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Introduction: Asthma is the most common chronic disease during pregnancy. Maternal asthma has been associated with a multitude of unwanted pregnancy outcomes, in some studies also with neurodevelopmental disorders. Here we investigated associations between maternal asthma and neurodevelopmental disorders. Material and Methods: We studied a retrospective population‐based cohort of 1 271 439 mother–child pairs from singleton live births in Finland between the years 1996–2018. We used multiple high‐cover registers for data collection. Adjusted unconditional Cox regression models were used to investigate associations between maternal asthma, asthma medication used during pregnancy, and offspring's neurodevelopmental disorder diagnoses. Results: We identified 106 163 mother–child pairs affected by maternal asthma. We found that maternal asthma was associated with offspring neurodevelopmental disorders, but the differences in absolute prevalence between the control and exposure groups were small. Attention‐deficit hyperactivity disorder (ADHD) was found in 4114 (3.9%) offspring with maternal asthma and in 32 122 (3.0%) controls (adjusted hazard ratio (HR): 1.49; 95% CI 1.44–1.54); autism in 1617 (1.5%) offspring vs 13 701 (1.3%) controls (HR: 1.33; 95% CI 1.26–1.40); motor‐developmental disorder in 1569 (1.5%) offspring vs 12 147 (1.1%) controls (HR: 1.37; 95% CI 1.30–1.45); language disorder in 3057 (2.9%) offspring vs 28 421 (2.7%) controls (HR: 1.13; 95% CI 1.08–1.17), learning disabilities in 849 (0.8%) offspring vs 6534 (0.6%) controls (HR: 1.51; 95% CI 1.41–1.62); mixed developmental disorder in 1633 (1.5%) offspring vs 14 434 (1.3%) controls (HR 1.20; 95% CI, 1.14–1.26); and intellectual disability in 908 (0.9%) vs 9155 (0.9%) controls (HR: 1.12; 95% CI 1.04–1.20). No substantial differences were found between allergic and non‐allergic asthma phenotypes, and neither allergic tendency nor respiratory infection was associated with a similar likelihood of neurodevelopmental disorders. Conclusions: Maternal asthma and allergic and non‐allergic phenotypes showed weak associations with the offspring's neurodevelopmental disorders. The association is concerned especially with learning disabilities, ADHD, motor development, and autism. [ABSTRACT FROM AUTHOR]

Introduction: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease caused by a hypersensitivity reaction to antigens of Aspergillus fumigatus. Objective: The aim of this study was to evaluate the long-term clinical outcomes of omalizumab use in patients with ABPA. Methods: In this retrospective study, 12 patients diagnosed with ABPA and receiving omalizumab for at least 2 years, and 32 patients diagnosed with severe allergic asthma and receiving omalizumab for at least 2 years (control group) were evaluated. Results: Evaluation was made of a total of 44 participants, comprising 11 (25%) males and 33 (75%) females, who received omalizumab for at least 2 years with the diagnosis of the control group (n = 32) and ABPA (n = 12). The increase in asthma control test (ACT) score after omalizumab was significant at 12 months and at 24 months in patients with ABPA. After omalizumab, the use of oral corticosteroid (OCS), the annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in patients with ABPA. The increase in forced expiratory volume in 1 s (FEV1) (%) and ACT score after omalizumab were significant at 12 months and at 24 months in the control group. After omalizumab, the use of OCS, annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in the control group. Conclusion: Long-term omalizumab use in patients with ABPA seems to be an effective treatment for improving pulmonary function and reducing asthma exacerbations and hospitalizations. [ABSTRACT FROM AUTHOR]

BackgroundThe upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown.ObjectiveWe sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response.MethodsSaliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4 -6 were examined in gene-set enrichment analyses. Significant results were sought for replication in 114 African American and 158 Latino children with and without asthma. ICS-response-associated single nucleotide polymorphisms reported in the literature were evaluated as microbiome quantitative trait loci. Multiple comparisons were adjusted by the false discovery rate.ResultsGenes associated with exacerbation-related airway-microbiome traits were enriched in asthma comorbidities development (ie, reflux esophagitis, obesity, and smoking), and were likely regulated by trichostatin A and the nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein transcription factors (7.8 × 10-13 ≤ false discovery rate ≤ 0.022). Enrichment in smoking, trichostatin A, nuclear factor-κB, and glucocorticosteroid receptor were replicated in the saliva samples from diverse populations (4.42 × 10-9 ≤ P ≤ .008). The ICS-response-associated single nucleotide polymorphisms rs5995653 (APOBEC3B-APOBEC3C), rs6467778 (TRIM24), and rs5752429 (TPST2) were identified as microbiome quantitative trait loci of Streptococcus, Tannerella, and Campylobacter in the upper airway (0.027 ≤ false discovery rate ≤ 0.050).ConclusionsGenes associated with asthma exacerbation-related microbiome traits might influence asthma comorbidities. We reinforced the therapeutic interest of trichostatin A, nuclear factor-κB, the glucocorticosteroid receptor, and CCAAT/enhancer-binding protein in asthma exacerbations.

