Exhaled nitric oxide (Fe(NO)) is a biomarker of airway inflammation in mild to moderate asthma. However, whether Fe(NO) levels are informative regarding airway inflammation in patients with severe ...asthma, who are refractory to conventional treatment, is unknown. Here, we hypothesized that classification of severe asthma based on airway inflammation as defined by Fe(NO) levels would identify a more reactive, at-risk asthma phenotype.
Fe(NO) and major features of asthma, including airway inflammation, airflow limitation, hyperinflation, hyperresponsiveness, and atopy, were determined in 446 individuals with various degrees of asthma severity (175 severe, 271 non-severe) and 49 healthy subjects enrolled in the Severe Asthma Research Program.
Fe(NO) levels were similar among patients with severe and non-severe asthma. The proportion of individuals with high Fe(NO) levels (>35 ppb) was the same (40%) among groups despite greater corticosteroid therapy in severe asthma. All patients with asthma and high Fe(NO) had more airway reactivity (maximal reversal in response to bronchodilator administration and by methacholine challenge), more evidence of allergic airway inflammation (sputum eosinophils), more evidence of atopy (positive skin tests, higher serum IgE and blood eosinophils), and more hyperinflation, but decreased awareness of their symptoms. High Fe(NO) identified those patients with severe asthma characterized by the greatest airflow obstruction and hyperinflation and most frequent use of emergency care.
Grouping of asthma by Fe(NO) provides an independent classification of asthma severity, and among patients with severe asthma identifies the most reactive and worrisome asthma phenotype.
...we highlight the importance of collaboration in interdisciplinary large-scale consortia to enable precision medicine trials. ...basic research to fully elucidate type 2 pathways in severe asthma, ...combined with the development of more precise companion diagnostics that dissect these pathways, are urgently required. Targeting the Systemic Inflammation of Obesity Obesity is a key risk factor for developing severe asthma, and patients with severe asthma are frequently characterized by high body mass index and other obesity-associated comorbidities. Because obesity induces a state of low-grade systemic inflammation, it is intriguing to consider the possibility that obesity-associated inflammation may cause airway pathology in asthma. The Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes-Innovative Medicines Initiative and Severe Asthma Research Program projects have been deemed as highly successful collaborative projects (54). ...future joint efforts in severe asthma clinical trials will reach their full potential only if they follow established principles for collaboration in a consortium.
To reduce scan duration in hyperpolarized
Xe 1-point Dixon gas exchange imaging by utilizing flip angle (FA)/TR equivalence.
Images were acquired in 12 subjects (n = 3 radiation therapy, n = 1 ...unexplained dyspnea, n = 8 healthy) using both standard (TR = 15 ms, FA = 20°, duration = 15 s, 998 projections) and "fast" (TR = 5.4 ms, FA = 12°, duration = 11.3 s, 2100 projections) acquisition parameters. For the fast acquisition, 3 image sets were reconstructed using subsets of 1900, 1500, and 1000 projections. From the resulting ventilation, tissue ("barrier"), and red blood cell (RBC) images, image metrics and biomarkers were compared to assess agreement between methods.
Images acquired using both FA/TR settings had similar qualitative appearance. There were no significant differences in SNR, image mean, or image SD between images. Moreover, the percentage of the lungs in "defect", "normal", and "high" bins for each image (ventilation, RBC, barrier) was not significantly different among the acquisition types. After registration, comparison of 3D image metrics (Dice, volume similarity, average distance) agreed well between bins. Images using 1000 projections for reconstruction had no significant differences from images using all projections.
Using flip angle/TR equivalence, hyperpolarized
Xe gas exchange images can be acquired via the 1-point Dixon technique in as little as 6 s, compared to ~15 s for previously reported parameter settings. The resulting images from this accelerated scan have no significant differences from the standard method in qualitative appearance or quantitative metrics.
Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly.
Do baseline radiographic and ...clinical characteristics exist that predict response to BT?
We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response.
From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86).
To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response.
ClinicalTrials.gov; No.: NCT01185275; URL: www.clinicaltrials.gov
Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments.
