RESUMEN
BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.
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BACKGROUND: The mechanism of coronavirus disease 2019 (COVID-19) vaccine hypersensitivity reactions is unknown. COVID-19 vaccine excipient skin testing has been used in evaluation of these reactions, but its utility in predicting subsequent COVID-19 vaccine tolerance is also unknown. OBJECTIVE: To evaluate the utility of COVID-19 vaccine and vaccine excipient skin testing in both patients with an allergic reaction to their first messenger RNA COVID-19 vaccine dose and patients with a history of polyethylene glycol allergy who have not yet received a COVID-19 vaccine dose. METHODS: In this multicenter, retrospective review, COVID-19 vaccine and vaccine excipient skin testing was performed in patients referred to 1 of 3 large tertiary academic institutions. Patient medical records were reviewed after skin testing to determine subsequent COVID-19 vaccine tolerance. RESULTS: A total of 129 patients underwent skin testing, in whom 12 patients (9.3%) had positive results. There were 101 patients who received a COVID-19 vaccine after the skin testing, which was tolerated in 90 patients (89.1%) with no allergic symptoms, including 5 of 6 patients with positive skin testing results who received a COVID-19 vaccine after the skin testing. The remaining 11 patients experienced minor allergic symptoms after COVID-19 vaccination, none of whom required treatment beyond antihistamines. CONCLUSION: The low positivity rate of COVID-19 vaccine excipient skin testing and high rate of subsequent COVID-19 vaccine tolerance suggest a low utility of this method in evaluation of COVID-19 vaccine hypersensitivity reactions. Focus should shift to the use of existing vaccine allergy practice parameters, with consideration of graded dosing when necessary. On the basis of these results, strict avoidance of subsequent COVID-19 vaccination should be discouraged.
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Vacunas contra la COVID-19/efectos adversos , COVID-19 , Hipersensibilidad , Pruebas Cutáneas , COVID-19/prevención & control , Humanos , Hipersensibilidad/etiología , Inutilidad Médica , Estudios Retrospectivos , Excipientes de Vacunas/efectos adversos , Vacunas Sintéticas/efectos adversos , Vacunas de ARNm/efectos adversosRESUMEN
Background: Penicillin is the most common reported drug allergy. Previous literature suggests that there is increased prevalence of penicillin drug allergy in female patients in the outpatient setting. However, this is poorly described in the inpatient setting. Objective: This study was performed to determine whether female sex is an independent risk factor for penicillin allergy in the inpatient setting. Methods: A retrospective review of electronic medical records (January 1, 2001-December 31, 2017) was performed for patients with a history of penicillin allergy who underwent penicillin skin testing (PST). Each chart review included the age at initial skin testing, sex, medications, and medical co-morbidities. The study was approved by the institutional review board. Results: 30,883 patients underwent PST with 29,354 and 1,529 occurring in the outpatient and inpatient setting respectively. 170 patients tested positive with a ≥ 5x5 wheal. Of the 170 positive patients, 122 were female (72%) and 48 were male (28%). 15 patients tested positive in the inpatient setting. Of the 1506 adult patients tested in the inpatient setting, 809 were female and 697 were male. 12 females (92.3%) and 1 one male (7.7%) tested positive with a ≥ 5x5 wheal (OR-10.5; 95% CI-1.4-80.8; p-value=0.02). 23 pediatric patients were tested in the inpatient setting. Two pediatric male patients were positive and no female pediatric patients tested positive (OR-1.7; 95% CI-0.5-5.9; p-value=0.5). Conclusion: In the inpatient setting, adult females are 10 times more likely to have a positive PST compared to males. Female sex may be a potential risk factor for objective penicillin drug allergy in the inpatient setting.
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Hipersensibilidad a las Drogas , Penicilinas , Adulto , Antibacterianos/efectos adversos , Niño , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Femenino , Humanos , Pacientes Internos , Masculino , Penicilinas/efectos adversos , Factores de Riesgo , Pruebas Cutáneas/efectos adversosRESUMEN
Objective: Asthma poses an increased risk for serious pneumococcal disease, but little is known about the influence of asthma status on the 23-valent serotype-specific pneumococcal antibody response. We examined differences in antibody titers between pre- and post-vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in relation to asthma status. Methods: Asthma status was retrospectively ascertained by the Predetermined Asthma Criteria in an existing vaccine cohort through comprehensive medical record review. Twenty-three serotype-specific pneumococcal antibody titers measured at baseline and 4-6 weeks post-vaccination were analyzed. Vaccine responses to PPSV-23 were calculated from pre- to post-vaccine titers for each of the serotypes. Results: Of the 64 eligible and enrolled subjects, 18 (28%) had asthma. Controls (i.e., subjects without asthma) demonstrated a statistically significant fold change response compared to their baseline for all serotypes, while those with asthma did not mount a significant response to serotypes 7F, 22F, and 23F. The overall vaccine response as measured by fold change over baseline was lower in subjects with asthma than controls. Conclusions: Poorer humoral immune responses to PPSV-23 as measured by fold change were more likely to be observed in subjects with asthma compared to controls. We recommend the consideration of asthma status when interpreting vaccine response for immune competence workup through larger studies. Further studies are warranted to replicate these findings.