Background/Aims Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. Methods This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. Results Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. Conclusions SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

The most widespread chronic condition observed amid children globally is asthma. Only half of children with asthma adhere to their prescribed inhaled corticosteroids (ICS) therapy. Parents' emotions and perspectives regarding asthma have an impact on inhalation corticosteroid adherence. The participants in this study were 148 parents of children with asthma, with the aim to redintegrate their beliefs about medicines in general and specifically of ICS and the impact on ICS adherence in children with asthma. Children were mostly male (66.9%), older than five years (58.8%), parents were female, mean age 38, employed, and with a history of consumption of some form of corticosteroids. Parents' answers show that 50% of them disagreed with the statement that medicines are addictive, and 90% agree that medicine helps many to live better. A percentage of 77.7% of parents acknowledge that their child's health relies on inhaled corticosteroids (ICS), and 86.5% of parents agree that these medications safeguard their child from worsening health. Most of the parents (93.2%) adhere to the guidelines and instructions of the doctor. In summary, parents who hold the belief that medicines are neither overused nor harmful tend to exhibit a higher adherence. Furthermore, those with elevated adherence levels express lower levels of concern regarding the use of inhaled corticosteroids (ICS) in their children's asthma therapy. [ABSTRACT FROM AUTHOR]

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.

BackgroundAsthma is a heterogeneous disease. Clinical blood parameters differ by race/ethnicity and are used to distinguish asthma subtypes and inform therapies. Differences in subtypes may explain population-specific trends in asthma outcomes. However, these differences in racial/ethnic minority pediatric populations are unclear.ObjectiveWe investigated the association of blood parameters and asthma subtypes with asthma outcomes and examined population-specific eligibility for biologic therapies in minority pediatric populations.MethodsUsing data from 2 asthma case-control studies of pediatric minority populations, we performed case-control (N = 3738) and case-only (N = 2743) logistic regressions to quantify the association of blood parameters and asthma subtypes with asthma outcomes. Heterogeneity of these associations was tested using an interaction term between race/ethnicity and each exposure. Differences in therapeutic eligibility were investigated using chi-square tests.ResultsRace/ethnicity modified the association between total IgE and asthma exacerbations. Elevated IgE level was associated with worse asthma outcomes in Puerto Ricans. Allergic asthma was associated with worse outcomes in Mexican Americans, whereas eosinophilic asthma was associated with worse outcomes in Puerto Ricans. A lower proportion of Puerto Ricans met dosing criteria for allergic asthma-directed biologic therapy than other groups. A higher proportion of Puerto Ricans qualified for eosinophilic asthma-directed biologic therapy than African Americans.ConclusionsWe found population-specific associations between blood parameters and asthma subtypes with asthma outcomes. Our findings suggest that eligibility for asthma biologic therapies differs across pediatric racial/ethnic populations. These findings call for more studies in diverse populations for equitable treatment of minority patients with asthma.

Omalizumab is used for the treatment of severe allergic asthma. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe allergic asthma classified as super-responder or non super-responder to omalizumab. Comparisons were made of the laboratory data and clinical features of patients with severe allergic asthma. Patients who had no asthma exacerbation, no oral corticosteroid (OCS) use, asthma control test (ACT) score >20 and forced expiratory volume in 1 s (FEV1) >80% were considered super-responder after omalizumab. A total of 90 patients were included in the study, comprising 19 (21.1%) males. The age at onset of asthma, allergic rhinitis rate, number of endoscopic sinus surgeries (ESS), intranasal corticosteroid (INS) use, baseline FEV 1 (%) and ACT score were significantly higher in the omalizumab super-responder group (p = 0.013, p = 0.015, p = 0.002, p = 0.001, p = 0.001 and p < 0.001, respectively). The duration of asthma, rate of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), regular use of OCS, baseline eosinophil count and eosinophil-to-lymphocyte ratio were significantly higher in the omalizumab non super-responder group (p = 0.015, p < 0.001, p = 0.004, p < 0.001 and p < 0.001, respectively). Blood eosinophil count (AUC: 0.187, p < 0.001), eosinophil-to-lymphocyte ratio (AUC: 0.150, p < 0.001) and FEV1 (%) (AUC:0.779, p = 0.001) were determined to have diagnostic value in predicting the treatment response to omalizumab of patients with severe allergic asthma. High-blood eosinophil levels, CRSwNP and low pretreatment lung capacity may affect omalizumab treatment response in patients with severe allergic asthma. These results should be supported by further multicenter real-life studies. [ABSTRACT FROM AUTHOR]

The most prevalent children's chronic disease worldwide is asthma which has notable negative impacts on patients' and parent's quality of life. Daily inhaled corticosteroids (ICS) therapy is a preferred controller choice. This study was conducted on 148 parents of asthmatic children to establish parents' perception of illness and fear of inhaled corticosteroids using B-IPQ and TOPICOP questionnaires. Children were in the majority male (66.9%), older than five years (58.8%), with comorbidities, and family history of atopy. Parents were female, with a mean age of 38, employed, and with a history of some form of corticosteroid use. Most parents were not afraid of ICS usage (71.6%). Unemployed parents and parents who had no medical education had a statistically significantly higher fear of using ICS (p = 0.002, p = 0.03). A child's illness affects the parents' lives and parents who are afraid of using ICS react more emotionally to the child's illness. Better understanding and less concerned about child's disease are parents of children with controlled asthma. The parents' perspective of children's asthma will affect the duration and dose of ICS treatment they will give to their children and directly influence the level of asthma control. [ABSTRACT FROM AUTHOR]

