Secondhand SmokePhase 4NCT02797275
Secondhand Smoke Respiratory Health Study
A Phase 4 study testing Albuterol in people with Secondhand Smoke and Air Trapping, run by University of California, San Francisco at 2 sites in United States.
Trial summary
Exposure to secondhand tobacco smoke (SHS) is associated with diverse health effects in nonsmokers. Flight attendants (FA) who worked on commercial aircraft before the ban on tobacco smoking (exposed FAs) had high, long-term levels of occupational exposure to SHS and are a unique population for the study of long-term… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Secondhand Smoke, Air Trapping, Tobacco
- What is being tested?
- Albuterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Jun 2016to 31 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Never Smoking SHS-exposed Flight Attendants:
- aircraft cabin SHS exposure of >1 year while working for airlines
- Never smoker as defined by use of <100 cigarettes lifetime and none within the last year.
- Normal forced expiratory volume (FEV) FEV1/ forced vital capacity (FVC) ratio
- One of the following evidence of airflow obstruction:
- Presence of any airflow limitation on spirometry during the baseline visit
Show all 18Show fewer
- Development of airflow limitation on spirometry during any stages of exercise testing
- Residual volume to total lung capacity ratio of >0.35
- Exclusion Criteria:
- History of active cardiac disease, uncontrolled hypertension, congestive heart failure
- History of direct tobacco use of over 100 cigarettes in their lifetime
- History of established respiratory diseases such as asthma, emphysema, chronic bronchitis, interstitial lung disease, or sarcoidosis
- History of debilitating chronic illnesses such as severe lupus or rheumatoid arthritis
- History of other illnesses or therapy for illnesses that could affect lung function such as radiation therapy for breast cancer
- Physical inability to perform exercise testing
- BMI >30 kg/m2
- History of marijuana use of >100 joints lifetime, and none within the last year
- History of other recreational drug use
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Medical Center
San Francisco, California, 94121
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: Lung Anatomic, Physiologic, and Inflammatory Changes With Chronic Exposure to Secondhand Tobacco Smoke
Exposure to secondhand tobacco smoke (SHS) is associated with diverse health effects in nonsmokers. Flight attendants (FA) who worked on commercial aircraft before the ban on tobacco smoking (exposed FAs) had high, long-term levels of occupational exposure to SHS and are a unique population for the study of long-term health effects of chronic exposure to SHS.
In previous studies, we have shown that many never-smoking SHS-exposed FAs to have curvilinear flow-volume loops, decreased airflow at mid- and low-lung volumes, and static air trapping (elevated residual volume to total lung capacity ratio [RV/TLC]), abnormalities that are not diagnostic of overt Chronic Obstructive Pulmonary Disease (COPD), but do implicate the presence of an obstructive ventilatory defect, and are consistent with what has been recently described as preserved ratio impaired spirometry (PRISm).
The main objective of the study is to determine the effect of a bronchodilator to counter the physiologic abnormalities that are observed in the population of never-smoking SHS-exposed FAs as both proof of concept of the presence of an obstructive lung disease and as a possible therapeutic option to counteract the adverse respiratory effects of chronic exposure to SHS.
Read the detailed description
The objective of this research plan is to investigate the hypothesis that subclinical airflow limitation and air trapping in never-smoking SHS-exposed individuals with preserved ratio impaired spirometry (PRISm) causes reduced exercise capacity . This in turn will adversely affect their symptoms and quality of life. Furthermore, we hypothesize that exercise capacity, symptoms, and quality of life will improve with the use of inhaled bronchodilators.
We proposed to investigate the above hypotheses through the following specific aims:
Aim 1- Determine whether airflow limitation in never-smoking SHS-exposed individuals with airflow limitation or air trapping is associated with reduced exercise capacity and adverse health and health-related quality of life (HRQL). We propose to measure (1) maximum level of exercise (watts) and maximum oxygen uptake (VO2) in the laboratory setting, (2) level of physical activity during the subjects' routine daily life using an activity monitor, and (3) measure HRQL using survey tools. We propose to then explore associations between these measures and indices of air trapping at rest (RV/TLC) and progressive airflow limitation with exercise (end expiratory lung volume (EELV)and dynamic hyperinflation (DH)).
