In June we were welcomed to the Whittington Hospital for a day on breathlessness. We were joined by colleagues including respiratory specialist nurses, physiotherapists, specialist pharmacists, members of NHS England and a doctor from the Netherlands. A big tick in the multidisciplinary team curriculum box!
Breathlessness vs respiratory failure: what matters to patients and respiratory clinicians?
Dr Louise Restrick encouraged us to think differently in our approach to breathless patients, by taking a patient-centred perspective. When patients present with breathlessness to emergency services they are frightened by the feeling of breathlessness and they are worried that they might die. The clinicians who see them are focused on whether they have respiratory failure, and particularly acidosis. Key points included:
- oxygen must be prescribed and all those using it must be familiar with the relevant equipment
- a review of the national COPD audit (Roberts et al, Thorax 2011) showed that COPD patients did not always get NIV when appropriate, and not all those that received it were appropriate. Those with acidosis had a significant in hospital mortality
- high flow oxygen increased the mortality from 7% to 11%, again underlying the need to treat oxygen like a drug and consider the side effects as well as benefits
- there was discussion about the NNT for NIV in acute exacerbation of COPD with respiratory failure. The 2004 Cochrane review gives a figure of 8 with an end point of death
- if a patient is breathless but not in respiratory failure, community treatment should be considered
We were reminded that patients with COPD admitted to hospital with breathlessness often had complex needs, including social isolation, co-morbidities, and ongoing tobacco dependance. Breathless as a predictor of mortality was explored, and seen to be a predictor, even in the absence of a respiratory diagnosis:
- Tessier, J. F., et al. “Dyspnea and 8-year mortality among elderly men and women: the PAQUID cohort study.” European journal of epidemiology 17.3 (2001): 223-229
- Tinetti, Mary E., et al. “Effect of Chronic Disease–Related Symptoms and Impairments on Universal Health Outcomes in Older Adults.” Journal of the American Geriatrics Society 59.9 (2011): 1618-1627
- Abidov, Aiden, et al. “Prognostic significance of dyspnea in patients referred for cardiac stress testing.” New England Journal of Medicine 353.18 (2005): 1889-1898. This study found a x2 risk of dying in those who were breathless and had known CAD, and a x4 risk of dying in those who were breathless and ddid not have CAD.
Breathlessness was posited to be a better predictor of mortality than other familiar tools such as spirometry, with night time dyspnoea in particular predicting increased risk of death:
- Nishimura, Koichi, et al. “Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD.” CHEST Journal 121.5 (2002): 1434-1440
- Lange, Peter, et al. “Prevalence of night-time dyspnoea in COPD and its implications for prognosis.” European Respiratory Journal 43.6 (2014): 1590-1598.
The GP Palliative care and end of life care lead for Islington is Dr Patrick McDaid: his tips for end of life care planning can be found online. The integrated service at the Whittington works with him to provide breathlessness interventions. A quote from Dr Kate Granger, geriatrician, terminal cancer patient, and campaigner for better palliative care, reminded us not to undervalue compassion: “I’ve yet to meet a compassionate doctor who is not also competent.”
Breathlessness in COPD: reaching for the steroids
Dr Myra Stern took us through some case studies, and encouraged us to think twice before reaching for the steroids every time we saw a COPD patient with breathlessness. She questioned the evidence for benefit and reminded us of the treatments in COPD with good evidence: smoking cessation, pulmonary rehabilitation and LTOT. NICE guidelines recommend 30mg prednisolone for 7-14 days as a rescue pack, startted on the basis of a change in symptoms as part of a self-management programme. The problem is for those patients who end up on multiple courses of steroids with no clear benefit, and then who are unable to wean off. The question of whether we are underdiagnosing adrenal insufficiency proved difficult to answer. According to endocrinologist advice a SST can be done if a patient is on less than 10mg pred a day or less. Remember the daily doses of inhaled cortcosteroids that may lead to adrenal suppression: 800mcg beclomethasone, 400mcg fluticasone. In addition there is the risk of diabetes and osteoporosis with high dose oral or inhaled steroids. We were encouraged to review the pathogenesis of COPD vs asthma, and consider why steroids are likely to be effective at suppressing inflammation in asthma, but not in COPD.
- Barnes, Peter J. “Immunology of asthma and chronic obstructive pulmonary disease.” Nature Reviews Immunology 8.3 (2008): 183-192.