BackgroundSialic acid-binding immunoglobulin-like lectin (Siglec)-8 is expressed on mast cells and eosinophils, but information about Siglec-8 expression and function in the lung is limited. A humanized antibody, AK002, targeting Siglec-8 is undergoing development for treatment of diseases associated with mast cell and eosinophil-driven inflammation.ObjectiveTo characterize Siglec-8 expression in the airway in asthma and determine whether antibodies that target Siglec-8 (S8mAbs) can decrease airway eosinophils in asthma or inhibit lung mast cell activation.MethodsGene expression profiling and flow cytometry were used to characterize Siglec-8 expression in sputum cells from stable asthma. An antibody-dependent cellular cytotoxicity (ADCC) assay was used to determine whether an S8mAb can decrease eosinophils in sputum from asthma patients ex vivo. A mast cell activation assay was used to determine whether an S8mAb can inhibit mast cell activation in human lung tissue ex vivo.ResultsGene expression for Siglec-8 is increased in sputum cells in asthma and correlates with gene expression for eosinophils and mast cells. Gene expression for Siglec-8 is inversely and significantly correlated with measures of airflow obstruction in asthma patients. Siglec-8 is prominently expressed on the surface of eosinophils and mast cells in sputum. S8mAbs decrease eosinophils in sputum from patients with asthma and inhibit FcεR1-activated mast cells in lung tissues.Conclusions and clinical relevanceSiglec-8 is highly expressed on eosinophils and mast cells in asthmatic sputum and targeting Siglec-8 with an antibody is a plausible strategy to decrease sputum eosinophils and inhibit lung mast cells in asthma.

Objective: To provide updated prevalence estimates of asthma and asthma medication use for women of childbearing age in the United States.Methods: Using data from 11,383 women aged 18-44, including a subset of 1,245 pregnant women, enrolled in the National Health and Nutrition Examination Survey (2001-2016), we assessed the age-adjusted prevalence of self-reported diagnosed asthma. For women aged 18-44, we stratified by year, demographics, and other characteristics. Furthermore, we assessed asthma medication use among women aged 18-44 with asthma.Results: After age-adjustment, 9.9% (95% confidence interval (CI) 9.2%, 10.7%) of women aged 18-44 and 10.9% (95% CI 7.2%, 14.6%) of pregnant women reported having asthma. Asthma prevalence was highest in 2015-2016 (12.0% 95% CI 9.8%, 14.3%) and lowest in 2003-2004 (8.6% 95% CI 6.4%, 10.8%). Women aged 18-44 with Medicaid or State Children's Health Insurance Program insurance coverage (16.8% 95% CI 14.5%, 19.2%), obesity (14.4% 95% CI 12.9%, 15.8%), diabetes (18.7% 95% CI 12.1%, 25.2%), hypertension (16.6% 95% CI 14.2%, 19.0%), and current smokers (12.8% 95% CI 11.4%, 14.2%) had the highest asthma prevalence. Of women with asthma, 38.3% (95% CI 34.5%, 42.1%) reported using asthma medications in the past 30 days.Conclusions: Among women of childbearing ages, asthma burden varies across demographic and clinical characteristics and has increased in recent years.

Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICERs annual policy summit is supported by dues from Aetna, AHIP, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Synnott, Kumar, Adair, Rind, and Pearson are employees of ICER, which provided grants to the University of California, San Francisco, and the University of Colorado to perform work for these analyses. Tice and Walsh are employed by the University of California, San Francisco, and Campbell and Whittington are employed by the University of Colorado.

Clinical application of inhaled glucocorticoids (GCs) has been hampered in the case of steroid-resistant severe asthma. To overcome this limitation, we have developed a series of highly potent GCs, including VSGC12, VSG158, and VSG159 based on the structural insight into the glucocorticoid receptor (GR). Particularly, VSG158 exhibits a maximal repression of lung inflammation and is 10 times more potent than the currently most potent clinical GC, Fluticasone Furoate (FF), in a murine model of asthma. More importantly, VSG158 displays a unique property to reduce neutrophilic inflammation in a steroid-resistant airway inflammation model, which is refractory to clinically available GCs, including dexamethasone and FF. VSG158 and VSG159 are able to deliver effective treatments with reduced off-target and side effects. In addition, these GCs also display pharmacokinetic properties that are suitable for the inhalation delivery method for asthma treatment. Taken together, the excellent therapeutic and side-effect profile of these highly potent GCs holds promise for treating steroid-resistant severe asthma.

The most widespread chronic condition observed amid children globally is asthma. Only half of children with asthma adhere to their prescribed inhaled corticosteroids (ICS) therapy. Parents’ emotions and perspectives regarding asthma have an impact on inhalation corticosteroid adherence. The participants in this study were 148 parents of children with asthma, with the aim to redintegrate their beliefs about medicines in general and specifically of ICS and the impact on ICS adherence in children with asthma. Children were mostly male (66.9%), older than five years (58.8%), parents were female, mean age 38, employed, and with a history of consumption of some form of corticosteroids. Parents’ answers show that 50% of them disagreed with the statement that medicines are addictive, and 90% agree that medicine helps many to live better. A percentage of 77.7% of parents acknowledge that their child’s health relies on inhaled corticosteroids (ICS), and 86.5% of parents agree that these medications safeguard their child from worsening health. Most of the parents (93.2%) adhere to the guidelines and instructions of the doctor. In summary, parents who hold the belief that medicines are neither overused nor harmful tend to exhibit a higher adherence. Furthermore, those with elevated adherence levels express lower levels of concern regarding the use of inhaled corticosteroids (ICS) in their children’s asthma therapy.

