CHILDHOOD ASTHMA

DR ASHISH PRADHAN MD (JIPMER)

PROFESSOR, DEPARTMENT OF PEDIATRICS
SIKKIM MANIPAL INSTITUTE OF MEDICAL SCIENCES
GANGTOK/SIKKIM
 INTRODUCTION
Recent Lancet Asthma Commission (Lancet 2018; 391:350-400)
• Asthma should be used as an umbrella term that is used to describe a
constellation of clinical symptoms of wheeze breathlessness, chest
tightness and cough.

• Recognition of Asthma phenotype : Need for Individualized Approach

• The ultimate aim is to discover endotypes of asthma

• A phenotype is defined as the set of observable characteristics of
an individual resulting from the interaction of its genotype with
the environment.

• An endotype is defined as a subtype of a condition ,which is

defined by a distinct functional or pathobiological mechanism.

Phenotyping leads to rather nonspecific treatment whereas

endotyping leads to pathway specific therapies.
 PATHOPHYSIOLOGY OF CHILDHOOD ASTHMA
• The conventional view is that the root cause is airway inflammation
which
leads to airway hyper-responsiveness and secondary to repeated episodes of
inflammation ,airway remodeling.

• Critical recent reviews shows there is only a weak correlation at baseline

between eosinophilic inflammation and bronchial hyper-responsiveness.

• Airway inflammation in childhood asthma is usually airway eosinophilia

which responds to Inhaled Corticosteroids (ICS) although there is evidence
of entity of Neutrophilic Asthma
• Airway Hyper Responsiveness (AHR) can be present even before any
evidence of airway inflammation or remodeling. The likely pathological basis
is increased airway length and reduced radius leading to increased airway
resistance

• Airway neutrophilia in children appears to be beneficial rather than reverse.

• Il-6 driven airway inflammation and epithelial dysfunction is evident

• Novel pathways including those related to neuronal function ,WNT pathways

and actin cytoskeleton play a role.
 AIRWAY REMODELING
• Some aspects of remodeling like increased reticular basement membrane thickening
plateau in childhood and are non progressive into adult life.

• Remodeling precedes airway eosinophilia and is more steroid resistant.

• Reticular basement membrane thickening is inversely correlated with AHR.

• It is a protective measure designed to limit penetration of cytokines and chemokines into

the systemic circulation and protect the airway mucosa from tissue damaging enzymes.

• Increase in airway smooth muscle is adverse aspect of airway remodeling.

 ENDOTYPING
• Omics technology
Transcriptome Analysis
Gene expression Profiling
Micro-RNA array analysis
Cluster Analyses
U- BIOPRED AND SARP STUDY
The more sophisticated and expensive approaches to monitoring and
treatment are available , the more clinical skills become relevant.
 INFANT STUDY
• In Pre-school wheeze we should determine the treatable phenotype traits
and risks using
1. Blood Eosinophil count
2. Aeroallergen Sensitization
3. Response of wheeze intensity and oxygen saturation to beta agonists during
a wheezy attack
4. Adverse Trajectories of Lung Function
Risk factors for low lung function group include a history of Maternal
asthma , early life RSV lower respiratory tract infections. (Tuscon Study)
 DIAGNOSTICS OF ASTHMA
• Diagnose and treat Asthma with objective measurements.

• Phenotype the airway even in young children focusing on the treatable

traits.

• Consider and diagnose extra-pulmonary co-morbidities

CLASSIFICATION OF ASTHMA PHENOTYPES IN
CHILDREN
SYMPTOM BASED INFLAMMATORY FEATURES
•Age at onset •Eosinophilic
•Natural history •Neutrophilic
•Severity
PULMONARY FUNCTION
TRIGGER BASED TESTS
•Allergic vs non-allergic •Fixed vs bronchodilator-
•Exercise induced reversible airway obstruction
•Viral triggered vs multi triggered •Bronchial responsiveness to
exercise, cold air, chemical
RESPONSE TO TREATMENT
challenge
•Corticosteroid responsive
 THE DIAGNOSTIC ACCURACY OF FRACTIONAL EXHALED NITRIC
OXIDE TESTING

• Fractional exhaled nitric oxide (FeNO) concentration has been proposed to

aid asthma diagnosis.
• The FeNO concentration has moderate accuracy to diagnose asthma aged 5 y
and older. The 2011 American Thoracic Society guidelines recommended <
20 ppb in children for low FeNO as the most useful cut-offs to make the
determination that eosinophilic inflammation and response to corticosteroids
would be unlikely or likely, respectively.
• FeNO is sensitive to corticosteroids treatment and can therefore to used as a
method to monitor treatment.
 RECENT UPDATES IN GINA GUIDANCE
• A continuous cycle of assessment, treatment and review.
• Asthma management to include self-monitoring of symptoms and peak flow,
a written asthma action plan to recognise and respond to worsening asthma
and regular review of asthma control in partnership with a healthcare
professional.
• Treatment with low dose ICS for most patients of asthma, even those with
infrequent symptoms, to reduce the risk of serious exacerbations.
• Sublingual or Subcutaneous immunotherapy to aeroallergens is not
recommended for treatment of asthma in children.
• When stepping down from low dose ICS, add on LTRA may help. There is
insufficient evidence to step down to intermittent ICS with SABA.
• When prescribing short-term OCS, remember to advise patients about the
common side-effects (sleep disturbance, increased appetite reflux, mood
changes)
• Height should be checked at least yearly, as poorly- controlled asthma can
affect growth and growth velocity may be lower I the first 1-2 year of ICS
treatment.
• Effects of ICS on growth velocity are not progressive or cumulative
• Update of adherence strategies effective in real-life settings.
Box 3-5B Confirmation of diagnosis if necessary

