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The harm to human health from outdoor air pollution has been a worldwide concern for decades. Much less addressed, for a myriad of reasons, is the impact of poor indoor air quality (IAQ) on occupant health. COVID-19 increased our awareness of the importance of controlling indoor exposure to infectious viral bioaerosols and new recommendations and standards were quickly developed, for example ASHRAE Standard 241. While we have made progress in managing buildings when a clearly harmful airborne exposure event occurs, there is still significant debate on how to quantify and manage the everyday impact of IAQ on health. This column will not include IAQ and infectious microbes or alterations in our microbiome – that discussion will be my next column.

The first step in figuring out what to monitor indoors is to be clear about why we are measuring IAQ in the first place. If the goal is to manage HVAC systems to save energy, then monitoring ventilation rates (with the hope that outdoor air quality is okay) is enough. For buildings that are sheltering materials such as wood, paper, or food rather than people, controlling temperature and humidity might be adequate. 

To truly manage IAQ to support occupant health, however, we must monitor indoor metrics broadly and continuously to understand what contaminants are present and their sources. Next, to improve IAQ, outdoor air should also be measured in order to take effective steps to remediate the indoor contaminants. While this may sound straightforward, there are numerous and differing opinions about the number of indoor air metrics that should be monitored and managed to maintain health-supporting IAQ. Is controlling temperature, humidity, and odors to keep occupants comfortable adequate? Do carbon dioxide levels effectively represent occupancy and therefore can be used for ventilation setpoints? 

People cannot perceive all indoor air conditions and contaminants that are harmful to their physiology, so comfort surveys are inadequate for assessing IAQ. Rather, a range of indoor constituents that impact human physiology in the short-term and long-term must be measured and managed. 

To better understand the indoor air contaminants that we need to monitor to protect occupants, the health consequences of inhaled particles and gases will be discussed below. How do airborne gases and particles penetrate our tissues, and what happens once they are inside? How does exposure to multipollutants differ from individual contaminants? What differences do temperature and humidity make?  

Inhalation is the primary exposure route:   

To live means that we are obligated to breathe, no questions asked! Adults inhale approximately 10,000 Liters of air/day (12 to 14 breaths/minute with an average volume of 500mL/breath) making indoor air our most prevalent social media. In addition to the atmospheric gases essential for life, infectious and noninfectious particles, chemical aerosols, and contaminant gases also enter the nose and respiratory tract with each breath. Our lungs, both a target organ and a route of entry to the rest of our body, have the greatest exposure to airborne gases, particles and water vapor with a surface area on average over 25 times larger than the skin. Inhaled contaminants can also adhere to receptors in the nose and be transported more directly to the brain through chemical signals.  

There are generally three ways inhaled particles and gases affect our physiology: 1) directly influencing human cell membranes, cytoplasmic organelles, genetics, etc.; 2) triggering immune reactions such as inflammation, immune-suppression, auto-immunity, allergic reactions, etc. and; 3) altering the microbes that live within and on our bodies, known as our microbiome, causing dysbiosis related disorders. 

Let’s explore the chemical and structural properties of airborne contaminants that determine how they get penetrate our tissues and the down-stream pathways of harm.

The fate of inhaled particles:

Inhaled particulate matter (PM) from environmental, human-activity, and combustion are deposited within our nose and respiratory tract deposition according to the physics of sedimentation, impaction, diffusion, interception, and electrostatic precipitation. Larger particles, PM>10 microns in diameter, settle according to gravity and the velocity of the moving air. Mid-range particles tend to be deposited on airway branch points where the greatest impaction occurs. Tiny, submicron particles with diameters < 0.5 μm are deposited according to random Brownian motion in the airways and diffusion through cell membranes to reach the blood stream. Once in the circulatory system, their health impact can go further based on their reactivity with tissues and enzymes.

Particles of all sizes may be captured and neutralized by immune cells. This, however, may not be the end of particle-related harm! The very process of immune cell destruction can result in inflammation and the generation of reactive oxidant species (ROS). Increased formation of ROS disrupts the balance between anti- and pro-oxidant mechanisms, leading to ongoing cell death.  [See Figure 1]

Figure 1.