Precision medicine is expected to impact the care of people with asthma, given its high disease prevalence, heterogeneity of pathophysiologic mechanisms, and consequent clinical phenotypes. A novel phenotype-stratified clinical trial conducted by the NHLBI AsthmaNet Consortium, titled Steroids in Eosinophil Negative Asthma (SIENA), was a randomized, multicenter, clinical trial that prospectively stratified individuals according to their baseline level of sputum inflammation during a screening period. Two phenotypic strata were assigned based on an a priori defined extent of sputum eosinophilia (Eos Low versus Eos High). This article describes: the scientific premise for the trial design, including assumptions used for power calculations; modifications to the analysis plan implemented after the trial started due to a higher than expected prevalence of one phenotypic stratum which impacted the ability to accrue sufficient subjects within the planned budget and study period; investigator alternatives to address the strata imbalance weighing scientific impact and study feasibility; and the final modified SIENA study design and analysis plan. SIENA was successfully completed in a manner that maintained meaningful outcomes. We conclude with recommendations for incorporation of pre-specified contingency plans into phenotype-directed protocols, to address the potential for differences in observed compared to estimated prevalence of different phenotypes in a study population. These approaches can be applied to precision medicine trials for the future.

Abstract Background Adherence to inhaler medication is an important contributor to optimum asthma control along with adequate pharmacotherapy. The objective of the present study was to assess self-reported adherence levels and to identify the potential factors associated with non-adherence to the inhalers among asthma patients. Methods This facility-based cross-sectional study was conducted in the medicine outpatient department of Rajshahi Medical College Hospital from November 2020 to January 2021. A total of 357 clinically confirmed adult asthma patients were interviewed. Inhaler adherence was measured using the 10-item Test of Adherence scale (TAI).. Both descriptive and inferential statistics were used to express the socio-demographic of the patients and predictors of poor adherence to inhaler. Results A substantial number of participants were non-adherent (86%) to inhaler medication. Patients non-adherent to inhaler medication are often younger (23.15, 95% CI 3.67–146.08), lived in the rural area (23.28, 95% CI 2.43–222.66), less year of schooling (5.69, 95% CI 1.27–25.44), and belonged to the middle income (aOR 9.74, 95% CI 2.11–44.9) than those adherent with the inhaler. The presence of comorbidities (12.91, 95% CI 1.41–117.61), prolonged duration of inhaler intake (5.69, 95% CI 1.22–26.49), consulting non-qualified practitioners (13.09, 95% CI 3.10–55.26) were the significant contributor of non-adherence. Conclusion Despite ongoing motivation and treatment, non-adherence to inhalation anti-asthmatic is high and several factors have been found to contribute. Regular monitoring and a guided patient-centered self-management approach might be helpful to address them in long run.

Background/Aim. Asthma is a chronic inflammatory lung disorder. The effect of asthma drugs on oral health is still the subject of debate among researchers in dentistry. The aim of this study was t o e valuate dental status in asthmatic children and evaluate the possible effect of drugs treating asthma on dental health. Methods. Study participants were divided into two groups: the asthma (AG) and the non-asthma (NAG) group. Based on the symptoms of asthma and the possibility for effective control of the disease, the AG group was divided into two subgroups. The oral examination of the teeth was per-formed using a probe and mouth mirror under artificial light in accordance with the recommendations of the World Health Organization. Saliva analysis was carried out by the GC Saliva-Check Buffer, according to the manufacturer's instructions. Results. The study included 136 children aged 6 to 16 years (10.5 ± 3.3). The mean of decayed, missing, and filled teeth (dmft/DMFT) of the children in the AG group (6.0 ± 4.0/3.3 ± 4.4) was higher than in the NAG group (4.8 ± 4.4/2.5 ± 3.4), but significant differences were not observed between the groups. Salivary pH values were found to be similar in both groups, but the quantity and buffering capacity of the stimulated saliva were found to be significantly lower in the AG group (p < 0.001 and p < 0.05, respectively). Conclusion. Although the prevalence of dental caries in the AG group was similar to that of the NAG group in this study, decreased quantity and buffering capacity of the stimulated saliva in the A G group may contribute to higher values of dental caries in asthmatic children in the future.

Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis. National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs. Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80–0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk. Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation. [ABSTRACT FROM AUTHOR]

BackgroundAsthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.MethodsWe studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.ResultsThe rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06).ConclusionsIn children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

RationalePediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth.ObjectivesOur objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype.MethodsWe applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes.ResultsFour phenotypes were discovered in both datasets: allergic not obese (A+/O-), obese not allergic (A-/O+), allergic and obese (A+/O+), and not allergic not obese (A-/O-). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A+/O+ children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo (P = 0.011). The PP algorithm performed significantly better (P

BackgroundThere are limited data regarding the comparability of medication exposure information during pregnancy from maternal report and medical records, including for rheumatoid arthritis and asthma-related medications.MethodsThis study included pregnant women with rheumatoid arthritis (n = 216) and asthma (n = 172) enrolled in the MothertoBaby Pregnancy Studies (2009-2014). Women reported types and dates of medications used through semi-structured telephone interviews up to three times during pregnancy and once after delivery, and medical records were obtained. We calculated Cohen's kappa coefficients and 95% confidence intervals (CIs) and per cent agreement for agreement between report and records.ResultsFor rheumatoid arthritis, prednisone was reported most frequently (53%). During pregnancy, kappa coefficients for rheumatoid arthritis medications ranged from 0.32 (95% CI 0.15, 0.50) for ibuprofen, with 84.3% agreement, to 0.90 (95% CI 0.84, 0.96) for etanercept with 95.4% agreement, and was 0.44 (95% CI 0.33, 0.55) for prednisone, with 71.3% agreement. For asthma, albuterol was reported most frequently (77.9%). During pregnancy, kappa coefficients for asthma medications ranged from 0.21 (95% CI 0.08, 0.35), with 64.5% agreement for albuterol to 0.84 (95% CI 0.71, 0.96) for budesonide/formoterol, with 96.5% agreement. Where kappas for any use during pregnancy were less than excellent (i.e. ≤0.80), medication use was more frequently captured by report than record.ConclusionsAgreement was higher for medications typically used continuously than sporadically. Information on medication use from medical records alone may not be adequate when studying the impact of intermittently used medications during pregnancy on perinatal outcomes.

The most prevalent children’s chronic disease worldwide is asthma which has notable negative impacts on patients’ and parent’s quality of life. Daily inhaled corticosteroids (ICS) therapy is a preferred controller choice. This study was conducted on 148 parents of asthmatic children to establish parents’ perception of illness and fear of inhaled corticosteroids using B-IPQ and TOPICOP questionnaires. Children were in the majority male (66.9%), older than five years (58.8%), with comorbidities, and family history of atopy. Parents were female, with a mean age of 38, employed, and with a history of some form of corticosteroid use. Most parents were not afraid of ICS usage (71.6%). Unemployed parents and parents who had no medical education had a statistically significantly higher fear of using ICS (p = 0.002, p = 0.03). A child’s illness affects the parents’ lives and parents who are afraid of using ICS react more emotionally to the child’s illness. Better understanding and less concerned about child’s disease are parents of children with controlled asthma. The parents’ perspective of children’s asthma will affect the duration and dose of ICS treatment they will give to their children and directly influence the level of asthma control.

IntroductionAsthma is a common health condition for children in childcare. National recommendations for asthma in childcare exist. However, no studies have investigated the extent to which childcare centers adhere to these recommendations. We aimed to assess childcare center adherence to National Asthma Education and Prevention Program (NAEPP) recommendations for asthma care and preparedness and to identify characteristics associated with increased adherence to national asthma recommendations.MethodsWe developed a standardized instrument. Each childcare center received a score of 0 through 7 based on number of recommendations met. We conducted t-tests, chi square tests and linear regression to identify childcare center factors associated with increased asthma preparedness.Results36 out of 40 eligible childcare centers (90%) participated. These sites served 1570 children primarily between the ages of 2 to 5 years. On average, centers met 3.8 out of 7 (SD  =  1.3) recommendations. Staff familiarity caring for children with asthma (p

Biomarkers have been critical for studies of disease pathogenesis and the development of new therapies in severe asthma. In particular, biomarkers of type 2 inflammation have proven valuable for endotyping and targeting new biological agents. Because of these successes in understanding and marking type 2 inflammation, lack of knowledge regarding non-type 2 inflammatory mechanisms in asthma will soon be the major obstacle to the development of new treatments and management strategies in severe asthma. Biomarkers can play a role in these investigations as well by providing insight into the underlying biology in human studies of patients with severe asthma.

BackgroundGastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure.Case presentationOur patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting β2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting.ConclusionsLINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

The treatment of persistent asthma has been aided by the recent approval of new medications. The combined inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) powder inhaler fluticasone furoate (FF)/vilanterol trifenatate (VI) is one of these new agents, which was recently approved as a maintenance therapy for persistent asthma. This once-daily ICS/LABA inhaler has previously been approved and used in chronic obstructive pulmonary disease as a maintenance therapy. Both FF and VI individually have been shown to have efficacy in the treatment of persistent asthma; the combination of FF/VI at the dose of 100/25 μg daily improves trough peak expiratory flows and forced expiratory volume in 1 s. It also reduces the frequency of asthma exacerbations in patients with persistent asthma. The once-daily dosing is well tolerated, with limited clinically significant adverse events; the once-daily inhaled dosing regimen should also improve medication adherence. The data supporting the use of the FF/VI inhaler in persistent asthma are reviewed. The dry powder inhaler of FF/VI (100/25 μg) is an effective and well tolerated once-daily maintenance treatment for patients with persistent asthma.