Aim 2: Determine whether relief of airflow limitation using bronchodilators could improve exercise capacity in never-smoking SHS-exposed individuals with airflow limitation or air trapping in a double blind crossover placebo-controlled randomized clinical trial. We propose to examine the effect of bronchodilators on airflow limitation and air trapping and their effects in turn on exercise capacity, daily level of physical activity, and HRQL to show a cause-and-effect relationship. In this way, we plan to explore the utility of bronchodilators as a treatment option for the observed reduced exercise capacity.
- Conditions
- Secondhand Smoke, Air Trapping, Tobacco, Airflow Limitation, Hyperinflation, Obstructive Lung Disease
- Being tested
- Albuterol, Placebo
- Medical subject headings
- Lung Diseases, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlbuterolDrug
Also called ProAir
Beta agonist respiratory inhaler
PlaceboDrug
Also called Placebo obtained from Teva
respiratory inhaler with no medication
| Study group | Role | What they receive |
|---|---|---|
| Albuterol & Placebo | Experimental | Participants will be placed on the albuterol treatment (2 puffs twice a day, equivalent to 360 mcg per day) after the completion of the baseline screening visit. They will use albuterol for 4 weeks prior to their scheduled second visit during which they will undergo testing. Subsequently, and after a minimum washout period of 2 weeks, they will be placed on the placebo treatment for 4 weeks prior to their scheduled third visit, after which they will come back to undergo testing. Receives: Drug: Albuterol; Drug: Placebo |
| Placebo & Albuterol | Experimental | Participants will be placed on the placebo treatment after the completion of the baseline screening visit. They will use placebo for 4 weeks prior to their scheduled second visit during which they will undergo testing. Subsequently, and after a minimum washout period of 2 weeks, they will be placed on the albuterol treatment (2 puffs twice a day, equivalent to 360 mcg per day) for 4 weeks prior to their scheduled third visit, after which they will come back to undergo testing. Receives: Drug: Albuterol; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Oxygen Consumption (Max VO2)
Maximum oxygen consumption (Max VO2) as determined by a symptom-limited progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake (VO2) achieved. The protocol consisted of 3-min rest, 1-min unloaded (freewheeling) cycling at 60 rpm, followed by increasing work rate of 20-30 Watts each 2 minutes to a maximum tolerated, and 5-min of recovery. Twelve lead ECGs were monitored continuously and were recorded along with BP every 2 min. Oxyhemoglobin saturation (O2sat) determined by pulse oximetry was recorded continuously.
Measured: 4 weeks
Secondary outcomes (7)
Airflow Limitation
After 30 minutes period of rest, the subject will perform exercise at increasing work rates corresponding to 20%, 40%, 60%, and 80% of the maximum oxygen uptake attained in the first exercise with 2 minutes at each stage. Inspiratory capacity will be measured 2 to 3 times at each work rate while recording tidal flow-volume loops to assess for evidence of airflow limitation during exercise. Air flow limitation will be determined by calculating the percent overlap of tidal breathing over expiratory portion of maximum flow.
Measured: 4 weeks
Dynamic Hyperinflation
After 30 minutes period of rest, the subject will perform exercise at increasing work rates corresponding to 20%, 40%, 60%, and 80% of the maximum oxygen uptake attained in the first exercise with 2 minutes at each stage. Inspiratory capacity will be measured 2 to 3 times at each work rate while recording tidal flow-volume loops to assess for evidence of airflow limitation during exercise. Dynamic hyperinflation will be measured by changes in examining end-expiratory lung volume at each stage.
Measured: 4 weeks
Change in scores on the SF-12® Health Survey Short Form (SF-12)
The SF-12 is a 12-item questionnaire used to assess generic health outcomes from the patient's perspective. The SF-12 consists of a subset of 12 items from the SF-36® Health Survey (SF-36) and measures two composite outcomes assessing mental health composite score (MCS) and physical health composite scores (PCS). The PCS \& MCS are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The absolute change in item score by group from baseline up to 12 months was used to assess the quality of life/psychosocial impact on the patients with a larger scores indicating a greater degree of change on physical and mental health.
