Global warming and implications for epithelial barrier disruption and respiratory and dermatologic allergic diseases

Abstract

Global warming has direct and indirect effects, as well as short- and long-term impacts on the respiratory and skin barriers. Extreme temperature directly affects the airway epithelial barrier by disrupting the structural proteins and by triggering airway inflammation and hyperreactivity. It enhances tidal volume and respiratory rate by affecting the thermoregulatory system, causing specific airway resistance and reflex bronchoconstriction via activation of bronchopulmonary vagal C fibers and upregulation of transient receptor potential vanilloid (TRPV) 1 and TRPV4. Heat shock proteins are activated under heat stress and contribute to both epithelial barrier dysfunction and airway inflammation. Accordingly, the frequency and severity of allergic rhinitis and asthma have been increasing. Heat activates TRPV3 in keratinocytes, causing the secretion of inflammatory mediators and eventually pruritus. Exposure to air pollutants alters the expression of genes that control skin barrier integrity and triggers an immune response, increasing the incidence and prevalence of atopic dermatitis. There is evidence that extreme temperature, heavy rains and floods, air pollution, and wildfires increase atopic dermatitis flares. In this narrative review, focused on the last 3 years of literature, we explore the effects of global warming on respiratory and skin barrier and their clinical consequences.

Keywords: Climate change; allergic diseases; allergic rhinitis; asthma; atopic dermatitis; epithelial barrier; extreme temperature; global warming; pollution.

FIG 1.

Healthy and impaired respiratory epithelial barrier. Adjacent pseudostratified columnar ciliated airway cells are interconnected by TJ, adherens junctions, and desmosomes. Respiratory epithelium sits on basal membrane, attached to lamina propria. Neuronal TRPs are expressed in epithelial cells and regulate permeability of barriers. When disrupted by increased temperature, airborne allergens, and pollution, TJ proteins such as zonula occludens–associated occludin, claudin, and JAM are disrupted and epithelial junctions open. TRPV1 and TRPV4 are upregulated; HSP-70, HSP-90, and HSP-72 are increased, and ROS are formed. All these cause increased inflammation, increased paracellular permeability, increased mucus, reduced ciliary movement, damaged cilia, and epithelial shedding. JAM, Junctional adhesion molecules; ROS, reactive oxygen species.

FIG 2.

Direct and indirect effects of extreme heat on upper and lower respiratory epithelial barrier. Results are summarized of cell culture, animal models, and human studies; levels of evidence are indicated in text. HDM, House dust mite; ROS, reactive oxygen species; RR, respiratory rate; SIR, systemic inflammatory response; TRAP, traffic-related air pollution; TV, tidal volume.

FIG 3.

Hypothesized effects of heat and particulate matter on skin barrier structure. Skin is composed of epidermis and dermis; layers and components of these layers are labeled. Heat activates TRPV3 in keratinocytes, increasing TSLP, NGF, and PGE₂. (TRPV3 expression and function is increased in AD.) PM has several hypothesized effects in AD: (1) decreases expression of stratum corneum and TJ-related proteins, (2) induces expression of AKR1C3 (AKR1C3 variant is overexpressed in AD), (3) leads to differential expression of genes controlling skin barrier integrity and immune response, increasing skin inflammation, and (4) results in increased epidermal and dermal thickness and increased dermal inflammation. NGF, Nerve growth factor; PGE₂, prostaglandin E₂; TSLP, thymic stromal lymphopoietin.