Secondhand Smoke Respiratory Health Study

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.

Inclusion Criteria:

1. 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 FEV1/FVC ratio

- One of the following evidence of airflow obstruction:

- Presence of any airflow limitation on spirometry during the baseline visit

- Development of airflow limitation on spirometry during any stages of
exercise testing

- Residual volume to total lung capacity ratio of >0.35

2. 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