Radon Toxicity

Etiology

Radon is a highly radioactive element initially discovered in 1899 by physicist Ernest Rutherford in England. Radon is not a chemically produced gas; it is naturally found in rock and soil as a decay product of uranium and radium. Radon is the most important source of ionizing radiation found in nature.[3] It is an inert gas and the heaviest known gas, known to be 9 times denser than air. It is made of a single atom and thus can easily penetrate many materials such as paper, leather, plastic, concrete, wood paneling, and insulation. Radon occurs naturally in several isotopic forms, but only 2 are found in high environmental concentrations: radon-220 and radon-222. Radon-220, also known as thoron, is formed in the decay process of thorium-232 and has a half-life of 55 seconds.

Radon-222 has a half-life of 3.8 days and is the most stable and common isotope of radon. It is the immediate decay product of radium-226 and is transient in the decay process of uranium-238. Due to the longer half-life of radon-222, it can diffuse from the environment into homes. Radon-222 itself does not pose a health risk, but its decay to Polonium 218 and 214 and emission of alpha particles have the potential to damage DNA.[1] These more chemically reactive radon progeny (also known as “radon daughters”) are the primary source of human exposure to alpha radiation, resulting in cellular injury and DNA damage in the respiratory tract. These changes in the respiratory epithelium can lead to radon-induced lung disease and, if prolonged, lung cancer.[4] 

Human exposure to radon occurs primarily through inhalation and ingestion. Given that radon exists in groundwater, soil, rock, and confined spaces such as buildings and basements, humans are susceptible to exposure from multiple sources, including the ground, gas appliances, water supply, or pressure-driven flow in the home. Since it is also present in natural gas, radon (and its progeny) can be released into the air when it is burned in furnaces, fireplaces, heaters, and stoves. The inhalation of radon poses the most significant health concern due to direct injury to respiratory epithelium.[5]

Epidemiology

Radon exposure is both an environmental and a health issue globally. Recent studies in 2012 have noted the highest levels of radon in Armenia, where it is estimated to have contributed to 29% to 30% of lung cancer cases. Japan had the lowest levels, with an estimated 4% of lung cancers attributed to radon. In the US, it is believed that 9% to 13% of lung cancer cases are caused by radon exposure. Historically, it was thought that radon exposure increases in regions where cold climate causes people to spend longer periods indoors. However, climate change and air conditioning have altered this pattern. High levels of radon exposure in a given region depend on the availability of radon in the environment and its ability to make its way into confined spaces/water sources, the ability of radon to concentrate in high levels, and the human behaviors that contribute to increased exposure for long periods.

Radon is present at varying levels across the United States. Some states have mandated radon-level disclosure upon the sale of a home. Appropriate levels vary from one state to another. However, it is notably higher in North Dakota and Iowa. The United States Environmental Health Protection Agency (EPA) has developed a map of “radon zones” to show the different areas of high radon levels across the nation. There are 3 distinct zones designated for each county in each state: zone 1 designates a predicted radon level of greater than 4 pCi/L, zone 2 includes counties with predicted levels between 2 to 4 pCi/L, and Zone 3 includes counties with predicted levels less than 2 pCi/L. The map was developed to provide an overview of areas with higher radon levels. However, the EPA recommends that everyone in the United States test their homes for radon levels. 

People in the mining and building industry working in confined air spaces are at higher risk of radon exposure.[6] Historically, the link between lung cancer and radon exposure was first found in the mining community, and its pulmonary carcinogenesis is well established.[7][8] Recent studies have shown that uranium miners were at the highest risk of exposure. Appropriate ventilation can reduce this risk in miners. 