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Anticuerpos Antibacterianos/sangre , Asma/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Adulto , Anticuerpos Antibacterianos/inmunología , Asma/sangre , Asma/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Inmunidad Humoral , Inmunogenicidad Vacunal , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Estudios Retrospectivos , VacunaciónRESUMEN
OBJECTIVE: To determine patterns of adverse drug reactions (ADRs), including immediate drug hypersensitivity reactions (DHRs) and predictable ADRs, to thyroid replacement therapy (TRT). TRT is the treatment of choice for hypothyroidism. Levothyroxine (LT4) is among the most commonly prescribed medications in the United States, with over 70 million prescriptions annually. Documented immediate DHRs to TRT are rare, with only a few case reports. METHODS: An 11-year (2008-2018) retrospective medical chart review of identified patients with self-reported allergy to TRT. ADRs to TRT were divided into immediate DHRs and predictable ADRs. RESULTS: A total of 466 patients were included in our study. We found an overall incidence of ADRs to TRT of 0.3%. Median age was 61.2 years; 85.8% were women, and 94.4% were Caucasian. The principal indication for TRT was autoimmune hypothyroidism (73.6%), followed by postsurgical hypothyroidism (17.4%) and subclinical hypothyroidism (6.7%). Predictable ADR manifestations to TRT were reported more commonly than DHR manifestations (57.5% vs. 42.5%, respectively). The most frequently reported of the former were palpitations (16.4%), nausea/vomiting (9.3%), and tremor (6.3%), while rash (23.8%), hives (9.5%), and pruritus (7.1%) were the most common regarding the latter. Fifty-six percent of the patients with an ADR to TRT tolerated an alternative TRT presentation. CONCLUSION: In our cohort, the majority of self-reported allergies to TRT were due to predictable ADRs rather than an immediate DHR. ABBREVIATIONS: ADR = adverse drug reaction; DHR = drug hypersensitivity reaction; FDA = Food and Drug Administration; LT3 = liothyronine; LT4 = levothyroxine; SCAR = severe cutaneous adverse drug reaction; TRT = thyroid replacement therapy.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipersensibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Autoinforme , Tiroxina/efectos adversosRESUMEN
Despite their low frequency, drug hypersensitivity reactions (DHRs) can be serious and result in lifelong sequelae. The diagnosis is critical to avert future reactions and should identify the culprit drug or drugs and safe alternatives. However, making the diagnosis can be complex and challenging. Reliable in vitro tests can offer the potential to improve a diagnosis of DHR and influence medical decision making. Importantly, in vitro testing is frequently not performed as a test in isolation but rather as a component of a diagnostic algorithm along with additional tests. There are several in vitro approaches for the different endotypes of DHRs. However, only few are available for routine diagnosis, and many are restricted to research laboratories. In vitro tests exhibit varying sensitivity and specificity depending on the drug involved and the clinical phenotype. In vitro tests can complement skin tests, especially in patients with negative or equivocal skin test responses inconsistent with the clinical presentation and in severe reactions in which drug provocation tests are contraindicated. The main unmet need for many in vitro tests for the diagnosis of DHRs is validation in larger studies with standardized controls that could harmonize diagnostic management between the United States, European Union, and other regions of the world.
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Hipersensibilidad a las Drogas/diagnóstico , Animales , Toma de Decisiones Clínicas , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/patología , Humanos , Pruebas CutáneasRESUMEN
RATIONALE: Difficulty of asthma ascertainment and its associated methodologic heterogeneity have created significant barriers to asthma care and research. OBJECTIVES: We evaluated the validity of an existing natural language processing (NLP) algorithm for asthma criteria to enable an automated chart review using electronic medical records (EMRs). METHODS: The study was designed as a retrospective birth cohort study using a random sample of 500 subjects from the 1997-2007 Mayo Birth Cohort who were born at Mayo Clinic and enrolled in primary pediatric care at Mayo Clinic Rochester. Performance of NLP-based asthma ascertainment using predetermined asthma criteria was assessed by determining both criterion validity (chart review of EMRs by abstractor as a gold standard) and construct validity (association with known risk factors for asthma, such as allergic rhinitis). MEASUREMENTS AND MAIN RESULTS: After excluding three subjects whose respiratory symptoms could be attributed to other conditions (e.g., tracheomalacia), among the remaining eligible 497 subjects, 51% were male, 77% white persons, and the median age at last follow-up date was 11.5 years. The asthma prevalence was 31% in the study cohort. Sensitivity, specificity, positive predictive value, and negative predictive value for NLP algorithm in predicting asthma status were 97%, 95%, 90%, and 98%, respectively. The risk factors for asthma (e.g., allergic rhinitis) that were identified either by NLP or the abstractor were the same. CONCLUSIONS: Asthma ascertainment through NLP should be considered in the era of EMRs because it can enable large-scale clinical studies in a more time-efficient manner and improve the recognition and care of childhood asthma in practice.
