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1.
N Engl J Med ; 391(1): 32-43, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38819658

RESUMEN

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy. METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale (ratings range from "much worse" to "much better") at two or more consecutive time points within 12 hours after the first administration of the trial agent. Key secondary end points, assessed in a time-to-event analysis, were a reduction in attack severity (an improved rating on the Patient Global Impression of Severity [PGI-S] scale, with ratings ranging from "none" to "very severe") at two or more consecutive time points within 12 hours and complete attack resolution (a rating of "none" on the PGI-S scale) within 24 hours. RESULTS: A total of 136 participants were assigned to one of six trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief with the 300-mg dose and the 600-mg dose was faster than with placebo (P<0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively. The time to reduction in the attack severity with the 300-mg dose and the 600-mg dose was faster than with placebo (P = 0.004 and P = 0.003), with median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12). The time to complete resolution was faster with the 300-mg and 600-mg doses than with placebo (P = 0.002 and P<0.001). The percentage of attacks with complete resolution within 24 hours was 42.5% with the 300-mg dose, 49.5% with the 600-mg dose, and 27.4% with placebo. Sebetralstat and placebo had similar safety profiles; no serious adverse events related to the trial agents were reported. CONCLUSIONS: Oral sebetralstat provided faster times to the beginning of symptom relief, reduction in attack severity, and complete attack resolution than placebo. (Funded by KalVista Pharmaceuticals; KONFIDENT ClinicalTrials.gov number, NCT05259917; EudraCT number, 2021-001226-21.).


Asunto(s)
Estudios Cruzados , Humanos , Femenino , Método Doble Ciego , Masculino , Adulto , Administración Oral , Persona de Mediana Edad , Angioedemas Hereditarios/tratamiento farmacológico , Adolescente , Adulto Joven , Anciano , Angioedema Hereditario Tipos I y II/tratamiento farmacológico , Pirazoles
2.
Artículo en Inglés | MEDLINE | ID: mdl-38718950

RESUMEN

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVES: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ. CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

3.
J Allergy Clin Immunol Pract ; 12(6): 1614-1621, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38609017

RESUMEN

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.


Asunto(s)
Angioedemas Hereditarios , Humanos , Angioedemas Hereditarios/tratamiento farmacológico , Resultado del Tratamiento , Técnica Delphi , Encuestas y Cuestionarios , Ensayos Clínicos como Asunto , Consenso , Femenino , Evaluación de Resultado en la Atención de Salud
4.
J Allergy Clin Immunol Glob ; 3(2): 100226, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38495866

RESUMEN

Background: Hereditary angioedema with C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal disorder presenting with recurrent angioedema. Estrogen-containing medications trigger angioedema in some patients, and conversely, progesterone may decrease attack frequency. The mechanism by which estrogen may exacerbate angioedema in HAE-C1INH is not well characterized. Objective: Our aim was to investigate the link between estrogen and bradykinin constituents to better understand the specific underlying triggers that may exacerbate angioedema in patients with HAE-C1INH. Methods: As estrogen is contraindicated for patients with HAE-C1INH, females without a history of angioedema were recruited to evaluate whether estrogen-containing oral contraceptive pills (OCPs) alter plasma protein levels of bradykinin, cleaved high-molecular-weight kininogen (cHK), and activated factor XII (FXIIa). Blood (plasma) was collected before initiation of OCP administration and 3 months thereafter. High-molecular-weight kininogen (HK) was measured by ELISA and FXIIa and cHK were analyzed by Western blot analysis. Results: A total of 12 adult females without HAE-CINH (aged <40 years) had a median baseline plasma HK level of 33,976 ng/mL. After 3 months of OCP therapy, their median HK level increased to 38,202 ng/mL. With OCPs, there was also a significant increase in level of FXIIa protein (P <.01), as well as an increase in cHK protein level. Conclusion: This preliminary study, performed in females without HAE-C1INH, suggests that estrogen may exacerbate angioedema by increasing the production of cHK and FXIIa.

