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1.
Mayo Clin Proc Innov Qual Outcomes ; 6(1): 69-76, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35024565

RESUMO

OBJECTIVE: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs. METHODS: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning. RESULTS: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year. CONCLUSION: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

2.
Otolaryngol Head Neck Surg ; 166(2): 224-232, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33973823

RESUMO

OBJECTIVE: To provide a comprehensive state-of-the-art review of the emerging role of urine leukotriene E4 (uLTE4) as a biomarker in the diagnosis of chronic rhinosinusitis (CRS), aspirin-exacerbated respiratory disease (AERD), and asthma. DATA SOURCES: Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. REVIEW METHODS: A state-of-the-art review was performed investigating the role of uLTE4 as a diagnostic biomarker, predictor of disease severity, and potential marker of selected therapeutic efficacy. CONCLUSIONS: uLTE4 has been shown to be a reliable and clinically relevant biomarker for CRS, AERD, and asthma. uLTE4 is helpful in ongoing efforts to better endotype patients with CRS and to predict disease severity. IMPLICATIONS FOR PRACTICE: Aside from being a diagnostic biomarker, uLTE4 is also able to differentiate aspirin-tolerant patients from patients with AERD and has been associated with objective disease severity in patients with CRS with nasal polyposis. uLTE4 levels have also been shown to predict response to medical therapy, particularly leukotriene-modifying agents.


Assuntos
Asma/diagnóstico , Biomarcadores/urina , Leucotrieno E4/urina , Rinite/diagnóstico , Sinusite/diagnóstico , Asma/urina , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/urina , Doença Crônica , Humanos , Rinite/urina , Sinusite/urina
3.
Allergy Asthma Proc ; 42(4): 267-273, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34187619

RESUMO

Background: It remains unclear if asthma is a risk factor associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19). Methods: We performed a comprehensive database search for studies published from January 1, 2019, to October 2, 2020. We included studies that evaluated outcomes among patients with COVID-19 and underlying asthma. Outcomes of interest included the need for hospitalization, length of hospitalization, intensive care unit (ICU) admission, and death. The meta-analysis was conducted by using random-effects methodology. Results: A total of 389 studies were identified through data base searches. After abstract and full-text screening, 16 observational studies with 92,275 patients were included in the analysis. Of the 16 studies, 15 were retrospective and 1 was a prospective cohort study. The average age was 39.6 years, with 48% female patients. Six of the studies included pediatric patients, and one of these studies only evaluated pediatric patients. One study only evaluated pregnant patients. Among patients with COVID-19, the presence of asthma was not associated with any significant increase in risk of hospitalization (odds ratio [OR] 1.46 [95% confidence interval {CI}, 0.29-7.28]), length of hospitalization (1.59 days [-0.55 to 3.74]), ICU admission (OR 1.65 [95% CI, 0.56-4.17]), or death (OR 0.73 [95% CI, 0.38-1.40]). The overall risk of bias of the included studies was high. Conclusion: Among the patients with COVID-19, asthma did not seem to significantly increase the risk of hospitalization, length of hospitalization, ICU admission, or death.


Assuntos
Asma/terapia , COVID-19/terapia , Hospitalização , Adulto , Idoso , Asma/diagnóstico , Asma/mortalidade , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
5.
J Asthma ; 58(8): 1077-1086, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32315558

RESUMO

OBJECTIVE: While a single but truncated ICD code (493) had been widely used for identifying asthma in asthma care and research, it significantly under-identifies asthma. We aimed to develop and validate a diagnostic codes-based algorithm for identifying asthmatics using Predetermined Asthma Criteria (PAC) as the reference. METHODS: This is a retrospective cross-sectional study which utilized two different coding systems, the Hospital Adaptation of the International Classification of Diseases, Eighth Revision (H-ICDA) and the International Classification of Diseases, Ninth Revision (ICD-9). The algorithm was developed using two population-based asthma study cohorts, and validated in a validation cohort, a random sample of the 1976-2007 Olmsted County Birth Cohort. Performance of the diagnostic codes-based algorithm for ascertaining asthma status against manual chart review for PAC (gold standard) was assessed by determining both criterion and construct validity. RESULTS: Among eligible 267 subjects of the validation cohort, 50% were male, 70% white, and the median age at last follow-up was 17 (interquartile range, 8.7-24.4) years. Asthma prevalence by PAC through manual chart review was 34%. Sensitivity and specificity of the codes-based algorithm for identifying asthma were 82% and 98% respectively. Associations of asthma-related risk factors with asthma status ascertained by the code-based algorithm were similar to those by the manual review. CONCLUSIONS: The diagnostic codes-based algorithm for identifying asthmatics improves accuracy of identification of asthma and can be a useful tool for large scale studies in a setting without automated chart review capabilities.


