Dr Rossa Brugha Clinical Research Fellow 11th February 2014 Paediatric Asthma Dr Rossa Brugha Clinical Research Fellow 11th February 2014 April 2010

Paediatric asthma What is asthma in childhood? Pathology, signs and symptoms Diagnosis Principles of asthma management Self management Pharmacotherapy Assessing control What’s new

The scale of the problem % of 12 yr. olds Burr et al Thorax 2006;61:296-9 1 in 11 children and 1 in 12 adults in the UK are currently diagnosed with asthma; that’s 1.1 million children and 4.3 million adults. On average, two children in every school class have asthma – it is the commonest chronic illness in childhood. While for most people their asthma can be controlled with inhalers, over 1,000 people in the UK died from their asthma in 2009. That’s 3 people per day on average.   14 of those deaths were children under 12 years of age. A child is admitted to hospital with asthma every 17 minutes. The NHS spends around £1 billion on asthma and asthma treatments, 1% of the total NHS budget on just one disease.

Eder W et al. N Engl J Med 2006;355:2226-2235. Changes in the Prevalence of Diagnosed Asthma and Asthma Symptoms over Time in Children and Young Adults. The scale of the problem Figure 1. Changes in the Prevalence of Diagnosed Asthma and Asthma Symptoms over Time in Children and Young Adults. Data in Panel A are from Australia,2– 6 the United States, 7 Canada, 8, 9 Switzerland, 10 Germany, 11– 15 the United Kingdom, 16– 23 Norway, 24– 27 Finland, 28, 29 Estonia, 30, 31 Poland, 32 Italy, 33, 34 Spain, 35 Israel, 36, 37 Singapore, 38 Hong Kong, 39, 40 Taiwan, 41 and Korea. 42 Data in Panel B are from Australia, 2– 5 the United States, 43 Switzerland, 10 Germany, 11, 13, 15, 44 the Netherlands, 45 the United Kingdom, 16– 23, 46– 49 Sweden, 50 Norway, 25– 27 Estonia, 30, 31 Italy, 33, 51 Spain, 35 Singapore, 38 Hong Kong, 39, 40 and Korea. 42 Eder W et al. N Engl J Med 2006;355:2226-2235.

Asthma vs preschool wheeze Above age 5 Approx 1 in 11 children Inflammatory condition Responds to inhaled corticosteroids Age 1-5 Approx 1 in 3 children ‘Episodic viral’ wheeze Wheeze only with viral infections No evidence for ICS ‘Multi-trigger’ wheeze URTIs plus other triggers eg exercise, smoke, allergens Only give oral prednisolone in subgroup of those requiring admission See: Bush A, Grigg J, Saglani S. Managing wheeze in preschool children. BMJ 2014; 348

What is Asthma? A clinical diagnosis There is no agreed definition, no known cause Genetic susceptibility plus environmental trigger: 1st degree relative increases risk Identical environments in siblings with and without asthma Time course/“double hit” of atopic sensitization and viral infection eg hRV3; 1st year of life is crucial There is no one test result that determines that you have asthma – it requires the health care professional to amalgamate signs and symptoms while excluding other possible diagnoses All of the following have been suggested as risks for developing asthma: Fetal exposure to maternal smoking Viral respiratory infection in early life Cleaner food and water Traffic fumes Genetics Whether or not your maternal grandmother smoked (epigenetics) Antibacterial cleaning products (Hygiene hypothesis) Decreased exposure to animals

Clinical features that increase the probability of asthma More than one of the following symptoms: Wheeze, cough, DIB, chest tightness, particularly if symptoms: are frequent and recurrent are worse at night and in the early morning occur in response to, or are worse after, exercise or other triggers, such as exposure to pets, cold, damp air, or with emotions/laughter This is from the SIGN/BTS guideline Sign post other resources (BMJ e learning, Articles, Recognition of a sick child/DIB modules)

Clinical features that increase the probability of asthma Personal history of atopic disorder Family history of atopic disorder and/or asthma Widespread wheeze heard on auscultation History of improvement in symptoms or lung function in response to adequate therapy

