1%, respectively. EMA data will be collected using a personal smartphone and EMA software platform. Participants will be sent scheduled and random EMA notifications to assess asthma symptoms, environmental exposures, lung function, and mitigation strategies. After the 14-day data collection period, participants will respond to survey items related to acceptability, appropriateness, and feasibility. Results This study was funded in March 2021. We pilot tested our procedures and began recruitment in April 2022. The anticipated completion of the study is 2023. Conclusions Findings from this feasibility study will support a powered study to address the impact of home environmental exposures on asthma symptoms and develop tailored, home-based asthma interventions that are responsive to the changing home environment and home routines. Trial Registration ClinicalTrials.gov NCT05224076; https://clinicaltrials.gov/ct2/show/NCT05224076 International Registered Report Identifier (IRRID) DERR1-10.2196/39887


DESCRIPTION (provided by applicant):
The proposed K01 Award will provide the candidate, Dr. Kreniske, with the skills to achieve his long-term goal of being an independent HIV investigator and an international leader who leverages digital technology to improve AYA) uptake of HIV prevention (including PrEP and HIV testing) and linkage to adolescent and young adult (behavioral health care.The candidate is a developmental psychologist with experience in qualitative and cross-sectional research, domestically and internationally.The proposed training and research experience will expand the candidate's ability to design and evaluate interventions for AYA at high risk for HIV infection and address the high priority topic of the National Institute of Health (NIH) Office of AIDS Research (OAR) of reducing the incidence of HIV.To achieve his overall goals, Dr. Kreniske will receive additional training in: (1) longitudinal data analysis for the purposes of interpreting associations between mobile phone use and protective and risk factors for HIV infection in under-resourced settings; (2) adapting mobile phone-based interventions to address multiple HIV risk factors as they relate to HIV prevention and the HIV care cascade; (3) evaluating mobile phone-based interventions for AYA in underresourced settings using randomized controlled trials (RCT); and (4) professional skills for a successful independent research career, including grant and manuscript writing.The candidate has assembled a mentorship team of national and international leaders who will support his successful transition to independence through coursework, directed readings, one-on-one meetings, hands-on research activities, and completion of an independent research project.Dr. Kreniske's work is based in East and Southern Africa (ESA) where AYA have the highest rates of HIV infection worldwide.Mental health and substance use affect decision making about sexual and reproductive health and thus function as critical barriers to prevention of HIV infection.AYA, particularly in this socio-cultural context, face unique challenges in accessing counselors who can provide mental health and substance use assessment and treatment.To address these challenges the candidate will identify how technology is related to known HIV risk factors (e.g.sexual behaviors, mental health symptoms, substance use) and adapt and   • The candidate's detailed and comprehensive description of training goals and activities corresponds well to the research plan and will address critical gaps in his otherwise excellent preparation for becoming an independent researcher.
• The plan for monitoring and evaluating progress includes detailed benchmarks and frequent opportunities for guidance and feedback from the mentoring team.

Weaknesses
• None Noted by Reviewer

Strengths
• If successful, the planned research will address an urgent need for effective, scalable interventions to address multiple HIV risk factors among a most vulnerable population, adolescents and young adults in East and South Africa.
• Adding PrEP information and a component to address mental health and substance use issues to an existing intervention has the potential to strengthen its impact by simultaneously promoting an effective prevention method and ameliorating factors that interfere with use of preventive measures.
• Using SMS to deliver an intervention enhances feasibility.
• Described plans for adapting and pre-testing the intervention increase the likelihood that it will have the desired impact.
• Preliminary data support the premise that the targeted group is receptive to receiving health information via mobile phone.
• The proposed pilot RCT would provide essential preliminary data to serve as the basis for an R01 application.

