Risk factors associated with glucocorticoid-induced adverse effects in children with severe asthma

BACKGROUND: Although high-dose inhaled glucocorticoids (GCs) with or without chronically administered oral GCs are often used in children with severe persistent asthma, the adverse effects associated with their use have not been well-described in this patient population. OBJECTIVE: We sought to determine the GC-induced adverse effects profile of older children with severe persistent asthma. METHODS: A chart review of 163 consecutive children 9 years of age or older admitted to National Jewish for difficult to control asthma was done. RESULTS: The population studied consisted mostly of adolescents (mean +/- SD age, 14.4 +/- 2.1 years) with severe asthma receiving high-dose inhaled GC therapy (1675 +/- 94 microg/d) and averaging 6 systemic GC bursts per year. 50% required chronic oral GC therapy. GC-associated adverse effects were common and included hypertension (88%), cushingoid features (66%), adrenal suppression (56%), myopathy (50%), osteopenia (46%), growth suppression (39%), obesity and hypercholesterolemia (30%), and cataracts (14%). Height standard deviation scores of -0.44, -1.22, and -0.93 for those receiving intermittent, alternate day, and daily oral GCs, respectively, were smaller (less suppressed) than published values from the same institution before inhaled GC therapy (standard deviation scores of -1.26, -1.91, and -1.95, respectively). Osteopenia was strongly associated with growth suppression (odds ratio, 5.6; confidence interval, 2.7-11.8; P <.0001) and was found to be more common in female than male subjects, even after correcting for short stature (42% vs 18%, P <.006). CONCLUSIONS: GC-associated adverse effects are still unacceptably common among children with severe asthma, even in those not receiving chronically administered oral GC therapy yet receiving high-dose inhaled GCs. Therefore close monitoring and proper intervention are warranted, especially in female subjects, who appear to be at greater risk for osteopenia. There is clearly a need to consider alternative therapy or earlier intervention. The magnitude of growth suppression, while still a problem, appeared to be less severe with the addition of inhaled GC therapy. This observation suggests that high-dose inhaled GC therapy, by affording better asthma control and allowing less use of systemic therapy, has attenuated the growth-suppressive effects of poorly controlled asthma.     

Role of symptoms and lung function in determining asthma control in smokers with asthma

Background:  Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known.
Aim of the study:  The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV₁) value.
Methods:  This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with ≥15% reversibility in FEV₁ after salbutamol. All subjects completed the ACQ, recording FEV₁ and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler).
Results:  Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1–2.3) vs 2.8 (1.7–3.4); ( P  < 0.0001)] and in each of the six individual symptom question scores ( P  < 0.001), but no difference in FEV₁ levels ( P  = 0.908).
Conclusion:  Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV₁.     

Risk of developing asthma in young children with atopic eczema: a systematic review

BACKGROUND: It is commonly believed that the majority of infants and young children with early atopic eczema will develop asthma in later childhood. This belief is mainly based on cross-sectional population studies. Recent evidence suggests a more complex relationship between early eczema and asthma. OBJECTIVE: This systematic review was conducted to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life. METHODS: A sensitive search was performed to identify all prospective cohort studies on the topic. By pooling the eligible reports, we calculated the risk of developing asthma at 6 years of age or older in children with atopic eczema in the first 4 years of life. RESULTS: Thirteen prospective cohort studies were included, with 4 representing birth cohort studies and 9 representing eczema cohort studies. The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75). The prevalence of asthma at the age of 6 years in eczema cohort studies was 35.8% (95% CI, 32.2% to 39.9%) for inpatients and 29.5% (95% CI, 28.2% to 32.7%) for a combined group of inpatients and outpatients. CONCLUSION: Although there is an increased risk of developing asthma after eczema in early childhood, only 1 in every 3 children with eczema develops asthma during later childhood. This is lower than previously assumed. CLINICAL IMPLICATIONS: Our results may have important consequences for counseling patients with atopic eczema and their parents.     

Risk factors for asthma among children in Maputo (Mozambique)

BACKGROUND: Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique). METHODS: This case-control study included 199 age-matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast-feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child. RESULTS: The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P < 0.0001). Most of the asthmatic children lived in the urban area of Maputo [odd ratio (OR) = 6.73, CI = 3.1-14.0, P < 0.0001], had a parental history of asthma (OR = 26.8, CI = 10.8-68.2, P < 0.0001) or rhinitis (OR = 4, CI = 1.2-13.3, P = 0.005), had at least parent who smoked and were weaned earlier than the nonasthmatic children (OR = 2.4, CI = 1.3-4.4, P < 0.001). CONCLUSION: Childhood asthma was strongly associated with a family history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.     

