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BACKGROUND: Allergic sensitization to mold is a risk factor for poor asthma outcomes, but whether it accounts for disparities in asthma outcomes according to race or socioeconomic status is not well-studied. OBJECTIVE: We sought to 1) identify factors associated with allergic sensitization to molds and 2) evaluate associations of sensitization to molds with asthma exacerbations after stratifying by race. METHODS: We conducted a retrospective cohort study of adults with asthma who had an outpatient visit in a large health system between 1/1/2017-6/30/2023 and received aeroallergen testing to Aspergillus fumigatus, Penicillium, Alternaria, and Cladosporium. We used logistic regression models to evaluate factors associated with 1) mold sensitization and 2) the effect of mold sensitization on asthma exacerbations in the 12 months before testing, overall and then stratified by race. RESULTS: 2,732 patients met inclusion criteria. Sensitization to each mold was negatively associated with being a woman (odds ratios (ORs)≤0.59, p≤0.001 in five models) and positively associated with Black race (ORs≥2.16 versus White, p<0.0005 in five models). In the full cohort, sensitization to molds were not associated with asthma exacerbations (ORs 0.95-1.40, p≥0.003 in five models and all above the corrected p-value threshold). Among 1,032 Black patients, sensitization to Aspergillus fumigatus, but not to other molds, was associated with increased odds of asthma exacerbations (OR 2.04, p<0.0005). CONCLUSION: Being a man and Black race were associated with allergic sensitization to molds. Sensitization to Aspergillus fumigatus was associated with asthma exacerbations among Black patients but not the overall cohort, suggesting that Aspergillus fumigatus allergy is a source of disparities in asthma outcomes according to race.

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BACKGROUND: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood. OBJECTIVE: We sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts. METHODS: We used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum. RESULTS: 668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt of skin testing was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001). CONCLUSION: Guideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.

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Background: Aeroallergen testing informs precision care for adults with asthma, yet the epidemiology of testing in this population remains poorly understood. Objective: We sought to identify factors associated with receiving aeroallergen testing, the results of these tests, and subsequent reductions in exacerbation measures among adults with asthma. Methods: We used electronic health record data to conduct a retrospective, observational cohort study of 30,775 adults with asthma who had an office visit with a primary care provider or an asthma specialist from January 1, 2017, to August 26, 2022. We used regression models to identify (1) factors associated with receiving any aeroallergen test and tests to 9 allergen categories after the index visit, (2) factors associated with positive test results, and (3) reductions in asthma exacerbation measures in the year after testing compared with before testing. Results: Testing was received by 2201 patients (7.2%). According to multivariable models, receiving testing was associated with having any office visit with an allergy/immunology specialist during the study period (odds ratio [OR] = 91.3 vs primary care only [P < .001]) and having an asthma emergency department visit (OR = 1.62 [P = .004]) or hospitalization (OR = 1.62 [P = .03]) in the year before the index visit. Age 65 years or older conferred decreased odds of testing (OR = 0.74 vs age 18-34 years [P = .008]) and negative test results to 6 categories (P ≤ .04 for all comparisons). Black race conferred increased odds of testing (OR =1.22 vs White race [P = .01]) and positive test results to 8 categories (P < .04 for all comparisons). Exacerbation measures decreased after testing. Conclusion: Aeroallergen testing was performed infrequently among adults with asthma and was associated with reductions in asthma exacerbation measures.

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BACKGROUND: The availability of asthma biologics may not benefit all patients equally. OBJECTIVE: We sought to identify patient characteristics associated with asthma biologic prescribing, primary adherence, and effectiveness. METHODS: A retrospective, observational cohort study of 9,147 adults with asthma who established care with a Penn Medicine asthma subspecialist was conducted using Electronic Health Record data from January 1, 2016, to October 18, 2021. Multivariable regression models were used to identify factors associated with (1) receipt of a new biologic prescription; (2) primary adherence, defined as receiving a dose in the year after receiving the prescription, and (3) oral corticosteroid (OCS) bursts in the year after the prescription. RESULTS: Factors associated with a new prescription, which was received by 335 patients, included being a woman (odds ratio [OR] 0.66; P = .002), smoking currently (OR 0.50; P = .04), having an asthma hospitalization in the prior year (OR 2.91; P < .001), and having 4+ OCS bursts in the prior year (OR 3.01; P < .001). Reduced primary adherence was associated with Black race (incidence rate ratio 0.85; P < .001) and Medicaid insurance (incidence rate ratio 0.86; P < .001), although most in these groups, 77.6% and 74.3%, respectively, still received a dose. Nonadherence was associated with patient-level barriers in 72.2% of cases and health insurance denial in 22.2%. Having more OCS bursts after receiving a biologic prescription was associated with Medicaid insurance (OR 2.69; P = .047) and biologic days covered (OR 0.32 for 300-364 d vs 14-56 d; P = .03). CONCLUSIONS: In a large health system, primary adherence to asthma biologics varied by race and insurance type, whereas nonadherence was primarily explained by patient-level barriers.