Assuntos
Algoritmos , Asma/diagnóstico , Adolescente , Adulto , Criança , Estudos Transversais , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
6.
Laryngoscope ; 131(5): 961-966, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33001452

RESUMO

OBJECTIVES: Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS: A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS: Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores). CONCLUSION: Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:961-966, 2021.


Assuntos
Leucotrieno E4/urina , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Doença Crônica , Eosinófilos , Feminino , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/sangue , Pólipos Nasais/imunologia , Pólipos Nasais/urina , Seios Paranasais/diagnóstico por imagem , Estudos Retrospectivos , Rinite/sangue , Rinite/imunologia , Rinite/urina , Índice de Gravidade de Doença , Teste de Desfecho Sinonasal , Sinusite/sangue , Sinusite/imunologia , Sinusite/urina , Tomografia Computadorizada por Raios X
7.
JMIR Med Inform ; 8(10): e13567, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33103657

RESUMO

BACKGROUND: When older adult patients with hip fracture (HFx) have unplanned hospital readmissions within 30 days of discharge, it doubles their 1-year mortality, resulting in substantial personal and financial burdens. Although such unplanned readmissions are predominantly caused by reasons not related to HFx surgery, few studies have focused on how pre-existing high-risk comorbidities co-occur within and across subgroups of patients with HFx. OBJECTIVE: This study aims to use a combination of supervised and unsupervised visual analytical methods to (1) obtain an integrated understanding of comorbidity risk, comorbidity co-occurrence, and patient subgroups, and (2) enable a team of clinical and methodological stakeholders to infer the processes that precipitate unplanned hospital readmission, with the goal of designing targeted interventions. METHODS: We extracted a training data set consisting of 16,886 patients (8443 readmitted patients with HFx and 8443 matched controls) and a replication data set consisting of 16,222 patients (8111 readmitted patients with HFx and 8111 matched controls) from the 2010 and 2009 Medicare database, respectively. The analyses consisted of a supervised combinatorial analysis to identify and replicate combinations of comorbidities that conferred significant risk for readmission, an unsupervised bipartite network analysis to identify and replicate how high-risk comorbidity combinations co-occur across readmitted patients with HFx, and an integrated visualization and analysis of comorbidity risk, comorbidity co-occurrence, and patient subgroups to enable clinician stakeholders to infer the processes that precipitate readmission in patient subgroups and to propose targeted interventions. RESULTS: The analyses helped to identify (1) 11 comorbidity combinations that conferred significantly higher risk (ranging from P<.001 to P=.01) for a 30-day readmission, (2) 7 biclusters of patients and comorbidities with a significant bicluster modularity (P<.001; Medicare=0.440; random mean 0.383 [0.002]), indicating strong heterogeneity in the comorbidity profiles of readmitted patients, and (3) inter- and intracluster risk associations, which enabled clinician stakeholders to infer the processes involved in the exacerbation of specific combinations of comorbidities leading to readmission in patient subgroups. CONCLUSIONS: The integrated analysis of risk, co-occurrence, and patient subgroups enabled the inference of processes that precipitate readmission, leading to a comorbidity exacerbation risk model for readmission after HFx. These results have direct implications for (1) the management of comorbidities targeted at high-risk subgroups of patients with the goal of pre-emptively reducing their risk of readmission and (2) the development of more accurate risk prediction models that incorporate information about patient subgroups.

8.
Cancer Chemother Pharmacol ; 86(3): 375-382, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32778906

RESUMO

PURPOSE: Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2-4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. METHODS: We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan-Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. RESULTS: Median age at time of desensitization was 49.3 years (26.8-64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0-15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. CONCLUSION: Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Dessensibilização Imunológica/métodos , Glioma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Temozolomida/administração & dosagem , Administração Metronômica , Adulto , Idoso , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Glioma/imunologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
J Asthma ; 57(4): 381-390, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30784333

RESUMO

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.


