From sweltering hot summer days to frigid winter nights, many people can experience exacerbations in respiratory symptoms of asthma, allergic rhinitis, or viral infection. The incidence of extreme temperature conditions has been increasing for decades, exposing human upper airways to high vapor pressure deficit (VPD), also known as, "air dryness". Researchers are now reporting how breathing in these dehydrating atmosphere could promote airway inflammation leading to disease-causing effects on the lungs.
Published in Nature Communications Earth & Environment, research reveals how decreased humidity associated with global warming could exacerbate respiratory diseases by dehydrating and inflaming human airways, potentially worsening conditions like asthma and chronic obstructive pulmonary disease (COPD). This cross-institutional study, spearheaded by David A. Edwards, MD, at John Hopkins, includes UNC School of Medicine's Marsico Lung Institute members: Brian Button, PhD, professor of Biochemistry and Biophysics, as senior author, and Alessandra Livraghi-Butrico, PhD, associate professor in the Department of Medicine at the UNC School of Medicine as co-author. It also includes research conducted by: Justin Hanes, PhD, of Johns Hopkins; Kian Fan Chung, MD, of Imperial College London; Britt Burton Freeman, PhD, and Indika Endirisinghe, PhD, of Illinois Institute of Technology.
This research seeks to understand how our airways are designed to deal with breathing dry air and the effects of long-term dehydration associated with global warming. It also delves into how dehydration and inflammation can be exacerbated by mouth breathing, whose incidence is on the rise, and increased exposure to air-conditioned and heated indoor air.
As global temperatures climb due to climate change, the atmosphere's capacity to hold water vapor increases, driving a rise in VPD - a measure of air dryness that quantifies the difference between saturated and actual water vapor pressure. This shift, already evident over the past century, is amplifying water evaporation from ecosystems worldwide, with profound effects on both plant and human life. High VPD, exacerbated by extreme weather events, is becoming more frequent, particularly in urban and rural areas of the United States, where summer conditions are projected to push VPD high enough to be unable to saturate the air with water by 2060-2099, according to climate models.
This study introduces a novel mechanism to explain how increased VPD can affect airway epithelial cells. Researchers observed how airway mucus, a dilute hydrogel composed of salts, globular proteins, and mucin macromolecules secreted by the airway epithelia, undergoes transpiration - a water loss process similar to the one occurring when water evaporates over the surface of leaves. In plants, high VPD drives evaporation through a hydrogel-like leaf membrane, eventually causing compression of cells as it pulls water from the roots, leading the leaves to wilt.
Similarly, under conditions like rapid mouth breathing of low-humidity air, high VPD evaporates water from the mucus layer lining the airways, concentrating mucins near the surface to form a denser gel. This process, modeled using continuum mathematics by Drs. Edwards and Chung, thins the mucus and compresses epithelial cells - a stimulus sufficient to trigger inflammation -
Experimental evidence from donor human bronchial epithelial (HBE) cell cultures and a mouse model demonstrates that low-humidity environments-simulating the rising vapor pressure deficit (VPD) driven by climate change-cause airway mucus to thin and trigger inflammation. In Dr. Button's experiments, HBE cells exposed to dry air (with a high VPD) had thinner, more concentrated mucus, which is harder to clear out of the airways. Moreover, studies in collaboration with Drs. Freeman and Endirisinghe, indicated that these cells secrete high levels of cytokines, which are a marker of airway inflammation. These results agree with theoretical predictions that mucus thinning occurs in dry air environments and can produce enough cellular compression to trigger inflammation.
"This isn't just a lab experiment - it's a glimpse into how breathing hotter and drier air can result in more asthma flare-ups, worse allergies, and tougher breathing for millions of individuals," said Button. "It's a public health red flag we can't ignore."
The mucus transpiration hypothesis raises the possibility that global warming, together with the growing prevalence of chronic mouth breathing in the human population due to obesity, allergic rhinitis and aging, will soon represent a global threat to human respiratory health. Excessive mucus transpiration could exacerbate conditions at other mucosal surfaces including the eyes, as the ocular mucus lining can also be disrupted due to the lack of humidification.
"This research underscores the urgent need to address airway hydration as a public health priority, suggesting that without intervention, millions could face heightened risks of chronic respiratory diseases by century's end, while opening doors to new protective measures like enhanced humidity control or targeted therapies," said Button.
The team also confirmed that inflammatory mucus transpiration occurs during normal, relaxed breathing (also called tidal breathing) in an animal model of muco-inflammatory lung disease. Alessandra Livraghi-Butrico found that when mice with defective airway mucus clearance were exposed to intermittent dry air they exhibited increased lung inflammation as compared to the same type of mice exposed to standard room air. These in vivo findings pinpoint airway dehydration as a critical mechanism linking climate change to worsening lung health in susceptible individuals.
"This is the tip of the iceberg," said Livraghi-Butrico. "In our line of research we cannot change the trajectory of climate change. However, we can work on effective measures to prevent the exacerbations that these changes are causing. That's where our job gets the most rewarding, when our research can contribute to people living healthier lives, and in this case, breathe better."
A portion of this research was funded by NIH grants R01HL125280, P01HL164320, and P30DK065988.