Asthma vs COPD immunology Experiments have shown that inhaled steroids have no anti-inflammatory action in stable COPD (specifically no change in IL-8 levels, sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 in this case.
- Culpitt, Sarah V., et al. “Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.” American journal of respiratory and critical care medicine 160.5 (1999): 1635-1639.
Several longterm studies have shown no effect from longterm inhaled corticosteroids on FEV1:
- Editorials discussing several studies: Burge, P. Sherwood. “EUROSCOP, ISOLDE and the Copenhagen city lung study.” Thorax 54.4 (1999): 287-288.
- EUROSCOP: Watson, L., et al. “Predictors of lung function and its decline in mild to moderate COPD in association with gender: results from the Euroscop study.”Respiratory medicine 100.4 (2006): 746-753.
- ISOLDE: Burge, P. Sherwood, et al. “Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study.” Thorax 58.8 (2003): 654-658.
- TORCH showed a 25% reduction in exacerbations with combined therapy, but not on the rate of severe exacerbations requiring hospitalisation, compared with salmeterol. No effect on mortality.
NICE recommends combination therapy in those with 2+ exacerbations per year and severe disease (<50% predicted). This should be around 10% of patients, but a much greater proportion get given corticosteroids. It is important to remember that Seretide 250 is the single most expensive drug for the NHS, and 3 of the the top 5 drug costs were all Respiratory inhalers in 2011. More recent evidence suggests we are exposing patients to harm by inappropriately giving inhaled corticosteroids (increased risk of pneumonia). The NNT for inhaled corticosteroids is quoted as 44 to prevent 1 exacerbation over 3 years by Suissa et al. They propose a NNH (harm due to increased risk of pneumonia) of 20 for fluticasone-salmeterol.
Dr Rizwan Kaiser updated us on the treatment of acute PE, focusing on weighing up risks and benefits of treatment dependant on risk stratification. He began by reminding us that mortality in acute PE is largely due to acute RV dysfunction. Outcome is dependant on clot burden and cardiovascular reserve. Risk stratification is based on the European Society of Cardiology Guidelines 2008. High risk are those that are haemodynamically unstable but this is less than 5% patients. There remains debate in how to risk stratify those who are intermediate risk.
- How should these patients be identified (ie which investigations or clinical markers are most reliable)?
- What is the optimal treatment for this group?
- Is there any benefit from thrombolysis?
The investigations that are suggested to identify RH strain in teh context of PE in normotensive patients are:
- ECHO: Grifoni, Stefano, et al. “Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.” Circulation 101.24 (2000): 2817-2822.
- CT: Jiménez, David, et al. “Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.”Thorax (2013): thoraxjnl-2012. RV: LV >0.9 indicates RV dysfunction.
- Troponin:Lankeit, Mareike, et al. “Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism.” European heart journal 31.15 (2010): 1836-1844. Meta-analysis: Becattini, Cecilia, Maria Cristina Vedovati, and Giancarlo Agnelli. “Prognostic value of troponins in acute pulmonary embolism a meta-analysis.” Circulation116.4 (2007): 427-433. Troponins have a low PPV but a high NPV.
- Clinical prognostic indicators include the PESI score: Moores, Lisa, et al. “Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism.” European Respiratory Journal41.2 (2013): 354-359.
A combination of tests is better than any individual test ie: PESI + ECHO + USS Thrombolysis is effective in decreasing clot burden and reducing RV dysfunction acutely, but does this translate into better clinical outcomes short or long term? How should this be balanced against the risk of intracerebral haemorrhage? The evidence is limited.
- Kearon, Clive, et al. “Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines.” CHEST Journal 141.2_suppl (2012): e419S-e494S.
- Wan, Susan, et al. “Thrombolysis compared with heparin for the initial treatment of pulmonary embolism a meta-analysis of the randomized controlled trials.” Circulation 110.6 (2004): 744-749.
Current guidelines are conflicting and vague, due to the paucity of evidence.
- NICE 2012: no thrombolysis
- ESC 2008: thrombolysis may be considered
- ACCP 2012: advised in selected patients – who are they?
We moved on to consider the most up to date evidence.
- Konstantinides, Stavros, et al. “Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.” New England Journal of Medicine 347.15 (2002): 1143-1150.