Assuntos
Anticorpos Antibacterianos/sangue , Asma/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Asma/sangue , Asma/complicações , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Humoral , Imunogenicidade da Vacina , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Estudos Retrospectivos , Vacinação
10.
J Asthma ; 57(3): 241-252, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30656998

RESUMO

Objective: The older adult population is increasing worldwide, and a significant percentage has asthma. This review will discuss the challenges to diagnosis and management of asthma in older adults. Data Sources: PubMed was searched for multiple terms in various combinations, including asthma, older adult, elderly, comorbid conditions, asthma diagnosis, asthma treatment, biologics and medication side effects, and adverse events. From the search, the data sources that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Study Selections: Study selections that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Results: Asthma in older adults is frequently underdiagnosed and has higher morbidity and mortality rates compared to their younger counterparts. A detailed history and physical examination as well as judicious testing are essential to establish the asthma diagnosis and exclude alternative ones. Medical comorbidities, such as cardiovascular disease, cognitive impairment, depression, arthritis, gastroesophageal reflux disease (GERD), rhinitis, and sinusitis are common in this population and should also be assessed and treated. Non-pharmacologic management, including asthma education on inhaler technique and self-monitoring, is vital. Pharmacologic management includes standard asthma therapies such as inhaled corticosteroids (ICS), inhaled corticosteroid-long acting ß-agonist combinations (ICS-LABA), leukotriene antagonists, long acting muscarinic antagonists (LAMA), and short acting bronchodilators (SABA). Newly approved biologic agents may also be utilized. Older adults are more vulnerable to polypharmacy and medication adverse events, and this should be taken into account when selecting the appropriate asthma treatment. Conclusions: The diagnosis and management of asthma in older adults has certain challenges, but if the clinician is aware of them, the morbidity and mortality of this condition can be improved in this growing population.


Assuntos
Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Fatores Etários , Idoso , Asma/complicações , Asma/epidemiologia , Comorbidade , Progressão da Doença , Humanos , Polimedicação , Qualidade de Vida
12.
Int Forum Allergy Rhinol ; 8(9): 1047-1051, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29851243

RESUMO

BACKGROUND: Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes. METHODS: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes. RESULTS: ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin-exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. At median follow-up of 28 months (interquartile range [IQR], 10-47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and "all other CRS" 4% at median follow-up duration of 36, 28, 41, 37, 44, and 26 months, respectively. CONCLUSION: All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT-22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.


Assuntos
Seios Paranasais/cirurgia , Reoperação/estatística & dados numéricos , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Idoso , Doença Crônica , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/classificação , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Seios Paranasais/patologia , Estudos Retrospectivos , Rinite/classificação , Rinite/patologia , Fatores de Risco , Sinusite/classificação , Sinusite/patologia , Resultado do Tratamento
13.
F1000Res ; 7: 412, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29707206

RESUMO

Great strides have been made in the last five years in understanding the pathology of chronic rhinosinusitis (CRS). CRS is now accepted to be the end-stage manifestation of inflammation resultant from various pathogenetic mechanisms. This has resulted in increasing recognition of distinct CRS endotypes. Such endotypes encompass a cluster of patients with similar pathogenic mechanisms that may have common therapeutic targets and responsiveness to interventions. The elucidation of mechanisms leading to the development of chronic upper (sino-nasal) airway inflammation has to some extent paralleled investigations of aberrant pathways operant in asthma. In this review, we focus on recent developments in understanding the innate immune pathways as well as adaptive (late) immune responses in CRS and asthma and their implication as potentially modifiable targets in CRS. Specific biologic therapy (that is, monoclonal antibodies targeting cytokines, cytokine receptors, or specific key molecules targeting inflammation) is an exciting proposition for the future of medical management of CRS. As of the writing of this article, the agents described are not approved for use in CRS; many have partial approval for use in asthma or are considered experimental.

