Improved patient recovery and reduced mortality through the use of non-invasive ventilation (NIV) during acute exacerbations of chronic obstructive pulmonary disease (COPD)
Submitting InstitutionKing's College London
Unit of AssessmentClinical Medicine
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Human Movement and Sports Science
Summary of the impact
Very considerable changes worldwide, in the management of patients with
chronic obstructive pulmonary disease (COPD) admitted with acute
ventilatory failure, have been a major impact of the research of the
King's College London (KCL) Clinical Respiratory Physiology Group.
Previously, invasive ventilation to treat such COPD patients was
associated with complications which could be fatal. The KCL group
conducted the first randomised controlled trial in the world of treatment
by non-invasive ventilation (NIV). The trial demonstrated that NIV
reduces complications and death compared to invasive ventilation. The
study dramatically changed the treatment of hypercapnic flare-ups (where
there is too much carbon dioxide in the blood) of acute COPD worldwide.
NIV has become best and routine practice, and is advocated in national and
international guidelines, benefiting many thousands of COPD patients.
KCL research demonstrating that NIV is effective: The KCL Clinical
Respiratory Physiology Group, led by Professor John Moxham (KCL, 1982 -
present), designed and set up the first-ever trial of NIV in patients with
ventilatory failure due to flare-ups or worsening, known as
`exacerbations', of COPD (1). Supported by a grant from the British Lung
Foundation, the trial involved collaboration with colleagues from
Southampton General Hospital and the London Chest Hospital. NIV involves
patients wearing a nasal or facial mask connected to a mechanical
KCL longstanding research on the load on, and capacity of, the
respiratory muscle pump: The foundation for work on NIV was KCL
research on the respiratory muscle pump. People with COPD suffer from
narrowing of the airways, which is both progressive and irreversible.
Obstructed airways, difficulty in expanding the chest (due to
hyperinflation of the lungs) and incomplete exhalation increase the load
on the respiratory muscle pump. In parallel with the increased load on the
respiratory system, there is also a fall in the capacity of the
inspiratory muscles used for breathing in (2,3). This is largely due to
hyperinflation, which causes the inspiratory muscles to shorten and which
impairs their performance. The geometry of the chest alters and adversely
affects the mechanics of the respiratory muscles, so that they are less
able to lower pressure in the chest and thus allow patients to breathe in
KCL research into ventilatory failure: As respiratory diseases
such as COPD progress, the balance between the load on, and the capacity
of, the respiratory muscle pump changes, and the brain signals an increase
in neural respiratory drive (NRD) to maintain adequate ventilation (5).
KCL research found that when the imbalance reaches a critical point,
ventilatory failure occurs (6,7), meaning patients cannot rid their body
of carbon dioxide. When this happens, the carbon dioxide level in blood in
the arteries (PaCO2) rises, body fluids become acid (acidosis)
and enzymes sensitive to acid levels fail to function. These enzymes are
also needed to keep the respiratory muscles working normally. The result
is a downward spiral of breathlessness - often severe.
KCL research showing NIV buys time for treatment: An acute
imbalance between load and capacity of the respiratory muscle pump can be
corrected by mechanical ventilation. This temporarily relieves the load on
the respiratory muscle pump whilst doctors take corrective action. The
introduction of non-invasive ventilation (NIV) meant that this could be
achieved more easily and with less risk of complications or death compared
to invasive ventilation (as invasive ventilation involves intubating
patients by inserting a tube down into the patient's windpipe and sedating
and mechanically ventilating the patient). KCL research showed that NIV
can unload the respiratory muscle pump, control ventilatory failure,
reduce breathlessness and `buy time' for conventional treatment (steroids,
antibiotics, bronchodilators, oxygen, etc.) for COPD exacerbations to work
(6). Thereafter NIV can be discontinued.
Findings widely incorporated into clinical care: The trial
reported in the Lancet in 1993 (1) demonstrated that NIV was effective in
treating ventilatory failure in patients with acute exacerbations of COPD.
NIV reduced the carbon dioxide level in the blood (PaCO2),
reduced the acidity of body fluids, reduced breathlessness and reduced
mortality. In the days following admission to hospital and treatment with
NIV, the standard therapy for exacerbations could then reduce the load on
the respiratory muscle pump and increase the capacity of the respiratory
muscles (by reducing hyperinflation). Neural respiratory drive also
diminishes because the balance between load and capacity improves, and
patients become less breathless (5,7). This internationally leading work
by KCL on NIV improves outcomes for COPD patients admitted with
References to the research
1. Bott J, Carroll MP, Conway JH, Keilty SEJ, Ward EM, Brown AM, Paul EA,
Elliott MW, Godfrey RC, Wedzicha JA, Moxham J. Randomised
controlled trial of nasal ventilation in acute ventilatory failure due to
chronic obstructive airways disease. Lancet 1993;341:1555-7.
