Papers by Stanley Szefler
The Journal of Allergy and Clinical Immunology, Nov 1, 2019
Background: Asthma causes the unpleasant sensation of breathlessness (dyspnea) caused by airway o... more Background: Asthma causes the unpleasant sensation of breathlessness (dyspnea) caused by airway obstruction. Patients with poor perception of airway obstruction are at risk of delay in seeking medical attention and undertreatment, which can lead to avoidable deaths. Conversely, those with heightened perception are at risk of overtreatment and iatrogenic adverse effects with reliever medications, anxiety, and unnecessary use of health care resources. Objective: We sought to review evidence about symptom misperception in asthmatic patients and how to identify and manage affected patients, particularly with regard to reliever medications. Methods: We conducted a systematic literature search for studies of perception of airway function in asthmatic patients. We searched the OVID (Medline and Medline [R] in process [PubMed]), Embase, and Adisearch/Odyssey databases, restricting our search to human studies published in English from 1990-2018, with no restrictions on age, sex, or racial origin. Results: We found that both underperception and overperception assessed during induced bronchoconstriction or bronchodilation or during changes in airway resistance were common across all age groups and that aging, disease severity, smoking, sex, ethnicity, psychologic factors, and medication are all associated with differences in perception. Importantly, airway inflammation was associated with impaired perception and a history of severe or near-fatal asthma. We also identified knowledge gaps, such as whether an individual patient's perception varies over time and the influence perception has on patients' use of reliever medication. Conclusion: We found that abnormal perception of airway obstruction has important clinical implications for the management of patients with asthma.
The Journal of Allergy and Clinical Immunology, Feb 1, 2019
RATIONALE: Aspirin challenge and desensitization remains the gold standard in diagnosis and treat... more RATIONALE: Aspirin challenge and desensitization remains the gold standard in diagnosis and treatment of patients with aspirin-exacerbated respiratory disease (AERD), but the protocols can be time and resource intensive. The objective of this study is to provide evidence that oral aspirin challenge and desensitization can be safely performed in an outpatient setting in one day. METHODS: Forty-four patients with confirmed diagnosis of AERD, stable asthma and baseline FEV1 > _70% of predicted completed an oral aspirin challenge and desensitization protocol. The starting dose was 40.5mg with escalating doses of aspirin (81, 162.5, 325mg) at 90-minute intervals until symptoms were provoked. Desensitization was defined as tolerating a repeated administration of the provocative dose and at least one subsequent aspirin dose, bringing total aspirin ingested during the in-clinic desensitization to > _325mg. RESULTS: Ninety-three percent of patients completed the challenge and desensitization in one day, with an average protocol completion time of 9 hours and 29 minutes. Two patients (4.6%) chose to complete the protocol over two days. One patient (2.3%) was discontinued from the protocol due to ongoing abdominal discomfort and diarrhea. No patient required epinephrine, emergency department visit or hospitalization. CONCLUSIONS: Patients with AERD on a stable asthma regimen and with a baseline FEV1> _70% can be safely desensitized to aspirin using a 90minute dose escalation protocol, starting at a dose of 40.5mg, and defining desensitization as tolerance of the repeated provocation dose and at least one subsequent aspirin dose, bringing total cumulative daily dose to > _325mg. This protocol can routinely be completed in one day.