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BACKGROUND: Penicillin allergy in pregnancy is associated with increased morbidity and the use of less effective antibiotics. Penicillin allergy evaluation in pregnancy is now recommended as per obstetrical guidelines but remains infrequent. OBJECTIVE: We studied pregnant women who underwent penicillin allergy evaluation in an allergy clinic to assess the effectiveness and safety of penicillin skin testing (PST) and incremental drug challenge (IDC) in pregnancy. METHODS: Index drug reactions, PST, and IDC results were reviewed. Antibiotic use, pregnancy outcomes, and pregnancy complications were compared with a control cohort of pregnant women with penicillin allergy who did not undergo allergy evaluation before delivery. RESULTS: Penicillin allergy was evaluated in 136 women. Culprit drugs included penicillin (37%), amoxicillin (30%), and unknown (20%). Index reactions occurred greater than 5 years ago in 91%, and these reactions were cutaneous or unknown in 92%. Of the 133 patients who underwent skin testing, 131 (99%) had negative or equivocal results and proceeded to incremental challenge. All 131 women passed penicillin IDC. Of the 69 women who ultimately used intrapartum beta-lactam antibiotics, all but 1 patient tolerated them. Women who underwent penicillin allergy evaluation did not have an increased risk of cesarean delivery or other pregnancy complications when compared with women without penicillin allergy evaluation. CONCLUSION: PST and IDC can be safely conducted in pregnant women. When evaluated as low risk, most women tolerate IDC and can receive penicillin intrapartum without adverse reactions or negative pregnancy outcomes.

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BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. METHODS: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry. RESULTS: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10-9 M, 1.00 × 10-8 M, 1.78 × 10-8 M, 3.16 × 10-8 M, 5.62 × 10-8 M, and 1.00 × 10-7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10-8 M and 3.16 × 10-8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). CONCLUSION: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10-8 M for future study of clinical utility.

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BACKGROUND: Treatment of aspirin-exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy. METHODS: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression. RESULTS: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36). CONCLUSION: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications.

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Inadequate inhaler technique in persistent asthma is frequently reported. However, there is little consensus on inhaler checklists, and critical elements of technique are not uniformly described. In addition, inhaler error rates and risk factors for poor technique are variable across studies. This Clinical Commentary Review summarizes the literature on inhaler design, use, and interventions to improve technique. Our aim is to help clinicians identify patients with poor inhaler technique, recognize the most important errors, and correct technique using evidence-based interventions.

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BACKGROUND: Poor inhaler technique has been shown to be associated with less asthma control and increased health care utilization. Little is known about the impact of inhaler technique on the most vulnerable patients. OBJECTIVE: This study examined inhaler technique in low-income, inner-city adults with uncontrolled asthma. METHODS: Inhaler technique data and other patient characteristics were evaluated in adults drawn from 2 studies conducted at the University of Pennsylvania. Subjects were from low-income Philadelphia neighborhoods and had uncontrolled asthma. Baseline characteristics were collected. Inhaler technique was rated by research coordinators who were trained with written materials. RESULTS: In 584 adults, 56% of metered dose inhaler users and 64% of dry powder inhaler users had adequate visually assessed inhaler technique. Inhaler technique did not vary by reading comprehension or numeracy levels. CONCLUSIONS: In this group of patients with uncontrolled asthma, visually assessed inhaler technique was adequate in more than one-half. Although incorrect inhaler technique is generally common and must be routinely addressed, this study suggests that other factors that lead to poor control must be identified.

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