To apply a ...segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma.
In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area. The resulting AT segment score (0-19) was related to patient outcomes.
AT varied at the lung segment level and tended to persist at the patient and lung segment levels over 3 years. Patients with widespread AT (⩾10 segments) had more severe asthma (
< 0.05). The mean (±SD) AT segment score in patients with a body mass index ⩾30 kg/m
was lower than in patients with a body mass index <30 kg/m
(3.5 ± 4.6 vs. 5.5 ± 6.3;
= 0.008), and the frequency of AT in lower lobe segments in obese patients was less than in upper and middle lobe segments (35% vs. 46%;
= 0.001). The AT segment score in patients with sputum eosinophils ⩾2% was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9;
< 0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48% vs. 18%;
⩽ 0.0001).
In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging, whereas those who are obese have less severe trapping because their lower lobe segments are spared.
Como punto de partida del proyecto de Investigación Estado del Arte de Ingeniería en Informática como programa académico y disciplina profesional se establece un desarrollo de la gnoseología o sea ...los Fundamentos Teóricos, Conceptuales, Epistemológicos, como también, la ontología de sus objetos (objetos de estudio, objetos de formación, objetos de conocimiento), demandas sociales, dominios de estudio y dominio material que le permiten formular perfiles profesionales, ocupacionales, dominio profesional, objetivos de formación, ejes de formación, núcleos problemicos, espacios académicos y plan de estudio. En el presente artículo se plantea los resultados Gnoseológicos de la Investigación: - Construcción de los Objetos del Programa *Esencia del Programa *Objeto de Estudio del Programa *Objetos de Estudio para la formación Profesional *Objetos de Conocimiento *Objetos de Formación *Dominio Material (Objetos del Programa) - Demandas Sociales - Redacción de Perfiles; Profesional y Ocupacional - Dominio Disciplinar - Objetivos Educativos del Programa - Núcleos Problemicos - Ejes de Formación - Como se configura un Objeto de Estudio en un Espacio Académico
Objective
The mandible is the most common fractured craniofacial bone of all craniofacial fractures
in the Philippines, with the mandibular body as the most involved segment of all mandibular
...fractures. To the best of our knowledge, there are no existing guidelines for the diagnosis and
management of mandibular body fractures in particular. General guidelines include the American
Academy of Otolaryngology – Head and Neck Surgery Foundation (AAOHNSF) Resident Manual
of Trauma to the Face, Head, and Neck chapter on Mandibular Trauma, the American Association
of Oral and Maxillofacial Surgeons (AAOMS) Clinical Practice Guidelines for Oral and Maxillofacial
Surgery section on the Mandibular Angle, Body, and Ramus, and a 2013 Cochrane Systematic
Review on interventions for the management of mandibular fractures. On the other hand, a
very specific Clinical Practice Guideline on the Management of Unilateral Condylar Fracture
of the Mandible was published by the Ministry of Health Malaysia in 2005. Addressing the
prevalence of mandibular body fractures, and dearth of specific guidelines for its diagnosis and
management, this clinical practice guideline focuses on the management of isolated mandibular
body fractures in adults.
Purpose
This guideline is meant for all clinicians (otolaryngologists – head and neck surgeons, as
well as primary care and specialist physicians, nurses and nurse practitioners, midwives and
community health workers, dentists, and emergency first-responders) who may provide care
to adults aged 18 years and above that may present with an acute history and physical and/
or laboratory examination findings that may lead to a diagnosis of isolated mandibular body
fracture and its subsequent medical and surgical management, including health promotion and
disease prevention.
It is applicable in any setting (including urban and rural primary-care, community centers,
treatment units, hospital emergency rooms, operating rooms) in which adults with isolated
mandibular body fractures would be identified, diagnosed, or managed.
Outcomes are functional resolution of isolated mandibular body fractures; achieving
premorbid form; avoiding use of context-inappropriate diagnostics and therapeutics; minimizing
use of ineffective interventions; avoiding co-morbid infections, conditions, complications and
adverse events; minimizing cost; maximizing health-related quality of life of individuals with
isolated mandibular body fracture; increasing patient satisfaction; and preventing recurrence in
patients and occurrence in others.