In the US, lung cancer is a leading cause of death for men and women. Smoking remains the main cause of lung cancer. Radon exposure is the second-leading cause of lung cancer overall and the number one cause in nonsmokers. The risk of lung cancer is greatly increased in smokers who are also exposed to radon, and it is estimated to be 10 to 20 times greater. Children, due to smaller lung sizes and faster breathing rates, are at greater risk due to higher radon inhalation.[9][10]

Of historical significance, the contrast agent thorium dioxide, more widely known by its trade name thorotrast, was used in the 1930s and 1940s. It was considered a safe agent, and its high radiodensity made it ideal for angiography. It was later determined to undergo alpha decay to thorium-232 and then radium-228, leading to the deposition of alpha particles throughout the reticuloendothelial system. The lifelong exposure to ionizing radiation led to the development of multiple malignancies, and it was withdrawn from the market.[11] 

Pathophysiology

The health hazards of radon are due to its decay products. As radon decays, it emits alpha, beta, and gamma particles and x-rays. An alpha particle consists of a helium nucleus (2 protons and 2 neutrons) and can transfer large amounts of energy into human tissue. Although with limited tissue penetration capability, Alpha particles are more biologically destructive than beta or gamma radiations. This is due to its high relative biological effectiveness (RBE).[12] This leads alpha particles to interact much more readily with DNA and produce oxidative decimation through radiolysis. Ionizing radiation from alpha particles can cause chromosomal abnormalities, double-strand DNA breaks, and the production of reactive oxygen species, leading to carcinogenesis.

Ultimately, the decay products of radon (polonium-218, polonium-214, and lead-214) become charged and attach to aerosol particles. The charged aerosolized particles aggregate, forming clusters that could readily attach to dust in the air, which is inhaled and deposited in the trachea, bronchi, and bronchioles. Upon entering the respiratory epithelium, the alpha particles can cause DNA damage, ultimately contributing to tumor genesis and lung cancer.[13][14]

Studies have investigated the role of radon and the tumor suppressor gene TP53, which codes for the p53 protein and maintains the normal cell cycle. In both the mining and non-mining populations, there appear to be no mutation patterns associated with radon exposure.[12] 

History and Physical

Risk factors for lung cancer include radon exposure, family history of lung cancer, history of cigarette smoking, and amount of cigarette smoke exposure. A good history is essential in assessing radon risk and exposure. Important exposure history includes:

1. Occupational history, especially if a person has ever worked in areas of confined air or where there is direct or indirect radon exposure (eg, miners, builders, excavators)
2. Year home was built/age of home.
3. Family history (to evaluate for risk of lung cancer)
4. Smoke exposure (in the home or at work)
5. Types of gas appliances 
6. Radon measurements in the home 
7. Time spent in confined spaces (such as basements)
8. Ventilation systems in the home 

Knowledge of past medical history is essential to narrow the differential diagnosis. A history of past lung disease is significant since radon targets the lungs. Increased levels of radon exposure do not manifest with any specific signs and symptoms, which makes evaluation more challenging. Since increased exposure to radon may lead to lung cancer, physical examination should focus on the respiratory system and signs of lung cancer. The physical examination may not be specific to radon exposure. However, it can aid in making the diagnosis.

Some of these symptoms include:

1. Shortness of breath
2. Wheezing
3. Hemoptysis
4. Cough
5. Chest pain
6. Weight loss

Other changes related to lung cancer include lymphadenopathy in the upper chest and lower neck, clubbing of the nails, and recurrent pneumonia. The results from the history and physical exam, along with clinical judgment, determine the next step in the assessment. This may include further testing and consults.

Evaluation

Lung cancer is the primary concern for long-term radon exposure. It is estimated that 21,000 deaths per year are due to lung cancer secondary to radon exposure, with an estimated 3-15% of all lung cancers worldwide due to radon. Since routine exposure to radon does not initially present with irritating symptoms or warning signs, it is important to screen patients for radon toxicity, especially if they present with a history or physical that is consistent. The National Comprehensive Cancer Network recommends a low-dose computed tomography (CT) scan for anyone over the age of 50 with at least a 20-pack-year smoking history and a history of radon exposure. However, the American Academy of Family Physicians has concluded that there is insufficient evidence for or against the use of low-dose CT to screen for lung cancer in individuals who are at high risk.

