Non-invasive Ventilation Versus Sham Ventilation in Chronic Obstructive Pulmonary Disease (COPD)
Non-invasive Ventilation Versus Sham Ventilation in Chronic Obstructive Pulmonary Disease (COPD)
The investigators hypothesize that continuation of non-invasive ventilation (NIV) at home
 after an episode of acute hypercapnic respiratory failure (AHRF) treated by NIV in COPD
 patients would reduce the likelihood of death and recurrent AHRF requiring NIV or intubation.
 The investigators designed this study in a way that recruited COPD patients would be started
 on home NIV or sham treatment after an episode of AHRF requiring acute NIV. The patients are
 acclimatised to NIV application after a few days of acute use. The investigators chose
 occurrence of life-threatening event (recurrent AHRF and death) as the primary endpoint.
Non-invasive ventilation (NIV) has been shown in randomised controlled trials to improve
 arterial blood gases, reduce intubation and mortality rates in patients suffering from
 exacerbations of chronic obstructive pulmonary disease (COPD) complicated by acute
 hypercapnic respiratory failure (AHRF) [1-7]. Despite success of NIV in AHRF of COPD,
 survivors of this group of patients might suffer from further episodes of AHRF after
 discharge. It has been found in a recent study that COPD patients who survived AHRF after
 treatment with acute NIV had a high risk of readmission and life-threatening events in the
 ensuing year [8]. At one year after discharge, 80% had been readmitted for respiratory
 diagnoses, 63% had another life-threatening event and 49% had died, mainly due to respiratory
 failure. Survivors spent a median of 12% time hospitalized in the subsequent year. A
 significant proportion of survivors required repeated NIV for recurrent AHRF. Another study
 showed that in COPD patients who declined intubation for AHRF and were treated with acute
 NIV, these outcomes were even worse, with a 1-year survival of only 30% [9]. It becomes
 imperative to find ways to reduce the occurrence of life-threatening events in the survivors.

 There has been uncontrolled data to suggest that home NIV might reduce both hospital
 admissions and clinic visits in severe COPD with hypercapnic respiratory failure. In 11
 severe stable COPD patients with chronic hypercapnia who did not respond to conventional
 treatment, Jones et al put them on home NIV [10]. Hospital admissions and clinic visits were
 halved in the subsequent year, together with a sustained improvement in arterial blood gases.
 Cost saving was demonstrated with home NIV in severe COPD in another study [11]. However,
 results from randomized controlled studies (RCTs) are conflicting. Three early studies
 suggested that home NIV was not superior to standard treatment in stable severe COPD [12, 13,
 14]. On the other hand, Meecham-Jones et al found that NIV with long term oxygen therapy
 (LTOT) significantly improved daytime blood gases, nocturnal gas exchange and sleep quality
 in severe COPD [15]. A long-term RCT on home NIV in severe COPD showed that home NIV
 significantly reduced dyspnoea ratings, improved psychomotor coordination and decreased
 hospital admissions at 3 month, though reduction in hospital admissions was no longer evident
 by 12 months [16]. However, these randomized studies have been criticized for including
 chronic stable COPD patients who were not hypercapnic enough to benefit from home NIV, using
 inadequate inflation pressures, inadequate patient acclimatization time and not selecting the
 optimal outcome variables [17]. In the most recent RCT [18], home NIV with LTOT was shown to
 significantly improve gas exchange, dyspnoea score and quality of life; there was also a
 trend to reduced hospital and ICU admissions. However, the study was only powered to detect
 improvement in daytime PaCO2 in the NIV group.

 We hypothesize that continuation of NIV at home after an episode of AHRF treated by NIV in
 COPD patients would reduce the likelihood of death and recurrent AHRF requiring NIV or
 intubation. We design this study in a way that recruited COPD patients would be started on
 home NIV or sham treatment after an episode of AHRF requiring acute NIV. The patients are
 acclimatised to NIV application after a few days of acute use. We choose occurrence of
 life-threatening event (recurrent AHRF and death) as the primary endpoint.
Inclusion Criteria:

 -  COPD patient with AHRF who survives after treatment with NIV and successfully weaned
 off for at least 48 hours.

 -  Patients who have been intubated and mechanically ventilated can be included if they
 have also been treated with NIV in the same hospital admission

 -  Significant obstructive sleep apnoea ruled out by overnight polysomnography done after
 successful weaning of NIV (Apnoea-hypopnoea index, AHI, < 10/hr

 -  Patients willing to give their written informed consent to participate in the study

 -  Patients understand that he/she would be randomised into receiving home NIV or sham
 ventilation

 -  Patients who are able to use the home pressure support ventilators after a period of
 acclimatisation and training before discharge from the hospital

 Exclusion Criteria:

 -  Patients with non-COPD causes of AHRF (e.g. asthma, bronchiectasis or lobar pneumonia,
 fibrothorax, acute pulmonary oedema, etc)

 -  Patients who have contraindications to NIV and those who refused or failed NIV during
 an initial 15-minute acclimatization period

 -  Active smoker

 -  An increase of ≥ 15% in FEV1 after inhaled salbutamol (200μg)

 -  Obstructive sleep apnoea (OSA) with apnoea-hypopnoea index (AHI) of ≥ 10/hr

 -  Other significant co-morbid conditions that in the investigators' view, would confer
 an adverse prognosis during the study period, e.g., congestive heart failure,
 uncontrolled diabetes mellitus, tuberculosis, neoplasms, peripheral vascular disease
 threatening organ functions

 -  Adverse psycho-social circumstances not conducive to home NIV treatment (Appendix 2)

 -  On long-term systemic steroid (prednisolone ≥ 7.5 mg per day for ≥ 3 months)