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1.
N Engl J Med ; 381(11): 1046-1057, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31509675
2.
J Manag Care Spec Pharm ; 25(2): 148-151, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30698094

RESUMO

DISCLOSURES: No funding supported the writing of this commentary. The author reports personal fees from BioCryst, CSL Behring, Shire, and Pharming and grants from Ionis. He is chair of the US HAEA Medical Advisory Board and scientific advisor for HAE International.


Assuntos
Angioedema Hereditário Tipos I e II/tratamento farmacológico , Modelos Econômicos , Análise Custo-Benefício , Angioedema Hereditário Tipos I e II/economia , Angioedema Hereditário Tipos I e II/fisiopatologia , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos
4.
JAMA ; 320(20): 2108-2121, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30480729

RESUMO

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P < .001); -1.44 (95% CI, -1.84 to -1.04; P < .001); and -1.71 (95% CI, -2.09 to -1.33; P < .001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805.

5.
J Allergy Clin Immunol Pract ; 6(4): 1132-1141, 2018 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30033914

RESUMO

Angioedema is an acute swelling of the deeper layers of the skin or mucosa resulting from a transient increase in vascular permeability. Angioedema can occur in the absence or presence of hives, be hereditary or acquired, and be caused by various potential mediators, including histamine and bradykinin. Bradykinin-mediated angioedema can be difficult to diagnose but is responsible for a disproportionate percentage of the serious morbidity and mortality associated with angioedema. Our understanding of the basic biology of angioedema has dramatically expanded over recent years. The classification of angioedema has correspondently undergone major changes. Optimal management of patients with angioedema requires that an accurate diagnosis be established and that treatment be tailored to the patient's specific form of angioedema. In this article, we review the biology of bradykinin-mediated angioedema as well as the clinical approach to the evaluation of angioedema with a focus on bradykinin-mediated angioedema. Recognizing how the underlying pathophysiology and mechanisms of bradykinin dysregulation contribute to angioedema can help guide the clinical approach to the patient.

6.
Clin Exp Allergy ; 48(11): 1429-1438, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29957871

RESUMO

BACKGROUND: The lack of specific biomarkers makes the diagnosis of hereditary angioedema (HAE) with normal levels of C1-inhibitor (C1INH) protein (HAE-nl-C1INH) and idiopathic non-histaminergic angioedema (INHA) difficult. Confirming or excluding these diagnoses is a significant challenge for clinicians evaluating patients with angioedema. OBJECTIVE: To develop a reliable biomarker that would aid the diagnosis of HAE-nl-C1INH and INHA. METHODS: A total of 154 consecutive patients referred for angioedema at a single centre were enrolled and evaluated. Subjects were clinically phenotyped based on clinical history and response to treatment by clinicians blinded to laboratory assay results. Plasma kallikrein activity was measured by the cleavage of the fluorometric substrate Z-Phe-Arg-AMC-HCL in plasma samples stimulated ex vivo with submaximal doses of dextran sulphate. RESULTS: Stimulated plasma kallikrein activity (mean relative fluorescence units/min ± SD) was significantly increased in both HAE-nl-C1INH (1804 ± 600) and INHA (1579 ± 371) subjects compared to non-swelling controls (171 ± 46) and histaminergic angioedema (133 ± 30) subjects. Using a threshold cut-off based on the normal controls, HAE-nl-C1INH and INHA subjects could be differentiated from histaminergic angioedema subjects with high sensitivity (negative predictive value 86%-89%) and specificity (positive predictive value 80%-100%). CONCLUSION AND CLINICAL RELEVANCE: The stimulated kallikrein activity assay allows differentiation of bradykinin- from histamine-mediated angioedema. The assay could feasibly be considered as a potential clinical tool for the diagnosis of bradykinin-mediated angioedema.

7.
J Allergy Clin Immunol ; 141(3): 884-885, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29410040
8.
Immunol Allergy Clin North Am ; 37(3): 527-539, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687107

RESUMO

Hereditary angioedema (HAE) is a rare autosomal dominant disease clinically characterized by recurrent, often unpredictable attacks of subcutaneous and mucosal swelling. Acute episodes are debilitating, painful, disfiguring, and potentially fatal. HAE type I and type II result from a deficiency in the plasma level of functional C1 inhibitor. HAE with normal levels of C1 inhibitor has been recognized. There is evidence that contact activation underlies the recurrent attacks of swelling. This article reviews laboratory parameters to detect contact system activation and implications for diagnosis of HAE and other forms of bradykinin-mediated angioedema.