The study of autophagy ('self-eating'), a fundamental cell fate pathway involved in physiological and pathological subcellular processes, opens a new frontier in the continuous search for novel therapies for human asthma. Asthma is a complex syndrome with different disease phenotypes. Autophagy plays a central role in cell physiology, energy and metabolism, and cell survival. Autophagy's hallmark is the formation of double-membrane autophagic autophagosomes, and this process is operational in airway epithelial and mesenchymal cells in asthma. Genetic associations between autophagy genes and asthma have been observed including single nucleotide polymorphisms in Atg5 which correlate with reduced lung function. Immune mechanisms important in asthma such as Th2 cells and eosinophils also manifest autophagy. Lastly, we address the role of autophagy in extracellular matrix deposition and fibrosis in asthmatic airways remodeling, a pathologic process still without effective therapy, and discuss potential pharmacologic inhibitors. We end by offering two opposing but plausible hypotheses as to how autophagy may be directly involved in airway fibrosis.

The use of inhaled corticosteroids (ICSs) plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA) to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD) and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF) and the LABA vilanterol trifenatate (VI) with indications for use in both COPD and asthma. This dry powder inhaler (DPI) comes in two doses of FF (100 or 200 μg) both combined with VI (25 μg). This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients.

BackgroundThe clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS.MethodsWe performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory effects (n = 357, age: 4-12 years, the Netherlands), BREATHE (n = 820, age: 3-22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age: 2-16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n = 172, age: 5-12 years, USA), the Genes- environment and Mixture in Latino Americans II- study (n = 745, age: 8-21, USA) and the Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5-18, UK) to test the robustness of the findings. Finally, all results were meta-analysed.ResultsTwo SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma-related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013) and OR = 1.22 (P = 0.0017), respectively.Conclusion and clinical relevanceA novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.

Mast cells are known as central players in allergy and anaphylaxis, and they play a pivotal role in host defense against certain pathogens. Chlamydia pneumoniae is an important human pathogen, but it is unclear what role mast cells play during C. pneumoniae infection. We infected C57BL/6 (wild-type [WT]) and mast cell-deficient mice (Kit(W-sh/W-sh) [Wsh]) with C. pneumoniae. Wsh mice showed improved survival compared with WT mice, with fewer cells in Wsh bronchoalveolar lavage fluid (BALF), despite similar levels of cytokines and chemokines. We also found a more rapid clearance of bacteria from the lungs of Wsh mice compared with WT mice. Cromolyn, a mast cell stabilizer, reduced BALF cells and bacterial burden similar to the levels seen in Wsh mice; conversely, Compound 48/80, a mast cell degranulator, increased the number of BALF cells and bacterial burden. Histology showed that WT lungs had diffuse inflammation, whereas Wsh mice had patchy accumulations of neutrophils and perivascular accumulations of lymphocytes. Infected Wsh mice had reduced amounts of matrix metalloprotease-9 in BALF and were resistant to epithelial integral membrane protein degradation, suggesting that barrier integrity remains intact in Wsh mice. Mast cell reconstitution in Wsh mice led to enhanced bacterial growth and normal epithelial integral membrane protein degradation, highlighting the specific role of mast cells in this model. These data suggest that mast cells play a detrimental role during C. pneumoniae infection by facilitating immune cell infiltration into the airspace and providing a more favorable replicative environment for C. pneumoniae.

Background and Aim: Saliva is an essential fluid for protecting the mouth, and any change in its quality or quantity affects the health of the oral cavity. Asthma and the medications used to treat it may decrease salivary flow and change salivary components, including changes in the pH of the dental plaque. The purpose of this study was to determine the salivary flow and pH in asthmatic and non-asthmatic patients referring to the Asthma Clinic of Masih Daneshvari Hospital in Tehran, Iran, in 2019. Materials and Methods: This cross-sectional study was performed on 70 patients aged 18-60 years (35 asthmatic patients and 35 healthy controls). After completing the datasheets, saliva was collected by the spitting method for 5 minutes. Its flow rate was recorded in ml/minute, and its pH was measured by a pH meter. The results were analyzed via SPSS 20 software according to the t-test and Mann-U-Whitney statistical test. Results: The mean salivary flow rate was 4.22 ml/minute in the asthmatic group and 5.44 ml/minute in the healthy group (P

BackgroundDespite the substantial burden of asthma-related emergency department (ED) visits, there have been no recent multicenter efforts to characterize this high-risk population.ObjectiveWe aimed to characterize patients with asthma according to their frequency of ED visits and to identify factors associated with frequent ED visits.MethodsA multicenter chart review study of 48 EDs across 23 US states. We identified ED patients ages 18 to 54 years with acute asthma during 2011 and 2012. Primary outcome was frequency of ED visits for acute asthma in the past year, excluding the index ED visit.ResultsOf the 1890 enrolled patients, 863 patients (46%) had 1 or more (frequent) ED visits in the past year. Specifically, 28% had 1 to 2 visits, 11% had 3 to 5 visits, and 7% had 6 or more visits. Among frequent ED users, guideline-recommended management was suboptimal. For example, of patients with 6 or more ED visits, 85% lacked evidence of prior evaluation by an asthma specialist, and 43% were not treated with inhaled corticosteroids. In a multivariable model, significant predictors of frequent ED visits were public insurance, no insurance, and markers for chronic asthma severity (all P < .05). Stronger associations were found among those with a higher frequency of asthma-related ED visits (eg, 6 or more ED visits).ConclusionThis multicenter study of US adults with acute asthma demonstrated many frequent ED users and suboptimal preventive management in this high-risk population. Future reductions in asthma morbidity and associated health care utilization will require continued efforts to bridge these major gaps in asthma care.

