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.

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 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
     • 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