The Journal of Pediatrics, Mar 1, 2013
Objective-To identify the predictive factors of early childhood wheezing in children of low socio... more Objective-To identify the predictive factors of early childhood wheezing in children of low socioeconomic status. Study design-The Childhood Asthma Prevention Study (CAPS) enrolled 177 low-income children (9-24 months old) with frequent wheezing. At age 7 years, presence of asthma was assessed through caregiver reports of physician diagnosis of asthma (CRPDA) and corroborated by assessment of bronchial hyperresponsiveness (BHR). Lung function, inflammatory markers, and asthma symptom severity were compared for children with ±CRPDA, ±BHR, and asthma. Baseline predictors for CRPDA, BHR and asthma at 7 years of age were examined. Results-Maternal symptom report strongly differentiated children with +CRPDA (50%) despite comparable airflow measurements (p<0.0001), and spirometric lung function measurements were different for +BHR (65%) vs. −BHR (p<0.005). Univariate analyses revealed different baseline predictors of +CRPDA and +BHR for children at age 7 years. Higher levels of maternal psychological resources were associated with +CRPDA, but not +BHR. Only 39% of children with a history of frequent wheezing met the conservative definition of asthma at age 7 years, with the following significant predictors found: low birth weight, baseline symptom severity and maternal psychological resources. Conclusions-This low-income, multi-ethnic group of wheezing infants represents a unique population of children with distinct characteristics and risks for persistent asthma. Determination of asthma status at 7 years of age required objective measurement of BHR in addition to CRPDA. The association of maternal psychological resources with +CRPDA may represent a previously unrecognized factor in determination of asthma status among low-income groups. Elevated asthma prevalence and morbidity among low-income minority children remain a significant public health problem in the U.S.(1) Low-income children with persistent wheezing have been found to have recurrent asthma symptoms since early infancy. Because most prospective studies of early asthma onset have enrolled families from middle to higher
The Journal of Allergy and Clinical Immunology, May 1, 2019
The Journal of Allergy and Clinical Immunology, Sep 1, 2010
Background-The assumption that the assessment of FEF 25-75 does not provide additional informatio... more Background-The assumption that the assessment of FEF 25-75 does not provide additional information in asthmatic children with normal FEV 1 % predicted has not been adequately tested. Objective-To determine whether the measurement of the FEF 25-75 % predicted offers advantages over the FEV 1 % predicted and the FEV 1 /FVC % predicted for the evaluation of childhood asthma. Methods and Measurements-This is a secondary analysis of data from the "Pediatric Asthma Controller Trial" and the "Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid" trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operator characteristic (ROC) curves were constructed. Results-Among 437 children with normal FEV 1 % predicted, FEF 25-75 % predicted and FEV 1 / FVC % predicted were (1) positively correlated with log 2 methacholine PC 20 , (2) positively correlated with morning and evening peak expiratory flow % predicted, and (3) negatively correlated with log 10 FeNO and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF 25-75 % predicted was better correlated with bronchodilator
Pediatric Allergy and Immunology, Mar 29, 2021
Background: There are limited data describing lung function changes in children after an asthma e... more Background: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. Methods: We used a data set of children with asthma where lung function (including FEV 1 , FEV 1 /FVC ratio and FEF 25-75) was measured at 3-month intervals over a year. Mixed-level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3-month periods. Results: For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV 1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long-acting beta-agonist, but in this category, %FEV 1 at assessment 4 had returned to the value at assessment 1. %FEV 1 did not change over a 12-month period within and between the three exacerbation categories (n = 809). Conclusion: One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of individuals, lung function does fall after an exacerbation but returns to pre-exacerbation values after a period of months.
EGULAR USE OF LONG-ACTING  2-agonists has been shown to be more effective than regular use of al... more EGULAR USE OF LONG-ACTING  2-agonists has been shown to be more effective than regular use of albuterol sulfate, a shortacting  2-agonist, at improving peak expiratory flow (PEF) and reducing asthma symptoms. 1,2 Asthma treatment guidelines 3 recommend addition of a longacting  2-agonist for asthma inad-Author Affiliations and Financial Disclosures are listed at the end of this article.
Annals of Allergy Asthma & Immunology, Dec 1, 2016
Inhaled corticosteroids (ICSs) effectively deliver corticosteroids to target sites in the lungs a... more Inhaled corticosteroids (ICSs) effectively deliver corticosteroids to target sites in the lungs and reduce systemic effects compared with oral corticosteroids, but long-term systemic exposure from inhaled corticosteroids remains a concern. To discuss ICS systemic effects on the eye and the hypothalamic-pituitary-adrenal (HPA) axis. Relevant publications were used to augment discussion. The most common adverse effects of exogenous corticosteroids on the eye are secondary open-angle glaucoma and posterior subcapsular cataracts. Study findings conflict about whether ICS use is associated with increased risk of glaucoma or elevated intraocular pressure, but studies might not have addressed the question in the right population. Increased risk of glaucoma may be limited to a few susceptible individuals, such as individuals with a family history of glaucoma. Large population-based studies reveal that high daily doses or high lifetime exposure of ICSs is associated with a higher risk of posterior subcapsular cataracts. More research is needed to determine the risk from low to moderate doses during long periods. For the HPA axis, there are several measures for detecting systemic effects. Short-term measures are more sensitive for detecting the systemic effects of ICSs but have less predictive value in identifying clinically important adverse effects. Several studies have found that ICSs have a dose-dependent effects on cortisol suppression that can be used to estimate equivalent dosages among ICSs. Because of systemic effects on the HPA axis, high doses of ICS should be avoided where possible. Adult patients undergoing high-dose or long-term ICS therapy should be monitored for cataracts.
