The INTERvening for LUNG Health Trial (INTERLUNG)

The INTERvening for LUNG Health (INTERLUNG) Trial: A Pragmatic Hybrid Implementation-Effectiveness Trial of Community-Based Interventions to Improve Respiratory Health in Bhaktapur, Nepal

This research study is being done to find out whether a community health volunteer-delivered, multi-component program can improve lung health for people at risk of chronic respiratory diseases (such as asthma or COPD) in Bhaktapur, Nepal. The program focuses on reducing tobacco smoke exposure, reducing indoor and outdoor air pollution exposure, preventing respiratory infections (including vaccination and mask use during viral seasons), and encouraging safe physical activity. The "index participant" is the main enrolled participant in the household who is randomized to the intervention or control arm.

The participant will be in the study for about 40 months and will have 11 research visits: one at baseline and then every 4 months through month 40. At visits, staff will do breathing tests (spirometry before and after an inhaled medicine), measure exhaled carbon monoxide, check blood pressure, measure height/weight at selected visits, and ask questions about symptoms, smoking, infections, vaccines, and quality of life. The participant will also wear an activity monitor (accelerometer) for 2 weeks at baseline and at follow-up visits. If individual is a household member (not the index participant), the participant may be asked to complete baseline and follow-up assessments every 4 months through month 40, will receive the influenza vaccine and will primarily be asked to use masks and handwashing during household respiratory illness episodes (only if the index participant is randomized to the intervention) and will not be asked to wear an activity monitor. If the participant is in the pilot phase, participation will last about 2 months. the participant will complete baseline procedures and pilot follow-up visits during those 2 months instead of the full 40-month schedule.

Study Overview

• Status: Not yet recruiting
• Conditions: Spirometry
• Intervention / Treatment: Behavioral: Community health worker-delivered multi-component respiratory health intervention

Detailed Description

Chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease (COPD), and chronic bronchitis, represent a major global health challenge, accounting for over 455 million cases and 4 million deaths annually, with the greatest burden in low- and middle-income countries (LMICs). INTERvening for LUNG health (INTERLUNG) is a 40-month randomized controlled trial in Bhaktapur, Nepal, aimed at evaluating a multi-component, community health worker (CHW)-driven intervention for CRD prevention, targeting both environmental and infectious risk factors. The intervention integrates tobacco prevention (education, peer support, nicotine replacement therapy, quit lines), reduction of indoor and ambient air pollution (HEPA purifiers, vacuum cleaners, N95 masks for high pollution days), infectious risk mitigation (annual influenza vaccination and a one-time pneumococcal vaccination, surgical mask use during viral seasons or household illness, and handwashing support), and promotion of physical activity. Human-centered design (HCD) workshops and in-depth interviews with community members, healthcare practitioners, government officials, and multilateral organizations conducted in 2025 and early in 2026 informed adaptation to local context, addressing key implementation factors such as partner and community engagement, compatibility, and resource availability. Eight hundred index participants aged 9 years with impaired lung function (10th percentile or lower in FEV1/FVC Z-score) and chronic respiratory symptoms, along with household members, will be randomized to intervention or usual care, with outcomes assessed at 40 months. Clinical outcomes include improvements in lung function (primary outcome) and respiratory health-related quality of life (St. Georges Respiratory Questionnaire); secondary outcomes encompass implementation metrics such as adoption, acceptability, appropriateness, fidelity, and scalability, evaluated through mixed methods including surveys, adherence monitoring, and qualitative interviews. The project leverages a multidisciplinary team with extensive experience in CRD research, implementation science, and community-based interventions in Nepal, and builds on robust infrastructure for population health research and environmental monitoring. By integrating evidence-based strategies for tobacco control, air pollution reduction, vaccination, and physical activity promotion into a scalable CHW-driven model, INTERLUNG addresses critical gaps in CRD prevention and management in LMICs, aligns with global health priorities and Sustainable Development Goals, and provides a framework for future scale-up and policy integration. The anticipated impact includes improved lung function trajectories and quality of life for at-risk populations, enhanced health system capacity for chronic disease management, and generation of actionable data to inform broader implementation of multi-component respiratory health interventions in urban LMIC settings. The intervention is adaptable for both children and adults, reflecting a life-course approach. It also addresses the need for culturally relevant education and training for primary healthcare staff. The inclusion of environmental monitoring and objective adherence measures (e.g., air quality sensors, pedometer logs) will strengthen outcome assessments and inform best practices for future implementation. By focusing on both clinical effectiveness and implementation outcomes, INTERLUNG will provide critical insights into the feasibility, acceptability, and scalability of comprehensive CRD interventions in resource-limited urban settings. The results are expected to inform national and regional policy, support integration into universal health coverage packages, and contribute to the global evidence base for CRD prevention and management in LMICs. Ultimately, INTERLUNG aims to reduce the burden of CRDs, improve respiratory health equity, and advance sustainable health system strengthening in Nepal and similar contexts.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: William Checkley, MD, PhD; Phone Number: +1 443-287-4587; Email: wcheckl1@jhmi.edu
• Study Contact Backup: Name: Erika Miller, MHS; Phone Number: +1 443-287-4235; Email: emille76@jhmi.edu

