Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD). OBJECTIVE: We aimed to assess the overall efficacy and safety of dupilumab treatment in AD. METHODS: PubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively). RESULTS: Six trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04). CONCLUSIONS: Our analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.

Anti-interleukin 5 Therapy for Eosinophilic Asthma: a Meta-analysis of Randomized Clinical Trials.

Recently, more and more clinical trials have been performed to evaluate the effects of anti-interleukin (IL)-5 antibodies in eosinophilic asthma. However, a confirm conclusion has not been well established. We therefore sought to conduct a meta-analysis to assess the overall efficacy and safety of anti-interleukin 5 treatments in eosinophilic asthma. RCTs of anti-interleukin 5 treatments in eosinophilic asthma published up to June 2016 in PubMed, Embase, Cochrane library databases, and CBM, which reported pulmonary functions, quality-of-life scores, asthmatic exacerbations, and adverse events were included. Fixed-effect models were used to calculate mean difference, relative risks (RR), and 95 % CIs. Twelve studies involving 3340 patients were identified. Pooled analysis revealed significant improvements in FEV1 (nine trials, 1935 subjects; MD = 0.12; 95 % CI, 0.08-0.16), and Asthma Quality-of-Life Questionnaire scores (five trials, 1334 subjects; MD = 0.23; 95 % CI, 0.13-0.34). Anti-interleukin 5 treatment was also associated with significantly decreased exacerbation risk than placebo (six trials, 875 subjects; RR = 0.52; 95 % CI, 0.46 to 0.59) and a lower incidence of adverse events (eight trials, 1754 subjects; RR = 0.93; 95 % CI, 0.89 to 0.97). Anti-interleukin 5 treatment is well tolerated and could significantly improve FEV1, quality of life, and reduced exacerbations risk in patients with eosinophilic asthma. Further trials are necessary to assess the baseline blood eosinophil count to identify the optimal patients of eosinophilic asthma that could benefit from anti-interleukin 5 therapy.

Role of Neutrophil Extracellular Traps in Asthma and Chronic Obstructive Pulmonary Disease.

OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases. DATA SOURCES: Articles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of "asthma" or "pulmonary disease, chronic obstructive", "neutrophils" and "extracellular traps." STUDY SELECTION: Articles were obtained and reviewed to analyze the role of NETs in asthma and COPD. RESULTS: NETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease. CONCLUSIONS: Excessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

Efficacy and Safety of Anti-Interleukin-5 Therapy in Patients with Asthma: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent trials have assessed the efficacy and safety of novel monoclonal antibodies such as reslizumab and benralizumab. However, the overall efficacy and safety anti-interleukin (IL) 5 treatment in asthma have not been thoroughly assessed. METHODS: Randomized controlled trials (RCTs) of anti-IL-5 treatment on patients with asthma published up to October 2016 in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) that reported pulmonary function, quality of life scores, asthmatic exacerbation rate, blood and sputum eosinophil counts, short-acting ß-agonist (SABA) rescue use, and adverse events were included. The pooled mean difference, and relative risks (RR), and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Twenty studies involving 7100 patients were identified. Pooled analysis revealed significant improvements in FEV1 (first second forced expiratory volume) (MD = 0.09, 95% CI: 0.06-0.12, I2 = 10%), FEV1% (MD = 3.75, 95% CI: 1.66-5.83, I2 = 19%), Asthma Quality of Life Questionnaire (AQLQ) score (MD = 0.22, 95% CI: 0.15-0.30, I2 = 0%), decreased blood, sputum eosinophils and asthmatic exacerbation (RR = 0.66, 95% CI: 0.59-0.73, I2 = 51%); peak expiratory flow (PEF) (MD = 5.45, 95% CI: -2.83-13.72, I2 = 0%), histamine PC20 (MD = -0.62, 95% CI: -1.92-0.68, I2 = 0%) or SABA rescue use (MD = -0.11, 95% CI: -0.3-0.07, I2 = 30%) were unaffected; adverse events were not increased (RR = 0.93, 95% CI: 0.89-0.98, I2 = 46%). No publication bias was observed (Egger's P = 0.78). CONCLUSIONS: Anti-interleukin 5 monoclonal therapies for asthma could be safe for slightly improving FEV1 (or FEV1% of predicted value), quality of life, and reducing exacerbations risk and blood and sputum eosinophils, but have no significant effect on PEF, histamine PC20, and SABA rescue use. Further trials required to establish to clarify the optimal antibody for different patients.

Biomarkers of in vivo fluorescence imaging in allergic airway inflammation.

Airway inflammation is a central component of the manifestation of asthma but is relatively inaccessible to study. Current imaging techniques such as X-ray CT, MRI, and PET, have advanced noninvasive research on pulmonary diseases. However, these techniques mainly facilitate the anatomical or structural assessment of the diseased lung and/or typically use radioactive agents. In vivo fluorescence imaging is a novel method for noninvasive, real-time, and specific monitoring of lung airway inflammation, which is particularly important to gain a further understanding asthma. Compared to conventional techniques, fluorescent imaging has the advantages of rapid feedback, as well as high sensitivity and resolution. Recently, there has been an increase in the identification of biomarkers, including matrix metalloproteinases, cathepsins, selectins, folate receptor-beta, nanoparticles, as well as sialic acid-binding immunoglobulin-like lectin-F to assess the level of airway inflammation in asthma. Recent advances in our understanding of these biomarkers as molecular probes for in vivo imaging are discussed in this review.