The Journal of Allergy and Clinical Immunology, Sep 1, 2017
In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and p... more In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management.
US respiratory & pulmonary diseases, 2023
Pediatric Allergy Immunology and Pulmonology, Sep 1, 2018
There is increasing recognition of phenotypic variability in pediatric asthma, providing the oppo... more There is increasing recognition of phenotypic variability in pediatric asthma, providing the opportunity for a more personalized approach to therapy. Increasingly biologic therapies, in particular those targeting the ''allergic'' (or T helper 2) pathway, are being considered for children with severe asthma. However, there is a great deal of variability in the extent these biologic therapies have been studied in children, as well as efficacy of results thus far. The goal of this article is to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of the biologic medications focusing on the pediatric population, in an effort to establish a more personalized approach to asthma in the pediatric population for the 21st century.
The Journal of Allergy and Clinical Immunology, May 1, 2009
Background-Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent ... more Background-Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits. However, determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment. Objective-To determine if demographic and atopic features predict response to ICS in preschool children at high-risk for asthma. Methods-Two years of treatment with an ICS, fluticasone propionate (88mcg twice daily), was compared to matching placebo in a double-masked, randomized, multi-center study of 285 two and three year olds at high-risk for asthma development. Baseline demographic and atopic features were related to clinical outcomes in a post-hoc subgroup analysis.
European Respiratory Journal, 2020
An update of the International Primary Care Respiratory Group (IPCRG) Research Needs Statement is... more An update of the International Primary Care Respiratory Group (IPCRG) Research Needs Statement is currently being undertaken using an e-Delphi method. The aim of this analysis is to identify the main respiratory research themes from the perspective of primary care practitioners worldwide. Participants were recruited via the IPCRG network of 34 member countries. An initial open questionnaire elicited participants’ views on the most important respiratory conditions seen in their daily practice and invited suggestions of 5-10 relevant research questions within these conditions in the following domains: diagnosis, management, monitoring, self-management and prognosis. Using thematic qualitative analysis we identified the main cross-cutting research themes. 112 participants (69% physicians, 10% nurses, 21% other, 64% had special interest in respiratory) from 27 countries responded with 608 suggested research questions. Asthma was reported as the most clinically important condition (25.7%...
Annals of Allergy, Asthma & Immunology, 2020
Acute asthma exacerbations account for 750,000 pediatric emergency department (ED) visits, 200,00... more Acute asthma exacerbations account for 750,000 pediatric emergency department (ED) visits, 200,000 hospitalizations and 5.2 billion in excess healthcare costs in the US annually. 1 Current ED treatment of acute exacerbations is based on severity at initial presentation as determined by clinical scoring tools, which are limited by subjectivity and poor association with actual airway function. 2 Traditional methods to objectively assess lung function, including spirometry and peak flow, are not feasible or reproducible in younger children. 3,4 Peak flow also tends to underestimate worsening lung function. 5 Consequently, ED treatment is variable leading to inefficient use of asthma therapies, prolonged ED length of stay, and unnecessary hospitalizations. 6
Journal of Allergy and Clinical Immunology, 2018
, our tertiary care pediatric academic center initiated a Complex Asthma Clinic (CAC) to provide ... more , our tertiary care pediatric academic center initiated a Complex Asthma Clinic (CAC) to provide comprehensive outpatient care by allergists to at-risk children with prior asthmarelated Emergency Department (ED) visits/hospitalizations. METHODS: A patient registry was created for children evaluated in the CAC between 2011 and June 30, 2017, followed by a retrospective review of asthma-related ED visits/hospitalizations in the year before and year after initial evaluation. RESULTS: Two-hundred and sixty-two patients completed at least one CAC visit (mean53.9+3.5 visits); mean age56.3+4 years, 67% (N5176) male, 50% (N5132) African American, and 73% (N5190) receiving Medicaid. Prior to CAC evaluation, 85% (N5222) of children were prescribed asthma controller medication, 75% (N5166) of which were medium or higher dose inhaled corticosteroids. Previous to CAC evaluation, lung function testing had been performed in 23% (N536) of children >5 years old and 10% (N525) had previous allergy testing performed. At initial CAC evaluation, 86% (N5226) were prescribed additional medications and/or higher dosages of existing therapy. While receiving care within the CAC, 75% (N5201) of children underwent skin prick testing, with 93% (N5186) being positive to at least one aeroallergen (57% any indoor, 51% any outdoor). Comparing the year before to the year after the initial visit, children evaluated in CAC had a 47% reduction in ED visits (mean51.1 vs. 0.6; P<0.0001) and 44% reduction in hospitalizations (mean50.4 vs. 0.2; P<0.01). CONCLUSIONS: Children with a history of ED visits or hospitalizations for asthma benefited from specialty evaluation and management by allergists in an outpatient specialty asthma clinic.