Assuntos
Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/metabolismo , Biomarcadores , Bradicinina/metabolismo , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Transdução de Sinais
9.
Ann Allergy Asthma Immunol ; 118(4): 456-460.e1, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28283277

RESUMO

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost. OBJECTIVE: To examine the hidden cost of anabolic androgen use related to the risk of developing non-HAE comorbidities. METHODS: Patients with HAE were identified in the Southern California Kaiser Permanente database using clinical and laboratory findings compatible with HAE. These patients were stratified into anabolic androgen exposed and nonexposed groups. Matched controls were selected from the Kaiser database who did not have HAE or anabolic androgen exposure. Using multivariate analysis, we determined the number of non-HAE comorbidities linked to anabolic androgen use. We next determined the association between dosing and increasing exposure to anabolic androgens and the likelihood of having various comorbidities. RESULTS: Patients with HAE exposed to anabolic androgens had a 28% increase (P = .04) in non-HAE comorbidities when compared with their matched (nonexposed) controls. With each gram per month increase in exposure, a 12% increase in non-HAE comorbidities is observed (P < .01). The most commonly occurring non-HAE comorbidities were psychiatric, muscle cramps, obesity, and hyperlipidemia. CONCLUSION: Our data suggest that long-term anabolic androgen use enhances the risk of developing comorbid health conditions, thus amplifying the cost of care. Our report provides additional support for the preferred use of newer, targeted therapies for the management of HAE.


Assuntos
Anabolizantes/uso terapêutico , Androgênios/uso terapêutico , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Adolescente , Adulto , Anabolizantes/administração & dosagem , Anabolizantes/efeitos adversos , Anabolizantes/economia , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Androgênios/economia , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Proteína Inibidora do Complemento C1/economia , Proteína Inibidora do Complemento C1/uso terapêutico , Custos de Medicamentos , Feminino , Angioedema Hereditário Tipos I e II/diagnóstico , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
10.
J Allergy Clin Immunol ; 140(1): 101-108.e3, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28279492

RESUMO

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD. OBJECTIVE: We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD. METHODS: Blood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2 metabolite and leukotriene E4 levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes. RESULTS: ILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2 metabolite and leukotriene E4 levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity. CONCLUSIONS: ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.


Assuntos
Asma Induzida por Aspirina/imunologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Linfócitos/imunologia , Mucosa Nasal/imunologia , Adulto , Idoso , Asma Induzida por Aspirina/sangue , Asma Induzida por Aspirina/urina , Contagem de Células , Dessensibilização Imunológica , Dinoprosta/urina , Feminino , Humanos , Cetorolaco/administração & dosagem , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/citologia
11.
N Engl J Med ; 376(12): 1131-1140, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28328347

RESUMO

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).


Assuntos
Proteína Inibidora do Complemento C1/administração & dosagem , Angioedema Hereditário Tipos I e II/prevenção & controle , Adulto , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Angioedema Hereditário Tipos I e II/classificação , Humanos , Injeções Subcutâneas , Masculino , Risco , Autoadministração , Índice de Gravidade de Doença
12.
J Allergy Clin Immunol Pract ; 5(2): 442-447.e1, 2017 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27818136

