Evaluating Severe Therapy-Resistant Asthma in Children: Diagnostic and Therapeutic Strategies
Abstract
:1. Introduction
- Untreated severe asthma due to misdiagnosis, lack of access to medical care or non-compliance with treatment, usually in a low- and middle-income settings. It should be noted that there is an underclass of poverty where medications may not be available, even in the most affluent countries. In this group, the main problem is usually that patients cannot access controller treatments. Shamefully, worldwide, this is the largest group of severe asthma patients. Political action is the answer for this group.
- Difficult-to-treat severe asthma resulting from comorbid conditions or adverse environmental circumstances.
- Treatment-resistant severe asthma (STRA), which includes patients in whom control is not achieved despite high-dose therapy or for whom control can only be maintained with such therapy.
- What is the positive evidence that this child has asthma at all?
- Is there evidence that there is a different or additional diagnosis?
1.1. Does the Child Have Asthma at All?
1.2. Case Study
1.3. Is There Evidence of an Alternative or Accessory Diagnosis?
2. Approach to the Child with Apparent Severe, Therapy-Resistant Asthma (STRA)
2.1. The First Step: A Multidisciplinary Team Assessment
- Difficult asthma, which will respond to treatment if the basic management steps are corrected
- Asthma plus co-morbidities such as obesity, a breathing pattern disorder and uncontrolled allergic rhinitis
- True STRA (uncommon)
2.2. Can They Take the Prescribed Treatment?
2.3. Are They Taking the Prescribed Treatment?
2.4. Case Study
- Obstructive spirometry and elevated FeNO at the start of monitoring, good adherence during monitoring, spirometry and FeNO normal at the end of monitoring. The explanation is that this is a previously poorly adherent child who took treatment while being monitored, and it worked during the monitoring period.
- Continued low adherence and poor outcomes during monitoring. The explanation is either a child with refractory difficult asthma, a child who is unpersuadable to take therapy or a child with true STRA who has become disillusioned with taking treatments which do not work.
- Good adherence but continued poor outcomes. These are the children who have true STRA requiring beyond guidelines therapy.
- Poor adherence but good outcomes. These children have previously been overtreated, so this is rational poor adherence.
2.5. Are There Important Adverse Environmental Factors? Allergens
2.6. Are There Important Adverse Environmental Factors? Irritants
2.7. Are There Important Psychosocial Issues?
2.8. Case Study
2.9. The Role of Breathing Pattern Disorders and Exercise-Induced Laryngeal Obstruction (EILO)
3. After the Assessment: Treat and Reassess
4. Options for Biologics in Children
4.1. Omalizumab
4.2. Mepolizumab
4.3. Dupilumab
4.4. Tezepelumab
4.5. Benralizumab
4.6. Options for Biologics: Summary
5. Is There a Role for Bronchoscopy?
6. Asthma Plus: Obesity
7. The Attack-Prone Asthmatic Child
8. Future Research Needs
9. Conclusions: The Child with Symptoms Suggestive of Asthma Which Do Not Respond to Asthma Medications
Funding
Acknowledgments
Conflicts of Interest
References
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Method | Test | Comment |
---|---|---|
Objective documentation of wheeze | Wheeze heard by physician Wheeze recording on mobile telephone (Futuristic) e-stethoscope on parental mobile telephone | ‘Wheeze’ often used by families to describe non-specific noises |
Variable airflow obstruction | Acute response to short-acting β-2 agonist if airway obstruction present (spirometry, impulse oscillometry) Home peak flow monitoring including response to exercise and short-acting β-2 agonist Exercise test Histamine or methacholine challenge | Histamine and methacholine challenge testing rarely needed; used to rule out asthma as a cause of symptoms |
Atopic status | History of eczema, allergic rhinitis, food allergy Total and specific IgE to relevant allergens Skin prick testing to relevant allergens | Non-atopic asthma is well described, but in children, most severe asthma is atopic |
Airway inflammation | Blood eosinophil count Exhaled nitric oxide Induced or spontaneously expectorated sputum eosinophilia Bronchoscopy, bronchoalveolar lavage and endobronchial biopsy | Blood eosinophil count and exhaled nitric oxide may be elevated in non-asthmatic, atopic children Reserved for really severe asthma in tertiary centres |
Points in the History | Comment | Points on Examination | Comment |
---|---|---|---|
Very sudden onset of symptoms | Consider foreign body aspiration | Digital clubbing | Often overlooked. Consider CF, PCD, bronchiectasis and chILD |