5.
J Allergy Clin Immunol Pract ; 12(4): 849-862, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38355013

RESUMEN

Airway inflammation in asthma has been well recognized for several decades, with general agreement on its role in asthma pathogenesis, symptoms, propensity toward exacerbation, and decline in lung function. This has led to universal recommendation in asthma management guidelines to incorporate the use of inhaled corticosteroid as an anti-inflammatory therapy for all patients with persistent asthma symptoms. However, there has been limited attention paid to the presence and potential impact of systemic inflammation in asthma. Accumulating evidence from epidemiological observations and cohort studies points to a host of downstream organ dysfunction in asthma especially among patients with longstanding or more severe disease, frequent exacerbations, and underlying risk factors for organ dysfunction. Most studies to date have focused on cognitive impairment, depression/anxiety, metabolic syndrome, and cardiovascular abnormalities. In this review, we summarize some of the evidence demonstrating these abnormalities and highlight the proposed mechanisms and potential benefits of treatment in limiting these extrapulmonary abnormalities in patients with asthma. The goal of this commentary is to raise awareness of the importance of recognizing potential extrapulmonary conditions associated with systemic inflammation of asthma. This area of treatment of patients with asthma is a large unmet need.


Asunto(s)
Asma , Insuficiencia Multiorgánica , Humanos , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/diagnóstico , Sistema Respiratorio , Inflamación , Antiinflamatorios/uso terapéutico
6.
PLoS One ; 19(2): e0297616, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38349898

RESUMEN

BACKGROUND: Post-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site. RESEARCH QUESTION: Do WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity? STUDY DESIGN AND METHODS: We collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants. RESULTS: Of the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses. INTERPRETATION: Our results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.


Asunto(s)
Asma , Ataques Terroristas del 11 de Septiembre , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/diagnóstico , Asma/complicaciones , Asma/epidemiología , Morbilidad , Citocinas
7.
J Allergy Clin Immunol Pract ; 12(1): 201-211.e6, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37730089

RESUMEN

BACKGROUND: Symptoms of hereditary angioedema (HAE) often first occur during childhood, and HAE attacks in children can be severe and substantially affect health-related quality of life (HRQoL). However, there are no approved long-term prophylaxis treatments for children aged less than 6 years. OBJECTIVE: The SPRING Study (NCT04070326) evaluated the safety, pharmacokinetics, and efficacy of lanadelumab and HRQoL in patients aged 2 to less than 12 years. METHODS: Over 52 weeks of treatment, patients aged 2 to less than 6 years received lanadelumab 150 mg every 4 weeks (Q4W) and patients aged 6 to less than 12 years received 150 mg every 2 weeks (Q2W) but could switch to Q4W if they were attack-free for 26 weeks. RESULTS: We enrolled 21 patients (aged 2 to less than 6 years: n = 4; aged 6 to less than 12 years: n = 17), 20 of whom completed the study. There were no reported serious treatment-emergent adverse events or discontinuations resulting from such events. Treatment-emergent adverse events were reported for 17 patients (81.0%). The most common TEAE was injection site pain. Overall systemic exposure was comparable for both age groups. The mean (SD) attack rate during treatment decreased by 94.8% from baseline (1.84 [1.53] to 0.08 [0.17] attacks/mo), and 16 (76.2%) patients were attack-free. The attack rate reduction in both age groups was similar during the first 26-week fixed-dosing treatment. Seven patients switched from Q2W to Q4W and remained attack-free. A large, clinically meaningful increase in the Pediatric Quality of Life Inventory Generic Core Scale Total Score and a large increase in the Pediatric Quality of Life Inventory Generic Core Scale-Family Impact Module Total Score from baseline to end of study (better HRQoL) were observed. CONCLUSIONS: Findings support safety, efficacy, and improved HRQoL with lanadelumab 150 mg Q2W and Q4W regimens for the prevention of HAE attacks in patients aged 2 to less than 12 years.


