Effects of NIMV on the Health Status of Chronic Obstructive Pulmonary Disease (COPD )Patients
Effects of NIMV on the Health Status of Chronic Obstructive Pulmonary Disease (COPD )Patients
In this proposal, we will implement a randomized controlled trial to determine whether
 nocturnal NIMV applied for 3 months: 1) improves (disease-specific) health related quality of
 life (HRQL) of COPD patients compared to a control group of patients treated with sham NIMV
 therapy (primary outcome); 2) improves exercise tolerance and walking capacity of COPD
 patients; and 3) improves heart rate variability and decreases sympathetic tone in COPD.
COPD is one of the fastest growing conditions in the world, affecting over 16 million people
 in the US and over 1 million in Canada and costing society over $23 billion per annum (in the
 US). Its prevalence has risen by 41% since 1982, and the age-adjusted death rate has
 increased by 17% between 1966 and 1982 (in contrast to the decline in the age-adjusted death
 rates from all other causes during the same time period). By 2020, COPD will become the third
 leading cause of death (currently 4th representing 5% of all deaths worldwide) and 5th
 leading cause of disability (currently 12th) worldwide. Ironically, despite the rapidly
 growing public health burden of COPD, it is the most underfunded disease among all major
 causes of mortality in North America. Despite some progress in the management of COPD over
 the past two decades, there is still a paucity of efficacious therapies that can effectively
 modify the natural course of this disease.

 There is a growing interest in nocturnal non-invasive mechanical ventilation (NIMV) therapy
 for long-term COPD management for several reasons. It may restore inspiratory rate, which
 diminishes by 30% during rapid eye movement (REM) sleep, improve gas exchange, and rest
 chronically tired respiratory muscles in COPD. Indeed, several uncontrolled studies have
 provided some empirical evidence to support the use of nocturnal NIMV in COPD. However, there
 is a paucity of well-designed controlled trials evaluating this novel therapy particularly
 for COPD patients at a high-risk for morbidity and mortality.

 In this proposal, we will implement a randomized controlled trial to determine whether
 nocturnal NIMV applied for 3 months: 1) improves (disease-specific) health related quality of
 life (HRQL) of COPD patients compared to a control group of patients treated with sham NIMV
 therapy (primary outcome); 2) improves exercise tolerance and walking capacity of COPD
 patients; 3) reduces the number of clinical relapses in COPD patients; 4) improves heart rate
 variability and decreases sympathetic tone in COPD; and 5) is a "cost-effective" therapy.

 We will carefully select COPD patients ready for discharge from an acute care hospital and
 will be invited to participate in this trial. Participants will then undergo a "run-in" phase
 of 4 weeks during which their clinical status will be stabilized. Patients experiencing a
 clinical exacerbation during the "run-in" phase will be excluded from the study. After the
 "run-in" phase, patients will be randomly assigned to one of two groups: nocturnal NIMV
 therapy + standard medical therapy or "sham" + standard medical therapy. The Chronic
 Respiratory Questionnaire (CRQ) and the Health Utilities Index Mark 2/3 (HUI 2 and HUI 3)
 will be used to measure HRQL of study participants at baseline and then at 2, 4, 6, 8, 10 and
 12 weeks. We will also measure the study participants' exacerbation rate during the study
 period. A six-minute walk test will be used to determine the walking capacity of the study
 participants. In addition, 2-D echocardiography and 24-hour ambulatory electrocardiographic
 monitoring will be used to determine the effect of nocturnal NIMV on cardiac performance over
 a 3 month period. Finally, we will perform a comprehensive economic analysis to determine the
 costs as well as the benefits associated with the nocturnal NIMV therapy.

 We anticipate that this study will show that those treated with nocturnal NIMV therapy will
 have better HRQL at 3 months compared to those on sham therapy and this will be associated
 with improved walking capacity and decreased rates of exacerbation. We also anticipate that
 nocturnal NIMV therapy will improve heart rate variability and lower pulmonary arterial
 pressure (during daytime).
Inclusion Criteria:

 -  A clinical diagnosis of COPD and meeting the American Thoracic Society's definition of
 COPD

 -  Age 55 years of age or older;

 -  A history of 10 pack-years or more of cigarette smoking;

 -  FEV1 to FVC ratio of less than 70% and a postbronchodilator FEV1 of less than 50% of
 predicted (at baseline and after the run-in);

 -  PaC02 of 45 mm Hg or greater measured at rest on room air (at baseline and after
 run-in)

 Exclusion Criteria:

 -  Coexisting medical conditions that make survival for at least 6 months unlikely;

 -  Refusal to participate;

 -  Cognitive impairment which makes it impossible to obtain informed consent;

 -  Patient on a lung transplant list;

 -  Clinical history of left ventricular heart failure;

 -  Body mass index of 35 kg/m2 or greater;

 -  (Obstructive) apnea-hypopnea index (AHI) of > 15 on polysomnography;

 -  Evidence of Cheyne-Stokes respiration on polysomnography;

 -  Impaired left ventricular ejection (LVEF of < 40% as determined on 2-D
 echocardiography);

 -  Patients who require rehospitalization, or an emergency visit for COPD during the
 run-in phase