The Journal of pediatrics, 2016
elf-management programs for chronic illnesses were first described regarding children with asthma... more elf-management programs for chronic illnesses were first described regarding children with asthma at The Children's Asthma Research Institute and Hospital. 1,2 This group approached asthma care by involving the patient in his/her own illness management. 2 The importance of self-management for improved asthma care has long been recognized. In 1976, 3 programs were funded by the National Heart, Lung, and Blood Institute (NHLBI) to develop self-management programs in pediatric asthma: Columbia University, the National Asthma Center, and the American Institutes of Research. 3,4 Considerable energy and funding have been dedicated to creating and evaluating self-management programs to improve asthma care, and this has been a priority for the Global Initiative for Asthma and the NHLBI. 5,6 These self-management approaches have evolved over time, and novel technologies are being used for asthma self-management. 7 We review self-management programs in general and specifically the use of technology as an asthma self-management tool in the adolescent population. Efficacy of Asthma Self-Management Programs Self-management programs for pediatric asthma are very likely to work: a meta-analysis of 32 randomized controlled trials demonstrated that participants in the selected self-management programs demonstrated improved lung function and self-efficacy, decreased missed school days, and reduced activity limitations and emergency department visits. 8 An ideal self-management program would be free, easy to use, and individually tailored for different populations (age, sex, patient preference). The program components may vary depending on the patients' needs, but a comprehensive program would include options for asthma education, an interactive asthma action plan (AAP), a reminder system, adherence monitoring with feedback, and options for interacting with asthma educators/nurses/clinicians. Why Do We Need Self-Management Programs? Although some patients with asthma are poorly controlled despite excellent adherence to maximal therapy, most patients with poorly controlled asthma have poor adherence 9,10 and/or poor recognition of symptoms. 11 Indeed, fatal asthma has been attributed, in part, to poor self-management. 12 Tailoring self-management programs to different target audiences may improve efficacy. 13 Adolescents cite a variety of reasons for poor adherence, including competing priorities, their belief that medications are unnecessary and/or do not help, and that the medications have too many side effects. 14,15 Adolescents, therefore, are prime targets for self-management programs that can improve adherence.
The Journal of Allergy and Clinical Immunology, Jun 1, 2003
Clinical and Translational Allergy, 2016
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of ... more Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma. Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. Discussion: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.
Pediatrics, 2006
Despite improvements in neonatal care, bronchopulmonary dysplasia (BPD) continues to occur in app... more Despite improvements in neonatal care, bronchopulmonary dysplasia (BPD) continues to occur in approximately one third of newborns who have birth weights of <1000 g and contributes to significant morbidity in this population. Gaps in knowledge about the prevention and treatment of BPD remain, resulting in unintended short- and long-term sequelae. In addition to chronic lung disease, preterm newborns with BPD are more likely to develop language delay, cerebral palsy, and cognitive impairments compared with preterm newborns without BPD. The pulmonary group identified 3 critical needs to enhance the design of clinical trials in neonates with BPD: (1) identify the stages of BPD; (2) define BPD more clearly; and (3) identify subtypes of BPD patients. The group determined that trials are needed for 3 areas of BPD: (1) prevention of BPD; (2) treatment of evolving BPD; and (3) treatment of established BPD. The severity of BPD is defined as mild, moderate, and severe, and subgroups among t...
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Papers by Stanley Szefler