Management and prevention of exacerbations of COPD
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5237 (Published 22 September 2014) Cite this as: BMJ 2014;349:g5237
All rapid responses
An omission from an otherwise excellent overview of exacerbations of COPD is the role of relevant co-morbidities, and in particular oropharyngeal dysphagia (swallow disorder). It is now recognized that oropharyngeal dysphagia is common in both pneumonia among older people (1) and in exacerbations of COPD (2). It has also found to be an independent risk factor in the readmission of older patients with both aspiration and non-aspiration pneumonia (3). All older patients with exacerbations of COPD and pneumonia should be assessed for OPD: if identified, multidisciplinary involvement is warranted in order to reduce risk of further complications and poorer outcomes for this group of patients
1. Cabré M, Serra-Prat M, Force L, Almirall J, Palomera E, Clavé P. Oropharyngeal dysphagia is a risk factor for readmission for pneumonia in the very elderly persons: observational prospective study. J Gerontol A Biol Sci Med Sci 2014;69:330-7.
2. Robinson DJ, Jerrard-Dunne P, Greene Z, Lawson S, Lane S, O’Neill D. Oropharyngeal dysphagia in exacerbations of chronic obstructive pulmonary disease. European Geriatric Medicine 2011;2, 201-203.
3. Cabre M, Serra-Prat M, Force L, Almirall J, Palomera E, Clave P. Prevalence and prognostic implications of dysphagia in elderly patients with pneumonia. Age Ageing. 2010;39:39–45. doi:10.1093/ageing/afp100
4. O’Rourke F, Vickers K, Upton C, Chan D, et al. Swallowing and oropharyngeal dysphagia. Clin Med. 2014;14:196–199. doi:10.7861/clinmedicine.14-2-196
Competing interests: No competing interests
“State of the art” is defined as the level of knowledge and development achieved in a technique, science, etc. [1]. It implies a process of growth, building on existing knowledge.
It is therefore a pity to have to point out again such a serious flaw in an otherwise masterly, inspiring and comprehensive review [2]. In this review, the only mention of smoking is as a risk factor for development of pneumonia. The effect of quitting smoking is not just a matter of removing the most important risk factor for the development and progression of COPD [3], but also that of reversing the well-known effects of smoking on drug metabolism (via induction of several cytochrome P450 enzyme pathways) and tissue oxygen delivery (via raised carboxyhaemoglobin levels). These mechanisms compromise the effectiveness of many interventions mentioned in Dr Aaron’s review.
Although the review focused on clinical trial data, every article needs an introduction, and the key role of smoking cessation should have been mentioned at this stage. Dr Hopkinson and colleagues have already made this point among other issues [4,5], and Dr Aaron’s defence [6] was that he was only asked to review randomised controlled trial (RCT) data. However, RCTs are only one type of scientific evidence, and in fact plenty of space was allocated to non-RCT data (e.g. physiological observations in figure 2 and studies of time onset and duration of exacerbation in figure 3). Furthermore, of the 99 references included only about a third are reports of RCTs.
It is important that key messages don’t get lost in our worship of the RCT. The ground-breaking work of Fletcher, Peto and others [3] is still excellent evidence on which to base clinical practice.
Yours sincerely,
Robert W Fowler
Honorary Consultant Physician
BHR University Hospitals NHS Trust
[1] Collins English Dictionary
[2] Aaron SD. Management and prevention of exacerbations of COPD. BMJ 2014;349:g5237
[3 Fletcher C, Peto R, Tinker CM, Speizer FE. The Natural History of Chronic Bronchitis and Emphysema. An eight-year study of early chronic obstructive lung disease in working men in London. Oxford University Press 1976. [4] Hopkinson NS et al.. High value interventions for reducing exacerbations in COPD. BMJ 2014;349:g5237/rr765299 [5] Hopkinson NS. Re: Management and prevention of exacerbations of COPD. BMJ 2014;349:g5237/rr779519 [6] Aaron SD. Re: Management and prevention of exacerbations of COPD. BMJ 2014;349:g5237/rr/777921
Competing interests: No competing interests
There is more to the function of the lung than gaseous movement throughout its spaces; restriction to FEV1 as an outcome measure is unfortunate. If we consider that the function of the lung is to provide oxygenated blood to the left atrium: other outcome measures permit consideration of pulmonary structures beyond the airways.
I have reported in a single case (myself), the possibility of using relatively cheap PPDE-5 inhibitors to reduce the pulmonary arterial pressure and thereby the proportion of deoxygenated blood passing through the alveoli (relative to that bypassing the system via the AV shunt) and so improving overall lung function in the infected lung(1). More recently Vugik et al have hypothesized on the significance of endothelial changes in COPD. (2)
While the current fixation on FEV1 as an outcome measure may benefit the pharmaceutical industry that makes profits on expensive drugs and delivery systems to increase pulmonary gas flow, reference to capillary pa02 (easily measured using a cheap device that patients can easily use for self-monitoring) has the potential to measure the overall function of the lungs and the outcomes of other promising interventions, including smoking cessation and pulmonary vascular health.