In this RCT there was no difference in mortality. However, there was lower than expected mortality in the heparin only group 2.2%. A number of reasons have been suggested for the lack of difference between the groups: low patient numbers so trial underpowered; patients in the trial did not truly have ‘submassive PE’; physicians were not in equipoise which may have affected recruitment; all studies allow for thrombolysis if patient becomes haemodynamically unstable, diluting the effect.
- Meyer, Guy, et al. “Fibrinolysis for patients with intermediate-risk pulmonary embolism.” New England Journal of Medicine 370.15 (2014): 1402-1411.
The PEITHO study had a positive result for the composite end point of all cause mortality or haemodynamic collapse within 7 days, but not for the outcome of all cause mortality alone. There was only a 1.8% mortality in the heparin group. It was suggested that tenecteplase decreased deaths from PEs but increased deaths from bleeding ie haemorrhagic stroke. A subgroup analysis suggested that thrombolysis should only be offered to patients with intermediate risk PE who were under 75years old.
- Sharifi, Mohsen, et al. “Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial).” The American journal of cardiology111.2 (2013): 273-277.
The MOPPETT trial used low dose thrombolysis. This trial was not powered for mortality. Instead the primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months. There were fewer adverse events, and there was a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months. Overall, we concluded that current evidence suggested there was a group of patients that would benefit from thrombolysis but that they were difficult to identify and the risks were significant. Advice was:
- monitor patients closely in HDU/CCU
- give an iv heparin bolus 80units/kg then LMWH (or iv heparin if it can be monitored appropriately ie in HDU)
- be ready to thrombolyse ie have the tenecteplase ready
- this must ALWAYS be a Consultant decision, and should be a Respiratory Consultant decision ideally
Dr Amit Patel discussed the acute presentations of ILDs. He highlighted the fact that ILD is more frequent than previous thought, perhaps 3-26/100000. The prevalence of undiagnosed ILD in the community is unknown. The clinico-pathologico-radiological classification of ILDs has gone through a number of revisions over the years, the latest being from the ERS/ATS:
- Demedts, M., and U. Costabel. “ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.” European Respiratory Journal 19.5 (2002): 794-796.
- Some relevant papers are collated by the ATS
ILD presents with breathlessness, cough, fatigue, sleep disturbance (underrecognised), sputum production, malaise, myalgia, and low mood. It can have a significant effect on social/working life. On imaging infiltrates are seen, and on pulmonary function tests there is a restrictive defect and decrease in TLCO. We were reminded that to aid diagnosis, ILDs can be classified into acute, episodic and chronic:
- allergy – drug reaction
- toxins – cytotoxic drugs, toxic fumes
- vasculitis – WG, CS, SLE
- pulmonary eosinophilias – ask about drugs (NSAIDs, antibiotics, cocaine, heroin, cannabis)
- Organising pneumonia
- Idiopathic NSIP
- inorganic dusts
Some cases helped to illustrate presentation and diagnostic pathways. We then considered acute exacerbations of IPF and the difficulties in distinguishing exacerbation from infection. The challenge is that the treatments are different – antibiotics vs steroids. Acute lung injury is identified when there is PaO2:FiO2 <300, often with opacities, and a lack of LV failure. ALI (mortality 30-40%) vs AIP (mortality 70%) vs AEIPF (mortality 50%) may be difficult to distinguish.
Cardiac causes of breathlessness – myth to magic
Dr Suzanna Hardman, Consultant Cardiologist at the Whittington, gave us a Cardiologist’s view on breathlessness and how to distinguish heart failure from other diagnoses. She began with some true or false statements, which helped to emphasise some key points:
- heart failure is not a diagnosis in itself – always look for the underlying cause
- breathlessness on lying flat is not pathognomonic of a cardiac cause. Obesity and respiratory muscle weakness also cause this
- a unilateral effusion is uncommon in heart failure, but is not rare
- the severity of breathlessness does not correlate well with the degree of structural damage
- breathless patients are often complex, with multiple contributing causes to their symptoms
- illness beliefs and psychological factors are very important in determining symptom burden
We were reminded of the array of cardiac causes of shortness of breath:
- angina variant – narrowed coronary artery vessels leading to shortness of breath on exertion (rather than chest pain). Patient will have risk factors for IHD, and generally good LV function. They may describe a ‘walk-through’ distance such that they can push on through the breathlessness and continue to exert themselves. Diagnosis is by demonstration of ischaemia. An angiogram is required. Symptoms resolve with treatment eg PCI.
