Nonsteroidal anti-inflammatory-induced inhibition of signal transducer and activator of transcription 6 (STAT-6) phosphorylation in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin desensitization provides long-term clinical benefits. The exact mechanisms of aspirin desensitization are not clearly understood. OBJECTIVE: We sought to evaluate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on T-cell activation of the IL-4 pathway in aspirin-sensitive patients with asthma and control subjects. METHODS: A total of 11 aspirin-sensitive patients with asthma, 10 aspirin-tolerant patients with asthma, and 10 controls without asthma were studied. PBMCs were stimulated with an anti-CD3 antibody and IL-4 or IL-12, with and without the presence of NSAIDs. The expression of phosphorylated signal transducers and activators of transcription 6 (pSTAT6), phosphorylated signal transducers and activators of transcription 4, and IL-4 was detected in CD4 T cells by flow cytometry. RESULTS: Stimulation with a combination of anti-CD3 and IL-4 induced pSTAT6 in CD4 T cells from all subjects. The induction of pSTAT6 was significantly higher in aspirin-sensitive patients with asthma than in controls subjects. The increase in pSTAT6 was inhibited in a dose-dependent manner by aspirin and indomethacin and minimally by sodium salicylate. This inhibition was strongest in aspirin-sensitive patients. Two-group comparisons showed significant differences in pSTAT6 inhibition by all concentrations of indomethacin and aspirin: between aspirin-sensitive and aspirin-tolerant groups and between aspirin-sensitive and control groups. No differences were found between aspirin-tolerant and control groups at all 3 concentrations. The inhibition of pSTAT6 was associated with reduced IL-4 expression. CONCLUSIONS: NSAIDs inhibited signal transducers and activators of transcription 6 signaling in CD4 T cells. This inhibition was significantly higher in aspirin-sensitive patients than in aspirin-tolerant subjects and was associated with reduced expression of IL-4. These findings have implications for clinical benefits of aspirin desensitization in aspirin-sensitive patients with asthma.

Factors associated with negative histamine control for penicillin allergy skin testing in the inpatient setting.

BACKGROUND: Identification of factors adversely affecting the utility of allergy skin testing is important in optimizing patient care. Inpatient penicillin skin test data from 1997 through 2007 demonstrate that up to 20% of attempted penicillin skin tests are indeterminate owing to a negative histamine test response, despite exclusion of H1 antagonists. Critical illness, vasopressors, steroid use, and psychotropic medications have been postulated to influence outcomes, but large studies are lacking. OBJECTIVE: To identify factors associated with a negative histamine test response for the inpatient setting. METHODS: Fifty-two cases were identified with a negative histamine response after penicillin skin testing in the absence of antihistamine therapy for 72 hours before testing. One hundred twenty-five controls with a normal histamine response were randomly selected from same population. Independent variables assessed included stay in the intensive care unit (ICU), skin color, diabetes, age, use of vasopressors, H2 blocker, steroids, other immunosuppressive drugs, thyroid replacement, proton pump inhibitors, diuretics, 5 categories of psychotropic medications, and amiodarone. RESULTS: Mean age was 68 years for cases vs 60 years for controls (P = .002). Bivariate analysis showed ICU stay was more frequent in cases than in controls (73.1% vs 33.6%, P < .001). Regression analysis yielded odds ratios (ORs) of 8.18 (95% confidence interval 3.22-20.76) for ICU status, 3.76 (1.30-10.92) for systemic corticosteroids, and 4.90 (1.17-20.62) for H2 blockers as associated with lack of histamine response. For every additional year in age, there was increase in the OR of 1.04 (1.01-1.07). CONCLUSION: Regression analysis supports ICU stay during skin testing as associated with a high OR for a negative histamine response independent of age. Systemic corticosteroids, H2 blockers, and older age are associated with a significant OR for a negative histamine response. This is one of largest studies on factors associated with a negative histamine response for the inpatient setting and has significant implications for clinical practice.

