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Table of Contents

    Topic review

    Difficult Asthma in Children

    Subjects: Pediatrics
    View times: 49
    Submitted by: Federica Porcaro


    Difficult asthma is asthma that is uncontrolled despite GINA step 4 and 5 (medium or high dose ICS with a second controller; maintenance of oral corticosteroids), or that requires such treatment to maintain good symptoms control and reduce the risk of exacerbations.

    1. Introduction

    Once a diagnosis of difficult asthma has been confirmed, all possible risk factors or comorbidities need to be considered in patients with persistent symptoms despite standard treatment[1][2]. Periodical and careful assessments carried out by the specialist and by the family pediatrician can help identify potentially modifiable factors responsible for poorly controlled asthma. Indeed, poor symptom control is a consequence of modifiable factors that need to be carefully assessed, such as (1) nonadherence to medication or inadequate inhalation technique, (2) persistent environmental exposures, (3) comorbidities, and (4) psychosocial factors.

    2. Adherence to Medication

    Good adherence is most commonly defined as taking between 70–80% of prescribed treatment[3]. Suboptimal adherence to ICS leads to poor asthma control, severe asthma attacks, and frequent use of healthcare resources[4]. Although it is known that half of difficult-to-treat patients have poor adherence to prescribed medication or improperly use the suggested devices[5][6], clinicians are not used to always check adherence and inhaler technique at the time of patient’s evaluation[7]. Explaining and showing the spacer’s correct use is the most effective model to improve the inhaler technique and asthma control[8][9].

    Several measurement tools, both subjective and objective, have been developed to assess adherence in adults and children with asthma[10] (Table 1). Unfortunately, each of these measures has limitations, such as the unavailability of self-report adherence questionnaires validated for the pediatric population, the often poor availability of electronic monitoring devices (EMD), the high production costs, the ability of patient/parent to manipulate the data, and the ability of EMD to measure inhalation and inhaler technique[10].

    Table 1. Tools for monitoring the adherence to prescribed treatment.

    Measurement Tools of Treatment Adherence


    Physician assessment of adherence

    Self-report questionnaires

    ·                     Morisky scale

    ·                     Medication adherence report scale


    Drug levels

    Exhaled nitric oxide

    Prescription data

    Weighing inhaler canisters

    Dose counters

    Directly observed therapy

    Nurse home visits

    Electronic monitoring devices

    Integrating digital technologies

    3. Environmental Exposures

    3.1. Tobacco Smoke

    It is known that exposure to environmental tobacco smoke increases pediatric asthma severity[11] and, in particular, increases resistance to steroids[12]. Therefore, the assessment of passive and/or active smoke exposure is mandatory for all children with difficult asthma. As parents and patients (especially if teenagers) can deny the exposure to tobacco smoke, levels of salivary or urinary cotinine can be used to determine actual exposure[13].

    3.2. Air Pollution

    There is increasing evidence of the association between air pollution and asthma exacerbations as well as new onset of asthma in children. Air pollution is a mixture of particles and gases emitted from several sources or generated in the atmosphere through chemical reactions (fine particles < 2.5 µm in diameter, nitrogen dioxide, and ozone). All these elements can cause oxidative stress into the airways, leading to inflammation and remodeling, especially in asthmatic children[14].

    3.3. Allergen Exposure

    Children with poor asthma control despite proper treatment should be investigated for allergy sensitization[15]. Several studies reported the increased risk of asthma in children with a family history of atopy, early-onset atopic dermatitis, sensitization to egg or milk in the first years of life[16]. In addition, the poor control of asthma symptoms is directly correlated with both specific IgE levels and the number of sensitizations[15]. Consequently, it is essential that allergen exposure is minimized in all patients with difficult asthma before any drug escalation.

    4. Comorbidities

    Co-morbidities are important in the management of difficult asthma[17], as they may contribute to poor disease control, as well as mimicking asthma symptoms (Table 2). Researching and optimizing the management of these conditions also through a multidisciplinary team is mandatory in all asthmatic patients with poor symptom control [18].

    Table 2. Asthma comorbidities.




    Rhinosinusitis/nasal polyposis

    ENT evaluation

    Sinus CT

    Topic CS


    Allergic rhinoconjuctivitis

    Anamnestic data

    SPT test

    Specific IgEs

    Allergen avoidance

    Topic CS



    Dysfunctional breathing

    Anamnestic data

    Nijmegen questionnaire

    Breathing rehabilitation

    Vocal cord dysfunction

    ENT evaluation


    Speech retraining




    Obstructive sleep apnea

    Anamnestic data


    Weight loss

    Nocturnal CPAP

    Gastroesophageal reflux

    PPI trial



    Lifestyle changes


    Chest CT scan

    Hypertonic solutions



    Bronchopulmonary aspergillosis

    Total IgE

    IgE for Aspergillus Fumigatus IgG for Aspergillus Fumigatus

    Chest CT scan




    5. Psychosocial Factors

    Although the literature on psychiatric and behavioral disorders among children with asthma is conflicting, most research reported that children with asthma display more emotional and behavioral problems than their healthy peers[19].

    Anxiety, depression, and symptoms of inattention, hyperactivity, and oppositional behaviors are often reported by patients and their parents. Children with asthma and internalizing disorders are at risk of having worse asthma control, increased use of rescue medications, more access to healthcare facilities for attacks, poorer pulmonary outcomes, and more missed school days[20][21][22]. Moreover, the caregivers of children with asthma can suffer too from chronicity, developing emotional difficulties that can interfere with the management of the young patient.

    Questionnaires assessing the quality of life for both the child and family (Pediatric asthma quality of life questionnaire; PAQLQ)[23] as well as symptom control (Asthma control test; ACT)[24] are useful tools to estimate the severity and the impact of the disease on patient’s life. Consequently, psychosocial interventions, including educational programs, behavioral support, cognitive-behavioral therapy, and family interventions can be considered to reduce the psychological impact of the disease and to better control asthma symptoms.

    6. Socioeconomic Factors

    In addition, we must not forget that low socioeconomic status (low income, educational level, parents’ occupation) is often associated with poor asthma control (need for rescue therapy for asthma exacerbation, need for emergency health service visits, need for hospitalization for asthma exacerbation and fatal outcome)[25]. In these cases, the role of the family pediatrician becomes fundamental in identifying children vulnerable to asthma with a worse prognosis.

    7. Conclusion

    Poor controlled asthma represents a challenge for physicians; therefore, a multidisciplinary systematic assessment is warranted. Early identification of modifiable factors for children with difficult-to-treat asthma allows establishing better control of asthma without the need for further invasive investigations and treatment escalation. 

    This entry is adapted from 10.3390/children7120286


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