Children 6-11 years Symptom control & modifiable

risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Child and parent goals
Personalized asthma management:
Assess, Adjust, Review response
Symptoms
Exacerbations
Side-effects
Lung function
Child and parent
Treatment of modifiable risk factors
satisfaction STEP 5
& comorbidities
Non-pharmacological strategies
Refer for
Education & skills training
Asthma medication options: phenotypic
Asthma medications STEP 4
Adjust treatment up and down for assessment
± add-on
individual child’s needs STEP 3 Medium dose therapy,
STEP 2 ICS-LABA e.g. anti-
Low dose Refer for IgE
PREFERRED STEP 1
CONTROLLER Daily low dose inhaled corticosteroid (ICS) ICS-LABA, or expert advice
to prevent exacerbations (see table of ICS dose ranges for children) medium dose
and control symptoms ICS

Other Low dose ICS Leukotriene receptor antagonist (LTRA), or Low dose High dose ICS- Add-on anti-IL5,
controller taken whenever low dose ICS taken whenever SABA taken* ICS+LTRA LABA, or add- or add-on low
options SABA taken*; or on tiotropium, dose OCS,
daily low dose ICS or add-on LTRA but consider
side-effects
RELIEVER As-needed short-acting β2 -agonist (SABA)

* Off-label; separate ICS and SABA inhalers; only one study in children
 NEW IN THE MANAGEMENT OF ACUTE
ASTHMA
• Efficient assessment using objective measurements

• Appropriate use of delivery devices

• Not to hold back on oxygen use

• Regular monitoring for response to treatment.

•  Treatment of a severe attack must include all of short acting -agonists, oxygen and
steroids. Spacer devices have been shown to be equally if not more effective in
mild to moderate attacks.
• It is important to recognise that inhaled -agonists bronchodilators can occasionally
exacerbate hypoxemia in patients with asthma, regardless of how they are
administered. Hypoxemia can be lethal and pulse oximeters are advised
particularly in primary care setting
• The Cochrane review concluded treatment with nebulized MgSO4 has not shown
clinical benefit in recent well-designed trails.
• One pilot study has shown the benefit of high-flow nasal cannula oxygen therapy
compared to face mask oxygen therapy in the emergency department.
 NEW IN LONG TERM
MANAGEMENT OF ASTHMA
 LONG ACTING MUSCARINIC
ANTAGONIST
• Tiotropium is a long acting muscarinic antagonist (LAMA)
• Tiotropium binds equally well to M1, M2 and M3 cholinergic receptors but
dissociates slowly from the M1 and M3 cholinergic receptors hence the long
duration of bronchodilator effect. It can be given once daily as the effects
lasts for 35 h with maximum effect within 60 min.
• Tiotropium has shown promising results in five recent paediatric randomised
controlled trials studies and can be used in over the age of 6 year
• GINA guidelines recommend Tiotropium as add-on therapy to ICS option at
Steps 4 and 5and have shown to improve lung function.
 VITAMIN D FOR THE MANAGEMENT OF
ASTHMA
• In-vitro data suggest vitamin D enhances steroid sensitivity and also
impacts airway smooth muscle remodelling.
• A recent meta-analysis in people with predominantly mild to moderate
asthma suggests that vitamin D is likely to reduce both the risk of severe
asthma exacerbation and heath care utilization.
MACROLIDE ANTIBIOTICS FOR THE MANAGEMENT OF
ASTHMA
• In children and young adults with asthma the role of macrolide antibiotics
is uncertain and use of long term macrolides is not recommended at
present.
 BIOLOGICAL MONOCLONAL ANTIBODY
TREATMENT
• Omalizumab, an anti-IgE is used for moderate to severe allergic asthma in
children aged at least 6 years with IgE greater than 30 IU/L. It has shown to
reduce exacerbations and hospital admissions.

• Mepolizumab, is neutralising antibodies that target interleukin-5 and is

licensed for adolescence. It reduces severe asthma exacerbations and reduce
need for oral corticosteroid therapy.

• Reslizumab, Dupilumab
 TEMPERATURE –CONTROLLED LAMINAR
AIRFLOW DEVICE
• The temperature controlled laminar airflow(TLA) is a device which can be
employed over a bed in a domestic environment and can result in massive
reductions in allergen /particulate exposure.
• The device works by controlling nocturnal exposure to particulate exposure
by delivering cooled and filtered air overhead of an individual with asthma
during sleep.
• The greater density of the cooled air reverses the normal convection current
and displaces allergen bearing particles out of the breathing zone.
• Bolye et al. showed significant improvement in asthma specific quality of
life (mini AQLQ and Pediatric AQLQ) and significantly decreased FeNO.
 ELECTRONIC MONITORING AND ADHERENCE
DEVICES
• Electronic monitoring devices can be attached onto a metered dose inhaler
or is designed as a part of the inhaler.
• Currently developed models can record that an actuation has occurred and
the time, give an audio reminder for the child and parent and transmit this
data wirelessly.
• Directly observed therapy and feedback via mobile device is a new concept
inhaler technique monitoring- Mobile Direct Observation of Therapy
(MDOT).
• A pilot study using MDOT showed improvement in inhaler technique
asthma control and reduction in FeNO.
 SUMMARY
• Asthma still causes considerable morbidity and mortality globally.

• The recent Lancet commission highlighted that our concept of asthma is too
simplified.

• The recent advances focuses on the need for personalised treatment plans
based on phenotyping and endotyping.

• There are various recent advances on pharmacological treatments and

monitoring devices for asthma.
THANK YOU