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a life-threatening disorder characterized by recurrent angioedema. Icatibant, a subcutaneous bradykinin-B2-receptor antagonist, is an effective on-demand therapy. Data outside the United States suggest that self-administration is tolerated and patient-preferred compared with administration by health care professionals at medical facilities (HCP-administration). OBJECTIVE: A prospective, multicenter study was conducted in the United States to compare icatibant self-administration and HCP-administration. METHODS: Subjects 18 years or older with type I or II HAE were recruited. The first 2 HAE attacks after enrollment were treated at medical facilities. Subjects were instructed by a health care professional on self-administration during icatibant treatment for the second HAE attack. Icatibant was self-administered for all subsequent attacks. For each treated HAE attack, efficacy, safety, and tolerability data were recorded. RESULTS: Nineteen patients with HAE received icatibant for 79 distinct HAE attacks. Mean attack duration was significantly shorter with self-administration (n = 50; 547 ± 510 minutes) than with HCP-administration (n = 29; 968 ± 717 minutes; P = .006). Mean time to treatment was significantly shorter with self-administration (143 ± 226 minutes) than with HCP-administration (361 ± 503 minutes; P < .0001). Shorter times to treatment were associated with shorter time from treatment to symptom resolution (r = 0.35; P = .02). Improvements in visual analog scale score and patient symptom score from pretreatment to 4 hours postinjection were comparable between self-administration and HCP-administration. There were no serious adverse events or discontinuations due to adverse events with self-administration or HCP-administration. CONCLUSIONS: Icatibant self-administration shortened attack duration and time to treatment, with no difference in safety or local tolerability compared with HCP-administration. These findings support icatibant as an effective on-demand option for home-based treatment.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Bradicinina/análogos & derivados , Serviços de Assistência Domiciliar , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioedemas Hereditários/epidemiologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Bradicinina/administração & dosagem , Bradicinina/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/administração & dosagem , Pessoal de Saúde , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Preferência do Paciente , Estudos Prospectivos , Autoadministração , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia , Escala Visual Analógica , Adulto Jovem
13.
J Allergy Clin Immunol Pract ; 5(1): 128-134.e4, 2017 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27665386

RESUMO

BACKGROUND: Emergency department (ED) management of hereditary angioedema (HAE) has been hindered by misdiagnosis and limited treatment options. Food and Drug Administration approval of 4 on-demand HAE therapies starting in 2009 and the publication of ED guidelines for angioedema management in 2014 should facilitate improvement of HAE management in the ED. OBJECTIVE: The objective of this study was to identify patient-reported areas for improvement in ED management of HAE attacks. METHODS: Patients with self-reported HAE with C1 inhibitor deficiency who attended the 2015 HAE Association Patient Summit were asked to complete an anonymous 30-question survey. Questions addressed patient characteristics and HAE management in the ED. RESULTS: Patients indicated that understanding of HAE in the ED needed improvement (99%, 104 of 105 patients). Recognition of HAE as a diagnosis (48%, 50 of 105 patients), appreciation of HAE as a serious disease (45%, 47 of 105 patients), and medication management (59%, 62 of 105 patients) were identified as areas needing improvement. Among 39 patients who required ED care within the last year, 6 did not receive any HAE-targeted therapy, and treatment with corticosteroids (n = 3), epinephrine (n = 2), and antihistamines (n = 7) was reported. Among 68 patients whose treatment plan was to receive home on-demand therapy, 26 required ED care because of an inability to receive on-demand therapy at home as outlined in their treatment plan. Having a treatment plan was associated with a greater likelihood of receiving HAE therapy in the ED (99% vs 74%, P = .002). CONCLUSION: HAE management in the ED can be improved with a focus on recognition of HAE attacks and administration of effective HAE therapies.


Assuntos
Angioedemas Hereditários/diagnóstico por imagem , Angioedemas Hereditários/epidemiologia , Serviço Hospitalar de Emergência , Satisfação do Paciente , Melhoria de Qualidade , Adolescente , Angioedemas Hereditários/terapia , Criança , Pré-Escolar , Erros de Diagnóstico , Gerenciamento Clínico , Serviços Médicos de Emergência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Inquéritos e Questionários , Estados Unidos , United States Food and Drug Administration
14.
Clin Rev Allergy Immunol ; 51(2): 216-29, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27459852