Clinical features that lower the probability of asthma Symptoms with colds only, with no interval symptoms Isolated cough in the absence of wheeze or difficulty breathing History of moist cough Prominent dizziness, light-headedness, peripheral tingling Ask the audience to think of alternate diagnoses: CF/bronchiectasis Habitual cough Anxiety/ hyper-ventilation Gastro-oesophageal reflux Inhaled foreign body

Clinical features that lower the probability of asthma Repeatedly normal physical examination of chest when symptomatic Normal peak expiratory flow (PEF) or spirometry when symptomatic No response to a trial of asthma therapy Clinical features pointing to alternative diagnosis

Airway pathology in asthma The hallmark of asthma is chronic airway inflammation This is the classic immune pathway by which an allergen inappropriately triggers inflammation in the airway. Inhaled allergen is sensed by an antigen presenting cell (macrophage or dendritic cell) which activates a Th2 cell. Via Th2 cytokines (IL-4, IL-5, IL-13) mast cells are stimulated to release histamine, and eosinophils release basic proteins. Both classes of cells release leukotrienes and prostaglandins, which act on blood vessels to increase blood supply tot he area, and recruit other immune cells, resulting in a positive feedback cycle of escalating inflammation. It is not just allergens that can trigger this cycle – viruses are the commonest triggers, and may cause ‘runaway’ inflammation via Th1 and Th17 pathways as well. Air pollutants and cigarette smoke may also act via these pathways. From: Bradding, P., Walls, A.F. & Holgate, S.T. (2006). The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol 117, 1277–84

Airway pathology in asthma This is the result of chronic inflammation – the airway appears like a chronic wound – think of it like a leg ulcer – hypertrophied, hyper-sensitive, mucousy

Signs and symptoms The result of airway inflammation is airway narrowing Airflow in a bronchus is like water flowing in a hose. If it is smooth there is lots of flow and no noise. If it is narrow there is less flow and the airflow is turbulent – this results in wheezing

Self management Avoid triggers Air pollution Passive (active) smoking Aeroallergens when/if possible Healthy diet Studies in adults and children have shown that a high intake of fresh fruit and vegetables is associated with fewer asthma symptoms and better lung function Triggers – extremely difficult to avoid Almost impossible to remove all house dust mite – trigger unlikely to be dose dependent so deep cleaning/constant washing is not recommended Laminar airflow systems show promise Avoid busy roads/episodes of air pollution Don’t get a pet if you are known to be sensitive (eg on skin prick test) (but don’t get rid of a pet if you already have one)

Self management Exercise Warm up and warm down Use bronchodilator pre-exercise Good evidence that exercise helps asthma Complementary treatments Buteyko breathing (a technique to control hyperventilation) has been shown to reduce symptoms Encourage exercise – improves lung health Signpost non-pharmacological therapies with an evidence base, as pts will seek them out

Pharmacotherapy Montelukast Steroids Monoclonal anti-IgE (omalizumab, Xolair) Preventers act on the immune system Steroids act on the cell nucleus to decrease transcription of pro inflammatory genes Montelukast is a leukotriene receptor antagonist IgE is blocked by omalizumab New monoclonals coming soon include anti IL-5 and anti IL-13 Lebrikizumab: anti IL-13 Mepolizumab: anti IL-5 Pascolizumab: anti IL-4

Management of chronic asthma The aim of asthma care is complete control of symptoms on minimal therapy Step up and step down decisions can be very difficult – some patients don’t want to step down due to fear of exacerbations, other don’t want to step up due to concerns about steroid side effects What would the audience consider good control? Rough guide is no exacerbation (time off school/work) for 6-12 mo and not needing to use salbutamol more than 1-2 puffs per week Sign post BTS, BMJ e-learning, BMJ Dx and Mx of Asthma

For the under 5s – lower dose steroids, no LABA, early introduction of montelukast