Weaknesses
• It is unclear how Aim 1 activities designed to assess the impact of mobile phone ownership on HIV incidence is relevant to the work planned in Aims 2 and 3, as the intervention to be developed is not intended to reduce phone use.• It appears that the planned intervention's impact on mental health and substance use may be entirely dependent on users linking to school counselors and then receiving effective intervention from those counselors.However, the application does not make a strong case for expecting that linkage will have the desired impact on mental health and substance use.If the SMS intervention itself is expected to have a direct effect on these issues, the mechanism and premise for such an effect is not clear.
• The candidate's statement that technological limitations prevent proposing an interactive mental health and substance use intervention seems to underestimate the potential for SMS as a delivery platform for intervention.A review of literature in this area would have been useful to clarify the point.
• The primary endpoint (as described in 4.C.6.1) will be "the binary indicator whether there is an increase in any of these HIV prevention strategies following the intervention; PrEP uptake, number of HIV tests within study period, and safer sexual behaviors."This definition is vague, and outcomes judged by this criterion are not likely to be informative.
• The power analysis based on the primary endpoint offers no justification for the expected proportion who would "increase their HIV prevention strategies" either with or without intervention.

Strengths
• The mentoring team is highly qualified to provide support in the career development and research activities described in this application.
• The primary mentor (Santelli) currently serves as the candidate's mentor in the postdoctoral fellowship.

Weaknesses
• None Noted by Reviewer

Strengths
• Letters from the department chair, mentors, and others demonstrate a strong commitment to the candidate's development as an independent researcher.
• Resources adequate to support the candidate's development and conduct of the research project are currently in place.• The research plan has been scaled back with regard to number of subjects for Aim 3 key informant interviews, and the current plan seems feasible.Formal training in mHealth has been added.Details regarding the intervention to be adapted have been added.

Training in the Responsible Conduct of Research:
Acceptable Comments on Format (Required): • Combination of directed study, coursework, and training workshops.
Comments on Subject Matter (Required): • Training will be broad, covering all required topics.
Comments on Faculty Participation (Required; not applicable for mid-and senior-career awards): • Mentors will engage regularly in discussions of ethics.
Comments on Frequency (Required): • Exceed criterion.Overall Impact: This is a well-written application by a strong candidate.Although relatively new to the HIV prevention and treatment field, he has an excellent publication record and is highly committed to this science.The mentorship team and research and field environments are exceptional.The career development plan has been significantly strengthened in the resubmission, and it is closely aligned with the research plan.The research plan, which addresses a highly significant population with an innovative yet scientifically grounded intervention, has also been clarified and strengthened in the resubmission.The prospects for successful completion of the pilot study and submission of an R01 are raised considerably.There are some moderate weaknesses in the research plan, but overall impact is likely to be high.

Strengths
• The candidate was awarded his PhD.In 2016.His publication record since then is impressive.
• Letters of recommendation are highly supportive.
• Although relatively new to the HIV field, Dr. Kreniske has conducted advanced work for the research plan in Uganda.

Weaknesses
• The development and research plans are ambitious given the candidate's limited prior experience in this field.

Strengths
• The development plan focuses on longitudinal data analysis, adaptation and evaluation of behavioral interventions, and career skills for publishing and grantsmanship.
• The development plan is aligned with the research plan.• The development plan includes a challenging publication timeline.

Weaknesses
• None Noted by Reviewer

Strengths
• The recruitment and retention plan is supported by existing infrastructure in Uganda; parents will receive invitations for their children to participate through schools.
• The m4RH intervention to be adapted was shown to be efficacious in Kenya and Tanzania.
• The adapted intervention will Incorporate PrEP information and mental health and alcohol use measures and components.
• The pilot trial includes 140 youth randomized to the intervention or control conditions; this should provide sufficient data for feasibility and acceptability assessments as well as preliminary efficacy evaluation.
• The resubmission now includes completion and evaluation of the pilot trial by the middle of Year 4, such that an R01 can be considered and submitted by the end of Year 4. The intervention will use the same phone technology platform as the m4RH now being rolled out (but not evaluated) in Uganda, presumably for an older age group.
• The HBM theoretical model, with the addition of peer influence, appears quite appropriate for the target population.
• The outcome measures and analyses are well designed.