Measured: Up to 12 months
Change in scores on the Airway questionnaire (AQ20)
The AQ20 is given to patients to measure HRQOL related to asthma and chronic obstructive pulmonary disease (COPD) . It contains 20 items, with scores ranging from 0 to 20 - high scores indicate poor HRQOL. The absolute change in item score by group from baseline up to 12 months will be reported
Measured: Up to 12 months
Change in scores on the International Physical Activity Questionnaires (IPAQ)
The IPAQ measure a participants physical activity by either telephone interview or self-administered methods. IPAQ assesses physical activity undertaken across a comprehensive set of domains including: leisure time physical activity, domestic and gardening (yard) activities, work-related physical activity, and transport-related physical activity. Based on the participant responses, results are categorized into Low, Moderate, or High levels of physical activity. The absolute change in score by group from baseline up to 12 months will be reported
Measured: Up to 12 months
Change in level of physical activity over time
Real world (outside lab) level of physical activity will be measured using an activity monitor (Actigraph) over a period of a week starting the third week during their treatment. The Actigraph is a monitor that allows collection and analysis of daily activity information about subjects in their normal daily living environment, which records both the number of steps and the time interval during which the steps are taken. The change in score by group from baseline up to 12 months will be reported
Measured: Up to 12 months
Association between respiratory abnormalities and HRQOL outcomes.
The association between respiratory abnormalities and HRQOL outcomes at 12 months will be determined using pearson/spearman correlation. The aim is to show that at least 8%-10% of the variation in level of physical activity or score on our survey tools are explained by the observed lung function abnormalities and cabin SHS exposure (a correlation coefficient of at least 0.28). Correlation coefficients range from + 1 to -1, with a coefficient of 0=no correlation.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study start6 Jun 2016
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Secondhand SmokeStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Flight Attendant Medical Research Institute
- Responsible party
- Sponsor
- Investigators
- Mehrdad Arjomandi, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797275
- Sponsor's protocol ID
- SHS
- Other IDs
- 13631
- Status last verified
- Jun 2026
- First submitted
- 6 May 2016
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abbaspour Kaboudan F, Zeng S, Abrham Y, Roman J, Butner K, Merati M, Arjomandi M. Determinants of Reclassification of Exercise Performance across Cardiopulmonary Exercise Testing Prediction Equations. Med Sci Sports Exerc. 2026 Nov 1;58(11):2570-2580. doi: 10.1249/MSS.0000000000004065. Epub 2026 Jul 3.
PubMed 42492489
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Anatomic, Physiologic, and Inflammatory Changes With Chronic Exposure to Secondhand Tobacco Smoke
- ClinicalTrials.gov ID
- NCT02797275
- Acronym / sponsor ID
- SHS
- Conditions
- Secondhand Smoke, Air Trapping, Tobacco, Airflow Limitation, Hyperinflation, Obstructive Lung Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 107 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Flight Attendant Medical Research Institute
- Study start
- 6 Jun 2016 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 13 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Exposure to secondhand tobacco smoke (SHS) is associated with diverse health effects in nonsmokers. Flight attendants (FA) who worked on commercial aircraft before the ban on tobacco smoking (exposed FAs) had high, long-term levels of occupational exposure to SHS and are a unique population for the study of long-term health effects of chronic exposure to SHS.
In previous studies, we have shown that many never-smoking SHS-exposed FAs to have curvilinear flow-volume loops, decreased airflow at mid- and low-lung volumes, and static air trapping (elevated residual volume to total lung capacity ratio [RV/TLC]), abnormalities that are not diagnostic of overt Chronic Obstructive Pulmonary Disease (COPD), but do implicate the presence of an obstructive ventilatory defect, and are consistent with what has been recently described as preserved ratio impaired spirometry (PRISm).
The main objective of the study is to determine the effect of a bronchodilator to counter the physiologic abnormalities that are observed in the population of never-smoking SHS-exposed FAs as both proof of concept of the presence of an obstructive lung disease and as a possible therapeutic option to counteract the adverse respiratory effects of chronic exposure to SHS.
Detailed description
The objective of this research plan is to investigate the hypothesis that subclinical airflow limitation and air trapping in never-smoking SHS-exposed individuals with preserved ratio impaired spirometry (PRISm) causes reduced exercise capacity . This in turn will adversely affect their symptoms and quality of life. Furthermore, we hypothesize that exercise capacity, symptoms, and quality of life will improve with the use of inhaled bronchodilators.