Asunto(s)
Angioedemas Hereditarios , Niño , Preescolar , Humanos , Angioedemas Hereditarios/tratamiento farmacológico , Angioedemas Hereditarios/prevención & control , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Reacción en el Punto de Inyección , Calidad de Vida , Resultado del Tratamiento
8.
J Allergy Clin Immunol ; 153(2): 408-417, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38000696

RESUMEN

BACKGROUND: Black adults are disproportionately affected by asthma and are often considered a homogeneous group in research studies despite cultural and ancestral differences. OBJECTIVE: We sought to determine if asthma morbidity differs across adults in Black ethnic subgroups. METHODS: Adults with moderate-severe asthma were recruited across the continental United States and Puerto Rico for the PREPARE (PeRson EmPowered Asthma RElief) trial. Using self-identifications, we categorized multiethnic Black (ME/B) participants (n = 226) as Black Latinx participants (n = 146) or Caribbean, continental African, or other Black participants (n = 80). African American (AA/B) participants (n = 518) were categorized as Black participants who identified their ethnicity as being American. Baseline characteristics and retrospective asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids [SCs], emergency department/urgent care [ED/UC] visits, hospitalizations) were compared across subgroups using multivariable regression. RESULTS: Compared with AA/B participants, ME/B participants were more likely to be younger, residing in the US Northeast, and Spanish speaking and to have lower body mass index, health literacy, and <1 comorbidity, but higher blood eosinophil counts. In a multivariable analysis, ME/B participants were significantly more likely to have ED/UC visits (incidence rate ratio [IRR] = 1.34, 95% CI = 1.04-1.72) and SC use (IRR = 1.27, 95% CI = 1.00-1.62) for asthma than AA/B participants. Of the ME/B subgroups, Puerto Rican Black Latinx participants (n = 120) were significantly more likely to have ED/UC visits (IRR = 1.64, 95% CI = 1.22-2.21) and SC use for asthma (IRR = 1.43, 95% CI = 1.06-1.92) than AA/B participants. There were no significant differences in hospitalizations for asthma among subgroups. CONCLUSIONS: ME/B adults, specifically Puerto Rican Black Latinx adults, have higher risk of ED/UC visits and SC use for asthma than other Black subgroups.


Asunto(s)
Asma , Población Negra , Adulto , Humanos , Asma/complicaciones , Asma/epidemiología , Asma/etnología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Hispánicos o Latinos/etnología , Hispánicos o Latinos/estadística & datos numéricos , Morbilidad , Estudios Retrospectivos , Estados Unidos/epidemiología , Puerto Rico/etnología , Negro o Afroamericano/etnología , Negro o Afroamericano/estadística & datos numéricos , Pueblos Caribeños/estadística & datos numéricos , África/etnología , Población Negra/etnología , Población Negra/estadística & datos numéricos
9.
Allergy Asthma Clin Immunol ; 19(1): 48, 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37248521

RESUMEN

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies. METHODS: A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019. RESULTS: Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%). CONCLUSIONS: Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.

10.
J Allergy Clin Immunol Pract ; 11(8): 2315-2325, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37116793

RESUMEN

Hereditary angioedema (HAE) is a rare disease characterized by sudden and often unprovoked episodes of swelling that can be potentially life-threatening when it involves the upper airway. The treatment options for both acute episodes of HAE and LTP, used to minimize the frequency and severity of angioedema attacks, were limited historically to very few options, had considerable side effects, and/or had considerable burden of treatment. Fortunately, through the elucidation of the pathophysiology of HAE, the development of newer targeted therapies has been possible both for acute therapy and long-term prophylaxis and even more are on the horizon. Because of the rapid development of these therapies, it can be challenging for clinicians to keep abreast of newer and developing treatments for HAE. This review article will outline the current and potential future treatments for HAE. It will also highlight important considerations when treating special HAE patient populations including women and pediatric patients.