Weaknesses
• Data on mental health problems among AYA are not provided.
• The measures of mental distress appear to be those that have been well-validated in high income Western countries.In this context, including in the ongoing research by the mentors working in Uganda, the measures all appear to be exploratory.No prior or proposed validation procedures are apparent in the application.

Strengths
• The mentor team includes the candidate's current mentor as primary mentor, together with an extraordinarily qualified team of experts in both the development plan and the Uganda-based research plan.
• The letters of support are very strong.
• The mentors have a history of collaboration as well as mentorship.

Strengths
• The research environment at Columbia is excellent.
• The field research infrastructure in Uganda is in place.
• There is institutional commitment to the candidate, including the appointment to a faculty position without regard to the success of the K award.Overall Impact: This K01 resubmission is very responsive to reviewer comments.Dr. Kreniske is an exceptional candidate in HIV prevention research among adolescent and young adults (AYA) in southwest Uganda.Dr. Kreniske is completing his postdoc at the HIV Center at New York State Psychiatric Institute/Columbia University.There is strong institutional and mentor support for the candidate, who has been productive in his research and publications thus far.The candidate's longterm career goal is to become an independent investigator in HIV prevention with AYAs in underresources settings.The candidate's research plan maps onto the training plan, which is comprehensive.The proposed research will randomize 140 AYA to an mHealth intervention versus a control.The primary outcome is increased HIV prevention strategies post-intervention.It is unclear what the control group is, however.If successful, the research may yield a potentially high public health impact, in that this intervention could be scaled-up and adapted for other countries.• Reference letters from the candidate's mentors and collaborators are highly supportive.

Candidate: Strengths
• The candidate currently has 7 first-authored manuscripts with several papers under review.
• The candidate was a silver medalist for the NYAS James McKeen Cattell Dissertation Award.
• The candidate's work in East and Southern Africa (ESA) has examined the impact of disparities on health outcomes and this work has set the stage for the training grant.
• The candidate has conducted research on mHealth interventions and has more recently focused his area in HIV prevention and linkage to care, which led to the development of this application.The K01 would help to establish the candidate in the HIV prevention field, specifically in mHealth interventions with AYA.

Strengths
• Career development goals are clearly defined and align with the research plan and future R01 submission.
• The proposed trips to Uganda will enhance the learning experience; it is also important for a PI to be present at study locations.
• The candidate has a well-balanced training plan that covers broad topics such technology and statistics and across various formats, including formal learning, field experience, and mentorrelated training.
• The distribution of effort, and types of training, across activities is excellent.

Weaknesses
• No major concerns.

Strengths
• The proposed study is highly significant, as East and Southern Africa have the highest rate of incident HIV infections globally, with AYA at greatest risk.Text messaging is widely used and is a viable medium for interventions, including sexual health education via text messaging.
• The candidate proposes to adapt and evaluate an evidence-based mobile phone-delivered sexual health program, to include PrEP information, as well as mental health and alcohol use screening and linkage to school-based counselors for AYA in southwest Uganda.
• This work leverages established structure developed by mentor Dr. Ssewamala.
• FHI 360 adapted m4RH for 10-24 AYA in Uganda to address their sexual and reproductive health information needs; adapting m4RH for HIV prevention information is a logical next step.
• The research Aims are clear and the research plan is nicely described for each step of ADAPT-ITT as well as study implementation.• The primary outcome is an increase in any of the HIV prevention strategies post-intervention, including PrEP uptake, number of HIV tests within study period, and safer sexual behaviors (cites in Table 7).
• The mixed methods approach will yield rich data.
• The candidate added new feasibility measures plus a threshold for intervention feasibility and acceptability.

Weaknesses
• There is no information about the control group.
• Uptake of HIV prevention strategies is more clearly defined; however, there is limited information regarding how HIV prevention information will actually be incorporated into the intervention.
• Theatre testing now includes 12 KII (up from 6) which should be enough to assess preliminary feasibility and acceptability.
• It would be helpful to list the outcome variables in Table 7, rather than list citations.

