Association Between Short-Term Exposure to Environmental Air Pollution and Atopic Dermatitis Flare in Patients Treated With Dupilumab

This study sought to explore the association of short to medium-term exposure to airborne pollution on atopic dermatitis (AD) flares in patients who are treated with dupilumab.

Patients with moderate-to-severe AD in treatment with dupilumab were identified in the electronic medical records of the Dermatology Unit of the University Hospital of Verona, Italy between December 2018 and December 2021. Inclusion criteria included patients having ≥3 consecutive measurements of Eczema Area and Severity Index (EASI) at 3-month intervals, patients with residency within 10 km from the air pollutants collection and patients with at least 1 disease flare defined as the highest EASI score ≥7 between 2 dermatological visits separated by a timeframe of 3 months. Data were obtained on 169 of 528 patients with AD that met criteria and had 1130 follow-up visits and 5840 air pollutant concentration measurements. Mean age of participants was 41.4±20.3 years. Patients on other immunomodulators, other AD biologics, and phototherapy were excluded.

This study used an observational case-crossover analysis design. The exposure of interest is compared at different time periods in the same patient group, and patients served as their own controls. Patients with moderate-to-severe AD on treatment with dupilumab were included. The exposure of interest was the mean concentrations of coarse and fine particulate matter (PM 10, PM 2.5), nitrogen dioxide (No₂), and oxides (No_x). AD flare was defined as the visit with the highest EASI score >and the control visit was defined as the visits with EASI ≤7. The variable of time was investigated by studying different intervals from 1 to 60 days before both the AD flare and control visit. A conditional logistic regression analysis adjusted for systemic treatments was used to estimate the incremental odds (%) of flare every 10 ug/m 3 pollutant concentration. Patients were visited every 3 months for a median follow-up of 5 visits, were exposed to a mean concentration of pm 10 30.64 ug/m 3, pm 2.5 20.45 ug/m 3, No_x 41.16 ug/m 3, and No 2 22.94 ug/m 3. The median EASI at flare was 18 and at control was 1. Mean and area under the curve air pollutant concentrations were higher during the 60 days before the flare compared with the control visits. Other baseline data and demographics collected were age, sex, disease duration, BMI, blood total levels of IgE, history of asthma, and history of rhino-conjunctivitis.

The incremental odds curve indicated a significant positive trend of AD flare for all pollutants in all time windows. At 60 days, every 10 ug/m 3 pm 10, PM 2.5, No_x, and No₂ increase concentration was associated with 82%, 67%, 28%, and 113% odds of AD flare respectively. In all considered time intervals, PM 10, PM 2.5, No_x, and No₂ exposures were associated with higher odds of AD flare. There was a significant positive trend of AD flare for all pollutants in all time windows.

For patients with moderate-to-severe AD treated with dupilumab, acute air pollution exposure is associated with an increased risk for AD flare in a dose-response manner. Environmental air pollutants may be considered triggers of AD, and they may explain AD flares that are not necessarily caused by loss of response to targeted drug treatments such as dupilumab.

This study acknowledged the gap in the literature and sought to explore the association of air pollutants and atopic dermatitis flares in patients who were specifically on biologics. The study, however, included only patients on dupilumab, and the study did not explain the rationale for choosing this specific biologic and not tralokinumab. The study was limited by its study population all being from the same city in Northeast Italy, which may make study results challenging to apply to other locations. Additionally, the study was limited by its lack of inclusion of patients with mild disease, of demographics such as socioeconomic status or smoking habits, and of the ability of patients to apply topical treatments. Future studies are warranted to further review the impact of air pollutants and atopic dermatitis flares in patients with mild to severe disease, on varying treatments from topicals to biologics, and with diverse backgrounds to better understand the significance of air pollutants on atopic dermatitis.