Phenotype specific treatment of asthma in childhood

doi:10.1016/S1526-0542(04)90018-8

Paediatric Respiratory Reviews

Volume 5, Supplement 1, January 2004, Pages S93-S101

https://doi.org/10.1016/S1526-0542(04)90018-8 Get rights and content

Abstract

The term “asthma syndrome” encompasses a range of disorders, all characterised clinically by combinations of cough, wheeze and breathlessness. In older children, evidence of variable airway obstruction is manifest by change in peak flow over time or with treatment, reduction in peak flow on exercise, and a positive methacholine challenge. The underlying pathology includes combinations of bronchial hyperreactivity (BHR), airway inflammation and alterations in underlying baseline airway calibre or compliance. This is not merely of academic importance, but is fundamental to organizing appropriate treatment. In children with symptoms with viral colds and also between colds, and in particular if they are atopic, the underlying abnormality is likely to be T-cell driven, eosinophil-mediated airway inflammation. There is compelling evidence that early treatment with inhaled corticosteroids is essential if airway remodelling is to be avoided and optimum long-term lung function is to be achieved. The pathophysiology of wheezing with viral colds in the non-atopic infant is completely different; such infants have evidence of abnormal lung function soon after birth and before their first episode of viral wheeze, and no evidence of either bronchial hyperreactivity or airflow inflammation. Response to inhaled steroids is very poor. For most infants with wheeze, it is currently not possible to predict whether they will go on to the picture of established asthma. Post-bronchiolitic asthma syndrome also does not respond to inhaled steroids, because prolonged symptoms are likely due to abnormal pre-morbid airway function, albeit worsened by atopy. Phenotype-specific treatment is also important in older children who have severer asthma and do not respond to high dose inhaled steroids. We have delineated a group with marked BHR but no evidence of inflammation who respond to subcutaneous terbutaline, and a second group with steroid resistant inflammation who may do better with cyclosporin. A phenotype-specific treatment approach may also help to delineate which add on therapy (long-acting beta agonist, leukotriene receptor antagonist, theophylline) is best for children with moderate asthma not controlled by moderate dose (400mcg/day) inhaled corticosteroids. Asthma is not one disease but many, and attention to delineating clinical phenotypes, rather than being obsessed with guidelines based on large heterogeneous groups, may allow rational individual treatment.