14.
Int Forum Allergy Rhinol ; 8(7): 797-805, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29437297

RESUMO

BACKGROUND: Endotypic and prognosticating features of chronic rhinosinusitis without nasal polyposis (CRSsNP) are poorly understood. Our objectives were to use an unbiased symptom-based approach to: (1) study symptoms, clinical and endotypic features; and (2) identify features predicating outcomes from endoscopic sinus surgery (ESS). METHODS: Clinical, computed tomography (CT), histopathology, and 22-item Sino-Nasal Outcome Test (SNOT-22) data was collected on 146 adult CRSsNP patients who underwent ESS. Unsupervised network modeling of presurgical SNOT-22 scores was performed to classify symptom-based clusters. Subject characteristics and post-ESS SNOT-22 scores were compared between clusters. RESULTS: Baseline characteristics of the subject population were as follows: females, 56.2%; revision ESS status in 35%; asthma prevalence, 32.6%; median Lund-Mackay CT score, 8; and median SNOT-22 total score, 43. Network mapping and unsupervised clustering of preoperative SNOT-22 scores revealed 4 clusters: (A) severely burdened with high scores in all 4 subdomains; (B) moderately burdened with high scores in the rhinologic subdomain; (C) moderately burdened with high scores in psychological-sleep subdomains; and (D) mildly burdened. The number of previous ESS and asthma prevalence differed significantly between clusters; CT scores were similar. Asthma burden and tissue eosinophilia were greatest in cluster A (p = 0.03). All groups showed significant improvement at 3 months post-ESS (p < 0.0001). At 6 months, patients in cluster C tended to worsen. CONCLUSION: SNOT-22-based network modeling of CRSsNP patients yielded 4 clusters with distinct features. Asthma prevalence and tissue eosinophilia were highest in the cluster with highest SNOT-22 scores. All patients showed significant improvement from ESS at 3 months; those with high sleep-psychosocial symptoms tended to show worsening at 6 months.


Assuntos
Asma/epidemiologia , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Adulto , Idoso , Doença Crônica , Análise por Conglomerados , Eosinofilia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Rinite/epidemiologia , Sinusite/epidemiologia , Inquéritos e Questionários , Estados Unidos
15.
Allergy Asthma Proc ; 39(1): 51-58, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29279060

RESUMO

BACKGROUND: Although human leukocyte antigen (HLA)-DR and HLA-DQ genes and gluten play crucial roles in developing celiac disease (CD), most patients with these risk factors still do not develop CD, which indicates additional unrecognized risk factors. OBJECTIVE: To determine the association between asthma and the risk of CD in children. METHODS: We conducted a population-based retrospective case-control study in children who resided in Olmsted County, Minnesota. We identified children with CD (cases) between January 1, 1997, and December 31, 2014, and compared these with children without CD (controls) (1:2 matching). Asthma status was ascertained by using the predetermined asthma criteria (PAC) and the asthma predictive index (API). Data analysis included conditional logistic regression models and an unsupervised network analysis by using an independent phenome-wide association scan (PheWAS) data set. RESULTS: Although asthma status as determined by using PAC was not associated with the risk of CD (odds ratio [OR] 1.4 [95% confidence interval {CI}, 0.8-2.5]; p = 0.2), asthma status by using the API was significantly associated (OR 2.8 [95% CI, 1.3-6.0]; p = 0.008). A subgroup analysis indicated that children with both asthma as determined by using PAC and a family history of asthma had an increased risk of CD compared with those without asthma (OR 2.28 [95% CI, 1.11-4.67]; p = 0.024). PheWAS data showed a cluster of asthma single nucleotide polymorphisms and patients with CD. CONCLUSION: A subgroup of children with asthma who also had a family history of asthma seemed to be at an increased risk of CD, and, thus, the third factor that underlies the risk of CD might be related to genetic factors for asthma. Heterogeneity of asthma plays a role in determining the risk of asthma-related comorbidity.


Assuntos
Asma/genética , Doença Celíaca/etiologia , Adolescente , Asma/complicações , Asma/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Anamnese , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Fatores de Risco
17.
Ann Allergy Asthma Immunol ; 118(5): 614-620, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28254202