Prominent upper airway symptoms | Can be misinterpreted as wheeze | Nasal polyps | CF most common cause, also seen in PCD |
Symptoms from first day of life | Consider congenital abnormality and PCD | Large tonsils, marked rhinitis | Are symptoms being misinterpreted as wheeze? Consider PCD |
Chronic wet cough > 4–8 weeks duration | Not due to asthma; exclude CSLD | Signs of weight loss | Eliminate other respiratory and systemic disease depending on context |
Continuous and unremitting symptoms | Even those with severe asthma usually have periods of remission | Unusually severe chest deformity | Consider CSLD |
Fever and weight loss | Exclude tuberculosis | Crackles | Coarse: consider CF, PCD, bronchiectasis Fine: consider chILD |
Vomiting, back arching when feeding | Consider gastro-oesophageal reflux | Stridor, fixed monophonic wheeze | Fixed large airway obstruction |
Symptomatic when eating or drinking | Consider unsafe swallow | Signs of cardiac and systemic disease | Full and careful physical examination mandatory |
Anything suggestive of cardiac or systemic disease | White differential diagnosis including immune deficiency |
Severe asthma | BDP ≥ 800 mcg/day (age 6–12 years) or ≥2000 mcg daily (age > 12) PLUS (or failed trials of)
|
Uncontrolled asthma: ≥1 of: |
|
PAPA Framework | Problem | Proposed Solutions |
---|---|---|
Practicality | Forgetfulness ± chaotic lifestyle | Simplify regime Mobile phone alerts Directly observed therapy at school |
Practicality | Lack of parental supervision | Identify the problem, which is often not appreciated Directly observed therapy at school |
Practicality | Complex regime | Simplify; consider once-daily combination of ICSs and LABAs or SMART regime |
Practicality | Visibility—not wanting to appear different | Consider regimes which do not require medication to be taken out of the home |
Practicality | The family cannot afford medications which have to be purchased in high-income countries because there is no universal health coverage | Obtain charity funding or benefits Use the cheapest generic that can be found |
Perception | Lack of understanding of correct usage | Asthma education |
Perception | Discarding ICSs because no immediate gratification | Asthma education |
Perception | Concerns about side-effects | Asthma education |
Adherence Tool | Comment |
---|---|
Asking the child and family, including questionnaires | Non-judgemental questions, assuming that non-adherence is normal may help, but this is generally unreliable; questionnaires seem to work better in a research context. |
Prescription records | Picking up a prescription does not mean it has been cashed or, if cashed, has been correctly utilised. If the prescription has not been utilised, non-adherence is certain |
Home visit (face-to-face or virtual) | If the medication cannot be located or is out of date or is stockpiled in original boxes, poor adherence is likely |
Monitoring of medication blood levels | Applicable for theophylline or prednisolone, but neither often used for maintenance therapy; blood levels of inhaled medications not routinely available |
Electronic activation monitor, e.g., smart inhaler | Can only say if and when the device has been activated, not whether used correctly |
Electronic devices with inspiratory flow sensor | Not yet widely available and usually only measures peak inspiratory flow, not inspired volume. Probably the gold standard |
Directly observed therapy—a response means previous non-adherence | At school, but only if child attends regularly. Does not work if child does not go to school; not on weekend or during school holidays Using mobile phone: very resource intensive Admission to hospital: very resource intensive |
Response to a single dose of intramuscular triamcinolone | Tests if the child is steroid-sensitive; good response highly suggestive of previous poor adherence |
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Bush, A. Evaluating Severe Therapy-Resistant Asthma in Children: Diagnostic and Therapeutic Strategies. Medicina 2024, 60, 1799. https://doi.org/10.3390/medicina60111799
Bush A. Evaluating Severe Therapy-Resistant Asthma in Children: Diagnostic and Therapeutic Strategies. Medicina. 2024; 60(11):1799. https://doi.org/10.3390/medicina60111799
Chicago/Turabian StyleBush, Andrew. 2024. "Evaluating Severe Therapy-Resistant Asthma in Children: Diagnostic and Therapeutic Strategies" Medicina 60, no. 11: 1799. https://doi.org/10.3390/medicina60111799
APA StyleBush, A. (2024). Evaluating Severe Therapy-Resistant Asthma in Children: Diagnostic and Therapeutic Strategies. Medicina, 60(11), 1799. https://doi.org/10.3390/medicina60111799