Risk factors and characteristics of early-onset asthma in Taiwanese children.

BACKGROUND AND PURPOSE: Early-onset asthma has been reported to be associated with a family history of allergy and exposure to environmental factors. This study was designed to evaluate the relationship between age of onset of asthma and genetic and environmental factors with asthma severity in Taiwanese children. METHODS: A group of 352 children with asthma (220 males and 132 females), ranging in age from 5 to 15 years, were enrolled in this study. The subjects were divided into 2 groups: early-onset asthma (up to and including age 3) and late-onset asthma. General characteristics including family history of allergies and exposure to domestic pets and tobacco smoke were recorded. The subjects underwent pulmonary function testing and analysis of serum immunoglobulin E (IgE), eosinophil counts, and specific IgE for common allergens. RESULTS: Early-onset asthma was present in 149 subjects and late-onset asthma in 203. Family history of allergies included a sibling with asthma or urticaria predisposed to early-onset asthma (asthma, p=0.034; urticaria, p=0.024). Food and milk allergen sensitization were more common in early-onset asthma (food allergens, p=0.025; milk, p=0.034). Children with early-onset asthma had higher eosinophil counts (p=0.041). However, there was no correlation between age at onset and pulmonary function testing, the levels of total IgE and IgE specific for Dermatophagoides pteronyssinus or Dermatophagoides farinae. CONCLUSIONS: A history of asthma or urticaria in a sibling is a risk factor for early-onset asthma. A greater prevalence of food allergen sensitization and high eosinophil counts are characteristic of early-onset disease.     

Adherence in young children with asthma

PURPOSE OF REVIEW: To discuss the unique challenges of managing asthma in young children and to review the literature over the past year with regard to regimen adherence in this relatively understudied population. RECENT FINDINGS: Young children and their families face unique challenges in dealing with asthma and these have the potential to affect regimen adherence. They include the time and effort required by asthma-management activities (e.g. nebulizer use), dependency on parents for asthma care, and the limited ability of children to communicate about their symptoms. Five published studies were found for the past year. They covered three areas: adherence assessment (e.g. electronic monitoring versus diary cards), device impact on adherence (e.g. influence of the novelty of medication-delivery device), and adherence interventions (e.g. parental education regarding symptoms). SUMMARY: Research suggests that several components need to be considered when designing interventions to improve adherence for young children with asthma: to consider the strain in the caregiver role when developing the treatment regimen, to provide devices that parents and children can use, to monitor adherence with electronic monitoring, and to address parents' concerns and perceptions about treating prodromal symptoms of an asthma exacerbation. Because many parents are hesitant to treat cough symptoms, an additional training component may need to be added to address this concern.     

Risk factors for development of bronchial asthma in children in Delhi.

BACKGROUND: Information on the magnitude of the problem of childhood asthma in India and the factors influencing its occurrence is inadequate. OBJECTIVE: To measure the prevalence of asthma in schoolchildren in Delhi and study the factors determining its occurrence. METHODS: A questionnaire-based study carried out in nine randomly selected schools in Delhi. The age range was 5 to 17 years. The questionnaires were distributed to all the children (n = 21,367) for answering by either parent. The key questions relate to complaints of recurrent wheezing in the past, during the immediate last 1-year, and also wheezing exclusively induced by exercise or colds. In all, 19,456 questionnaires were received back (response rate 91%). Out of these, 18,955 were complete and analyzed. RESULTS: The prevalence of current asthma was 11.9% while past asthma was reported by 3.4% of children. Exclusive exercise-induced asthma was reported by 2.1% while that associated with colds by 2.4% of children. Boys had a significantly higher prevalence of current asthma as compared with girls (12.8% and 10.7%, respectively). Multiple logistic regression analysis showed that male sex, a positive family history of atopic disorders, and the presence of smokers in the family were significant factors influencing the development of asthma while economic class, air pollution (total suspended particulates), and type of domestic kitchen fuel were not. CONCLUSIONS: The prevalence of current asthma in children in Delhi is 11.9%. Significant risk factors for its development are male sex, a positive family history of atopic disorders, and the presence of smokers in the family.     