RESUMO

BACKGROUND: A subset of patients with common variable immunodeficiency (CVID) develop granulomatous lymphocytic interstitial lung disease (GLILD), which is associated with early mortality. OBJECTIVE: To determine a set of clinical and/or laboratory parameters that correlate with GLILD. METHODS: A retrospective, nested case-control (patients with CVID diagnosed with GLILD compared with patients with CVID without a diagnosis of GLILD) medical record review was undertaken at Mayo Clinic, Rochester, MN. Network and univariate analysis was used to identify clinical and laboratory parameters at the time of diagnosis that are associated with GLILD. RESULTS: Twenty-six cases with radiologic evidence of GLILD were included in this study. Eighteen cases (69%) cases had coexistent splenomegaly with lower IgA levels (P = .04) compared with the controls. Patients with low IgA levels (<13 mg/dL) also had percentage expansion of low CD21 B cells (CD21low >5%) (P = .007). Univariate analysis revealed that splenomegaly (odds ratio [OR], 17.3; 95% confidence interval [CI], 3.9-74.5), history of immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA) (OR, 4.8; 95% CI, 1.1-20.2), low IgA level (OR, 3.6; 95% CI, 1.2-11.9), and percentage expansion of CD21low (OR, 5.8; 95% CI, 1.6-24.7) were independently associated with GLILD. Logistic regression analysis revealed that splenomegaly, history of ITP or AIHA, low IgA level, and percentage expansion of CD21low B cells are highly sensitive in predicting presence of GLILD (area under the receiver operating curve of 0.86). CONCLUSION: Presence of splenomegaly, history of ITP or AIHA, low serum IgA level, and percentage expansion of CD21low B cells may be useful to identify a group of patients at high risk for development of GLILD.


Assuntos
Imunodeficiência de Variável Comum/complicações , Granuloma/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Algoritmos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Contagem de Leucócitos , Masculino , Fenótipo , Curva ROC , Testes de Função Respiratória , Estudos Retrospectivos
18.
J Allergy Clin Immunol Pract ; 5(4): 990-997.e1, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28202405

RESUMO

BACKGROUND: Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. OBJECTIVE: To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies. METHODS: We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed. RESULTS: The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively. CONCLUSIONS: ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.


Assuntos
Aspirina/efeitos adversos , Asma/urina , Inibidores de Ciclo-Oxigenase/efeitos adversos , Hipersensibilidade a Drogas/urina , Leucotrieno E4/urina , Biomarcadores/urina , Humanos
19.
Int Forum Allergy Rhinol ; 7(4): 373-379, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28042687

RESUMO

BACKGROUND: Endotyping chronic rhinosinusitis (CRS) through simplified cytokine assays may help direct individualized therapy such as corticosteroids, antibiotics, or biologics. We performed an unsupervised network analysis to endotype CRS and control subjects using a commercially available cytokine-chemokine immunoassay. METHODS: A 41-plex cytokine-chemokine array along with major basic protein (MBP) assay was performed on sinonasal surgical tissue of 32 adults. Subjects were defined as non-CRS controls (n = 6), CRS with nasal polyps (CRSwNP; n = 13), and CRS without nasal polyps (CRSsNP; n = 13). Unsupervised network modeling was performed to reveal association cytokine-chemokine ("analyte") clusters and "subject" groups. RESULTS: Network mapping and unsupervised clustering revealed 3 analyte clusters and 3 subject groups. Analyte cluster-1 was composed of T helper 1 (Th1)/Th17 type markers, analyte cluster-2 Th2 markers, and analyte cluster-3 chemokines (CC) and growth factors (GF). Subject group-1 was devoid of CRSwNP, had fewer asthmatics, and was associated most strongly with analyte cluster-3 (CC/GF) (p < 0.001). Subject group-2 was characterized with the most asthmatics (86%) and CRSwNP (100%) patients, and was associated with analyte cluster-2 (Th2; p < 0.001). Subject group-3 was associated with both analyte cluster-1 (Th1/Th17) and analyte cluster-3 (CC/GF) (p < 0.001), and had the highest proportion of CRSsNP patients (62.5%). Tissue levels of MBP, eosinophilia, and computed tomography (CT) scores were significantly higher in subject group-2 vs other groups (p ≤ 0.05). CONCLUSION: An unbiased network-mapping approach using a commercially available immunoassay kit reveals 3 distinct tissue cytokine-chemokine signatures that endotype CRS patients and controls. These signatures are prominent even in a limited number of patients, and may help formulate individualized therapy and optimize outcomes.


Assuntos
Citocinas/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Doença Crônica , Feminino , Humanos , Imunoensaio , Masculino , Seios Paranasais/imunologia , Rinite/classificação , Sinusite/classificação
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