Wheezing in pre-school children

Dr Tshegofatso MabelaBChB; MBA; M. Fam Med; FCFP (SA); Dip Allerg (SA); Cert Allerg (SA); M. Phil Allergy (UCT) ASTHMA diagnosis and management in under 5yrs old children Introduction

• Management of asthma in young children is associated with many challenges • Diagnosis could be difficult as wheezing can occur in this age without asthma and confirmatory lung function tests are difficult to perform • Preschool children consume a disproportionately high amount of health-care resources compared with older children and adults with wheeze or asthma

Global Initiative for Asthma (GINA). Pocket Guide for Asthma Management and Prevention in Children 5 Years and Younger, updated April 2015. Available from www.ginasthma.org. What is asthma?

• Heterogeneous condition characterised by chronic inflammation • Defined by history of respiratory symptoms such as wheeze, shortness of breath, tight chest and cough that vary over time and intensity, together with variable expiratory airflow limitation

Global initiative for asthma. Global strategy for asthma management and prevention. 2018. www.ginaasthma.org Asthma epidemiology

• The global prevalence of asthma varies worldwide with 1-18% of the population affected in different countries. • Global Burden of Asthma report suggests a very high mortality rate for asthma in South Africa. • South Africa ranks 25th worldwide for the prevalence of asthma • 4th in asthma mortality in the 5–34 year age group and 5th asthma- case fatality rates with an estimated 18.5 per 100 000 asthmatics

Global initiative for asthma. Global strategy for asthma management and prevention. 2018. www.ginaasthma.org Van der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: A systematic review. J Allergy Clin Immunol 2007;120(3):565-569. https://doi.org/10.1016/j.jaci.2007.05.042 Gray CL, Levin ME, Zar HJ, et al. Food allergy in South African children with atopic dermatitis. Pediatr Allergy Immunol 2014;25(6):572-579. https://doi.org/10.1111/pai.12270 Asthma epidemiology in Limpopo

• International Studies of Asthma and Allergies in Children (ISAAC) phase III (2002) was conducted in a rural population in Polokwane, Limpopo, in 4 660 children aged 13-14 years. • 12 months prevalence of asthma was 18% • Asthma is considered to be an emerging health problem in Limpopo.

Zar HJ, Ehrlich RI, Workman L, Weinberg EG. The changing prevalence of asthma, allergic rhinitis and atopic eczema in African adolescents from 1995 to 2002. Pediatr Allergy Immunol 2007;18(7):560–565 wheezing phenotypes

• mild episodic viral wheeze phenotype- often in association with a viral cold and with absence of wheeze between episodes (remission) • multi-trigger atopic wheeze- symptoms between episodes (persistent)

❑25% of children with persistent asthma started to wheeze by the age of six months and 75% by the age of three years

Just J, Saint-Pierre P, Gouvis-Echraghi R, Boutin B, Panayotopoulos V, Chebahi N, Ousidhoum-Zidi A, Khau CA. Wheeze phenotypes in young children have different courses during the preschool period. Ann Allergy Asthma Immunol 2013;111(4):256-261.

More likely asthma if…

• History of repeated: ✓Coughing ✓Wheezing ✓Shortness of breath or fast breathing ✓Chest tightness ❑Symptoms occur/worsen at night, waking the child

Severity of symptoms

• Absences from school? • Extra doctor visits? • ED visits? • Hospitalizations? Diagnosis

• Based largely on symptom patterns (wheeze, cough, breathlessness, activity limitation, and nocturnal symptoms) and frequency, combined with a clinical assessment of family history and physical findings. • Around half of preschool wheezers become asymptomatic by school age irrespective of treatment

❑NOT ALL WHEEZE IS ASTHMA Asthma Predictive Index (API)

• API is a guide to determining which small children will likely have asthma persistent asthma. High-risk children (under 3yrs) who have had 4 or more wheezing episodes in the past year lasting >1 day, much more likely to have persistent asthma after the age of five, if they have either of the following: MAJOR: ❖One major criteria: ✓ Parent with asthma ✓ Physician diagnosis of atopic dermatitis ✓ Evidence of sensitization to allergens in the air • OR ❖Two minor criteria: ✓ Evidence of food allergies ✓ >4 percent blood eosinophilia (Increased numbers of white blood cells called eosinophils are made by the body to fight off allergic disease. They can collect in tissues and cause damage to the airways of the lung.) ✓ Wheezing apart from colds ❑ Not always reliable in South African population, not all children are atopic! Support or confirm diagnosis? Atopy? Modified bronchodilator test (also + in some viral wheezers

What else in under 5?

Infections Congenital/perinatal problems Post-viral wheezing Tracheomalacia Tuberculosis (e.g. glandular compression of airways) Congenital malformation narrowing the intrathoracic HIV disease (e.g. lymphocytic interstitial pneumonia) airway

Chronic lung disease of the newborn Mechanical problems Cystic fibrosis (excessive cough, mucus, GIT Foreign body aspiration (sudden onset, unilateral sx) symptoms)

Primary ciliary dyskinesia syndrome (recurrent Gastro-oesophageal reflux disease (GORD) infection, productive cough, sinusitis)

Immune deficiency (recurrent, unusual, difficult to treat)

Congenital heart disease (e.g. L-R shunts- murmur) Treatment steps

REFER ALLERGIST

STEP 5

STEP 4

STEP 3 PREFERRED STEP 1 STEP 2 CONTROLLER CHOICE

Double dose Low dose ICS 3months trial ICS

Other Consider low Leukotriene receptor antagonists (LTRA) Low dose controller Theophylline not dose ICS ICS+LTRA options recommended

RELIEVER As-needed SABA As-needed short-acting beta2-agonist (SABA)

EVW: Daily low-dose ICS or montelukast may be used as maintenance therapy GINA 2017, Box 3-5, Step 1 (4/8) Key changes in GINA 2017 – role of SLIT

• Provide guided self-management education REMEMBER • Treat modifiable risk factors and comorbidities TO... • Advise about non-pharmacological therapies and strategies • Consider stepping up if … uncontrolled symptoms, exacerbations or risks, but check diagnosis, inhaler technique and adherence first • Consider adding SLIT in adult HDM-sensitive patients with allergic rhinitis who have exacerbations despite ICS treatment, provided FEV1 is 70% predicted • Consider stepping down if … symptoms controlled for 3 months + low risk for exacerbations. Ceasing ICS is not advised.