Accumulating evidence suggests that the upper airway bacterial microbiota is implicated in asthma inception, severity, and exacerbation. Unlike bacterial microbiota, the role of the upper airway ...fungal microbiome (mycobiome) in asthma control is poorly understood.
What are the upper airway fungal colonization patterns among children with asthma and their relationship with subsequent loss of asthma control and exacerbation of asthma?
The study was coupled with the Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (ClinicalTrials.gov Identifier: NCT02066129) clinical trial. The upper airway mycobiome was investigated using Internal transcribed spacer 1 (ITS1) sequencing of nasal blow samples collected from children with asthma when asthma was well controlled (baseline, n = 194) and during early signs of loss of asthma control (yellow zone YZ, n = 107).
At baseline, 499 fungal genera were detected in the upper airway samples, with two commensal fungal species, Malassezia globosa and Malassezia restricta, being most dominant. The relative abundance of Malassezia species varies by age, BMI, and race. Higher relative abundance of M globosa at baseline was associated with lower risk of future YZ episodes (P = .038) and longer time to development of first YZ episode (P = .022). Higher relative abundance of M globosa at YZ episode was associated with lower risk of progression from YZ episode to severe asthma exacerbation (P = .04). The upper airway mycobiome underwent significant changes from baseline to YZ episode, and increased fungal diversity was correlated highly with increased bacterial diversity (ρ = 0.41).
The upper airway commensal mycobiome is associated with future asthma control. This work highlights the importance of the mycobiota in asthma control and may contribute to the development of fungi-based markers to predict asthma exacerbation.
Background
Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV1) in patients ...with moderate‐to‐severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854).
Methods
Changes from baseline in pre‐ and post‐bronchodilator (BD) FEV1 and 5‐item Asthma Control Questionnaire (ACQ‐5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2–150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide FeNO ≥25 ppb; type 2–300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non‐exacerbators.
Results
In exacerbators and non‐exacerbators, dupilumab increased pre‐BD FEV1 by Week 2 vs placebo; differences were maintained to Week 52 (type 2–150/25: LS mean difference (LSMD) vs placebo: 0.17 L (95% CI: 0.10–0.24) and 0.17 L (0.12–0.23); type 2–300/25: 0.22 L (0.13–0.30) and 0.21 L (0.15–0.28)), in exacerbators and non‐exacerbators, respectively (p < .0001). Similar trends were seen for post‐BD FEV1. Dupilumab vs placebo also showed significantly greater improvements in post‐BD FEV1 0–42 days after first severe exacerbation in type 2–150/25 (LSMD vs placebo: 0.13 L 0.06–0.20; p = .006) and type 2–300/25 (0.14 L 0.06–0.22; p = .001) patients. ACQ‐5 improvements were greater with dupilumab vs placebo in both groups.
Conclusion
Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study.
This analysis assessed the effect of dupilumab on FEV1 in QUEST patients with moderate‐to‐severe asthma and elevated type 2 biomarkers. Dupilumab significantly increased FEV1, regardless of number of severe exacerbations; FEV1 recovery was more rapid in dupilumab‐ vs placebo‐treated patients. Dupilumab produced rapid and sustained improvement in lung function, including in patients experiencing severe exacerbations.Abbreviations: ACQ‐5, 5‐item Asthma Control Questionnaire; BD, bronchodilator; BL, baseline; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; LS, least squares; q2w, every 2 weeks
Bronchial thermoplasty is a device-based therapy for treatment of severe refractory asthma that uses radiofrequency energy to reduce airway smooth muscle and decrease bronchoconstriction. BT improves ...quality of life and decreases the rate of severe exacerbations with no known major long-term complications. The effectiveness of bronchial thermoplasty persists at least 5 years after the treatment is completed. Further investigation is needed to better define the specific subpopulation of patients with severe asthma who would best benefit from this treatment.
PDF