- valvular disease – typically AS but others may also lead to breathlessness
- arrythmias – AF and AVNRT particularly
- heart failure
The NICE 2010 chronic heart failure, and 2014 acute heart failure guidelines were highlighted, including their reference to the critical role of the specialist, and the need for an integrated approach to care by an MDT. Audits show that the quality of care during the index admission dictate in hospital and subsequent mortality in heart failure. So the overall message from Dr Hardman was make a diagnosis of heart failure and it’s cause on objective measures, and refer to your local heart failure specialist for management.
Obesity and Respiratory Physiology
Dr Swapna Mandel made us all feel slim with her overview of obesity, and reminded us of the physiological effects of this growing problem, seen ever more frequently on our wards and in our clinics. Between 1980 and 2008 there was an increase in BMI of 0.41kg/m2/yr worldwide. The WHO estimates that 1.2 billion people are obese (BMI >30kg/m2). By 2050 (according to Public Health England) the prevalence of obesity in the UK is expected to be 60% adult men, 50% adult women and 25% children. The cost of obesity to the NHS, currently estimated to be >£4.2 billion, is predicted to double by 2050. There are many medical complications of obesity, which contribute to these high costs, and to significant morbidity and mortality in these patients:
- Diabetes – obesity is believed to account for 80-85% of the risk of developing type 2 diabetes, and research suggests that obese people are up to 80 times more likely to develop type 2 diabetes than those with BMI <22kg/m2.
- Hypertension – 66% of HTN is linked to obesity
- Cancer – particularly endometrial, breast and colon cancer
- NASH – over 66% of overweight people, and over 90% of obese individuals are at risk of NAFLD, which may progress to NASH
- CAD and therefore angina, MI, arrhythmia
Obesity has many adverse effects on the respiratory system. An excellent review summarises these, and the basic approach to investigation and treatment:
- Mandal, Swapna, and Nicholas Hart. “Respiratory complications of obesity.”Clinical Medicine 12.1 (2012): 75-78
Obesity has significant effects on pulmonary mechanics. BMI correlates directly with the degree of airways resistance and work of breathing, and is inversely correlated with thoracic lung volumes. Reductions in FRC and ERV are associated with early airway closure and therefore gas trapping, causing VQ mismatching. Obesity leads to a restrictive defect due to the mass on the chest wall, with a reduction in chest wall compliance. Breathing at low lung volumes causes expiratory flow limitation due to early airway closure with generation of intrinsic PEEP. All these changes are exaggerated during sleep.
- Pelosi, Paolo, et al. “The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia.” Anesthesia & Analgesia 87.3 (1998): 654-660
Not all obese patients develop respiratory failure. Neural respiratory drive is important.
Sleep disordered breathing includes OSA (recurrent rapid desaturations) and OHS (prolonged desaturations with prolonged periods of hypoxia – 30% of obese patients woth OSA have an element of OHS).
There is a spectrum of disease: OSA –> hypercapnic OSA –> OHS
Hypercapnia is important to identify due to it’s link with mortality, as described by Nowbar:
- Nowbar, Sogol, et al. “Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome.” The American journal of medicine116.1 (2004): 1-7
Screening for sleep disordered breathing (particularly OSA) is facilitated by standardised questionnaires:
There is no questionnaire that can easily screen for hypercapnia. The use of ABGs or CBGs may be inconvenient for large numbers, and in clinic/primary care settings. Helpfully, simple physiological tools of clinic SpO2 and FVC can be used to predict hypercapnia with high sensitivity, in patients with a BMI>30kg/m2 and evidence of sleep disordered breathing, and therefore streamline assessment pathways.
- Men: FVC <3.5L SpO2 <95%
- Women: FVC <2.3L SpO2 <93%
Mandal, S., et al. “A cohort study to identify simple clinical tests for chronic respiratory failure in obese patients with sleep-disordered breathing.” BMJ Open Respiratory Research 1.1 (2014): e000022
Taking a Symptom-based Approach to Breathlessness: IMPRESS
Following lunch (where there was a disappointing lack of meat-free options….) we heard from Sian Williams, IMPRESS Programme Manager, on a symptom-based approach to breathlessness. A summary of the work and links to the resources produced can be found on the IMPRESS site.
The day closed with talks on the radiology of Respiratory disease, and breathlessness in asthma. Unfortunately I have no notes for these sessions, so if anyone would like to share theirs, get in touch.