Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. RESEARCH QUESTION: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? STUDY DESIGN AND METHODS: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment. RESULTS: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy.

Allergy Development in Adulthood: An Occupational Cohort Study of the Manufacturing of Industrial Enzymes.

BACKGROUND: Occupational allergy may serve as a model of allergy development in adults. OBJECTIVE: We aimed at describing respiratory allergy and IgE sensitization across different exposure strata defined by time, technology, and exposure control. METHODS: In a retrospective (1970-2017) cohort of industrial enzyme production employees, monitored by an occupational medical center, 5024 individuals were surveyed. Five exposure groups and risk levels for sensitization and allergic disease were analyzed on the basis of demographic characteristics, hiring decade, and smoking status. RESULTS: Of all persons entering the company 47 years from 1970, 149 developed occupational allergy (incidence rate, 2.72/1000 person-years). In a multivariate cause-specific Cox proportional hazards model, the hazard of allergy was significantly related to decade of recruitment. Compared with the 1970s, the hazard ratio (HR) uniformly decreased from 0.85 (95% CI, 0.57-1.27) in the 1980s to 0.16 (95% CI, 0.05-0.52) in the 2010s. Compared with expected highest exposed group, the HRs were 0.48 (95% CI, 0.31-76) and 0.13 (95% CI, 0.06-0.30) in less exposed production areas and 0.92 (95% CI, 0.48-1.73) and 0.23 (95% CI, 0.10-0.53) in different laboratory areas. The HR of smoking was 2.03 (95% CI, 1.41-2.93). The pattern of sensitizations also showed clear associations to recruitment decade, exposure, and smoking. Among individuals sensitized but not yet allergic, a high IgE level was the only risk factor (HR, 3.03; 95% CI, 1.82-5.04) for subsequent allergy development. CONCLUSIONS: The impact of exposure is dose-related and linked to the sensitization step, which may subsequently lead to allergy development. For primary prevention of enzyme allergy, exposure control is mandatory and achievable despite increasing production volumes.

Incidence of skin and respiratory diseases among Danish hairdressing apprentices.

BACKGROUND: Hairdressing is one of the professions with the highest risk of occupational skin and respiratory diseases. The incidence of these diseases in hairdressing apprentices has been studied only sparsely. OBJECTIVE: To determine the incidence of skin and respiratory diseases in hairdressing apprentices, and to explore whether hairdressing apprentices leave the trade during training because of these diseases. METHODS: A 3-year follow-up questionnaire study was conducted among 248 hairdressing apprentices and a control group comprising 816 young adults from the general population. RESULTS: The incidence rate ratios (IRRs) for contact urticaria (IRR 4.7, 95%CI: 2.6-8.6), hand eczema (IRR 1.7, 95%CI: 1.1-2.6) and rhinitis symptoms (IRR 1.6, 95%CI: 1.2-2.2) were significantly increased in the hairdressing apprentices, whereas wheezing was similar between groups. During the follow-up period, 21.8% of the hairdressing apprentices had left the trade, and 70.3% of these had left because of health complaints. The most frequently reported reasons for leaving were musculoskeletal pain (47.4%) and skin diseases (47.4%), followed by respiratory symptoms (23.7%). CONCLUSIONS: Hairdressing apprentices are at increased risk for contact urticaria, hand eczema and rhinitis symptoms compared with the general population, and a substantial proportion leave the trade because of these diseases, causing a 'healthy worker survivor effect.'

High occurrence of rhinitis symptoms in hairdressing apprentices.

BACKGROUND: Little is known about the occurrence of respiratory symptoms among hairdressing apprentices during their training. Therefore, in this study, we examined whether hairdressing apprentices are at increased risk of rhinitis and asthma symptoms when compared with other young adults from the general population. METHODS: A questionnaire was completed by 504 hairdressing apprentices and 1400 control participants from the general population with a similar age, gender, and geographic distribution. RESULTS: The 1-year prevalence of rhinitis symptoms was higher in hairdressing apprentices than in controls (58.1% vs 46.6%; odds ratio, 1.59; 95% confidence interval, 1.30-1.98), and the prevalence was higher among hairdressing apprentices in the last years of training compared with apprentices in the first year of training (62.4% vs 41.8%, p = 0.003). Current smoking was more common in hairdressing apprentices (28.4% vs 17.2%, p < 0.001). Asthma symptoms were equally common in the 2 groups; however, hairdressing apprentices had a later age of onset of wheezing than did the controls (18 years vs 14 years, p < 0.00001) and a decreased risk of wheezing (odds ratio, 0.72; 95% confidence interval, 0.54 to 0.95) after adjusting for smoking, education level, and degree of rurality. Bleaching products were the most frequently reported cause of rhinitis and asthma symptoms in hairdressing apprentices. CONCLUSIONS: Hairdressing apprentices seem to have an increased risk of occupational rhinitis, and bleaching products are the main cause of respiratory symptoms. In addition, our findings suggest that a healthy worker effect exists in relation to asthma among hairdressing apprentices.

Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark.

Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT.

Human leukocyte antigen-G and regulatory T cells during specific immunotherapy for pollen allergy.

BACKGROUND: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). METHODS: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. RESULTS: During SIT, the main changes in the peripheral blood were an increase in CXCR3(+)CD4(+)CD25(+)CD127(low/-) Tregs and a decrease in CCR4(+)CD4(+)CD25(+)CD127(low/-) Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4(+)CD25(+)CD127(low/-) Tregs and ILT2(+)CD4(+)CD25(+)CD127(low/-) Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. CONCLUSIONS: The changes in CXCR3(+)CD4(+)CD25(+)CD127(low/-) Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2(+) Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.

The impact of light source on discrimination ability in subjects with age-related macular degeneration.

PURPOSE: To examine the influence of light source on letter contrast sensitivity in subjects with age-related macular degeneration (AMD). METHODS: Halogen incandescent bulbs and low-energy fluorescent tubes were tested with 70 subjects with AMD. The subjects' contrast sensitivity was determined in a randomized single-blind crossover study for each light source using photopically illuminated Pelli Robson contrast sensitivity charts. The test subjects' subjective light source preference was also determined. RESULTS: The mean contrast sensitivity for the incandescent light source was 1.28 ± 0.29 (mean ± SD), and for the fluorescent light source 1.17 ± 0.29, p < 0.001. The illuminance was 338 lux (± 9) for the incandescent light, and 339 lux (± 11) for the fluorescent light. Forty-nine subjects preferred the incandescent light source, while none preferred the fluorescent light source for maximum detail and clarity. Nineteen had no preference. This finding is statistically significant. Fifteen of the 19 subjects without a preference had no difference in contrast sensitivity, which supports their lack of preference. There was no significant difference with regard to sex or order of exposure to light source. Subjects with AMD had significantly reduced contrast sensitivity compared with expected normal values. We found no relationship between visual acuity and contrast sensitivity. CONCLUSION: We are only able to recommend photopic full spectral radiance incandescent light sources to visually impaired subjects for their domestic surroundings. Furthermore, we recommend the use of full spectral radiance light sources for the illumination of Pelli-Robson contrast sensitivity charts. Given equal illuminance, as in our study, the findings show that contrast sensitivity was better by illumination with incandescent light with full spectral radiance compared with fluorescent light with interrupted spectral radiance.