2. Polkey MI, Kyroussis D, Hamnegård C-H, Mills GH, Green M, Moxham J.
Diaphragm strength in Chronic Obstructive Pulmonary Disease. Am J
Respir Crit Care Med. 1996;154:1310-7.
3. Polkey MI, Kyroussis D, Mills GH, Hamnegård C-H, Keilty SEJ, Green M,
Moxham J. Inspiratory pressure support reduces slowing of
inspiratory muscle relaxation rate during exhaustive treadmill walking in
severe COPD. Am J Respir Crit Care Med. 1996;154:1146-50.
4. Luo YM, Hart N, Mustafa N, Lyall RA, Polkey MI, Moxham J.
Effect of diaphragm fatigue on neural respiratory drive. J Appl
5. Jolley CJ, Luo YM, Steier J, Reilly C, Seymour J, Lunt A, Ward K,
Rafferty GF, Polkey MI, Moxham J. Neural respiratory drive in
healthy subjects and in COPD. Eur Respir J. 2009;33: 289-97.
6. Stell IM, Paul G, Lee K, Ponte, Moxham J. Non-invasive
ventilator triggering in Chronic Obstructive Pulmonary Disease: a
test-lung comparison. Am J Respir Crit Care Med. 2001;64:2092-7.
7. Murphy PB, Kumar A, Reilly C, Jolley C, Walterspacher S, Fedele F,
Hopkinson NS, Man WDC, Polkey MI, Moxham J, Hart N. Neural
respiratory drive as a physiological biomarker to monitor change during
acute exacerbations of COPD. Thorax 2011;66:602-8.
Details of the impact
Significant impact on treatment of COPD exacerbations: The
evidence provided by the first- ever randomised clinical trial of NIV in
acute hypercapnic exacerbations of COPD (1) has had a significant impact
on the management of this common critical medical condition. The trial,
and subsequent research which confirmed the findings, resulted in modified
guidelines for managing acute exacerbations of COPD in the UK, Europe, USA
and worldwide, and an increase in the use of NIV. Thousands of patients
who would have died or would have suffered complications from invasive
ventilation have survived (8).
Considerable improvement in outcomes for patients with ventilatory
failure in acute exacerbations of COPD: The number of patients
admitted with acute exacerbations of COPD in England each year is 100,000.
The mortality rate in patients with ventilatory failure (high arterial
PaCO2 and acidosis) at the time of admission who do not respond
to conventional treatment (bronchodilators etc.) is high if they are not
mechanically ventilated (9).
Across England around 7% of all COPD admissions (7,000 patients) are
treated with NIV, saving 800-1,000 lives. One of the indicators in the NHS
Outcomes Framework 2012/13 is "preventing people from dying prematurely".
NIV is highly effective in preventing premature deaths: NICE guidelines
(12) present evidence for the benefits of NIV, including reducing deaths
The British Thoracic Society (BTS) indicates that "Non-invasive
ventilation in the management of acute type II respiratory failure in COPD
patients represents one of the major technical advances in respiratory
care...with a reduction in mortality of approximately 50% demonstrated in
Guidelines recommend NIV: The Joint British Thoracic Society (BTS)
/ Royal College of Physicians / Intensive Care Society Guidelines
recommend "NIV should be considered for all COPD patients with a
persistent respiratory acidosis after a maximum of one hour of standard
medical therapy (grade A recommendation) (10). The National Institute for
Health and Care Excellence (NICE) recommends non-invasive ventilation as
the treatment of choice for COPD exacerbations (12). Recognition of this
clinical advance by the BTS and NICE guidelines means that more and more
hospitals are now offering NIV (11).
Use of NIV to treat COPD patients rises: One of the quality
indicators in the NHS Atlas of Variation in Health Care for People with
Respiratory Disease 2012 (11) is "Proportion of patients admitted with
COPD receiving non-invasive ventilation (NIV) by Primary Care Trust
(PCT)". In England, 97% of acute care hospitals now offer NIV for COPD
patients although the proportion of patients admitted with COPD treated
with NIV shows a seven-fold variation between different
hospitals/PCTs/boroughs. As healthcare commissioners and healthcare
providers are seeking to address this variation, the use of NIV in acute
COPD continues to rise. BTS indicates that "There has been a rapid
expansion in the provision of NIV services with over 90% of UK admitting
hospitals offering this intervention" (10).