RESUMO

Remarkable progress in understanding the pathophysiology and underlying mechanisms of hereditary angioedema has led to the development of effective treatment for this disorder. Progress in three separate areas has catalyzed our understanding of hereditary angioedema. The first is the recognition that HAE type I and type II result from a deficiency in the plasma level of functional C1 inhibitor. This observation has led to a detailed understanding of the SERPING1 mutations responsible for this deficiency as well as the molecular regulation of C1 inhibitor expression and function. The second is that the fundamental cause of swelling is enhanced contact system activation leading to increased generation of bradykinin. Substantial progress has been made in defining the parameters regulating bradykinin generation and catabolism as well as the receptors that transduce the biologic effects of kinins. The third is the understanding that tissue swelling in hereditary angioedema primarily involves the function of endothelial cell adherens junctions. This knowledge is driving increased attention to the role of endothelial biology in determining disease activity in hereditary angioedema. While there has been considerable progress made, large gaps still remain in our knowledge. Important areas that remain poorly understood include the factors that lead to very low plasma functional C1 inhibitor levels, the triggers of contact system activation in hereditary angioedema, and the role of the bradykinin B1 receptor. The phenotypic variability of hereditary angioedema has been extensively documented but never understood. The mechanisms discussed in this chapter likely contribute to this variability. Future progress in understanding these mechanisms should provide new means to improve the diagnosis and treatment of hereditary angioedema.


Assuntos
Angioedemas Hereditários/etiologia , Angioedemas Hereditários/metabolismo , Androgênios/metabolismo , Angioedemas Hereditários/diagnóstico , Bradicinina/metabolismo , Permeabilidade Capilar , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Citocinas/metabolismo , Progressão da Doença , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Receptores da Bradicinina/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais
15.
J Allergy Clin Immunol Pract ; 4(5): 948-955.e15, 2016 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27329469

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling. 17-α-Alkylated androgens (AA) have been used prophylactically to reduce HAE severity, but there are many questions about the efficacy and tolerability of AA. OBJECTIVE: The objective of this study was to investigate the tolerability and effectiveness of AA therapy in a large cohort of patients with HAE. METHODS: We performed a retrospective cross-sectional study on 650 subjects with HAE utilizing a one time, anonymous, web-based survey. Based on an initial questionnaire, patients were routed to one of the following questionnaires: currently using AA, previously used but discontinued AA, or never used AA. RESULTS: Statistical analysis revealed that androgens decreased attack frequency and severity in previous AA users (P < .0001) and current AA users (P < .0001). Substantial variability in the effectiveness was observed. Users who discontinued AA reported significantly lesser benefit. No dose effect was seen for the beneficial effect of AA; however, almost all users reported frequent side effects that were dose related and often severe. CONCLUSIONS: AA therapy is usually effective for the treatment of HAE although a substantial fraction of patients with HAE do not achieve adequate benefit. In contrast, the side effects of AA are seen in almost all subjects who take the medicines. If used, AA should only be recommended in the lowest effective and tolerated dose for carefully selected patients.


Assuntos
Androgênios/efeitos adversos , Androgênios/uso terapêutico , Angioedemas Hereditários/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Autorrelato , Inquéritos e Questionários , Resultado do Tratamento
16.
Br J Haematol ; 173(6): 831-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27071490

RESUMO

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling that can result in significant morbidity and even mortality. Several novel therapies introduced since 2008 have dramatically transformed the approach to management. In this review we will discuss the current understanding of the pathophysiology of HAE, diagnostic evaluation of recurrent angioedema without urticaria, and the therapeutic approach to HAE. We advocate taking an integrative approach to care in order to normalize the lives of affected patients.


Assuntos
Angioedemas Hereditários , Adolescente , Adulto , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/genética , Angioedemas Hereditários/terapia , Criança , Gerenciamento Clínico , Feminino , Humanos , Masculino , Recidiva , Adulto Jovem
17.
Clin Pediatr (Phila) ; 55(10): 935-42, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26581355

RESUMO

Hereditary angioedema (HAE) typically presents in childhood. Large gaps remain in our understanding of the natural history of HAE during childhood. We examined age of onset, delay in diagnosis, androgen exposure, and their influence on ultimate disease severity in a large cohort of patients with HAE. Median age of first swelling was 11 years with a median age at diagnosis of 19 years. Earlier onset of symptoms correlated with longer delays in diagnosis (P < .001) and predicted a more severe disease course, including increased number of attacks per year (P = .0009) and hospital admissions (P = .009). Earlier age of onset also significantly correlated with increased perceived HAE severity (P = .0002), negative overall life impact (P < .0001), and use of anabolic androgen. Our observations highlight the importance of early HAE diagnosis and suggest the necessity of a disease management plan once the diagnosis has been made.


