Prognostic utility of pre‐biologic treatment correlates of childhood severe asthma exacerbation risk: Real world evidence

Intermittent Asthma and Risk of Severe Exacerbation in Children.

PurposeMinimizing the future risk of asthma exacerbation (AE) is one of the main goals of asthma management. We investigated prognostic factors for risk of severe AE (SAE) in a real-world clinical setting.MethodsThis is an observational study evaluating subjects who were diagnosed with asthma and treated with anti-asthmatic medications from January 1995 to June 2018. Risk factors for SAE were analyzed in 2 treatment periods (during the initial 2 years and the following 3–10 years of treatment) using the big data of electronic medical records.ResultsIn this study, 5,058 adult asthmatics were enrolled; 1,335 (28.64%) experienced ≥ 1 SAE during the initial 2 years of treatment. Female sex, higher peripheral eosinophil/basophil counts, and lower levels of forced expiratory volume in 1 second (FEV1; %) were factors predicting the risk of SAEs (P < 0.001 for all). Higher serum total immunoglobulin E levels increased the risk of SAEs among the patients having ≤ 2 SAEs (P = 0.025). Patients with more frequent SAEs during the initial 2 years of treatment had significantly higher risks of SAEs during the following years of treatment (P < 0.001, for all) (patients with ≥ 4 SAEs, odds ratio [OR], 29.147; those with 3 SAEs, OR, 14.819; those with 2 SAEs, OR, 9.867; those with 1 SAE, OR, 5.116), had higher maintenance doses of systemic steroids, and showed more gradual decline in FEV1 (%) and FEV1/forced vital capacity levels maintained during the following years of treatment (P < 0.001 for all).ConclusionsAsthmatics having risk factors for SAEs (female sex, higher peripheral eosinophil/basophil counts, and lower FEV1) should be strictly monitored to prevent future risk and improve clinical outcomes.

Context: Virus infection is a well-known risk factor for asthma exacerbations in temperate and subtropical countries, particularly in atopic children. However, the risk has not been well-described in tropical countries including Vietnam. Aims: To compare the odds of virus infection in hospitalized children with severe versus moderate asthma exacerbations. Settings and Design: A cross-sectional study was conducted at Children’s Hospital 1, Ho Chi Minh City, Vietnam. Children who were admitted to the hospital and diagnosed with severe or moderate asthma exacerbations were recruited for the study. Materials and Methods: Data were collected from interviews and medical records. Virus infection was confirmed by multiplex real-time polymerase chain reaction. Inhalant allergy was confirmed by a skin prick test with common indoor aeroallergens. Statistical Analysis Used: Associations among age, gender, passive smoking, child’s history of eczema, family history of asthma, virus infection, and inhalant allergy with the odds of severe asthma exacerbations were tested by binary logistic regressions. Multivariable logistic regression was done to measure the association between virus infection with the odds of severe asthma exacerbations adjusted for passive smoking. The odds ratio (OR) and its 95% confidence interval (CI) were reported to show the strength of the associations. Results: Nearly half of the children were infected by a virus (48.5%) and had passive smoking (49.2%). The percentage of children with a positive skin prick test was 83%. The most common indoor aeroallergen was house dust mites (81.1%). The odds of severe asthma exacerbations in children with virus infection was three times higher than that in those without virus infection (OR: 3.21, 95% CI: 1.20‐8.60, P = 0.021). Conclusions: Immunization and other healthcare programs should be deployed to prevent asthmatic children from virus infection and passive smoking to reduce the risk of severe asthma exacerbations.

BackgroundSevere asthma exacerbation reduces patients’ quality of life, results in visits to the emergency department (ED) and hospitalization, and incurs additional medical costs. Antipsychotics block receptors with bronchodilation function; however, the association between antipsychotic use and severe asthma exacerbation is unknown. This study aimed to investigate the effects of antipsychotics on asthma-related ED visits and hospitalizations.MethodsA case-crossover design was used in this study. Using the 2003–2017 Taiwan National Health Insurance Reimbursement Database, we established a cohort of 18,657 adults with asthma exacerbation leading to ED visits or hospitalization. Univariate and multivariate conditional logistic regressions were conducted to explore the association between antipsychotic use and severe asthma exacerbation. Subgroup analyses of different classes, doses, receptor functions of antipsychotics, different psychiatric disease, and sensitivity analyses of excluding patients with schizophrenia were also performed.ResultsAntipsychotic use was associated with a higher risk of severe asthma exacerbation (adjusted odds ratio [OR]: 1.27; 95% confidence interval [CI] 1.05–1.54; P = 0.013) compared with no use of antipsychotics. The use of typical antipsychotics increased the risk of severe asthma exacerbation (adjusted OR: 1.40, 95% CI 1.10–1.79, P = 0.007), whereas the use of atypical antipsychotics did not. These results did not change after the exclusion of patients with schizophrenia. There was a dose-dependent effect of antipsychotics (trend test, P = 0.025). Antipsychotics that block the M2 muscarinic or D2 dopaminergic receptors were associated with an increased risk of severe asthma exacerbation (adjusted OR: 1.39, 95% CI 1.10–1.76, P = 0.007 and adjusted OR: 1.33, 95% CI 1.08–1.63, P = 0.008, respectively). However, use of antipsychotics did not increase risk of severe asthma exacerbation in patients with psychiatric disorder.ConclusionsThe use of typical antipsychotics is associated with a dose-dependent increased risk of severe asthma exacerbation, especially for patients without psychiatric disorders. Further research on the impact of typical antipsychotics on asthma exacerbation is warranted.