Asthma and COVID-19 Outcomes: A Prospective Study in a Large Health Care Delivery System.

Introduction: Previous studies on the outcomes of asthma and COVID-19 have shown inconsistent results. This study aimed to elucidate the association between asthma and COVID-19 outcomes. Methods: We conducted a prospective study with a large health plan to compare the incidence of COVID-19 infection, hospitalization and ICU admission in a cohort of 41,282 patients with asthma and a 1:1 age-, sex-, and race-ethnicity-matched cohort without asthma across the following pandemic periods: pre-Delta (03/01/2020 to 05/31/2021), Delta (06/01/2021 to 12/31/2021), and Omicron (01/01/2022 to 08/13/2022). Demographic factors, comorbidities, COVID-19 test results, inpatient utilization, and COVID-19 vaccination status were collected from electronic health records. Results: Subjects with asthma were more likely than controls to undergo COVID-19 testing during the three pandemic periods and were less likely to test positive in the Omicron period (fully adjusted odds ratio=0.92; 95% CI=0.86-0.98; p=0.01). Relative to controls, patients with asthma had an increased risk of hospitalization for COVID-19 (fully adjusted hazard ratio=1.33; 95% CI=1.08-1.64; p=0.01) and borderline significant (p=0.05) higher rates of ICU admissions in the pre-delta period but not during the delta or Omicron periods. The increased risk of COVID-19 hospitalization associated with asthma was more pronounced in patients with severe asthma and in women compared with men. None of the associations were significantly modified by vaccination status. Conclusion: Asthma was associated with a lower risk of COVID-19 infection but only during the Omicron period. Asthma was an independent risk factor for hospitalization for COVID-19 in the pre-delta period and this association was stronger for severe asthma and in women.

Impact of student ethnicity and primary childhood language on communication skill assessment in a clinical performance examination.

BACKGROUND: Clinical performance examinations (CPX) with standardized patients (SPs) have become a preferred method to assess communication skills in US medical schools. Little is known about how trainees' backgrounds impact CPX performance. OBJECTIVE: The objective of this paper is to examine the impact of student ethnicity, primary childhood language, and experience of diversity on the communication scores of a high-stakes CPX using SPs. DESIGN: This research was designed as an observational study. PARTICIPANTS: The participants of this study were third-year medical students at one US medical school. MEASUREMENTS AND MAIN RESULTS: The measurements used in this study were CPX scores from mandatory exam, student demographics and experience with diversity measured by self-report on a survey, and Medical College Admission Test (MCAT) and United States Medical Licensing Examination (USMLE) scores. A total of 135 students participated. Asian and black students scored lower than white students on the communication portion of the CPX by approximately half a standard deviation (Asian, 67.4%; black, 64.4%; white, 69.4%, p < .05). There were no differences by ethnicity on history/physical exam scores. Multivariate analysis controlling for MCAT verbal scores reduced ethnic differences in communication scores (Asian-white mean differences = 1.95, p = 0.02), but Asian-white differences were eliminated only after sequential models included primary childhood language (difference = 0.57, p = 0.6). CONCLUSIONS: Even after controlling for English language knowledge as measured in MCAT verbal scores, speaking a primary childhood language other than English is associated with lower CPX communication scores for Asian students. While poorer communication skills cannot be ruled out, SP exams may contain measurement bias associated with differences in childhood language or culture. Caution is indicated when interpreting CPX communication scores among diverse examinees.

Role of Small Airways in Asthma.

Asthma is an inflammatory condition of both the small and large airways. Recently the small airways have gained attention as studies have shown significant inflammation in the small airways in all severities of asthma. This inflammation has correlated with peripheral airway resistance and as a result, noninvasive methods to reliably measure small airways have been pursued. In addition, recent changes in asthma inhalers have led to alterations in drug formulations and the development of extrafine particle inhalers that improve delivery to the distal airways.