Cleveland Asthma is a chronic respiratory condition frequently seen in primary care, accident and emergency departments, inpatient hospital environments and presenting to the ambulance service (Bahadori et al, 2009). The prevalence is growing worldwide which is increasing costs to over a billion pounds per year in the UK National Health Service (Bahadori et al, 2009; Mukherjee et al, 2014). Recent recommendations from the National Review of Asthma Deaths (NRAD) (Levy et al, 2014) have recognised the significant burden of associated morbidity, amongst avoidable factors that commonly contribute towards asthma deaths. The review found that of all patients who suffered a fatal asthma exacerbation 10% (n=195) had been seen and discharged by a healthcare professional within the previous 28 days.
The NRAD have also expressed concerns regarding the underuse of both inhaled and oral steroids in asthma, in particular, under-prescribing of all types of preventer medication (Levy et al, 2014). This practice has changed very little in the sixteen years since delayed prescribing of oral steroids was reported by Janson et al (1998) despite the vast quantity of newer guidelines and research published since then intended to guide clinical practice. Using a patient case study (Box 1) this essay will critique and evaluate the current literature to form evidence based treatment recommendations applicable to the example patient scenario. There is a high incidence of viral and allergic asthma (Rowe et al, 2004) associated with frequent relapse statistics and a slow initiation of steroids by clinicians. This gives grounds to investigate whether oral steroids should be routinely supplied to post-exacerbation asthmatics to prevent relapse.
Pathophysiology and pharmacology of asthmatic relapse
Acute asthma presentations are caused by many reasons, but they are most commonly due to an upper respiratory infection, allergens, or poor control of chronic asthma (Rowe et al, 2004). Rowe et al (2007) found that approximately 12-16% of patients discharged from an accident and emergency department re-exacerbate due to unresolved inflammation causing airway hypersensitivity within a fortnight of discharge and many patients will experience a relapse within 10 days. Levy et al (2014) also found that 80% (n=195) of fatal asthma patients were under-prescribed inhaled corticosteroids. Additionally, patients with allergic and viral induced asthma were receiving delayed rather than early initiation of oral steroidal therapy.
The mechanism of steroids in combating this relapsing airway inflammation is multi-factorial as they suppress components of allergic and non-allergic inflammation, cell recruitment and airway permeability. The production of inflammatory cytokines which are thought to be involved in airway immunology and cellular remodelling are suppressed by steroids (Rowe et al, 2004). Vasoconstriction also occurs in the deep airway capillaries following steroid administration which decreases membrane permeability leading to a reduction in mucus production (Edmonds et al, 2012). However, this vasoconstriction behaviour is thought to be more considerable in the inhaled steroid route than with oral steroids and it is this difference that suggests the mechanisms between the two routes are not the same (Rowe et al, 2004). The differing physiological effects of oral versus inhaled steroids can also be found in their reactions with exhaled nitric oxide in several studies discussed below. Exhaled nitric oxide is measured as a marker test for inflammatory products in the asthmatic airway; levels of nitric oxide are elevated in asthma patients and levels are further elevated during exacerbations (Currie et al, 2009; Kharitonov and Barnes, 2006). Khoo and Lim (2009) found that in discharged hospital patients following exacerbation withdrawing oral steroids resulted in increased nitric oxide levels despite continuing inhaled steroid treatment. Aside from the significance of these findings, other researchers have found that titrating steroid dosages to exhaled nitric oxide levels did not result in a reduction in reported symptoms, but instead resulted in higher dosages of steroids being used which is also unwanted (Szefler et al, 2008). Unfortunately, it must be concluded that the full effects of inhaled versus oral steroids upon inflammation, lung function and symptoms remain not fully understood (Khoo and Lim, 2009). Assessing which patients may benefit from oral steroids. However, certain classes of asthma patients are more likely to require systemic steroids than others such as the severely brittle asthma patient whereby inhaled reliever and preventer treatment is not sufficient to control symptoms (Edmonds et al, 2012). Although there is a lack of evidence to show inhalers and oral steroids have equal efficacy (Edmonds et al, 2012; Khoo and Lim, 2009; Reddel and Barnes, 2006) no studies have found evidence to support inhaler only treatment in moderate to severe cases (Edmonds et al, 2012). When applying this to the case study presentation, in a moderate to severe exacerbation the patient would require, at the minimum, a visit to an accident and emergency department. If not, then hospital admission would be appropriate (Manser et al, 2008; Rowe et al, 2008). Therefore, supplying a course of steroids on scene in these cases would not be necessary in specialist paramedic practice. However, there is scope for patients who have previously suffered a life threatening exacerbation to hold a rescue box of a one week course of oral steroids to prevent deterioration in the community (Hasegawa et al, 2000). The British Thoracic Society (2014) Asthma Guidelines advocate this practice. Again, although this would be prescribed under the patient's general practitioner or asthma specialist and not supplied by paramedics, it is a good indicator to identify the severe asthma patient and their use should be considered (Levy et al, 2014).