Risk of stroke in male cigarette smokers

From 1965 to 1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry in a prospective study of cardiovascular disease. Of the subjects who had not had a stroke by the time of study entry, 3435 were cigarette smokers and 4437 were nonsmokers. In 12 years of follow-up, 171 smokers and 117 nonsmokers had a stroke. As compared with nonsmokers, cigarette smokers had two to three times the risk of thromboembolic or hemorrhagic stroke, after control for age, diastolic blood pressure, coronary heart disease, and other risk factors (P less than 0.001). Subjects who continued to smoke in the course of follow-up had the highest risk of stroke. When these subjects were compared with those who never smoked, their risk of hemorrhagic events was increased four- to six-fold (P less than 0.001). Subjects who were smokers at study entry but stopped smoking in the course of follow-up had a slight excess risk of stroke. When these subjects were compared with those who continued to smoke, however, their risk was reduced by more than half after adjustment for risk factors (P less than 0.05), indicating that stopping smoking had significant benefits.     

Tiotropium in children and adolescents with asthma

BackgroundAsthma is a major cause of morbidity in children, despite the availability of various treatments. In adults, tiotropium—a long-acting muscarinic antagonist—as add-on therapy to an inhaled corticosteroid with or without a long-acting β₂-agonist provides clinical benefit with a safety profile similar to placebo.ObjectiveTo review published evidence on the efficacy and safety of tiotropium as add-on a long-acting muscarinic antagonist therapy in children and adolescents with asthma that is uncontrolled despite use of an inhaled corticosteroid with or without additional controller medication(s).MethodsWe searched PubMed from inception until June 12, 2018, for randomized controlled trials of children and adolescents aged 1 to 17 years treated with tiotropium and reporting a primary outcome of any pulmonary function test and a secondary outcome of adverse events.ResultsOverall, 7 randomized controlled trials of 1902 preschool children (aged 1-5 years; n = 102), school-age children (aged 6-11 years; n = 905), and adolescents (aged 12-17 years; n = 895) with moderate to severe asthma were included in the analysis. Once-daily tiotropium (5, 2.5, or 1.25 μg) improved lung function parameters, including peak and trough forced expiratory volume in 1 second, vs placebo. Commonly reported adverse events across treatment groups included asthma worsening or exacerbations, decreased peak expiratory flow rate, nasopharyngitis, viral respiratory tract infection, and respiratory tract infection.ConclusionOnce-daily tiotropium as add-on therapy is efficacious and safe in adolescents and children with moderate to severe asthma. These results support the expanded indication by regulatory authorities for add-on tiotropium in patients 6 years or older.     

Fenoterol dose-response study in children with asthma

We have studied the effect of fenoterol, a selective beta-2 adrenergic agent, on airway obstruction in children with asthma. The drug was administered orally in single doses of 2.5, 5, and 7.5 mg to 20 children with chronic stable asthma of moderate severity. The mean age of the children was 11.6 yr. Pulmonary function tests were performed as baseline at zero time and at intervals over a 6-hour period after drug administration. Onset of action for all doses was within 1 hr with a peak effect noted at 1.5 to 3 hr, and sustained improvement was observed over the entire 6 hr. The doses of 5 mg and 7.5 mg were equally effective in producing significant improvement of pulmonary function compared to 2.5 mg (p less than 0.05). Side effects remained acceptable for all patients. The 5 and 7.5 mg doses produced significant adverse effects that involved the central nervous and musculoskeletal systems, whereas the 7.5 mg dose caused a significant incidence of tachycardia. Our findings indicate: (1) fenoterol is a potent oral bronchodilator for large and small airways in children, (2) the 7.5 mg dose does not achieve any additive effect over a 5 mg dose; and (3) 5 mg is the optimal oral dose of fenoterol for children from age 8 to 12 yr.     

Digital health interventions in children with asthma

Although healthcare providers are actively involved in offering education, information and interventions for asthmatic patients, medication and therapeutic adherence remain low in the paediatric population, with estimates suggesting that adherence rates hover below 50%. A range of available digital health interventions has been explored in paediatric asthma with promising but variable results, limiting their widespread adoption in clinical practice. They include emerging technologies that yield the advantage of tracking asthma symptoms and medications, setting drug reminders, improving inhaler technique and delivering asthma education, such as serious games (video games designed for medical- or health-related purposes), electronic monitoring devices, speech recognition calls, text messaging, mobile apps and interactive websites. Some of the proposed digital interventions have used multiple components, including educational and behavioural strategies and interactions with medical professionals. Overall, the implementation of such interventions may offer the opportunity to improve adherence and asthma control. In a state of emergency as the COVID-19 pandemic, telemedicine can also play a central role in supporting physicians in managing children with asthma. This review evaluates the published literature examining digital health interventions for paediatric asthma and explores the most relevant issues affecting their implementation in practice and the associated evidence gaps, research limitations and future research perspectives.