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Asma/epidemiología , Registros Electrónicos de Salud/estadística & datos numéricos , Procesamiento de Lenguaje Natural , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Minnesota/epidemiología , Prevalencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Thus far, no algorithms have been developed to automatically extract patients who meet Asthma Predictive Index (API) criteria from the Electronic health records (EHR) yet. Our objective is to develop and validate a natural language processing (NLP) algorithm to identify patients that meet API criteria. METHODS: This is a cross-sectional study nested in a birth cohort study in Olmsted County, MN. Asthma status ascertained by manual chart review based on API criteria served as gold standard. NLP-API was developed on a training cohort (n = 87) and validated on a test cohort (n = 427). Criterion validity was measured by sensitivity, specificity, positive predictive value and negative predictive value of the NLP algorithm against manual chart review for asthma status. Construct validity was determined by associations of asthma status defined by NLP-API with known risk factors for asthma. RESULTS: Among the eligible 427 subjects of the test cohort, 48% were males and 74% were White. Median age was 5.3 years (interquartile range 3.6-6.8). 35 (8%) had a history of asthma by NLP-API vs. 36 (8%) by abstractor with 31 by both approaches. NLP-API predicted asthma status with sensitivity 86%, specificity 98%, positive predictive value 88%, negative predictive value 98%. Asthma status by both NLP and manual chart review were significantly associated with the known asthma risk factors, such as history of allergic rhinitis, eczema, family history of asthma, and maternal history of smoking during pregnancy (p value < 0.05). Maternal smoking [odds ratio: 4.4, 95% confidence interval 1.8-10.7] was associated with asthma status determined by NLP-API and abstractor, and the effect sizes were similar between the reviews with 4.4 vs 4.2 respectively. CONCLUSION: NLP-API was able to ascertain asthma status in children mining from EHR and has a potential to enhance asthma care and research through population management and large-scale studies when identifying children who meet API criteria.
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Asma , Minería de Datos/métodos , Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , Algoritmos , Automatización , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality in the United States. Intrapartum administration of antibiotics to mothers with positivity to GBS is performed for prevention, with penicillin being the drug of choice. Previous studies have noted an increase in atopic diseases other than drug allergy associated with intrapartum antibiotic exposure. OBJECTIVE: To determine whether intrapartum exposure to penicillin for GBS increases the likelihood of penicillin allergy in children. METHODS: Retrospective chart review was performed for patients from a birth cohort. The birth cohort included children born in 2007 at a tertiary care hospital and had local addresses. Information on GBS status of the mother, intrapartum antibiotic exposure, delivery mode, and birth order was collected and analyzed. RESULTS: Of 927 children identified, 804 were included in the cohort. Eighty children (10%) had a reported penicillin allergy; most were white (79%) and boys (61%). Intrapartum exposure to penicillin (odds ratio 0.84, 95% confidence interval 0.45-1.57, P = .59) or to amoxicillin or ampicillin (odds ratio 0.22, 95% confidence interval 0.01-3.71, P = .29) did not increase the risk of penicillin allergy in children. In addition, all other factors evaluated did not affect the risk of penicillin allergy in children. CONCLUSION: To the authors' knowledge, this is the first study to evaluate intrapartum exposure to penicillin for GBS treatment and subsequent development of penicillin allergy in the child. In contrast to other atopic diseases, intrapartum antibiotic exposure does not alter the risk of penicillin allergy. Parents and obstetricians should be reassured when using penicillin for prevention of neonatal GBS.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Hipersensibilidad a las Drogas/epidemiología , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Niño , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Intercambio Materno-Fetal , Minnesota/epidemiología , Embarazo , Estudios Retrospectivos , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/transmisión , Streptococcus agalactiaeAsunto(s)
Anafilaxia/epidemiología , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Vacuna nCoV-2019 mRNA-1273 , Adulto , Anciano , Anciano de 80 o más Años , Anafilaxia/inmunología , Vacuna BNT162 , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Inmunoterapia/efectos adversos , Infusiones Subcutáneas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/inmunología , Adulto JovenAsunto(s)