Strengths
• The candidate has assembled a stellar multidisciplinary mentorship team that has a history of collaboration.
• Primary mentor, Dr. Santelli, is an expert in AYA health and medicine, social determinants and social transitions, sexual health, and HIV risk factors.• Content will focus on behavioral research, the development mHealth technology, • and research with youth in under-resourced international settings.
Comments on Faculty Participation (Required; not applicable for mid-and senior-career awards): • Dr. Santelli will provide guidance on ethical issues related to adolescent sexual health (Years 1-4).Dr. Mellins provide guidance on ethical training focused on evaluation and treatment of mental health among global youth.Dr. Ybarra will lead training on digital technology and ethical issues.Footnotes for 1 K01 MH122319-01A1; PI Name: Kreniske, Philip NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-18-197 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-197.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.

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The planned timeline describes a logical progression of activities that should be feasible to carry out within the time frame of the project.Potential sources of risk are appropriately minimized, and overall risk to participants is low.Sex/Gender: Distribution justified scientifically• Race/Ethnicity: Distribution justified scientifically

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The resubmission includes additional rigorous training in statistics, mHealth, and RCT design and execution.

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Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable • Inclusion/Exclusion Based on Age: Distribution justified scientifically • Foreign men and women ages 15Responsive, including changes recommended to the training and research plans Training in the Responsible Conduct of Research: Directed readings, coursework and mentor meetings Comments on Subject Matter (Required): • Digital technology, youth sexual health and mental health Comments on Faculty Participation (Required; not applicable for mid-and senior-career awards): Mentor meetings at least every 4 months, course work and workshops approximately once per year /Career Goals /Plan to Provide Mentoring: 2 Research Plan: 3 Mentor(s), Co-Mentor(s), Consultant(s), Collaborator(s): 1 Environment Commitment to the Candidate: 1

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Co-mentor, Dr. Mellins, is an expert in AYA development and mental health, HIV prevention interventions, and global mental health.• Co-mentor, Dr. Wingood, has expertise in implementation science and intervention adaptation for health and HIV-related interventions; and has developed the ADAPT_ITT model to facilitate adapting evidence-based HIV interventions to diverse populations.•The advisers have expertise in fields relevant to the candidate's career development plan, including advanced longitudinal data analysis and RCT evaluation (Wei), design and evaluation of HIV prevention RCTs in under-resourced settings (Ssewamala), design of mHealth interventions in under-resourced settings (Chang) and mHealth for AYA (Ybarra).

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The HIV Center at NYSPI and Columbia University have outstanding resources, and it is clear from the letters of support that the candidate will be well-supported by his mentorship team.Well-detailed and realistic; more time has been set aside for evaluation, grant submission and manuscript preparation.Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically• For NIH-Defined Phase III trials, Plans for valid design and analysis: Scientifically acceptable • Inclusion/Exclusion Based on Age: Distribution justified scientifically RCR training format via one-on-one meetings with mentors and guided reading, as well as videoconferencing and a formal ethics training.Comments on Subject Matter (Required):

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Training is covered through years 1-4.Comments on Frequency (Required):• Monthly meetings with mentor and co-mentor.Recommend as Requested:THE FOLLOWING SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE, OR REVIEWERS' WRITTEN CRITIQUES, ON THE FOLLOWING ISSUES:

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The candidate has done exemplary doctoral and postdoctoral work, as noted in the very positive letters of support.

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Through his ethnographic and other work, the candidate has demonstrated his ability to conduct high quality research.

Career Development Plan/Career Goals & Objectives: Strengths•
The candidate's plan is very likely to contribute to his scientific development, specifically in the areas of longitudinal data analysis, mobile intervention development, intervention evaluation, and general professional skills.

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For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable • Inclusion/Exclusion Based on Age: Distribution justified scientifically • Plans for specific targeting of youth age 15-19 are appropriate due to vulnerability.

Authentication of Key Biological and/or Chemical Resources:
Candidate is a postdoc at the HIV Center for Clinical and Behavioral Studies at NYSPI and Columbia University and lectures in PopFam at Columbia.
• Table5succinctly describes the proposed ADAPT-ITT methodology by study year, phase, and methodology.