SLIT: sublingual immunotherapy

GINA 2017, Box 3-5 (3/8) (lower part) © Global Initiative for Asthma GINA assessment of symptom control

A. Symptom control Level of asthma symptom control Well- Partly Uncontrolled In the past 4 weeks, has the patient had: controlled controlled • Daytime asthma symptoms more than twice a week? Yes❑ No❑ • Any night waking due to asthma? Yes❑ No❑ None of 1-2 of 3-4 of • Reliever needed for symptoms* these these these more than twice a week? Yes❑ No❑ • Any activity limitation due to asthma? Yes❑ No❑

*Excludes reliever taken before exercise, because many people take this routinely

GINA 2017, Box 2-2A © Global Initiative for Asthma Stepping down

• Any step-down treatment depends on patient characteristics • Only a few step-down studies have been performed in children. • Approach each step as a therapeutic trial • Provide clear instructions and an asthma action plan.

SAMJ August 2018, Vol. 108, No. 8 Non medical management

• Written action plans are standard in the treatment and management of asthma • Asthma education should not be regarded as a single event but rather as a continuous process, repeated and supplemented at every subsequent consultation. • Education should be tailored according to the socio-cultural background of the family. Improving uptake of asthma management plans, both by families and by practitioners Patient study

• A 3 year old with 2 weeks history of cough present every night. Had a mild fever, but his temp has not been measured at home. His parents have been using a decongestant/antihistamine syrup and salbutamol syrup which were left over from a sibling. Initially the cough improved but it worsened over the next 2 days. He is noted to have morning sneezing and nasal congestion. There are colds going around the pre-school. He has had similar episodes in the past, but this episode is worse. He has no known allergies to foods or medications. • His past history is notable for eczema and dry skin since infancy. He is otherwise healthy and he is fully immunized. • His family history is notable for a brother who has asthma. • There are no smokers or pets in his environment. • Exam: VS T 38.1, P 100, RR 24, BP 85/65, oxygen saturation 99% in room air. He is alert and cooperative in minimal distress. His eyes are clear, nasal mucosa is boggy with clear discharge. He has multiple small lymph nodes palpable in his upper neck. His chest has an increased AP diameter and hyperresonant to percussion. Occasional wheezes are heard on auscultation, but there are no retractions. Heart is in a regular rhythm and no murmurs are heard. His skin is dry, but not flaky, inflamed or thickened. Patient study

• He is initially suspected to have possible moderately persistent asthma. Treated with asthavent MDI and spacer -tidal breathing technique, low dose inhaled steroids and oral corticosteroids for 5days. Also treated with an antihistamine at night to reduce his morning allergy symptoms. • In follow-up, his cough does not improve and he is still having fever (T 38.2C). A chest X-ray is obtained, but no radiographic evidence of pneumonia is present. His cough persists, but only with exercise. Patient study

• His chest now sounds clear. • After 1 week of no night or exercise cough is noted, his asthavent MDI is stopped. • He is continued on nightly antihistamines, low dose inhaled steroids and intranasal spray. He is given an asthma treatment plan which gives his parents clear instructions on which medications to start based on his symptoms and severity. NIHR Signal Intermittent inhaled steroids reduce asthma attacks in wheezing preschool children

Systematic review and meta-analysis of 22 randomized controlled trials of children up to six years of age with asthma or recurrent wheeze (two or more severe episodes in the last year requiring oral or intravenous steroids). o Treatments compared were daily inhaled steroids or intermittent inhaled steroids versus placebo or each other. o Looked at any regimen of inhaled steroids against montelukast. The trials lasted from 6 wks-5yrs, majority were for 12 wks. o Studies assessing the daily steroid strategy mostly used medium dosages and focused on children with persistent asthma. o Studies assessing intermittent steroids used higher doses and focused on children with intermittent asthma or viral-triggered wheezing. • Children with persistent asthma had fewer asthma attacks with daily steroids compared with placebo, 8.7% versus 18% (RR 0.56; 95% CI 0.46 to 0.70; eight studies, 2,505 children). • Children with intermittent asthma or viral-triggered wheezing had fewer asthma attacks with high-dose intermittent steroids compared with placebo, 33.9% versus 51.3% (RR 0.65; 95% CI 0.51 to 0.81; five studies, 422 children). • Only 2 studies directly compared daily vs intermittent steroids. Showed no difference between the two strategies in the rate of severe exacerbations. • Results for monteleukast were inconclusive as both studies were judged to be at high risk of bias.

Kaiser SV, Huynh T, Bacharier LB, et al. Preventing exacerbations in preschoolers with recurrent wheeze: a meta-analysis. Pediatrics. 2016;137(6);pii:e20154496. Conclusion

• Signs and symptoms of asthma are not the same with everyone, and may be mistaken for signs of other common childhood illnesses. • Asthma is frequently not diagnosed correctly. This causes many infants and young children to receive improper treatments. • Coughing without wheeze may be the child's only symptom of asthma. • Not all wheezes and coughs are caused by asthma, so treatment using asthma medicines is not always right. QUESTIONS