The United States Preventive Services Task Force (USPSTF) also has not established any benefit from screening asymptomatic patients. More studies are needed to determine the best method to screen for lung cancer in patients who are exposed to higher radon levels. Nonetheless, a detailed physical examination, history, chest x-rays, CT scan, sputum cytology, or a combination of these tests can aid in making the diagnosis.[15][16][17]

Treatment / Management

The most effective way to decrease the adverse effects of radon is to prevent exposure. The amount of radon in the air is commonly measured in pCi/L (picocuries per liter of air). About 0.4 pCi/L of radon is usually found in the outside air, and the US Congress has a goal of indoor radon levels never exceeding outdoor levels. Since radon toxicity does not present with warning signs or symptoms, measuring and keeping indoor radon levels low is essential. 

Screening homes for radon is a relatively inexpensive and noninvasive process, utilizing a caracole canister, which is permeable to radon gas but not to the radon progeny. The EPA recommends mitigation if the level is at or above 4 pCi/L.[2] 

Several methods exist to reduce radon levels. The EPA recommends hiring a trained contractor to assist in evaluating and reducing radon. Some techniques can reduce radon entry in the home, and others can reduce its levels after it has entered. One of the most common methods is soil suction, which draws radon from the house and vents it through a pipe to the air above the house, where it is then diluted. This method helps prevent exposure to radon within a home. There are 4 different types of soil suctioning. Determining the most effective method depends on the kind of house. 

For basement and slab-on-grade houses, radon levels are reduced by several types of soil suction: sub-slab suction, drain tile suction, sump hole suction, or block wall suction. In active sub-slab suction, suction pipes are installed through the floor slab and into the rock or soil underneath. They can also be inserted from outside the home below the concrete slab. A radon vent fan connected to this suction pipe can then draw the radon from below the house and release it into the air. Subslab suction can reduce radon levels by as much as 99%.  

At the same time, this creates a negative pressure under the slab. Passive subslab suction is similar to active subslab suction. However, it is not as effective at reducing radon levels. It relies primarily on natural pressure differentials instead of a fan. Certain types of houses have drain tiles or perforated pipes near the base of the house. Adding suction can help reduce radon levels. Another variation is a sump hole suction. When a sump that usually drains water from a house is capped, it can be used as a location for a radon suction pipe that removes radon with the expelled water. Finally, block wall suction can be utilized in basements with hollow block suction walls. This reduces radon, depressurizes the wall, and is usually used with a sub-slab suction. 

Crawlspace houses usually utilize submembrane suction to reduce radon levels. This requires the placement of a plastic sheet over the earth floor. A vent pipe and fan are then used to draw radon from under the sheet to the outdoors. 

Other types of radon-reducing methods that can be used in all types of houses include the following:

1. Sealing: Sealing cracks to reduce the flow of radon inside a home. However, the EPA does not recommend using this method alone because it has not been proven to significantly lower radon levels. 
2. House/room pressurization: Utilizes a fan to blow air into the basement or living area to create increased pressure. This will prevent radon from entering the house. This method is usually utilized if other methods have failed.
3. Heat recovery ventilator or air-to-air heat exchanger: Installed to increase ventilation in a home. 
4. Natural ventilation: This occurs in all homes by opening windows, doors, vents, etc. This is not a permanent or long-term method. Once the ventilation is closed, radon levels increase within 12 hours. 

All homes should be tested for radon levels and, if elevated, should be reduced. A new home built with radon-resistant features should be tested to ensure radon levels are below 4 pCi/L.

Differential Diagnosis

The differential diagnosis includes but is not limited to: 

• Lung cancer (small cell carcinoma occurs most frequently, adenocarcinoma, large cell carcinoma, and squamous cell carcinoma) 
• Pneumonia
• Bronchitis
• Leukemia[18]

Prognosis

Radon, usually a "silent killer," is responsible for about 21,000 deaths per year in the United States. Symptoms from radon exposure do not present until years later, when cancer symptoms begin to manifest. For this reason, the prognosis is usually guarded. However, it is estimated that lowering radon levels below 4 pCi/L can potentially decrease the mortality of lung cancer deaths anywhere from 2 to 4%.

Complications

Complications of radon exposure include the following:

• Lung cancer
• Frequent infections
• Emphysema
• Pulmonary fibrosis
• Alzheimer disease (there has been an increased risk of Alzheimer disease documented in the literature due to radon exposure)[19]
• Pleural effusion
• Metastasis
• Death