Mepolizumab inhibits IL-5 activity and reduces exacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma (SEA). Some patients remain ...dependent on OCS despite anti–IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms.
To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab.
We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment.
A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo, −0.23; 95% CI, −0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI, −0.26 to 0.42), St. George’s Respiratory Questionnaire (0.24; 95% CI, −3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI, −0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI, −4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%).
OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.
The reclassification of asthma based on subphenotypes Green, Ruth H; Brightling, Chris E; Bradding, Peter
Current opinion in allergy and clinical immunology,
2007-February, 2007-Feb, 2007-02-00, 20070201, Letnik:
7, Številka:
1
Journal Article
PURPOSE OF REVIEWDespite asthma being widely regarded as a heterogeneous disease, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the ...recognition of subphenotypes of asthma based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The present review discusses the important literature in this field, placing current work in its historical context.
RECENT FINDINGSThe use of noninvasive markers of airway inflammation has suggested the presence of four distinct phenotypeseosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their aetiology, immunopathology and response to treatment. Several studies have focused on refractory asthma as a distinct phenotype with evidence of a more distal pattern of airway inflammation and of upregulation of the tumour necrosis factor-α axis. Finally, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant.
SUMMARYThe present review will discuss limitations to current classification systems, identify key current studies based on identifying inflammatory subphenotypes and provide suggestions for a novel approach that may further improve our understanding in this area.
Chromosome 17q21 SNP and severe asthma Binia, Aristea; Khorasani, Nadia; Bhavsar, Pankaj K ...
Journal of human genetics,
01/2011, Letnik:
56, Številka:
1
Journal Article
Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with ...no differential treatment considerations for either sex.
To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care.
This is a post hoc analysis, stratifying patient outcomes by sex, of a 48-week, multicenter, randomized controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in CS treatment (inhaled and oral corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions, and lung function.
Of the 301 patients randomized, 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower CS dose versus standard care, which was not seen in males (effect estimate: females, 3.57; 95% CI, 1.14-11.18 vs males, 0.54; 95% CI, 0.16-1.80). In T2-biomarker–low females, reducing CS dose was not associated with increased exacerbations. Females scored higher in all domains of the 7-item Asthma Control Questionnaire, apart from FEV1, but with no difference when adjusted for body mass index/anxiety and/or depression. Dissociation between symptoms and T2 biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs 15.6%; P = .0002), whereas males were symptom low/T2-biomarker high (22.3% vs 11.4%; P < .0001).
This exploratory post hoc analysis identified that females achieved a greater benefit from biomarker-directed CS optimization versus symptom-directed treatment.
A study was conducted to determine if non-eosinophilic asthma might be associated with a poor response to corticosteroids. It was determined that non-eosinophilic asthma is associated with a poor ...response to inhaled corticosteroids.
BackgroundAsthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.QuestionWhat are differences between male and female patients with asthma with ...regard to asthma control, lung function, inflammation and exacerbations?MethodsWe performed a post hoc analysis in the ATLANTIS (Assessment of Small Airways Involvement in Asthma) study, an observational cohort study including patients with asthma from nine countries with a follow-up of 1 year during which patients were characterised with measures of large and small airway function, questionnaires, inflammation and imaging. We compared differences in baseline characteristics and longitudinal outcomes between male and female patients with asthma.Results773 patients were enrolled; 450 (58%) of these were female. At baseline, female patients with asthma were in higher Global Initiative for Asthma (GINA) steps (p=0.042), had higher Asthma Control Questionnaire 6 (F: 0.83; M: 0.66, p<0.001) and higher airway resistance as reflected by uncorrected impulse oscillometry outcomes (ie, R5-R20: F: 0.06; M: 0.04 kPa/L/s, p=0.002). Male patients with asthma had more severe airway obstruction (forced expiratory volume in 1 s/forced vital capacity % predicted: F: 91.95; M: 88.33%, p<0.01) and more frequently had persistent airflow limitation (F: 27%; M: 39%, p<0.001). Blood neutrophils were significantly higher in female patients (p=0.014). With Cox regression analysis, female sex was an independent predictor for exacerbations.InterpretationWe demonstrate that female patients are in higher GINA steps, exhibit worse disease control, experience more exacerbations and demonstrate higher airway resistance compared with male patients. The higher exacerbation risk was independent of GINA step and blood eosinophil level. Male patients, in turn, have a higher prevalence of persistent airflow limitation and more severe airflow obstruction. These findings show sex can affect clinical phenotyping and outcomes in asthma.Trial registration numberNCT02123667.
IntroductionThe COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer ...long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).Methods and analysisThe UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.Ethics and disseminationAll contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.ConclusionThis study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We ...investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics. Fifty-two subjects were recruited from a single center. A. fumigatus was cultured from 19 asthmatics. Asthma control, symptom score, lung function, and sputum cell count were not significantly different between the asthmatics with and without a positive A. fumigatus culture. All of the sputum mediators were numerically increased in subjects with a positive versus negative sputum A. fumigatus culture. Sputum TNF-R2 was significantly elevated (P=0.03) and the mediator that best distinguished A. fumigatus culture-positive from culture-negative subjects (receiver-operator characteristic area under the curve 0.66 95% CI: 0.51 to 0.82, P=0.045). A. fumigates-positive culture in moderate-to-severe asthma is associated with increased inflammatory sputum mediators.
Among the most common causes of chronic cough are asthma (25%) and nonasthmatic eosinophilic bronchitis (10%). In asthma, cough may present as an isolated symptom, in which case it is known as cough ...variant asthma. Variable airflow obstruction and airway hyper-responsiveness are cardinal features of asthma, which are absent in nonasthmatic eosinophilic bronchitis. The presence of eosinophilic airway inflammation is a common feature of asthma and is a diagnostic criterion for nonasthmatic eosinophilic bronchitis. At a cellular level, mast cell infiltration into the airway smooth muscle bundle, narrowing of the airway wall, and increased interleukin-13 expression are features of asthma and not nonasthmatic eosinophilic bronchitis. In most cases, the trigger that causes the cough is uncertain, but occasionally occupational exposure to a sensitizer is identified, and avoidance is recommended. In both conditions, there is improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia and increased exhaled nitric oxide. Generally, response to therapy in both conditions is very good, and the limited long-term data available suggest that both usually have a benign course, although in some cases fixed airflow obstruction may occur.
PDF