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Asthma is a common chronic disease in pediatric patients, and perimenstrual asthma (PMA), refers to the worsening of asthma symptoms during the perimenstrual period, mainly reported in adult women. However, there is limited information regarding the exacerbation of symptoms in the presence of premenstrual disorders (PMDs) in adolescents. The aim of this pilot observational study was to investigate the frequency and potential association of PMA and PMDs in a clinical sample of adolescents with asthma.
The study included 50 adolescents (aged 12-18 years, mean 16.08 ± 2.35) with asthma and at least 2 years of gynecological age. The participants completed the Asthma Control Test (ACT) to assess asthma control (considered pathological if ACT score < 20) and the modified Premenstrual Symptoms Screening Tool for Adolescents (PSST-A) to evaluate PMDs.
A total of 75.5% of adolescents reported PMA. The prevalence of premenstrual symptoms did not significantly differ between the PMA and no-PMA group. Among the study sample, 38.7% experienced symptoms indicative of moderate/severe premenstrual syndrome, and 8.1% exhibited symptoms of premenstrual dysphoric disorder. Compared with the no-PMA group, patients with PMA showed a significant impairment in daily and home activities (P = .03 and P = .02, respectively) and exhibited a difference in the frequency of asthma symptoms (P < .001) and medication use (P ≤ .01).
Perimenstrual worsening of asthma symptoms may be common in adolescents with a severe form of asthma. Prospective data collection through menstrual diaries is necessary to further explore the association between PMA and PMDs. Identifying early risk factors for PMA could facilitate the development of preventive strategies and early interventions for adolescents with asthma.
Fungal diversity in homes and asthma morbidity among school-age children in New York City
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Asthma development has been inversely associated with exposure to fungal diversity. However, the influence of fungi on measures of asthma morbidity is not well understood.
This study aimed to test the hypothesis that fungal diversity is inversely associated with neighborhood asthma prevalence and identify specific fungal species associated with asthma morbidity.
Children aged 7–8 years (n = 347) living in higher (11–18%) and lower (3–9%) asthma prevalence neighborhoods were recruited within an asthma case-control study. Fungal communities were analyzed from floor dust using high-throughput DNA sequencing. A subset of asthmatic children (n = 140) was followed to age 10–11 to determine asthma persistence.
Neighborhood asthma prevalence was inversely associated with fungal species richness (P = 0.010) and Shannon diversity (P = 0.059). Associations between neighborhood asthma prevalence and diversity indices were driven by differences in building type and presence of bedroom carpet. Among children with asthma at age 7–8 years, Shannon fungal diversity was inversely associated with frequent asthma symptoms at that age (OR 0.57, P = 0.025) and with asthma persistence to age 10–11 (OR 0.48, P = 0.043). Analyses of individual fungal species did not show significant associations with asthma outcomes when adjusted for false discovery rates.
Lower fungal diversity was associated with asthma symptoms in this urban setting. Individual fungal species associated with asthma morbidity were not detected. Further research is warranted into building type, carpeting, and other environmental characteristics which influence fungal exposures in homes.
Asthma transition from childhood into adulthood
2017, The Lancet Respiratory Medicine
Citation Excerpt :
Childhood and adult asthma resemble a complex syndrome rather than a single disease and present with different phenotypes1,2 that lead to the recognised state of variable airway obstruction, which at times is not fully reversible or even fixed during the disease course.3 Presumably, however, variable airway obstruction is affected through diverse underlying pathophysiological processes adding further to the complexity of our pathophysiological understanding.1,4 These diverse underlying mechanisms could be used to further define asthma, which is known as an asthma endotype.
Asthma is the most prevalent chronic respiratory disease both in children and adults and resembles a complex syndrome rather than a single disease. Different methods have been developed to better characterise distinct asthma phenotypes in childhood and adulthood. In studies of adults, most phenotyping relies on biomaterials from the lower airways; however, this information is missing in paediatric studies because of restricted accessibility. Few patients show symptoms throughout childhood, adolescence, and adulthood. Risk factors for this might be genetics, family history of asthma and atopy, infections early in life, allergic diseases, and lung function deficits. In turn, a large proportion of children with asthma lose their symptoms during school age and adolescence. This improved prognosis, which might also reflect a better treatment response, is associated with being male and with milder and less allergic disease. Importantly, whether clinical remission of symptoms equals the disappearance of underlying pathology is unknown. In fact, airway hyper-responsiveness and airway inflammation might remain despite the absence of overt symptoms. Additionally, a new-onset of asthma symptoms is apparent in adulthood, especially in women and in the case of impaired lung function. However, many patients do not remember childhood symptoms, which might reflect relapse rather than true initiation. Both relapse and adult-onset of asthma symptoms have been associated with allergic disease and sensitisation in addition to airway hyper-responsiveness. Thus, asthma symptoms beginning in adults might have originated in childhood. Equivocally, persistence into, relapse, and new-onset of symptoms in adulthood have all been related to active smoking. However, underlying mechanisms for the associations remain unclear, and future asthma research should therefore integrate standardised molecular approaches in identical ways in both paediatric and adult populations and in longitudinal studies.
Severe Asthma in Children
2014, Journal of Allergy and Clinical Immunology: In Practice
Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of inhaled corticosteroids or oral corticosteroids. Children with severe asthma may fall into 2 categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, or poor adherence due to adverse psychological or environmental factors. In contrast, treatment resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline-based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting β-agonists and other add-on therapies, such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control, including reviewing the diagnosis and removing causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future.
Steroid-Resistant Asthma
2012, Paediatric Respiratory Reviews
Citation Excerpt :
Pharmokinetic studies can reveal those who have incomplete absorption, fail to convert prednisone from an inactive state to its active state prednisolone, or have rapid CS elimination.39 Morning plasma cortisol and prednisolone levels after a course of steroid treatment can help assess adherence.13,26 Intramuscular triamcinolone or computerized delivery systems have also been suggested as a method to document patient compliance with steroid therapy.13,26
Steroid-resistant asthma (SRA) refers to patients with symptoms consistent with asthma who show very poor or no response at all to high doses of inhaled or even of systemic corticosteroids. The current article reviews the SRA related literature focusing on the problems associated with the definition of SRA (especially its association with difficult to control, or severe asthma), its various phenotypes, its molecular basis, and the potential treatment options. The article also discusses the limitations of some of the key criteria used for the determination of SRA and proposes a modified set of criteria that are more applicable to children.
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2008, Respiratory Medicine
Citation Excerpt :
The low persistence found in our study is consistent with the findings from previous studies that no valid criteria exist to prospectively identify children who will develop asthma within a group of wheezing children.1,2,18–20 Moreover, a great proportion of those who wheezed in their first years of life did so for other reasons than asthma.2–6 However, other studies did find certain factors to be associated with persistent wheeze and asthma later in life, including early allergic sensitization,1,9,18,21,22 atopic disease (such as rhinitis, eczema), eosinophilia,19,22,23 female sex,21 tobacco smoke exposure,21,22 a family history of asthma,1,9,19,22–25early and/or severe wheezing.18,19,25
In young children with asthmatic symptoms diagnostic difficulties lead to use of trials of asthma medication as a diagnostic tool. Our aim is to quantify the persistent use of asthma medication, initiated in the first year of life and identify determinants of this persistent use.
We identified 165 children within the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort who used asthma medication before the age of one. Persistent use was investigated during three years after the first prescription. A Cox regression analysis was performed to identify factors associated with persistent use.
A total of 58.8% of children continued using asthma medication after the first prescription and 10.3% continued during three years. Children with doctor-diagnosed asthma (Hazard ratio of discontinuation (HR) = 0.64, 95% CI: 0.45–0.91) or prescribed inhaled corticosteroids in the first year of life (HR of discontinuation = 0.59, 95% CI: 0.40–0.86) were 1.6–1.7 times more likely to continue using asthma medication.
Persistence of asthma medication, prescribed in the first year of life is very low and is positively associated with doctor-diagnosed asthma and use of inhaled corticosteroids. Characterizing persistent users of asthma medication is important to understand prescribing of asthma medication in this age group.