RationaleActivation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown.ObjectivesTo determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma.MethodsWe analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide.Measurements and main resultsEpithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment.ConclusionsIL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.

ImportanceIn asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.ObjectiveTo evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.Design, setting, and participantsThe VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.InterventionsOral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.Main outcomes and measuresThe primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).ResultsTreatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).Conclusions and relevanceVitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.Trial registrationclinicaltrials.gov Identifier: NCT01248065.

ObjectiveThe purpose of this study was to examine the incidence, characteristics of asthma morbidity and care, and ethnic differences that exist in older adults with asthma in California.MethodsData were from the 2009 California Health Interview Survey (CHIS). Characteristics of older adults (≥65 years) with and without asthma were compared using population-weighted estimates. Asthma-specific variables were compared among different ethnic groups. Multivariate analyses were preformed to determine factors associated with asthma status, asthma episodes/attacks, asthma symptom frequency and emergency department (ED) visits due to asthma.ResultsAsthma was present in 8.1% of older adults, among which, 67.3% reported taking medication daily for asthma. Asthma symptoms were experienced every day by almost 20%, with over 34% of seniors with asthma having symptoms at least once per week. Despite having a lower frequency of asthma symptoms, Hispanics were 5.31 times more likely to visit the ED due to asthma than were Caucasians.ConclusionsThe findings from the study showed that older adults with asthma had difficulty with asthma control. We recommend a focus on asthma education so that when symptoms do occur, options are available to avoid costly ED visits. Further research should focus on specific asthma management skills and adherence to asthma treatment regimen among ethnic groups.

ObjectiveTo compare asthma treatment decisions by pediatric residents to current asthma guidelines and to learn whether treatment decisions vary by postgraduate year in training.MethodsWe conducted a Web-based survey of residents from 10 training programs through the Continuity Research Network of the Academic Pediatric Association (CORNET). Surveys included 6 vignettes of patients receiving low-dose inhaled steroids with guideline- and non-guideline-based indicators of asthma status and 1 stable patient on high-intensity medication.ResultsThere were 369 resident respondents (65% response rate), 26% postgraduate year (PGY) 1, 38% PGY2, and 36% PGY3+. Seventy-five percent of each resident group reported seeing fewer than 1 asthma patient per continuity clinic session. A majority of residents made appropriate treatment recommendations in 2 of 4 vignettes of guideline-based indicators of asthma status: first, 97% overall stepping up treatment for mild persistent asthma; and second, 52% overall stepping down treatment for a patient with well-controlled asthma on high-intensity medications. Inconsistent with guideline recommendations, 82% of residents overall did not step down treatment for a patient with well-controlled asthma receiving low-intensity therapy; 75% of residents did not step up treatment for a patient with a recent hospitalization for asthma. Of the 3 vignettes evaluating non-guideline-based indicators of asthma status, a majority of residents (60%) stepped up treatment for parental reports of worse asthma, while a minority did so for a parental report of being bothered by their child's asthma (27%) or when wheezing was reported at physical examination (43%). There were no statistically significant differences for any of the comparisons by year in training.ConclusionsPediatric residents' management of asthma is consistent with national guidelines in some cases but not in others. There were no differences in the outpatient asthma management decisions between residents by years in training. Educational efforts should be focused on strategies to facilitate pediatric resident adherence to national asthma guideline recommendations for outpatient asthma management.

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow‐up and/or number of patients included were limited. We aim to describe the long‐term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real‐life cohort reported to date. Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow‐up. The primary outcome was the evolution of the annual number of moderate‐to‐severe exacerbations compared with the baseline period. Results: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P <.001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. Conclusion: In this large, long‐term, observational study, moderate‐to‐severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long‐term treatment in pediatric patients with severe persistent allergic asthma. [ABSTRACT FROM AUTHOR]

Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.

BackgroundTiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.ObjectiveWe sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.MethodsData from the double-blind, 3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for individual and differential treatment responses to salmeterol and tiotropium and predictors of a positive response to the end points FEV1, morning peak expiratory flow (PEF), and asthma control days (ACDs).ResultsAlthough approximately equal numbers of patients showed a differential response to salmeterol and tiotropium in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53, respectively), more showed a differential response to tiotropium for FEV1 (n = 104) than salmeterol (n = 62). An acute response to a short-acting bronchodilator, especially albuterol, predicted a positive clinical response to tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil count, fraction of exhaled nitric oxide, asthma duration, and body mass index were not.ConclusionAlthough these results require confirmation, predictors of a positive clinical response to tiotropium include a positive response to albuterol and airway obstruction, factors that could help identify appropriate patients for this therapy.

