When masks are used elevated CO
2 concentrations are inhaled [18-27]. Despite the compensatory mechanisms that occur [28] an arterial PaCO
2 rise is inevitable in the long term [29]. For example, breathing air with an inspired CO
2 fraction of 1% (≈ 8 mmHg) will increase arterial carbon dioxide by 1 mmHg, which increases ventilation at rest [28]. In a recent scoping review numerous important studies which provide statistically significant evidence for such CO
2 retention under the mouth-nose protection have been presented [11] and we have found additional studies that reveal scientific evidence of a carbon dioxide increase in the blood when masks are used. In total, significant changes (p<0.05) could be found in most of the evaluated studies that measured body CO
2 content during mask use [18,29-44] (Table 2). Experiments with relatively short evaluation times [45] or questionable study design [46,47] showed no effects caused by masks. However, some well conducted studies also found no statistical difference between mask and no mask use, though measured CO
2 levels were continuously higher in mask wearers [25,48]. Some of these studies were conducted under extreme conditions and within selected user groups [49]. Overall, the most prominent rise in CO
2 was observed while wearing N95 masks. This is due to the fact that the dead space volume is almost doubled and the breathing resistance is more than doubled, which leads to a significant re-breathing of CO
2 with every breathing cycle [11,21,22]. Due to compensatory mechanisms, carbon dioxide partial pressure (PaCO
2) in the blood is at a subthreshold generally in healthier people [28,29], but in sick people a partially pathological increase is detected [34]. However, all mask types like community masks, surgical mask, as well as N95 respirators can be responsible for a significant and comparable rise in the blood content of CO
2 [32].
The buildup of CO2 behind the masks is predominantly within the short term exposure limits of NIOSH and EN149 [17,19,20,24,27], but even with values which do not go beyond this limit in the short term [20,21,27], a long-term pathological consequence with clinical relevance is to be expected [15-17,19,21-23,27,50,51]. This is as a result of the longer lasting effect with a subliminal impact and significant shift in the pathological direction. This pathogenetic damage principle, whereby a chronic low-dose exposure leads to disease or to disease relevant conditions in the long term [52,53] has been extensively studied and described in many aspects of environmental medicine [11].
From a toxicological point of view, carbon dioxide is absorbed passively through the lungs from the breathed-in air. Human metabolism also produces carbon dioxide, which naturally requires elimination. Carbon dioxide is largely carried in the blood as bicarbonate, which is catalysed by the enzyme carbonic anhydrase. The excretion is accomplished mainly via the lungs although the kidneys also excrete small amounts. In expert literature, concentrations of >2% carbon dioxide in inhaled air are expected to cause adverse health effects [51]. At short exposure of CO2 levels above 1% an increase in cardiac output is often seen. Inhalation of between 2.5–3.5% carbon dioxide for up to 10 minutes may increase cerebral blood flow up to 100% and a dilatation of cerebral blood vessels may be responsible for the severe headache produced by carbon dioxide inhalation [30,51]. Exposure to increased carbon dioxide concentrations causes hyperventilation. Interestingly, due to compensatory mechanisms, acclimatisation occurs to chronic low concentrations of carbon dioxide [28,50,51]. Acute features usually resolve despite continuing exposure as carbon dioxide at concentrations up to 3%. However, in healthy adults metabolic changes are responsible for slight long-term damages at concentrations of <5% [51].
Some mechanisms of human adaptation to low level exposure of CO2 had been evaluated experimentally including levels of 1-2% [28, 50]. Regarding the referenced mask literature those carbon dioxide values of 1-2% can be assumed for masks [18,19,21-25,27]. In the human experiments with low level 1-2% CO2 exposure an increased respiratory minute volume of more than 34% was detected [50]. Moreover, higher arterial PaCO2 and bicarbonate levels produced an effective buffering of inhaled CO2. A correlation could be shown between changes in plasma calcium level, pH, and CO2, indicating that the bone CO2 store is a determining factor in the extended time periods of CO2 retention and elimination. Kidney and organ calcification was seen in animal studies frequently, emphasising the involvement of calcium metabolism in adaptation to elevated levels of carbon dioxide [50]. Recent studies raised interest in carbon dioxide in relationship with chronic and/or intermittent long-term exposure conditions that might induce pathologic states, in particular favour DNA alterations, nasal inflammation, and pulmonary inflammation [16].
Table 2 shows studies revealing evidence of carbon dioxide retention when masks are used.