Allergic asthmatics have a greater level or airway hyper-responsiveness due to sensitisation to environmental allergens such as fungi and house dust for example, but contradictory to this there is very little evidence to show that reducing patient contact to these triggers reduces symptoms (Currie et al, 2009). Although, it has been shown that in half of all fatal asthma attacks an allergen, viral infection or a asthma reactive medication contributed towards patient demise (Levy et al, 2014). Rowe et al (2004) concurs with this by stating that respiratory infections or allergens are some of the most common asthma triggers. Other general health interventions such as reducing exposure to second-hand cigarette smoke are also known to reduce symptoms and this can be seen particularly in younger patients (Levy et al, 2014). Early evidence published in the years 2000 and 2004 describe systemic steroids as the backbone of asthma treatment in the acute, sub-acute and post-discharge phases of an asthma exacerbation (Hasegawa et al, 2000; Rowe et al, 2004). This practice appears to have changed little since then, as more recent guidelines also place a similar significance on systemic steroids; however their supply and application to paramedic practice is under debate (College of Paramedics, 2009). Current research includes multiple Cochrane reviews, meta-analyses and systematic reviews which show a reduction in symptoms for the asthmatic patient, but the authors also recognise the risks associated with their usage (Jadad et al, 2000; Katzung et al, 2010; Manser et al, 2008; Reddel and Barnes, 2006; Rowe et al, 2008). The use of steroids must be balanced against the risk of adverse side effects caused by frequent, intermittent or continuous courses (Currie et al, 2009; Hasegawa et al, 2000; Reddel and Barnes, 2006). Also, although asthmatic, allergic and inflammatory symptoms may be decreased, symptoms reflective of excessive hormone levels may become apparent which are also undesirable (Douglas et al, 2009; Marieb and Hoehn, 2010).
A large proportion of patients are known to be non-adherent to taking oral steroids (Currie et al, 2009) and a number of established reasons are documented are in Box 2. One relevant, yet slightly dated study showed that 50% of patients were found to have poor concordance with taking oral steroids and the hesitance among clinicians to administer multiple doses of steroids for fear of inducing unwanted side effects will contribute little to avert patient's perceptions of steroidal therapy (Robinson et al, 2003). Other comparable data has showed that 34% of people with difficult asthma were collecting less than 50% of their prescriptions for combination inhalers (Currie et al, 2009). There is a broad consensus amongst these papers that, although this is not preferable prescribing practice, the reasons for this need to be explored thoroughly in future research in order to address the issue through patient education or by altering prescribing practices.
