Temperature-controlled laminar airflow in adult atopic dermatitis patients - an observational study

Atopic dermatitis (AD) patients are commonly sensitized to house dust mites (HDM). The current consensus-based European guideline underlines the impact of allergens inducing AD flares and the importance of allergen reduction in AD patients.1, 2 With regard to preventive measures in patients with AD, the use of mattress encasings aiming to reduce skin contacts to mite allergens in bed may be considered in HDM-sensitized patients. Thus far, however, a successful approach to reducing indoor allergen aerogenic exposure is lacking. The technology of ‘nocturnal temperature-controlled laminar airflow’ (TLA) has been developed to reduce allergen exposure by filtering the surrounding atmosphere, particularly of the head-neck region, during sleep. While effects of the use of this technology in patients with allergic asthma were shown, AD in adults including in-vitro analyses has not been addressed yet.3-5 We conducted a three-month observational study investigating the effect of an add-on treatment with TLA in 10 HDM-IgE-sensitized patients with moderate-to-severe AD and a history of clinically relevant HDM allergy (see Fig. 1a). In an extension phase, patients were advised to use the device for additional 9 months to complete a whole year of application. The study was in accordance with the principles of the Declaration of Helsinki and good clinical practice guidelines and approved by the ethics committee of Hannover Medical School (No. 7231). After 3 months of intervention, Scoring Atopic Dermatitis (SCORAD) (41.96 ± 9.78 vs. 34.15 ± 9.69, P = 0.037), local eczema intensity (local SCORAD) of the head-neck region (8.0 ± 1.7 vs. 6.4 ± 2.5, P = 0.037), and Eczema Area Severity Index (EASI; 10.01 ± 3.94 vs 8.41 ± 3.76, P = 0.038) improved significantly (Fig. 1b,c). The physician global assessment (PGA: 0 = clear (100% improvement), 1 = almost clear (90%–99%), 2 = significant improvement (50%–89%), 3 = moderate improvement (<50%), 4 = no improvement, 5 = worsening) displayed an improvement in seven of ten patients (Fig. 1c). Patient-assessed Dermatology Life Quality Index (DLQI) (12.55 ± 4.78 vs. 7.45 ± 4.66, P = 0.001) and subjective SCORAD symptoms (8.58 ± 4.47 vs. 4.86 ± 4.01, P = 0.038), including sleeplessness (3.52 ± 2.86 vs. 1.37 ± 2.16, P = 0.038), were also significantly ameliorated (Fig. 1d). After 12 months, five of eight patients showed an improvement measured by PGA, four even with an improvement of over 50% (Fig. 1e). In order to investigate the concomitant cellular immune response, peripheral blood mononuclear cells (PBMC) were stimulated in vitro with HDM extract. Proliferative responses of total T cells (P = 0.002), CD4+ T cells (P < 0.001), skin-homing CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.037), measured by carboxyfluorescein succinimidyl ester (CFSE), were significantly decreased after 3 months of TLA usage (Fig. 2a). Furthermore, we investigated HDM-specific T helper cells, defined by upregulation of CD154 (CD40L) after HDM antigen stimulation.6 Parallel staining of surface marker antigens allowed subgrouping into the polarization subtypes Th1 (CXCR3+/CCR4−/CCR6−/CCR10−), Th2 (CXCR3−/CCR4+/CCR6−/CCR10−) and Th17 cells (CXCR3−/CCR4+/CCR6+/CCR10−).7 By this, HDM-specific Th1 (P = 0.014) and Th17 cells (P = 0.039) were detected in significantly reduced extent in the circulation after 12 months (Fig. 2b). At this time point, the effect regarding the proliferation of total T cells (P = 0.455), CD4+ T cells (P = 0.453), skin-homing CD4+ T cells (P = 0.391), and CD8+ T cells (P = 0.383) was less pronounced compared with the measurement after 3 months, and the differences did not reach significance (data not shown). Cytokines were measured at both time points in serum by multiplex bead-based immunoassays. IL-9, hypothesized to be involved in allergic inflammation,8 was significantly reduced after 12 months compared with baseline (P = 0.039; Fig. 2c). Together, the findings of this proof-of-concept study indicate improvement of disease severity in HDM-sensitized adult AD patients during the add-on treatment with a TLA device. In conclusion, this study is the first to suggest beneficial effects of TLA in HDM-sensitized adult AD patients regarding objective, subjective and in vitro parameters. Of note, our data are preliminary evidence and further randomized-controlled studies on the use of the TLA technology are needed to verify these promising data for adult AD patients, especially concerning better disease control and long-term effects. The patients in this manuscript have given written informed consent to the publication of their case details. Figure 1a was created with biorender.com. Dr. Traidl received consultancy fees from Leo Pharma, Lilly and La Roche-Posay outside the submitted work. Dr. Roesner reports grants and personal fees from Novartis outside the submitted work. Mrs Kienlin, Mrs Begemann and Dr. Schreiber have nothing to disclose. Dr. Werfel reports grants and personal fees from Novartis, personal fees from Sanofi-Regeneron, grants and personal fees from LEO, personal fees from Galderma, personal fees from Lilly, grants and personal fees from AbbVie, grants from Pfizer, outside the submitted work. Dr. Heratizadeh received personal fees from Leo Pharma, Novartis, Pierre Fabre, Sanofi-Genzyme, Beiersdorf, Hans Karrer, Nutricia, Meda, Lilly, as well as grants from Janssen outside the submitted work. TLA devices were provided for free by Airsonett® for the duration of the study.