Asunto(s)
Angioedema , Angioedemas Hereditarios , Humanos , Femenino , Niño , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/uso terapéutico , Angioedema/tratamiento farmacológico
11.
World Allergy Organ J ; 15(3): 100627, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35497649

RESUMEN

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

12.
N Engl J Med ; 386(16): 1505-1518, 2022 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-35213105

RESUMEN

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).


Asunto(s)
Antiasmáticos , Asma , Beclometasona , Negro o Afroamericano , Glucocorticoides , Hispánicos o Latinos , Administración por Inhalación , Adulto , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/etnología , Beclometasona/administración & dosificación , Beclometasona/efectos adversos , Beclometasona/uso terapéutico , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Calidad de Vida , Encuestas y Cuestionarios , Brote de los Síntomas
13.
Allergy ; 77(7): 1961-1990, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35006617

RESUMEN

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.


Asunto(s)
Angioedemas Hereditarios , Angioedemas Hereditarios/prevención & control , Angioedemas Hereditarios/terapia , Niño , Proteína Inhibidora del Complemento C1/genética , Proteína Inhibidora del Complemento C1/uso terapéutico , Consenso , Femenino , Humanos , Embarazo
14.
J Asthma ; 59(3): 607-615, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33249956

RESUMEN

BACKGROUND: Cognitive impairment (CI) is highly prevalent in elderly asthmatics and is associated with worse asthma self-management (SM) and outcomes. CI may also explain why older adults may under-perceive asthma symptoms. We hypothesized that CI would be associated with low medication adherence and asthma symptom under-perception (ASP). We also hypothesized that ASP would mediate the relationship between CI and medication adherence. METHODS: Participants of this longitudinal cohort study were asthmatics (N = 334) ≥60 years (51% Hispanic, 25% Black). Cognitive measures assessed general cognition, attention, processing speed, executive functioning, memory, and language. Measures of SM were self-reported and electronically measured adherence to controller medications. ASP was assessed for 6 weeks by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter, followed by PEF blows. Participants were blinded to actual PEF values. Percentage of time that participants were in the over-perception zone was calculated as an average. RESULTS: In regression analyses, those with impairments in memory and general cognition had lower odds ratios (OR) for self-reported non-adherence (OR: 0.96, 95% CI 0.93 - 0.98 & OR: 0.90, 95% CI 0.83 - 0.96, respectively). CI was not associated with electronically measured non-adherence or ASP. In structural equation modeling, while CI was associated with adherence (ß = 0.04, SE = 0.021, p = 0.04), ASP did not mediate this relationship. CONCLUSIONS: While results confirmed the importance of cognition in asthma SM, these findings were not linked to ASP. Future analyses are needed to understand the role of confounding factors.


Asunto(s)
Antiasmáticos , Asma , Anciano , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/psicología , Cognición , Humanos , Estudios Longitudinales , Cumplimiento de la Medicación , Percepción
15.
Clin Transl Allergy ; 11(8): e12073, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34691392

RESUMEN

BACKGROUND: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. RESULTS: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. CONCLUSIONS: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

16.
Allergy Asthma Immunol Res ; 13(4): 646-654, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34212550

RESUMEN

T-regulatory cells (Tregs) play a key role in suppressing effector cells and maintaining self-tolerance. Studies of younger adults and children suggest that insufficient differentiation and functional defects of Tregs may contribute to the development of asthma; however, data from older patients with asthma are limited. To address the effects of aging on the relationship of Treg frequency and function with clinical outcomes, we collected induced sputum (differential cell count and Treg frequency) and peripheral blood (Treg function and frequency) from aged (> 60 years of age) and younger (20-40 years old) patients with asthma. In younger patients, low Treg suppression was associated with significantly higher mean numbers of emergency department (ED) (1.8 vs. 0.17, P = 0.02) and urgent care visits (2.3 vs. 0.17, P = 0.01) for asthma, and decreased asthma control (mean Asthma Control Test [ACT] score, 17 vs. 21.3, P = 0.01) compared to those with high Treg suppression. In older patients, however, a lower Treg function was not significantly associated with ACT scores (18.2 vs. 13.4, P = 0.10), or the number of ED (P = 0.9) or urgent care visits (P = 0.2). Our data suggest that Tregs have a weak relationship with asthma control and clinical asthma outcomes in older patients and differ from findings in younger patients, where Tregs are more likely to play a protective role.