Figure 1: Generation of inflammatory reactive oxygen species (ROS) by inhaled PM interacting with host cells and immune defenses. Adapted, with permission, Manzano-Covarrubias, Ana L. et al. Trends in Pharmacological Sciences, Volume 44, 2023.


The fate of inhaled gases:

Inhaled gases vary in their chemical and physical properties which dictate their uptake, reactions with upper airway or lung tissues, and potential absorption into blood. Two properties, water solubility and chemical reactivity, largely determine these steps and therefore their health impact. 

  • Solubility:

    • The interactions between a water-soluble gas and respiratory tract tissue is shown in Figure 2. Water-soluble gases readily dissolve in the watery, mucus lining of the upper respiratory tract. After dissolving in the aqueous mucus, gas molecules can diffuse into the underlying epithelial cells and potentially into the underlying blood capillaries and transport through the circulation to other tissues.
    • For example, a highly water-soluble gas, such as sulfur dioxide (SO2), dissolves in upper airway nasal and throat mucus, causing local irritation to underlying tissues as the gas is neutralized. In comparison, a less water-soluble gas but one with high reactivity, such as ozone (O3), will not dissolve in upper airway mucus and can harm fragile tissue in deeper layers of the lungs.
    • Some water-insoluble gases have high affinity for non-polar cell membranes and diffuse directly into cells lining the airways to then penetrate into underlying blood capillaries. More often, however, these insoluble molecules are blocked by the aqueous mucus layer and move into the deeper portions of the respiratory tract, and into the blood stream.  
  • Figure 2.

    Figure 2: Respiratory tract showing air, aqueous mucus and underlying epithelial cells. Water soluble molecules dissolve into the mucus and tissues, whereas insoluble molecules stay in the airways to travel into deeper lung layers. Reproduced from Centers for Health Research. through Generation of reactive oxygen species (ROS) by ihaled PM due to cellular interactions both before and after encountering immune cell defenses. Adapted, with permission, from Madl AK, et al., 2014 (84).


  • Reactivity:

    • The second important determinant for the fate of an inhaled gas in respiratory tissues and deeper penetration is chemical reactivity. See Figure 3. Reactive gases are neutralized though their interactions with components of the tissue, rapidly creating a concentration gradient away from deeper tissues. In fact, some gases react so rapidly that very little ever reaches the blood. In contrast, an inert gas does not react with respiratory tract tissues or fluids and ultimately diffuses through cell layers to eventually reach the blood. In turn, the blood carries these inert gases to other parts of the body where they may be quite toxic.
  • Figure 3.

    Figure 3: Respiratory tract showing air, aqueous mucus, epithelial cells, and the blood stream. Gas molecules flow from high to low concentrations. Removal by the blood results in a continual gradient leading harmful molecules into lung tissue. Reproduced from National Academy Press, “Air Pollution, Automobiles and Public Health."

  • Thermal:

    • The final metrics that we need to consider are temperature and humidity. High temperatures result in not only thermal discomfort, but also in decreased relative humidity causing drying of mucus membranes and impaired immune functioning. Additional harm from elevated temperatures and low humidity are increased resuspension of particles and higher levels of particle production from ozone reacting with unsaturated VOCs.

How much do these reactions and sites of deposition in our bodies really matter? A lot! Indoor air pollutants can impact people across their entire lifespan. Through the mechanisms discussed above, ozone, sulfur dioxide, nitrogen oxides, PM, and VOCs disrupt hormones, cause oxidative stress and inflammation, alter DNA and genes, damaging multiple organs to result in acute and chronic health problems and reduced overall life expectancy. The next generation is affected as well. Air contaminants are associated with decreased sperm production in men and hormone disruption in women, causing prolonged length of time to achieve pregnancy and delivery of lower birthweight babies 

Managing IAQ for health requires continuous and comprehensive monitoring to understand and mitigate harm to human physiology. Even for those who prefer to focus on outdoor pollutants, exposure and subsequent harm to humans are likely to happen indoors.