Changes in clinical practice: National and international
guidelines recommending NIV for acute COPD have had a considerable impact
on clinical practice. The 2010 UK National Institute for Health and
Clinical Excellence (NICE) guidelines (12) recommend: "NIV should be used
as the treatment of choice for persistent ventilatory failure during
exacerbations..." (p.389). The 2008 national COPD audit (13) (p.23) showed
that 79% of acute NHS units fully met and 18% partially met this NICE
The Department of Health specification on service to manage COPD
exacerbations (14) states that "Facilities for NIV should be available in
all acute care hospitals where people with exacerbations complicated by
respiratory failure are managed" (p.15). In England, Academic Health
Science Networks (AHSNs), which set out to drive best practice and the
requirement for all NHS providers within AHSNs to comply with
evidenced-based treatments, are further extending use of NIV for acute
COPD admissions where appropriate.
Considerable reduction in costs: The use of NIV has a considerable
impact on costs. NICE clinical guidelines (12) present evidence that (a)
NIV is cost effective in patients with a severe exacerbation of COPD as it
is more effective and less expensive, than standard therapy alone and (b)
the addition of ward based NIV to standard treatment is cost effective
when compared with standard treatment alone, with an incremental cost
effectiveness ratio of -£645 per death avoided.
Market for NIV devices expands: Success in treating acute COPD
patients with NIV and subsequent wider use has greatly expanded the market
for ventilators. For example, across KCL- associated hospitals, the number
of ventilators used for acute COPD has increased 10 fold. At the time of
the KCL research the ventilators were large, heavy and positioned on the
floor; now they are small, light and sit easily on the patient's bedside
locker. The challenge of devising NIV ventilators acceptable to
breathless, often distressed, COPD patients has driven innovation in
ventilator technology. Technical improvements have made NIV more
acceptable to patients with acute COPD and have helped extend the use of
NIV to patients with cystic fibrosis and to stable COPD patients with
chronic ventilatory failure.
Global reach of findings: National Institute for Health and Care
Excellence (NICE) guidelines have a considerable impact on treatment in
many countries across the world. The global smoking pandemic is driving up
the prevalence of COPD worldwide, particularly in China and India. NICE is
now collaborating with China on chronic disease, with an initial focus on
COPD and stroke (15). The NICE COPD guidelines are a starting point for
Sources to corroborate the impact
Treatment recommendations based on KCL group's work
- Cochrane collaboration: non-invasive positive pressure ventilation for
the treatment of respiratory failure due to exacerbations of chronic
obstructive pulmonary disease (Review). 2009. John Wiley & Sons,
Ltd. "Non-invasive positive pressure ventilation (NPPV) used in patients
with acute exacerbations of COPD substantially improves recovery....
NPPV...has been shown to be beneficial for such patients in reducing
hospital deaths and also the number of patients going on to require
tracheal intubation. NPPV has also been shown to reduce complications
associated with treatment and length of hospital stay" (p.2).
"Implications for practice: Published data from good quality randomised
controlled trials are now convincing for NPPV to be recommended as first
line intervention as an adjunct therapy to usual medical care in all
suitable patients for the management of respiratory failure secondary to
an acute exacerbation of COPD. A trial of NPPV should be considered
early in the course of respiratory failure and before severe acidosis
ensures, as a means of reducing the risk of endotracheal intubation,
treatment failure and mortality" (p.14). (Discusses results of the
first-ever NIV clinical trial (KCL) (1) and cites it throughout)
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global
strategy for the diagnosis, management, and prevention of chronic
obstructive pulmonary disease. Updated 2013. "NIV has been shown to
improve acute respiratory acidosis, decrease respiratory rate, work of
breathing, severity of breathlessness, complications such as ventilator
associated pneumonia and length of hospital stay. More importantly
mortality and intubation rates are reduced by this intervention." (Cites
 p.43 as Evidence A)
- Joint British Thoracic Society; Royal College of Physicians; Intensive
Care Society Guidelines 2008. The use of Non-Invasive Ventilation in the
management of patients with chronic obstructive pulmonary disease
admitted to hospital with acute type II respiratory failure. (Cites 
p.16, p.26) http://www.brit-thoracic.org.uk/Guidelines/NIPPV-NIV-in-Acute-Respiratory-Failure-Guideline.aspx
- NHS Atlas of Variation in Healthcare for People with Respiratory
National guidelines (and evidence for take-up of recommendations)
- National Institute for Health and Care Excellence (NICE) guidance
2010. Chronic obstructive pulmonary disease (updated) (CG101) Management
of chronic obstructive pulmonary disease in adults in primary and
secondary care. Full guideline.
- Report of The National Chronic Obstructive Pulmonary Disease Audit
2008: Resources and Organisation of Care in Acute NHS Units across the
- Service Specification: Service to Manage COPD Exacerbations. 2012.
- National Institute for Health and Care Excellence (NICE) signed a
memorandum of understanding with the China National Health Development
Research Center, Chinese Ministry of Health in October 2010.