Positive Airway Pressure for the Treatment of Asthma

Asthma is an extremely common disorder, which is becoming more prevalent. The purpose of this study is to examine how nocturnal lung volumes contribute to asthma severity, which may explain part of the link between asthma and obesity. The investigators seek to test the hypothesis that raising lung volumes during the night will improve asthma symptoms. The investigators work may lead to new targets for therapy.

Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness, which causes airflow obstruction. It is extremely prevalent, affecting an estimated 22 million Americans, and costly with loss of productivity and direct healthcare costs in the billions of dollars. The incidence and prevalence of asthma are increasing, both in the US and around the world. This increase comes despite greater understanding of the inflammatory and allergic basis for asthma, and despite better antiinflammatory medications. One explanation for the increasing prevalence of asthma is the concomitant increase in obesity, with the majority of Americans now overweight or obese. Numerous studies have convincingly linked asthma and obesity, and demonstrated increased obstruction with weight gain and decreased obstruction with weight loss. However, the mechanisms that underlie this linkage are not known.

We believe that low lung volumes contribute to the pathogenesis and severity of asthma. End-expiratory lung volume is decreased in obesity, and likely falls further during sleep, particularly in overweight and obese patients. Both upper and lower airway resistance increase with decreasing lung volumes, as airways become smaller. However, prior work has shown that lower airway resistance increases out of proportion to the decrease in lung volume that occurs during sleep in asthma patients. This difference between controls and people with asthma has not been further explored, yet may provide insight into asthma pathogenesis and provide potential targets for therapy.

Therefore, we propose a series of experiments to define the impact of lung volumes during sleep on airway resistance. One of these experiments will be to to test the hypothesis that lung stretch can be used therapeutically by tonically and dynamically increasing lung volumes during sleep using bi-level positive airway pressure. This research can help delineate asthma pathogenesis and may help improve therapeutic options in this exceedingly common disease.

• Asthma
• Sleep Apnea

• No Intervention: Baseline
  Subjects record asthma quality of life and symptoms, without intervention for 4 weeks.
• Experimental: Bi-level PAP
  Subjects wear Bi-level PAP during the night for 4 weeks, and record asthma quality of life and asthma symptoms.
  Intervention: Device: Bi-level positive airway pressure (bi-level PAP)

Inclusion Criteria:

• mild to moderate asthma, diagnosed by a physician, OR
• mild to moderate asthma and CPAP treated OSA. Must be compliant with CPAP therapy (greater than 4 hours per night, at least 4 nights/week)
• BM > 25 kg/m2

Exclusion Criteria:

• lung disease other than asthma or OSA
• medications known to affect respiratory function (apart from asthma and rhinitis therapy)
• abnormal nasal anatomy
• current smokers and ex-smokers (quit within the last 3 months, or >10 pack-years)
• pregnant women - women of child bearing age will undergo a urine pregnancy test before enrollment and during the course of the study, as some of the study procedures cannot be performed during pregnancy and because pregnancy often changes asthma symptoms and severity.
• severe asthma - defined as a recent exacerbation (doctor or ER visit for asthma, or oral steroid use, within the previous 4 weeks) or frequent exacerbations (>4 exacerbations in the last year.
• severe obstructive sleep apnea requiring supplemental oxygen in addition to CPAP therapy.
• the regular use of prescription (e.g. zolpidem) or over-the-counter sleep aids (e.g. Benadryl).