Study Locations

• Nepal
  • Kathmandu
    • Maharajgunj, Kathmandu, Nepal
      • Tribhuvan University
      • Contact: Arun Sharma; Phone Number: +977-985-1007462; Email: docarunsharma@iom.edu.np
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
      • Contact: William Checkley, MD, PhD; Phone Number: 443-287-4587; Email: wcheckl1@jhmi.edu
      • Contact: Erika Miller, MHS; Phone Number: +1 443-287-4235; Email: emille76@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Age ≥9 years at enrollment.
• Resident of the Bhaktapur district and member of a household willing to participate in study procedures.
• Pre-bronchodilator FEV1/FVC at or below the 10th percentile (Z-score ≤ -1.28) based on Global Lung Function Initiative reference equations.
• Presence of at least one respiratory risk factor, including:
• usual cough or phlegm, wheezing in the past 12 months, self-reported prior pulmonary tuberculosis, physician-diagnosed asthma, ever smoking, or occupational exposure to dust or smoke.
• Willing and able to provide written informed consent (or assent with parental/guardian permission for participants <18 years).
• Willing to participate in study assessments and follow-up visits during the 40-month study period.

Exclusion Criteria

• Medical condition that precludes safe performance of spirometry.
• Acute respiratory illness at the time of enrollment that would prevent reliable baseline spirometry testing.
• Plans to move out of the study area during the follow-up period. Inability or unwillingness to comply with study procedures or follow-up visits.
• Any other condition that, in the opinion of the investigators, would interfere with participation or interpretation of study results.

Household members:

• Household members of enrolled index participants may participate in certain assessments and receive selected intervention components if the index participant is randomized to the intervention arm and provides informed consent or assent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care (control) arm; Participants randomized to the usual care (control) arm will continue routine healthcare and daily practices and will not receive the study intervention during the 40-month follow-up period. Control participants will complete the same schedule of research assessments as the intervention arm, including spirometry, questionnaires, accelerometry, and other study measurements conducted at baseline and every four months. The participant will not receive community health worker visits, vaccines facilitated through the study, air purifiers, vacuum cleaners, masks, or behavioral counseling during the trial. At the conclusion of the study, control households will receive educational materials and will be offered an air purifier and vacuum cleaner.
Experimental: Intervention; Participants randomized to the intervention arm will receive a community health worker-delivered, multi-component intervention designed to reduce environmental and infectious respiratory risk factors and promote healthy behaviors over a 40-month follow-up period. Components include tobacco cessation counseling for participants who use tobacco; use of N95/KN95 masks during periods of high ambient air pollution; use of surgical masks and handwashing during household respiratory illness or viral seasons; provision and use of a HEPA air purifier with periodic filter replacement and a HEPA-filter vacuum cleaner; promotion of regular physical activity through goal setting and self-monitoring; facilitation of annual influenza vaccination for household members; and pneumococcal conjugate vaccination (PCV20) for eligible participants. These components are reinforced through regular home visits by trained community health volunteers.	Behavioral: Community health worker-delivered multi-component respiratory health intervention; Participants receive a community health worker-delivered, multi-component intervention designed to reduce environmental and infectious respiratory risk factors and promote healthy behaviors over 40 months. Components include tobacco cessation counseling for participants who use tobacco; use of N95/KN95 masks during periods of high ambient air pollution; use of surgical masks and handwashing during household respiratory illness or viral seasons; provision and use of a HEPA air purifier with filter replacement and a HEPA-filter vacuum cleaner; promotion of regular physical activity through goal setting and self-monitoring; facilitation of annual influenza vaccination for household members; and pneumococcal conjugate vaccination (PCV20) for eligible participants. Intervention activities are reinforced through regular home visits by trained community health volunteers.; Other Names: INTERLUNG intervention; Multi-component chronic respiratory disease prevention program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-bronchodilator FEV₁ Z-score at 40 months	Mean pre-bronchodilator FEV₁ Z-score measured by spirometry using Global Lung Function Initiative reference equations. The primary analysis will compare mean values between intervention and control groups at the end of follow-up. Lung function will be expressed as Global Lung Function Initiative (GLI) z-scores. A Z-score of 0 represents the population mean.Values below 0 indicate lower lung function and values above 0 indicate higher lung function. The study is powered to detect a difference of 0.25 standard deviations between arms.	40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-bronchodilator FVC Z-score	Mean pre-bronchodilator forced vital capacity (FVC) Z-score measured by spirometry using Global Lung Function Initiative reference equations. A Z-score of 0 represents the population mean.Values below 0 indicate lower lung function and values above 0 indicate higher lung function. The study is powered to detect a difference of 0.25 standard deviations between arms.	40 months
Pre-bronchodilator FEV₁/FVC Z-score	Mean pre-bronchodilator FEV₁/FVC Z-score measured by spirometry using Global Lung Function Initiative reference equations. A Z-score of 0 represents the population mean.Values below 0 indicate lower lung function and values above 0 indicate higher lung function. The study is powered to detect a difference of 0.25 standard deviations between arms.	40 months
Post-bronchodilator Spirometry Z-scores	Post-bronchodilator spirometry measurements (FEV1, FVC, and FEV1/FVC Z-scores) obtained 15 minutes after administration of inhaled bronchodilator. A Z-score of 0 represents the population mean.Values below 0 indicate lower lung function and values above 0 indicate higher lung function. The study is powered to detect a difference of 0.25 standard deviations between arms.	40 months
Respiratory Health-Related Quality of Life	Health-related quality of life measured using the St. George's Respiratory Questionnaire (SGRQ). Scores range from 0 to 100, with higher scores indicating worse respiratory health status. The minimal clinically important difference for the SGRQ is 4 points.	40 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Program Sustainability Assessment Tool	The Program Sustainability Assessment Tool (PSAT) score measures the program's capacity for long-term sustainability across domains such as funding stability, partnerships, organizational capacity, evaluation, and strategic planning, with higher scores indicating greater readiness to sustain intervention activities beyond the study period. The Program Sustainability Assessment Tool (PSAT) score ranges from 1 to 7, with higher scores indicating greater capacity of the program to sustain intervention activities over time across domains such as funding stability, partnerships, organizational capacity, evaluation, and strategic planning.	40 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Georgetown University; National Institute of Environmental Health Sciences (NIEHS); Medstar Health Research Institute; Tribhuvan University
• Investigators: Principal Investigator: William Checkley, MD, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Physical Activity; Air Pollution; Behavioral Intervention; Tobacco Prevention; Human-Centered Design; Infectious Risk
• Additional Relevant MeSH Terms: Behavior; Motor Activity
• Other Study ID Numbers: IRB00548883; R01ES037151 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in publications will be shared. Shared data will include baseline characteristics, spirometry measurements, questionnaire responses, environmental exposure measurements, and other study variables necessary to reproduce published analyses. Data will be de-identified in accordance with NIH and institutional data sharing policies to protect participant confidentiality.
• IPD Sharing Time Frame: De-identified individual participant data and supporting documents will become available beginning 12 months after publication of the primary study results or completion of the study, whichever occurs first. Data will remain available for at least 5 years after publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by the study investigators and the Johns Hopkins data access committee will be able to access the data. Requests must include a brief research proposal and a data use agreement. Data will be shared in de-identified form through a secure data repository or controlled-access data transfer consistent with NIH data sharing policies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No