We proposed to investigate the above hypotheses through the following specific aims:
Aim 1- Determine whether airflow limitation in never-smoking SHS-exposed individuals with airflow limitation or air trapping is associated with reduced exercise capacity and adverse health and health-related quality of life (HRQL). We propose to measure (1) maximum level of exercise (watts) and maximum oxygen uptake (VO2) in the laboratory setting, (2) level of physical activity during the subjects' routine daily life using an activity monitor, and (3) measure HRQL using survey tools. We propose to then explore associations between these measures and indices of air trapping at rest (RV/TLC) and progressive airflow limitation with exercise (end expiratory lung volume (EELV)and dynamic hyperinflation (DH)).
Aim 2: Determine whether relief of airflow limitation using bronchodilators could improve exercise capacity in never-smoking SHS-exposed individuals with airflow limitation or air trapping in a double blind crossover placebo-controlled randomized clinical trial. We propose to examine the effect of bronchodilators on airflow limitation and air trapping and their effects in turn on exercise capacity, daily level of physical activity, and HRQL to show a cause-and-effect relationship. In this way, we plan to explore the utility of bronchodilators as a treatment option for the observed reduced exercise capacity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albuterol & Placebo | Experimental | Drug: Albuterol, Drug: PlaceboParticipants will be placed on the albuterol treatment (2 puffs twice a day, equivalent to 360 mcg per day) after the completion of the baseline screening visit. They will use albuterol for 4 weeks prior to their scheduled second visit during which they will undergo testing. Subsequently, and after a minimum washout period of 2 weeks, they will be placed on the placebo treatment for 4 weeks prior to their scheduled third visit, after which they will come back to undergo testing. |
| Placebo & Albuterol | Experimental | Drug: Albuterol, Drug: PlaceboParticipants will be placed on the placebo treatment after the completion of the baseline screening visit. They will use placebo for 4 weeks prior to their scheduled second visit during which they will undergo testing. Subsequently, and after a minimum washout period of 2 weeks, they will be placed on the albuterol treatment (2 puffs twice a day, equivalent to 360 mcg per day) for 4 weeks prior to their scheduled third visit, after which they will come back to undergo testing. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Never Smoking SHS-exposed Flight Attendants:
- Exclusion Criteria:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlbuterolAlso: ProAirBeta agonist respiratory inhaler | Drug | Albuterol & Placebo, Placebo & Albuterol |
| PlaceboAlso: Placebo obtained from Tevarespiratory inhaler with no medication | Drug | Albuterol & Placebo, Placebo & Albuterol |
Primary outcome
Maximum Oxygen Consumption (Max VO2)
Time frame: 4 weeks
Maximum oxygen consumption (Max VO2) as determined by a symptom-limited progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake (VO2) achieved. The protocol consisted of 3-min rest, 1-min unloaded (freewheeling) cycling at 60 rpm, followed by increasing work rate of 20-30 Watts each 2 minutes to a maximum tolerated, and 5-min of recovery. Twelve lead ECGs were monitored continuously and were recorded along with BP every 2 min. Oxyhemoglobin saturation (O2sat) determined by pulse oximetry was recorded continuously.
7 secondary outcomes
Airflow Limitation
Time frame: 4 weeks
Dynamic Hyperinflation
Time frame: 4 weeks
Change in scores on the SF-12® Health Survey Short Form (SF-12)
Time frame: Up to 12 months
Change in scores on the Airway questionnaire (AQ20)
Time frame: Up to 12 months
Change in scores on the International Physical Activity Questionnaires (IPAQ)
Time frame: Up to 12 months
Change in level of physical activity over time
Time frame: Up to 12 months
Association between respiratory abnormalities and HRQOL outcomes.
Time frame: Up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Derived from this study: PubMed 42492489Abbaspour Kaboudan F, Zeng S, Abrham Y, Roman J, Butner K, Merati M, Arjomandi M. Determinants of Reclassification of Exercise Performance across Cardiopulmonary Exercise Testing Prediction Equations. Med Sci Sports Exerc. 2026 Nov 1;58(11):2570-2580. doi: 10.1249/MSS.0000000000004065. Epub 2026 Jul 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehrdad Arjomandi, MD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Albuterol in people with Secondhand Smoke and Air Trapping, run by University of California, San Francisco at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Oxygen Consumption (Max VO2) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02797275, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.