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Respiratory reviewPhenotype specific treatment of asthma in childhood

Abstract

Lancet

Lancet

J Pediatr

Lancet

Respir Med

Lancet

J Pediatr

Lancet

Lancet

Management of asthma: a consensus statement

Arch Dis Child

Asthma—time for a change of name?

Arch Dis Child

Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma: relationship to bronchial hyperreactivity

Am Rev Respir Dis

Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness

J Allergy Clin Immunol

Effect of inhaled corticosteroid on airway inflammation and symptoms in asthma

Am Rev Respir Dis

Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma

Am J Respir Crit Care Med

Inflammation and airway function in asthma

Am J Respir Crit Care Med

Activated peripheral blood CD4 and CD8 T-lymphocytes in child asthma: correlation with eosinophilia and disease severity

Pediatr Allergy Immunol

Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and ‘Th2-type’ cytokine mRNA expression

Pediatrics

Effect of oral glucocorticoid treatment on inflammatory markers in acute asthma

Arch Dis Child

Bronchial biopsy evidence for leukocyte infiltration and up-regulation of leukocyte endothelial adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways

J Clin Invest

Effect of inhaled endotoxin on bronchial reactivity in normal and asthmatic subjects

J Appl Physiol

Contribution of 92 kDa gelatinase/Type IV collagenase in bronchial inflammation during status asthmaticus

Am J Respir Crit Care Med

Bronchoscopic evaluation of severe asthma

Am J Respir Crit Care Med

Comparison of exhaled nitric oxide, serum eosinophilic cationic protein, and soluble interleukin-2 receptor in exacerbations of pediatric asthma

Pediatr Pulmonol

Nitric oxide: a new lung function test

Thorax

Clinical aspects of exhaled nitric oxide

Eur Respir J

Exhaled nitric oxide measurements in normal and asthmatic children

Pediatr Pulmonol

Asthma severity and inflammation markers in children

Pediatr Allergy Immunol

Evidence for different subgroups of difficult asthma in children

Thorax

Respiratory review
Phenotype specific treatment of asthma in childhood