Treating relapsing asthma with oral steroids
The British Thoracic Society (2014) provides guidance that recommends discharged patients from hospital must have access to inhaled bronchodilators alongside preventative inhaled and oral steroids. A Cochrane review (Rowe et al, 2007) has produced some compelling evidence towards the use of oral steroids for reducing relapse. The authors performed a meta-analysis of previously published randomised controlled trials which studied the effect of steroids on relapse rates, pulmonary function tests and quality of life following discharge from an acute care setting. Results from their review showed that significantly fewer patients relapsed at 7-10 days with an odds ratio of 0.35 with a number needed to treat to prevent relapse of 13. The authors do acknowledge however that if there was a more consistent definition of an asthma relapse such as either seeking medical assistance, treatment by an accident and emergency department, admission to hospital for example then there would be an even greater comparability of the research reviewed in the meta-analysis. This limitation does not appear to significantly detract from the findings which replicate and are consistent with two earlier and now superseded meta-analyses by Engel and Heinig (1991) and Rowe et al (1992).
Furthermore, the authors were able to establish an exact timeframe of three weeks during which the benefit of oral corticosteroids will be maintained for. The authors were able to draw this conclusion from one reviewed study that showed an almost unaltered benefit to the patient at 21 days post-discharge with an odds ratio of 0.33 compared to 0.35 at 7-10 days (NNT=13). However, Rowe et al (2007) did not name which study this is in their lengthy reviewed study list which hinders the reader's ability to evaluate the research for themselves. Unfortunately, Rowe et al (2007) published their findings in 2001 and their evidence was reviewed for a second time in 2007, however, the yearly incidence of fatal asthma exacerbations has not reduced in the last decade (Levy et al, 2014) despite these Cochrane reviews being well established in the literature.
Whilst there is compelling evidence that confirms the benefit of oral steroids to prevent asthmatic relapse, the importance of not offsetting this benefit by harmful side effects should not be underestimated. Whilst repeated exposure to courses of oral steroids increases the risk of related side effects (Currie et al, 2009), oral Prednisalone 40mg per day has been found to be effective, cheap and safe, and does not cause significant hypothalamic-pituitary-adrenal suppression when used for <7-10 days (Edmonds et al, 2002). It should certainly be observed that the same 7-10 day period is coincidentally the same timeframe recommended by Rowe et al (2007) in which to expect peak steroidal effects on reducing relapse. Again, Reddel and Barnes (2006) concur with this timescale but the authors add that there is no need to reduce doses by tapering towards the end of the course except to reduce side effects. This was confirmed back in the early 1990s when O'Driscoll et al (1993) carried out a double-blind randomised controlled trial on steroid tapering and found no difference in peak expiratory flow rates between patient groups during the tapering phase of the study. Perhaps it is the action of finishing courses of corticosteroids that may produce the most side effects, rather than simply the duration. However, the British Thoracic Society (2014) states that patients on long-term steroid tablets or patients requiring frequent courses of steroids will be at considerable risk of systemic side effects (Box 3). Additionally, the guideline states that there is a subgroup of patients whose asthma will be uncontrollable by all other treatments and for whom frequent or even continuous oral steroids will be required.
Conclusion
The impact of repeat exacerbations of asthma is considerable, with fatalities commonly being linked to recent treatment by healthcare staff. There is an increased risk of relapse for patients suffering with viral and allergic asthma and the initiation of steroids is also slow in these patient groups. Viral, allergic and medication induced asthma exacerbations are commonly known to contribute towards patient demise. The steroidal pharmacodynamics in treating relapse inducing airway inflammation is multifactorial and only partially understood. However, a 7-10 day course of oral steroids is recommended as an effective, cheap and safe option with minimal side effects for higher risk patients. There is no need to taper steroid dosages towards the end of the course except to reduce hormonal side effects. It must be remembered that there is a very high risk group of patients who require an emergency steroid supply in case of deterioration and also patients that require permanent steroids to maintain asthma control. In the case study, the patient could be assessed to have a higher than normal risk stratification due to allergic asthma. Therefore, he may benefit from a 7-10 day course of steroids to prevent a relapsing exacerbation.