Assuntos
Angioedemas Hereditários/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Índice de Gravidade de Doença , Adulto Jovem
18.
J Allergy Clin Immunol Pract ; 4(1): 76-81, 2016 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26342745

RESUMO

BACKGROUND: An increased prevalence of hypertension has been described in adult asthmatic patients. However, there is no information regarding the interaction of hypertension as a comorbidity with asthma severity. OBJECTIVE: The objective of this study was to investigate whether a concomitant diagnosis of hypertension had any impact on markers of asthma severity in adult asthmatic patients. METHODS: A total of 117,922 asthmatic subjects 18 years or older were identified in the Kaiser Permanente database. Case-control studies were conducted with cases defined by short-acting ß-agonist canister dispensing greater than 6 (SABA > 6), history of emergency department visits or hospitalizations (EDHO), and corticosteroid dispensings (CCS), respectively. Controls were matched by age and sex. Univariate and multivariate conditional logistic regression was applied to estimate the odds ratios (OR) and 95% confidence intervals (CI) for SABA > 6, EDHO, and CCS associated with the diagnosis of hypertension. RESULTS: Hypertension was associated with an increased odds of SABA > 6 (OR 1.19, CI 1.13-1.26, n = 15,855 cases and 76,060 controls), EDHO (OR 1.11, CI 1.03-1.19, n = 9,307 cases and 46,535 controls), and CCS (OR 1.15, CI 1.10-1.19, n = 53,690 cases and 53,690 controls) after adjusting for potential confounders. CONCLUSIONS: Asthmatic subjects with comorbid hypertension display evidence of enhanced of asthma morbidity.


Assuntos
Asma/epidemiologia , Hipertensão/epidemiologia , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Asma/tratamento farmacológico , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Serviços Médicos de Emergência , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos
19.
J Allergy Clin Immunol ; 137(1): 278-288.e6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26100084

RESUMO

BACKGROUND: Rhinovirus infection at an early age has been associated with development of asthma, but how rhinovirus influences the immune response is not clear. OBJECTIVE: Tolerance to inhaled antigen is mediated through induction of regulatory T (Treg) cells, and we examined whether rhinovirus infection of the respiratory tract can block airway tolerance by modulating Treg cells. METHODS: The immune response to intranasal ovalbumin in mice was assessed with concomitant infection with RV1B, and the factors induced in vivo were compared with those made by human lung epithelial cells infected in vitro with RV16. RESULTS: RV1B infection of mice abrogated tolerance induced by inhalation of soluble ovalbumin, suppressing the normal generation of forkhead box protein 3-positive Treg cells while promoting TH2 cells. Furthermore, RV1B infection led to susceptibility to asthmatic lung disease when mice subsequently re-encountered aeroantigen. RV1B promoted early in vivo expression of the TNF family protein OX40 ligand on lung dendritic cells that was dependent on the innate cytokine thymic stromal lymphopoietin (TSLP) and also induced another innate cytokine, IL-33. Inhibiting each of these pathways allowed the natural development of Treg cells while minimizing TH2 differentiation and restored tolerance in the face of RV1B infection. In accordance, RV16 infection of human lung epithelial cells upregulated TSLP and IL-33 expression. CONCLUSIONS: These results suggest that infection of the respiratory epithelium with rhinovirus can antagonize tolerance to inhaled antigen through combined induction of TSLP, IL-33, and OX40 ligand and that this can lead to susceptibility to asthmatic lung inflammation.


Assuntos
Citocinas/imunologia , Tolerância Imunológica , Interleucina-33/imunologia , Glicoproteínas de Membrana/imunologia , Infecções por Picornaviridae/imunologia , Rhinovirus , Fatores de Necrose Tumoral/imunologia , Animais , Antígenos/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Células Epiteliais , Humanos , Interleucina-13/imunologia , Interleucina-4/imunologia , Pulmão/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ovalbumina/imunologia , Hipersensibilidade Respiratória/imunologia , Linfócitos T/imunologia
20.
Allergy Asthma Proc ; 36(3): 213-7, 2015 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25976438

RESUMO

Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed.


Assuntos
Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/terapia , Adolescente , Adulto , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/prevenção & controle , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Gerenciamento Clínico , Progressão da Doença , Humanos , Lactente , Pessoa de Meia-Idade , Recidiva , Inquéritos e Questionários , Adulto Jovem
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