Can Chronic Inflammation Affect Lifespan of Mesothelioma Patients?
Chronic exposure to asbestos fibers is a major risk factor for development of mesothelioma. How asbestos induces asbestos-related disease, including mesothelioma, is being investigated and probably involves several mechanisms.
Sharp asbestos fibers damage cells
Damaging asbestos fibers appear to be sharp. They appear to induce cell death in some of the cells lining the chest cavity (mesothelium comprised of mesothelial cells). These dying cells induce the neighboring cells to fill the holes and the adjacent cells proliferate or make more cells,1 like patching a hole on the elbow of a favorite jacket. Some cells damaged by asbestos don’t die but have damaged DNA. One of these damaged cells transforms to cancer and grows into mesothelioma in approximately 4% of people who were chronically exposed to asbestos for decades.2
Exposure to damaging asbestos fibers usually triggers inflammation. As the cells are damaged, signals are sent to recruit white blood cells, such as neutrophils, that help clean up the damaged cells. Neutrophils comprise about 40% to 75% of the white blood cells. Neutrophils arrive quickly, and are a main component of pus from an infection or splinter. Although platelets are known to bind damaged blood vessels and form a clot to plug a leak, platelets also can amplify the inflammatory signals.3
Chronic inflammation and shorter overall survival
Chronic exposure to asbestos fibers can sustain chronic inflammation, which occurs in approximately 36% to 81% of mesothelioma patients. Chronic inflammation eventually can damage the surrounding normal tissue. The level of chronic inflammation is often measured by one or more of the five scores shown in Table 1. Surprisingly, some markers are more sensitive and find inflammation in more mesothelioma patients.
Table 1. Parameters that correlate with chronic inflammation
Parameter Abbreviation Value that corresponds to higher inflammation Percentage of mesothelioma patients with high inflammation by the marker Neutrophil-to-Lymphocyte Ratio NLR >5 38% Platelet-to-Lymphocyte Ratio PLR ≥ 300 36% C-reactive Protein CRP ≥ 10 (high levels) 77% Albumin ≤ 35 (very low levels; hypoalbuminemia) 45% Modified Glascow Prognostic Score mGPS ≥1, a composite score that includes CRP and albumin 81%
Pinato et al showed that some mesothelioma patients had high inflammation detected by high neutrophil-to-lymphocyte ratios (NLR) and high mGPS.4 Mesothelioma patients with high inflammation defined by NLR or mGPS scores lived significantly shorter than those who had had normal markers.4, 5 Thus chronic inflammation was associated with a shorter lifespan in mesothelioma patients.
Chronic inflammation and non-small-cell lung cancer (NSCLC)
Likewise, inflammation markers can also be used to predict the risk of regrowth of a type of lung cancer. Approximately 30% of patients with non-small cell lung cancer that had been surgically removed can have a return of the lung cancer within 5 years. NSCLC patients who have high neutrophil-to-lymphocyte ratios (NLR) often have shorter survival times (by 2 years) than those with a normal NLR.6
Is all inflammation bad?
No. Inflammation is the first step in healing a wound. Under normal circumstances, the wound heals and the body uses lipid-based molecules to turn off the inflammatory process.
For example, omega-3 fatty acids found in oily fish, walnuts, flaxseeds, and many green vegetables provide the building blocks (precursors) for the three mediators that turn off inflammation. These off switches or dimmer switches for inflammation are called maresins, resolvins and protectins.7
Interestingly, curcurmin, an antioxidant present in curry, can induce an inflammatory type of cell death (pyroptosis) in human mesothelioma cells in tissue culture. It’s also a potent antioxidant.8
Tips that can help reduce chronic inflammation
- Reduce your risk of exposure to irritants; wear a mask for example.
- Eat plenty of foods that are rich sources of omega-3 oils, such as walnuts, wild caught Alaskan salmon, cod liver oil, organic flaxseeds ground freshly ( coffee grinders work well).
- Eat 5-10 servings of darkly colored vegetables and fruits. They are rich in antioxidants and can help reduce chronic inflammation.
- Thompson JK, Westbom CM, MacPherson MB et al. Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation. Part Fibre Toxicol 2014;11(1):24.
- Reid A, de Klerk NH, Magnani C et al. Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis. Thorax 2014.
- Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol 2012;590(Pt 5):1023-1034.
- Pinato DJ, Mauri FA, Ramakrishnan R, Wahab L, Lloyd T, Sharma R. Inflammation-based prognostic indices in malignant pleural mesothelioma. Journal of thoracic oncology 2012;7(3):587-594.
- Abakay O, Tanrikulu AC, Palanci Y, Abakay A. The value of inflammatory parameters in the prognosis of malignant mesothelioma. J Int Med Res 2014;42(2):554-565.
- Pinato DJ, Shiner RJ, Seckl MJ, Stebbing J, Sharma R, Mauri FA. Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. Br J Cancer 2014;110(8):1930-1935.
- Serhan CN. Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators. J Thromb Haemost 2009;7 Suppl 144-48.
- Miller JM, Thompson JK, MacPherson MB et al. Curcumin: a double hit on malignant mesothelioma. Cancer Prev Res (Phila) 2014;7(3):330-340.