ObjectiveThis study aimed to identify factors associated with delayed or omission of indicated steroids for children seen in the emergency department (ED) for moderate-to-severe asthma exacerbation.MethodsThis was a retrospective study of pediatric (age ≤ 21 years) patients treated in a general academic ED from January 2006 to September 2011 with a primary diagnosis of asthma (International Classification of Diseases, Ninth Revision code 493.xx) and moderate-to-severe exacerbations. A moderate-to-severe exacerbation was defined as requiring 2 or more (or continuous) bronchodilators. We determined the proportion of visits in which steroids were inappropriately omitted or delayed (>1 hour from arrival). Multivariable logistic regression models were used to identify patient, physician, and system factors associated with delayed or omitted steroids.ResultsOf 1333 pediatric asthma ED visits, 817 were for moderate-to-severe exacerbation; 645 (79%) received steroids. Patients younger than 6 years (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.19-4.24), requiring more bronchodilators (OR, 2.82; 95% CI, 2.10-3.79), initially hypoxic (OR, 2.78; 95% CI, 1.33-5.83), or tachypneic (OR, 1.52; 95% CI, 1.05-2.20) were more likely to receive steroids. Median time to steroid administration was 108 minutes (interquartile range, 65-164 minutes). Steroid administration was delayed in 502 visits (78%). Patients with hypoxia (OR, 1.91; 95% CI, 1.11-3.27) or tachypnea (OR, 1.82; 95% CI, 1.17-2.84) were more likely to receive steroids 1 hour or less of arrival, whereas children younger than 2 years (OR, 0.16; 95% CI, 0.07-0.35) and those arriving during periods of higher ED volume (OR, 0.79; 95% CI, 0.67-0.94) were less likely to receive timely steroids.ConclusionsIn this ED, steroids were underprescribed and frequently delayed for pediatric ED patients with moderate-to-severe asthma exacerbation. Greater ED volume and younger age are associated with delays. Interventions are needed to expedite steroid administration, improving adherence to National Institutes of Health asthma guidelines.

Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting β-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting β-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting β-agonist combinations when implementing SMART (SOR B Recommendation)., Competing Interests: Conflict of interest: The authors report no potential conflict of interest relevant to this article., (© Copyright by the American Board of Family Medicine.)

Background: Asthma and molar incisor hypomineralization (MIH) are common diseases among children and have been suspected to be associated with each other. Aim: To examine the association between asthma or the use of asthma drugs and the prevalence of MIH. Design: In a population‐based cross‐sectional study, we recorded MIH in 9‐year‐old children in Aalborg Municipality, Denmark, born in the year 2000. We used a unique 10‐digit civil personal number to link data on MIH to population‐based medical register data. The exposure was inhaled asthma medication from birth date until date of dental examination. The outcome was the overall prevalence of MIH according to use of asthma medication. Odds ratios (OR) of having MIH were adjusted for gender, use of antibiotics and amoxicillin, maternal smoking, pre‐ and perinatal complication, and hospital admissions. Results: We examined 1837 children, of which 542 (29.5%) had one or more molar(s) with MIH. The adjusted odds ratio of having MIH was 0.95 (95% CI: 0.60‐1.51) among children with prescriptions of inhaled asthma medication. Conclusion: In this study, where the results have been adjusted for confounding, we found no association between use of inhaled asthma medication and the prevalence of MIH. [ABSTRACT FROM AUTHOR]

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma (n = 8) or steroid-treated asthma (n = 12) and in healthy controls (n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (+/-SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 +/- 836 pl/s and 143 +/- 66 ppb compared with 2,693 +/- 1,687 pl/s and 438 +/- 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl.s-1.ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 +/- 11.7, 8.71 +/- 5.74, and 3.13 +/- 1.57 pl.s-1.ppb-1 for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.

Background/Aim. Reslizumab is humanized monoclonal antibody produced by recombinant DNA technology which binds to circulating interleukin-5 (IL-5) and down-regulates the IL-5 signaling pathway. Reslizumab is indicated for the add-on maintenance treatment of patients 18 years and older with severe eosinophilic asthma phenotype whose symptoms were inadequately controlled with inhaled corticosteroids. The aim of this meta-analysis was to assess the efficacy and safety of reslizumab compared to placebo in patients suffering from inadequately controlled, moderateto- severe asthma with elevated blood eosinophil counts. Methods. Our meta-analysis was based on systematic search of literature and selection of high-quality evidence according to pre-set inclusion and exclusion criteria. The effects of reslizumab and placebo were summarized using Review Manager (RevMan) 5.3.5 and heterogeneity was assessed by the Cochrane Q test and I² values. Several types of bias were assessed and publication bias shown by Funnel plot and Egger’s regression. Results. The meta-analysis included 5 randomized, placebo-controlled clinical trials. Reslizumab 3.0 mg/kg produced substantial improvements in forced expiratory volume in 1. second (FEV 1) (mean difference 0.15 [0.10, 0.21]) and in forced vital capacity (FVC) (mean difference 0.21 [0.09, 0.32]) over the 15 or 16-week treatment period, substantial decrease versus placebo in Asthma Control Questionnaire (ACQ) score (mean difference -0.28 [-0.41, -0.16]), and substantial increase vs. placebo from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score (mean difference 0.24 [0.06, 0.43]). Also, reslizumab 3.0 mg/kg caused less adverse events versus placebo (OR 0.67 [0.51, 0.88]), especially asthma worsening (OR 0.53 [0.36, 0.77]) or bronchitis (OR 0.42 [0.24, 0.74]). Conclusion. On the basis of published clinical trials reslizumab could be considered as an effective and safe therapeutic option for severe, poorly controlled eosinophilic asthma for the time being. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175007]