Asthma control test During the past 4 weeks: How often did your asthma prevent you from getting as much done at work, school or home? How often have you had shortness of breath? How often did your asthma (wheezing, coughing, chest tightness, shortness of breath) wake you up? How often have you used your reliever inhaler? How would you rate your asthma control ? I would expect everyone here to be able to identify someone with poorly controlled asthma and refer them on appropriately. Asthma control test is a useful tool. Can be found on the asthma UK Web page – patients can take it for free – can do this before their follow-up appts with GP/practise nurse

Comorbidities Around 50% with asthma will have atopy Eczema Rhinitis Hayfever Antigen crossing via these sites can persistently sensitise the immune system Important to optimise epithelial health Barriers (emollient) Immunomodulators (topical steroid) Symptom control (antihistamines)

What’s in the pipeline Phenotyping asthma Via SNPs eg leukotrienes and ALOX-5 “Urine dip” for asthma By sputum leucocytes By exhaled breath cytokine pattern (Th1, Th2, Th17) Predicting exacerbations/inflammometry FeNO (probably not in children) Sputum eosinophil count (probably not in children) ACT score Peak flow fractals

Why phenotype? All that wheezes is not asthma Consider the approach to management of other chronic inflammatory conditions in childhood Joint arthropathies Inflammatory bowel disease

Asthma Review: Checklist The right diagnosis Check symptom control (ACT) Ask about and address smoking (child and parent) The right treatment at the right time (step-wise) Before initiating a new drug/step: check compliance with existing therapies, inhaler technique and try to eliminate trigger factors. Minimise side effects from treatment (i.e. growth if on high dose ICS) The right inhaler, correct technique Give inhaler training, ensure correct technique before writing prescription Referral pathways for smoking – find info to put in handout. Side effects – STEROID CARD SHINE – handout Demonstrate competence before they leave with their new inhaler.

Asthma Review: Checklist The gold standard is MDI + spacer Give Asthma education (repetition, reinforcement, signpost/give resources) All children should have an Asthma Plan Promote self-management Compliance Need regular review Annual review Review at 48-72 hrs and 30 days post exacerbation/admission Flu Jab Step up and down We will talk about asthma plans in the next talk

NICE Quality standards QS25 Statement 1. People with newly diagnosed asthma are diagnosed in accordance with BTS/SIGN guidance. Statement 2. Adults with new onset asthma are assessed for occupational causes. Statement 3. People with asthma receive a written personalised action plan. Statement 4. People with asthma are given specific training and assessment in inhaler technique before starting any new inhaler treatment. Statement 5. People with asthma receive a structured review at least annually. Statement 6. People with asthma who present with respiratory symptoms receive an assessment of their asthma control.

NICE Quality Standards QS25 Statement 7. People with asthma who present with an exacerbation of their symptoms receive an objective measurement of severity at the time of presentation. Statement 8. People aged 5 years or older presenting to a healthcare professional with a severe or life-threatening acute exacerbation of asthma receive oral or intravenous steroids within 1 hour of presentation. Statement 9. People admitted to hospital with an acute exacerbation of asthma have a structured review by a member of a specialist respiratory team before discharge. Statement 10. People who received treatment in hospital or through out-of-hours services for an acute exacerbation of asthma are followed up by their own GP practice within 2 working days of treatment. Statement 11. People with difficult asthma are offered an assessment by a multidisciplinary difficult asthma service.

Useful learning resources Acute breathing difficulties: http://abd.ocbmedia.com/home/ Spotting the Sick child; https://www.spottingthesickchild.com/ Adult & Paed case studies: http://real.educationforhealth.org/ Itchy Sneezy Wheezy: http://www.itchysneezywheezy.co.uk/ Asthma UK http://www.asthma.org.uk/ Summary slide is next – ask now if any questions

Further reading BTS Guidelines 2011/12 http://www.brit-thoracic.org.uk/guidelines/asthma-guidelines.aspx Atopic Eczema in Children (NICE) http://www.nice.org.uk/CG57 BNF for Children 2011/12 Nice guideline inhalers w

Questions April 2010 33

Summary Asthma is very common Large disease burden Morbidity & mortality Regular asthma review Assess control Assess technique Assess understanding, compliance/concordance Question the diagnosis Eg our 9yo with CF