1. Ashworth, A J. Enhanced recovery from respiratory infection following treatment with a PDE-5 inhibitor: a single case study. Prim. care respir. j.. 21(1):17, 2012 Mar. UI: 22382866
2. Persistent endothelial dysfunction turns the frequent exacerbator COPD from respiratory disorder into a progressive pulmonary and systemic vascular disease
Dugac Vukic, A. Ruzic, A. Samarzija M. Badovinac, S. Kehler, T. Jakopovic, M. Volume 84, Issue 2, Pages 155–158 Feb 2015 DOI: http://dx.doi.org/10.1016/j.mehy.2014.11.017
Competing interests: No competing interests
The reason for our initial rapid response was concern that a “State of the Art” review article on the management and prevention of exacerbations of COPD (AECOPD) [1] had omitted or downplayed key, high value interventions – smoking cessation and pulmonary rehabilitation.[2] Professor Aaron is correct when he says in his response that the Puhan meta-analysis of post-exacerbation pulmonary rehabilitation,[3] which found that it reduced readmissions as well as improving survival, health status and exercise capacity, did not report “exacerbation frequency” specifically as an outcome. However, the position that an intervention that reduces readmissions following AECOPD should be excluded from a review of how the condition is managed because some of the subsequent admissions are not due to COPD, never mind the other benefits, seems a little curious. Moreover, the Seymour paper in fact reports COPD exacerbations specifically and found them to be reduced in the post-exacerbation rehabilitation group [4].
We do not agree that it is reasonable to omit reference to smoking cessation as a part of a review of the management and prevention of AECOPD, simply because the evidence is not in the form of an RCT[5]. There is likewise a dearth of RCT data to confirm that smoking cessation prevents the development of COPD. The fact that it does, is not something we know merely “in our hearts” any more than knowledge of the effectiveness of intercostal drainage for tension pneumothorax is compromised by the absence of RCT data.
It has been suggested that evidence based medicine is “in crisis”[6]and this review is a neat illustration of what happens when what is true is considered through the limited prism of “what has been subjected to a randomised controlled trial.”
1. Aaron SD. Management and prevention of exacerbations of COPD, 2014.
2. Zoumot Z, Jordan S, Hopkinson NS. Emphysema: time to say farewell to therapeutic nihilism. Thorax 2014: 69(11): 973-975.
3. Puhan M, A., Gimeno-Santos E, Scharplatz M, Troosters T, Walters EH, Steurer J. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, Chichester, UK, 2011.
4. Seymour JM, Moore L, Jolley CJ, Ward K, Creasey J, Steier JS, Yung B, Man WDC, Hart N, Polkey MI, Moxham J. Outpatient pulmonary rehabilitation following acute exacerbations of COPD. Thorax 2010: 65(5): 423-428.
5. Au D, Bryson C, Chien J, Sun H, Udris E, Evans L, Bradley K. The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations. Journal of general internal medicine 2009: 24(4): 457-463.
6. Greenhalgh T, Howick J, Maskrey N. Evidence based medicine: a movement in crisis?, 2014.
Competing interests: No competing interests
I am surprised that my article has caused Dr. Hopkinson and colleagues such dismay. This was certainly not my intention. I did my best to synthesize a complex and evolving clinical trial literature related to management and prevention of COPD exacerbations. Inevitably it is likely that in reviewing such a complex topic some evidence will be inadvertenly missed or neglected.
However, in my defense, I have to state that the objective of my review was to sythesize evidence available from randomized controlled clinical trials related to treatment and prevention of AECOPD, and it is clearly stated throughout my review article that only RCT evidence was included. Dr. Hopkinson suggests in his letter to the editor that smoking cessation has been clearly shown to prevent AECOPD. Unfortunately, the evidence he quotes, namely the study by Au et al, is not evidence from an RCT, but rather evidence from an observational cohort study in which AECOPD event rates in current smokers and former smokers were compared. I am sure Dr. Hopkinson will agree that this observational study does not qualify as RCT evidence. In fact there is no RCT evidence that I can find to support Dr. Hopkinson's statement that there is 'clear evidence that smoking cessation reduces exacerbation risk.' I agree wholeheartedly with Dr. Hopkinson that smoking cessation is the key to successful therapy of COPD, but realistically even though I know in my heart that this must be true, I could not find the RCT evidence to justify including this intervention in a review article of RCT's specifically focussed on prevention of acute exacerbations of COPD.
Finally, Dr. Hopkinson quotes the Puhan meta-analysis to state that there is evidence that pulmonary rehabilitation post AECOPD prevents further admissions to hospital. I completely agree with him on this point. However the Puhan meta-analysis did not assess whether rehabilitation prevents future acute exacerbations of COPD, only whether rehabilitation prevents hospital admissions. Hospital admissions in these elderly patients with complex co-morbidities can often be entirely unrelated to exacerbations. The point of my review article was to focus on RCT studies of interventions that prevent AECOPD, not those that prevent nonspecific hospital admissions.
