Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.

BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms. OBJECTIVE: We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma. METHODS: In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function. RESULTS: Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08). CONCLUSIONS: Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes.

Several biomarkers have been used to assess sputum eosinophilia in asthma. It has been suggested that the diagnostic accuracy of these biomarkers might differ between asthma phenotypes. We investigated the accuracy of biomarkers in detecting sputum eosinophilia (≥3%) in different adult asthma phenotypes.Levels of eosinophils in blood and sputum, exhaled nitric oxide fraction (FeNO) and total immunoglobulin (Ig)E from 336 adult patients, enrolled in three prospective observational clinical trials and recruited at five pulmonology outpatient departments, were analysed. Areas under the receiver operating characteristics curves (AUC) for detecting sputum eosinophilia were calculated and compared between severe and mild, obese and nonobese, atopic and nonatopic and (ex-)smoking and never-smoking asthma patients.Sputum eosinophilia was present in 116 patients (35%). In the total group the AUC was 0.83 (95% CI 0.78-0.87) for blood eosinophils, 0.82 (0.77-0.87) for FeNO and 0.69 (0.63-0.75) for total IgE. AUCs were similar for blood eosinophils and FeNO between different phenotypes. Total IgE was less accurate in detecting sputum eosinophilia in atopic and obese patients than in nonatopic and nonobese patients.Blood eosinophils and FeNO had comparable diagnostic accuracy (superior to total IgE) in identifying sputum eosinophilia in adult asthma patients, irrespective of asthma phenotype such as severe, nonatopic, obese and smoking-related asthma.

Severe adult-onset asthma: A distinct phenotype.

BACKGROUND: Some patients with adult-onset asthma have severe disease, whereas others have mild transient disease. It is currently unknown whether patients with severe adult-onset asthma represent a distinct clinical phenotype. OBJECTIVE: We sought to investigate whether disease severity in patients with adult-onset asthma is associated with specific phenotypic characteristics. METHODS: One hundred seventy-six patients with adult-onset asthma were recruited from 1 academic and 3 nonacademic outpatient clinics. Severe refractory asthma was defined according to international Innovative Medicines Initiative criteria, and mild-to-moderate persistent asthma was defined according to Global Initiative for Asthma criteria. Patients were characterized with respect to clinical, functional, and inflammatory parameters. Unpaired t tests and χ(2) tests were used for group comparisons; both univariate and multivariate logistic regression were used to determine factors associated with disease severity. RESULTS: Apart from the expected high symptom scores, poor quality of life, need for high-intensity treatment, low lung function, and high exacerbation rate, patients with severe adult-onset asthma were more often nonatopic (52% vs 34%, P = .02) and had more nasal symptoms and nasal polyposis (54% vs 27%, P ≤ .001), higher exhaled nitric oxide levels (38 vs 27 ppb, P = .02) and blood neutrophil counts (5.3 vs 4.0 10(9)/L, P ≤ .001) and sputum eosinophilia (11.8% vs 0.8%, P ≤ .001). Multiple logistic regression analysis showed that increased blood neutrophil (odds ratio, 10.9; P = .002) and sputum eosinophil (odds ratio, 1.5; P = .005) counts were independently associated with severe adult-onset disease. CONCLUSION: The majority of patients with severe adult-onset asthma are nonatopic and have persistent eosinophilic airway inflammation. This suggests that severe adult-onset asthma has a distinct underlying mechanism compared with milder disease.

Scoping review of early pain-related outcome domains and measurement instruments after degenerative lumbar spine surgery.

BACKGROUND: Optimization of perioperative pain interventions in lumbar spine surgery could reduce the incidence of acute and persistent postoperative pain and opioid consumption. Standardization in early outcome measurement provides a solid foundation for future clinical and research practices and should be integrated in core outcome sets for long-term treatment outcome evaluations. This scoping review provides an overview of outcomes used when evaluating early perioperative pain interventions after lumbar spine surgery. OBJECTIVES: To create an overview of outcome domains and measurement instruments previously used in research on perioperative pain management for degenerative lumbar spine surgery. EVIDENCE REVIEW: A scoping review was performed to identify articles comprising outcome evaluations in adult patients who undergo degenerative lumbar spine surgery, mentioning perioperative pain interventions. 75 articles were included for review. Data on study characteristics, outcome domains and measurement instruments were extracted and structured using the three-tiered hierarchy of Porter. FINDINGS: 12 outcome domains were identified: pain intensity (93.3%), adverse events (76%), analgesic consumption (70.7%), length of stay (52%), patient satisfaction (24%), daily functioning (22.7%), (early) mobilization (22.7%), quality of life (12%), mortality (9.3%), quality of recovery (6.7%), physical function (4%), and quality of sleep (2.7%). 63 corresponding measurement instruments were found. CONCLUSIONS: This review portrays an extensive overview of outcome measurements used in perioperative pain management in lumbar spine surgery. A lack of consensus on the set of indicators exists. This scoping review is a call for action to create consensus on how to evaluate perioperative pain interventions in degenerative lumbar spine surgery.

Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma.

BACKGROUND: Persistent eosinophilic airway inflammation is an important driver for asthma exacerbations in non-smokers with asthma. Whether eosinophilic inflammation is also a predictor of asthma exacerbations in (ex)smokers is not known. OBJECTIVE: The aim was to investigate factors associated with frequent exacerbations in never smokers and (ex)smokers with asthma. METHODS: (Ex)smoking (n = 83) and never smoking (n = 70) patients with uncontrolled asthma despite high dose asthma medication (GINA treatment step 4-5) were selected from a cohort of 571 adult-onset asthma patients. Clinical, functional and inflammatory parameters were used in multivariate logistic regression analyses to identify factors associated with frequent exacerbations (≥3 oral corticosteroid (OCS) bursts in the previous year). RESULTS: Frequent exacerbations in (ex)smokers were independently associated with ICS dose (OR 1.2, 95%CI: 1.1-1.3) and blood neutrophil count (OR 1.5, 95%CI: 1.2-2.1). In never smokers frequent exacerbations were independently associated with blood eosinophil count (OR 18.9, 95%CI: 1.8-202.1). CONCLUSION AND CLINICAL RELEVANCE: This study shows that never smoking and (ex)smoking patients with severe asthma have different predictors of frequent exacerbations: higher blood neutrophils in (ex)smokers versus higher blood eosinophils in never smokers. This suggests that different types of systemic background inflammation play a role in the aetiology of exacerbations in these patients. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2217, NTR1846 and NTR1838.

Clinical profile of patients with adult-onset eosinophilic asthma.

Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L-1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L-1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7-8.1), 3.0 (95% CI 1.1-8.1) and 2.4 (95% CI 1.3-4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

Management of the patient with eosinophilic asthma: a new era begins.

Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion), typical lung function abnormalities ("fixed" airflow obstruction, reduced forced vital capacity and increased residual volume), typical comorbidities (nasal polyposis) and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.