Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study.

BACKGROUND: Asthma can occur at any age but the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. OBJECTIVE: To investigate differences in patients' characteristics by age at asthma onset. METHODS: From 5 European electronic databases, we created a cohort encompassing adult patients with doctor-diagnosed asthma in 2008 to 2013. Patients were categorized based on their age at asthma onset: childhood-onset (age at onset < 18 y), adult-onset (age at onset 18-40 y), and late-onset asthma (age at onset ≥ 40 y). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios and age- and sex-adjusted odds ratios (ORadj) comparing asthma-onset categories were estimated per database and combined in a meta-analysis using a random effect model. RESULTS: In total, 586,436 adult asthma patients were included, 81,691 had childhood-onset, 218,184 adult-onset, and 286,561 late-onset asthma. Overall, 7.3% had severe asthma. Subjects with adult-onset compared with childhood-asthma had higher risks for overweight/obesity (ORadj 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (ORadj 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (ORadj 1.8; 95% CI 1.2-2.6), overweight/obesity (ORadj 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (ORadj 1.4; 95% CI 1.2-1.7), and diabetes (ORadj 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (ORadj 2.8; 95% CI 1.7-4.5). CONCLUSIONS: This international study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults. Furthermore, patients with late-onset asthma had more frequent uncontrolled asthma.

Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study.

BACKGROUND: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. METHODS: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. RESULTS: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. CONCLUSIONS: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma.

Exploratory Study of Signals for Asthma Drugs in Children, Using the EudraVigilance Database of Spontaneous Reports.

INTRODUCTION: As asthma medications are frequently prescribed for children, knowledge of the safety of these drugs in the paediatric population is important. Although spontaneous reports cannot be used to prove causality of adverse events, they are important in the detection of safety signals. OBJECTIVE: Our objective was to provide an overview of adverse drug events associated with asthma medications in children from a spontaneous reports database and to identify new signals. METHODS: Spontaneous reports concerning asthma drugs were obtained from EudraVigilance, the European Medicine Agency's database for suspected adverse drug reactions. For each drug-event combination, we calculated the proportional reporting ratio (PRR) in the study period 2011-2017. Signals in children (aged 0-17 years) were compared with signals in the whole population. Analyses were repeated for different age categories, by sex and by therapeutic area. RESULTS: In total, 372,345 reports in children resulted in 385 different signals concerning asthma therapy. The largest group consisted of psychiatric events (65 signals). Only 30 signals were new, with seven, including herpes viral infections, associated with omalizumab. Stratification by age, sex and therapeutic area provided additional new signals, such as hypertrichoses with budesonide and encephalopathies with theophylline. Of all signals in children, 60 (16%) did not appear in the whole population. CONCLUSIONS: The majority of signals regarding asthma therapy in children were already known, but we also identified new signals. We showed that signals can be masked if age stratification is not conducted. Further exploration is needed to investigate the risk and causality of the newly found signals.

Hair cortisol and inhaled corticosteroid use in asthmatic children.

BACKGROUND: Adrenal suppression is a side effect of long-term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long-term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children. METHODS: A cross-sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6-21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography-mass spectrometry in the most proximal 3 cm of hair. RESULTS: Median HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54). CONCLUSION: We observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.

Antibiotic use in children with asthma: cohort study in UK and Dutch primary care databases.

OBJECTIVES: To compare the rate, indications and type of antibiotic prescriptions in children with and without asthma. DESIGN: A retrospective cohort study. SETTING: Two population-based primary care databases: Integrated Primary Care Information database (IPCI; the Netherlands) and The Health Improvement Network (THIN; the UK). PARTICIPANTS: Children aged 5-18 years were included from January 2000 to December 2014. A child was categorised as having asthma if there were ≥2 prescriptions of respiratory drugs in the year following a code for asthma. Children were labelled as non-asthmatic if no asthma code was recorded in the patient file. MAIN OUTCOME MEASURES: Rate of antibiotic prescriptions, related indications and type of antibiotic drugs. RESULTS: The cohorts in IPCI and THIN consisted of 946 143 and 7 241 271 person years (PY), respectively. In both cohorts, antibiotic use was significantly higher in asthmatic children (IPCI: 197vs126 users/1000 PY, THIN: 374vs250 users/1000 PY). In children with asthma, part of antibiotic prescriptions were for an asthma exacerbation only (IPCI: 14%, THIN: 4%) and prescriptions were more often due to lower respiratory tract infections then in non-asthmatic children (IPCI: 18%vs13%, THIN: 21%vs12%). Drug type and quality indicators depended more on age, gender and database than on asthma status. CONCLUSIONS: Use of antibiotics was higher in asthmatic children compared with non-asthmatic children. This was mostly due to diseases for which antibiotics are normally not indicated according to guidelines. Further awareness among physicians and patients is needed to minimise antibiotic overuse and limit antibiotic resistance.