Competing interests: No competing interests
Dear Editor,
We were dismayed to see the recent State of the Art Review on the management and prevention of exacerbations of chronic obstructive pulmonary disease, demonstrating a “blind spot” for important interventions in this condition, particularly as it has been published in a general medical journal. (1) Firstly, it contained no reference to smoking cessation as a treatment for COPD. There is clear evidence that smoking cessation reduces symptoms and exacerbation risk.(2) Despite this, provision of smoking cessation services remains uneven and the review misses an opportunity to focus attention on this unmet need. Nationally, the NHS spends over £2.7 billion a year on treating smoking-related illness, but less than £150 million on smoking cessation. (3)
Secondly, although space was given to novel pharmacological interventions, which may or may not turn out to have a significant benefit in the future, the only reference to pulmonary rehabilitation was a recent negative trial of a self-guided home exercise program(4). Data on conventional post-exacerbation pulmonary rehabilitation, including a Cochrane meta-analysis which calculated a number needed to treat of 4 to prevent one readmission and 6 to prevent one death were omitted.(5) Moreover, a 2013 Cochrane review also demonstrated that integrated disease management for COPD patients, which frequently encompasses pulmonary rehabilitation, produced a significant reduction in respiratory related hospital admissions.(6)
This review seems to us to have been a missed opportunity to highlight the need to prioritise and improve the systematic delivery(7) of effective, high value (Figure 1) non-pharmacological interventions(8) which will be key to ensuring a sustainable healthcare system.
1. Aaron SD. Management and prevention of exacerbations of COPD, 2014.
2. Au D, Bryson C, Chien J, et al. The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations. Journal of general internal medicine 2009;24(4):457-63.
3. London Respiratory Team. Final report from the London Respiratory Team three-year programme July 2010-June 2013, 2013.http://www.networks.nhs.uk/nhs-networks/london-respiratory-network
4. Greening NJ, Williams JEA, Hussain SF, et al. An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial, BMJ 2014. http://www.bmj.com/cgi/pmidlookup?view=long&pmid=25004917
5. Puhan M, A., Gimeno-Santos E, Scharplatz M, et al. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2011; (10). http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD00530....
6. Kruis AL, Smidt N, Assendelft WJ, et al. Integrated disease management interventions for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;10:CD009437.
7. Hopkinson NS, Englebretsen C, Cooley N, et al. Designing and implementing a COPD discharge care bundle. Thorax 2012;67(1):90-2.
8. Zoumot Z, Jordan S, Hopkinson NS. Emphysema: time to say farewell to therapeutic nihilism. Thorax 2014. http://thorax.bmj.com/content/early/2014/07/01/thoraxjnl-2014-205667.long
Competing interests: No competing interests
Antibiotics not always necessary in an acute COPD exacerbation in general practice.
Why are antibiotics the third step after bronchodilators and corticosteroids for an exacerbation of COPD in general practice and not the second step after bronchodilators as the review of Shawn Aaron (and GOLD/ERS) proposes (1)? We try to give three arguments.
First, there are more studies (RCT’s) in primary care than mentioned in the review of Aaron namely Sachs (1995), Jörgensen (1992) and ABC (2009). The conclusion was that in COPD exacerbations, no study justifies the use of AB systematically (2) (Streptococcus pneumoniae, Moraxella, Haemophilus inf. are ‘commensal’ in COPD and Pseudomonas is often present in very severe COPD) .
Second, according to the Belgian guideline, antibiotics are - as a rule - not indicated in exacerbations of COPD except: in very ill patients; when after 3 or 4 days there is no recovery even with maximal bronchus dilatation and oral corticoids; in patients with a lung function of FEV1 30% à 50% (while most patients in primary care have FEV1 > 50%); dyspnea at rest, tachypnea, tachycardia. All these symptoms are important but are a minority in most consulting patients with an exacerbation in primary care. (3)
Third, the groups of outpatients, inpatients and patients admitted to the intensive care unit are clinically too different to be summarized/studied in one study group/review. The risk for treatment failure is significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) are included but not when the analysis for outpatients is restricted to currently used antibiotics. (2) We think that the review of Aaron could make more distinction between different selected (outpatient and inpatient) groups.
The inconsistent effects of antibiotics in different (selected) populations call for more research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.
Further, this review and guidelines such as GOLD deserve a multidisciplinary guideline-development.(4)
1. Aaron SD. BMJ 2014;349:g5237. doi: 10.1136/bmj.g5237 state of the art review COPD
2. Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Cochrane Database Syst Rev. 2012 Dec 12;12:CD010257. doi: 10.1002/14651858.CD010257. Antibiotics for exacerbations of chronic obstructive pulmonary disease.
3. BAPCOC Belgian antibiotic policy coordination committee 2012. www.health.belgium.be/antibiotics
4. Kunz R, Fretheim A, Cluzeau F, Wilt TJ, Qaseem A, Lelgemann M, Kelson M, Guyatt G, Schünemann HJ; ATS/ERS Ad Hoc Committee on Integrating and Coordinating Efforts in COPD Guideline Development. Guideline group composition and group processes: article 3 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report. Proc Am Thorac Soc. 2012 Dec;9(5):229-33. doi: 10.1513/pats.201208-056ST.
Competing interests: No competing interests