18.
J Allergy Clin Immunol ; 148(6): 1526-1532, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34048855

RESUMEN

BACKGROUND: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. OBJECTIVES: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. METHODS: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. RESULTS: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients' lives. CONCLUSIONS: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients.


Asunto(s)
Angioedemas Hereditarios/terapia , Proteína Inhibidora del Complemento C1/genética , Piel/inmunología , Angioedemas Hereditarios/genética , Animales , Consenso , Manejo de la Enfermedad , Humanos , Guías de Práctica Clínica como Asunto , Calidad de Vida , Resultado del Tratamiento
19.
Contemp Clin Trials ; 101: 106246, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33316456

RESUMEN

BACKGROUND: Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended by asthma guidelines in all but the mildest cases of asthma, is generally poor. As-needed ICS has shown promise as a patient-empowering asthma management strategy, but it has not been rigorously studied in AA/B or H/L patients or in a real-world setting. Design and Aim The PeRson EmPowered Asthma RElief (PREPARE) Study is a randomized, open-label, pragmatic study which aims to assess whether a patient-guided, reliever-triggered ICS strategy called PARTICS (Patient-Activated Reliever-Triggered Inhaled CorticoSteroid) can improve asthma outcomes in AA/B and H/L adult patient populations. In designing and implementing the study, the PREPARE research team has relied heavily on advice from AA/B and H/L Patient Partners and other stakeholders. Methods PREPARE is enrolling 1200 adult participants (600 AA/Bs, 600H/Ls) with asthma. Participants are randomized to PARTICS + Usual Care (intervention) versus Usual Care (control). Following a single in-person enrollment visit, participants complete monthly questionnaires for 15 months. The primary endpoint is annualized asthma exacerbation rate. Secondary endpoints include asthma control; preference-based quality of life; and days lost from work, school, or usual activities. Discussion The PREPARE study features a pragmatic design allowing for the real-world assessment of a patient-centered, reliever-triggered ICS strategy in AA/B and H/L patients. Outcomes of this study have the potential to offer powerful evidence supporting PARTICS as an effective asthma management strategy in patient populations that suffer disproportionately from asthma morbidity and mortality.


Asunto(s)
Asma , Negro o Afroamericano , Corticoesteroides , Adulto , Asma/tratamiento farmacológico , Hispánicos o Latinos , Humanos , Calidad de Vida
20.
J Allergy Clin Immunol Pract ; 9(1): 132-150.e3, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32898710

RESUMEN

Scientific and clinical progress together with the development of effective novel therapeutic options has engendered multiple important changes in the diagnosis and management of hereditary angioedema (HAE). We now update and extend the 2013 United States Hereditary Angioedema Association Medical Advisory Board guidelines for the treatment and management of HAE. The guidelines are based on a comprehensive literature review with recommendations indicating both the strength of our recommendation and the quality of the underlying evidence. Guidelines are provided regarding the classification, diagnosis, on-demand treatment, prophylactic treatment, special considerations for women and children, development of a comprehensive management and monitoring plan, and assessment of burden of illness for both HAE due to C1 inhibitor deficiency and HAE with normal C1 inhibitor. Advances in HAE treatment now allow the development of management plans that can help many patients with HAE lead a normal life. Achieving this goal requires that physicians be familiar with the diagnostic and therapeutic transformations that have occurred in recent years.


Asunto(s)
Angioedemas Hereditarios , Médicos , Comités Consultivos , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Niño , Proteína Inhibidora del Complemento C1 , Femenino , Humanos , Estados Unidos
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