Predictive Properties of the Asthma Control Test and Its Component Questions for Severe Asthma Exacerbations

The benefits of drug therapy for asthma have been well established, but adherence to treatment is poor, and this might be associated with an increased risk of asthma exacerbations. The aim of this study was to review the literature on the association between adherence to asthma controller treatment and risk of severe asthma exacerbations in children and adults. A systematic literature search was performed in PubMed, Embase and Web of Science, from inception until January 2014. Studies were included if data on the association between medication adherence and severe asthma exacerbations were presented. Quality was assessed using a modified version of the Newcastle-Ottawa Scale. The search yielded 2319 unique publications, of which 23 met the inclusion criteria and underwent data extraction and quality scoring. High levels of heterogeneity across studies with regard to adherence and exacerbation measurements, designs and analysis precluded a formal meta-analysis. Although effect measures varied widely, good adherence was associated with fewer severe asthma exacerbations in high-quality studies. Good adherence tended to be associated with lower risk of severe asthma exacerbations. Future studies should use standardised methodology to assess adherence and exacerbations, and should consider inhaler competence.

Background: Severe asthma exacerbation is one of the common pediatric medical emergencies that necessitates hospital visits. The study aimed to identify risk factors associated with pediatric severe asthma exacerbations that might have the potential to guide the parents for early medical consultations and physicians at primary health care centers for proper management.Methods: A case-control study was conducted on over 100 asthmatic children below 12 years attending the Emergency Department of Alexandria University Children’s Hospital in acute exacerbation. Based on a modified pulmonary index score, the patients were allocated into 2 groups; study group (50 patients with severe asthma exacerbation) and control group (50 patients with mild asthma exacerbations). Demographic data, history of illness, alarming clinical signs, medications, and outcome of all participants were recorded.Results: Severe asthma exacerbations were more encountered among males, older age, and with a longer duration of asthma (X±SD=28.4±15.9 months) with significant differences when compared to controls. Comparing the studied groups revealed higher risk for severe asthma exacerbations mainly with; history of sudden onset of severe respiratory distress (Odds ratio “OR”=30.13, 95% CI, 13.78-66.69) and chronic steroid-dependent asthma (OR=14.46, 95% CI, 3.97-52.65). Cyanosis, lethargy, and inability to talk were alarming signs in patients with severe asthma exacerbation when compared to those with mild asthma exacerbation (p&lt;0.05).Conclusions: Severe asthma exacerbation in children is still associated with many risk factors that may alert the patients’ caregivers and physicians prospectively for early proper management.

Metabolic Medications and Youth Hospitalizations for Asthma: A Pre-Post Quasi-Experimental Study.

Proximity to a major road, vitamin D insufficiency, and severe asthma exacerbations in Puerto Rican children.

The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N= 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.

BackgroundLongitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe...

Vitamin D in asthma: Panacea or true promise?

Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Urinary LTE 4 Levels Identify Children with Tobacco Smoke Exposure At Risk for Asthma Exacerbation

BackgroundAs asthma symptoms worsen, patients typically rely on short-acting β2-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation.MethodsWe conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol–budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two actuations of 90 μg and 80 μg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 μg of albuterol and 80 μg of budesonide (with each dose consisting of two actuations of 90 μg and 40 μg, respectively [the lower-dose combination group]), or 180 μg of albuterol (with each dose consisting of two actuations of 90 μg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population.ResultsA total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P=0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P=0.052). The incidence of adverse events was similar in the three trial groups.ConclusionsThe risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies. (Funded by Avillion; MANDALA ClinicalTrials.gov number, NCT03769090.)