Anafilaxia/inducido químicamente , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Polisorbatos/efectos adversos , Piel/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/inmunología , Adulto , Vacuna BNT162 , COVID-19/inmunología , Femenino , Humanos , SARS-CoV-2/inmunología , Vacunas de ARNmAsunto(s)
Anticuerpos Antibacterianos/sangre , Inmunoglobulina G/sangre , Vacunas Neumococicas/inmunología , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/prevención & control , Adulto , Anciano , Anticuerpos Antibacterianos/inmunología , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Factores Sexuales , Vacunación , Adulto JovenAsunto(s)
Angioedema/inducido químicamente , Angioedema/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Registros Electrónicos de Salud , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Atención Terciaria de Salud , Población Blanca/estadística & datos numéricos , Adulto JovenAsunto(s)
Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Hipersensibilidad a las Drogas/diagnóstico , Polietilenglicoles/efectos adversos , Polisorbatos/efectos adversos , SARS-CoV-2/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Cutáneas , Adulto JovenRESUMEN
BACKGROUND: Secondhand smoke (SHS) exposure is known to trigger asthma, but asthma disease severity and comorbidities in children exposed to SHS are not very well quantified. OBJECTIVE: To identify comorbidities and understand health care usage in children with asthma exposed to SHS (cases) compared with children with asthma but without SHS exposure (controls). METHODS: A retrospective nested matched case-and-control study was conducted with children 5 to 18 years old who were enrolled in the Pediatric Asthma Management Program. Pulmonary function testing (spirometry, methacholine challenges, and exhaled nitric oxide) and body mass index were reviewed. Influenza vaccination rates, oral steroid usage, emergency department visits, and hospitalizations were assessed. Network analysis of the 2 groups also was conducted to evaluate for any associations between the variables. RESULTS: Cases had significantly higher body mass index percentiles (>75%, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.22-2.2, P = .001). Cases were less likely to have had a methacholine challenge (OR 0.49, 95% CI 0.36-0.68, P < .001) and an exhaled nitric oxide (OR 0.6, 95% CI 0.37-0.97, P = .04) performed than controls. The ratio of forced expiration volume in 1 second to forced vital capacity and forced expiration volume in 1 second were lower in cases than in controls (P < .05). Cases were less likely to have received an influenza vaccination (OR 0.61, 95% CI 0.45-0.82, P = .001) than controls. Unsupervised multivariable network analysis suggested a lack of discrete and unique subgroups between cases and controls. CONCLUSION: Children with asthma exposed to SHS are more likely to have comorbid conditions such as obesity, more severe asthma, and less health care usage than those not exposed to SHS. Smoking cessation interventions and addressing health disparities could be crucial in this vulnerable population.
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Asma/epidemiología , Exposición por Inhalación , Contaminación por Humo de Tabaco , Adolescente , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Preescolar , Comorbilidad , Espiración , Femenino , Volumen Espiratorio Forzado , Hospitalización/estadística & datos numéricos , Humanos , Vacunas contra la Influenza , Masculino , Cloruro de Metacolina , Óxido Nítrico/metabolismo , Obesidad/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Espirometría , Vacunación/estadística & datos numéricosRESUMEN
OBJECTIVE: Asthma Predictive Index (API) has been used for predicting asthma in prospective or cross-sectional studies, not for a retrospective study. We aim to develop and validate API for a retrospective study. METHODS: This is a cross-sectional study based on a convenience sample of children who participated in a previous retrospective cohort study. API was operationalized by two or more wheezing episodes in a year during the first 3 years of life PLUS one of the major or two of the minor criteria of the original API. We assessed validity of retrospective API against Predetermined Asthma Criteria (PAC) which has been extensively used in clinical studies for asthma. We assessed criterion validity by measuring kappa and agreement rate between API and PAC and construct validity by determining associations of API with known risk factors for asthma. RESULTS: Of the eligible 105 children, 55 (52.4%) were male, 90 (85.7%) Caucasians, and the mean age (±SD) was 5.8 years (±1.5). API criteria was met by 15 (14.3%), compared to 33 (31.4%) by PAC, respectively. The agreement rate and kappa between API and definite asthma of PAC were 89.5% and 0.66 (p < 0.01). Atopic conditions, lower parental education, no history of breastfeeding and family history of asthma were significantly associated with risk of asthma by API. CONCLUSIONS: Application of API to a retrospective study for ascertaining asthma status is suitable. Our study findings need to be replicated by future studies with a larger sample size.