Clinical efficacy and compliance of dupilumab therapy in adolescent and adult patients with atopic dermatitis in real clinical practice: An analysis of data from a single allergy clinic in Korea

Purpose@#Dupilumab (a monoclonal antibody to interleukin-4 receptor alpha) is the first biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD). We evaluated the clinical efficacy and compliance of dupilumab therapy for AD in real clinical practice. @*Methods@#Medical records of 132 adolescent and adult patients with AD who received at least one dose of dupilumab were retrospectively analyzed. Clinical efficacy of dupilumab was assessed by either changes in eczema area and severity index (EASI) or changes in the requirement of medications from baseline to weeks 16 and 42. Clinical response was determined by the proportion of patients with decreased EASI scores of at least 75% from baseline at week 16 (EASI–75). Clinical remission was defined as a complete withdrawal of all the medications for AD except dupilumab. @*Results@#Dupilumab was administered for 16 weeks (77.3%) and 42 weeks (63.6%) in 132 patients with AD. In patients who received reimbursement from National Healthcare Insurance of Korea (NHIK) for dupilumab therapy, the compliance of dupilumab therapy was 90.2% and 87.8%, and EASI–75 response rate was 92.5% and 100% at weeks 16 and 42, respectively. In patients who received the dupilumab therapy without NHIK reimbursement (self-payment), the compliance of dupilumab therapy was 71.4% and 52.7%, the clinical remission rate was 44.0% and 64.6%, and the median interval of dupilumab therapy was 4 weeks (range, 2–13 weeks) and 5 weeks (2–15 weeks) at weeks 16 and 42, respectively. @*Conclusion@#Dupilumab therapy may be clinically useful in the aspects of efficacy and compliance in patients with AD.

Management of allergic patients during severe acute respiratory syndrome coronavirus-2 pandemic

A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in China. The mutated coronavirus spread worldwide, and some patients infected with SARS-CoV-2 developed coronavirus disease 2019 (COVID-19) manifested with upper respiratory infection, pneumonia, or respiratory distress. Since the SARS-CoV-2 pandemic was declared with surging confirmed cases and mortality of COVID-19 worldwide, it has reshaped our way of living and how to manage patients with allergic diseases. The medical staff, including allergy specialists, has been at the forefront of fighting against the SARSCoV-2 pandemic and is struggling to guarantee safety to themselves and their patients. Thanks to vigorous research into the relationship between SARS-CoV-2 and allergic diseases, we have become able to treat allergic patients with the best of evidence to date. The clinician should make a careful decision on each clinical situation with regard to patient characteristics, local and national circumstances as well as the knowledge we have, since it is still limited. We hope further efforts to identify the nature of SARS-CoV-2 and COVID-19 clearer and effective SARS-CoV-2 vaccination will soon remove the grim picture of the worldwide pandemic and bring us back to normal.

Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

A Prospective Observation of Psychological Distress in Patients With Anaphylaxis

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics

PURPOSE: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. METHODS: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. RESULTS: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. CONCLUSIONS: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.

Which Factors Associated With Activated Eosinophils Contribute to the Pathogenesis of Aspirin-Exacerbated Respiratory Disease?

Eosinophils have long been recognized as a central effector cell in the lungs of asthmatic patients. They contribute to airway inflammation and remodeling through releasing several molecules such as cytokines, granule proteins, lipid mediators and extracellular traps/vesicles. Repeated evidence reveals that intense eosinophil infiltration in upper and lower airway mucosae contributes to the pathogenesis of aspirin-exacerbated respiratory disease (AERD). Persistent eosinophilia is found to be associated with type 2 immune responses, cysteinyl leukotriene overproduction and eosinophil-epithelium interactions. This review highlights recent findings about key mechanisms of eosinophil activation in the airway inflammation of AERD. In addition, current biologics (targeting type 2 immune responses) were suggested to control eosinophilic inflammation for AERD patients.

DNA damage to human genetic disorders with neurodevelopmental defects

Although some mutations are beneficial and are the driving force behind evolution, it is important to maintain DNA integrity and stability because it contains genetic information. However, in the oxygen-rich environment we live in, the DNA molecule is under constant threat from endogenous or exogenous insults. DNA damage could trigger the DNA damage response (DDR), which involves DNA repair, the regulation of cell cycle checkpoints, and the induction of programmed cell death or senescence. Dysregulation of these physiological responses to DNA damage causes developmental defects, neurological defects, premature aging, infertility, immune system defects, and tumors in humans. Some human syndromes are characterized by unique neurological phenotypes including microcephaly, mental retardation, ataxia, neurodegeneration, and neuropathy, suggesting a direct link between genomic instability resulting from defective DDR and neuropathology. In this review, rare human genetic disorders related to abnormal DDR and damage repair with neural defects will be discussed.