High Altitude and Its Effects on Oral Health: A Review of Literature

Abstract

Health deterioration at high altitudes is related to many pathophysiological processes. The literature contains much evidence describing the multiple factors responsible for this deterioration, including hypoxia, decreased oxygen saturation, and decreased barometric pressure. An increase in the levels of oxidative stress at high altitudes can lead to many serious health events, although the human body may be able to adapt to such changes in the case of people who are accustomed to living at a high altitude. The pathophysiological processes at high altitudes also have adverse effects on oral tissue health. The aim of this review is to summarize the major published findings about oral health deterioration of living in and travelling to high-altitude areas.

Most studies have noted the adverse effects of prolonged exposure to hypoxia at high altitudes on oral tissues, including the salivary gland, periodontal tissue, gingival crevicular fluids, and jawbone. These changes include increases in the levels of inflammatory mediators and periodontal inflammation parameters. In addition, the incidence and severity of dental fluorosis is higher in residents of high-altitude areas. Abrupt changes in barometric pressure in people who travel to high altitudes may cause dental barotrauma and appear to increase sensitivity to pain (barodontalgia). In conclusion, it is important to consider that travelling to and living in high-altitude areas is a possible risk factor for multiple oral diseases.

Introduction

Many geographic regions of the world are located at elevations higher than 10,000 feet and are defined as high-altitude areas. ¹ People living in these areas or travelling to them may experience significant health conditions, including chronic or intermittent hypoxia and acute mountain sickness. They may also be at high risk for high-altitude pulmonary edema and high-altitude cerebral edema.^1,2

The duration of residence in a high-altitude area is related to the degree of oxidative stress, which may persist for some time even after the individual returns to sea level. Although the physiological and medical consequences of increased oxidative stress are not clear, ³ hypoxia may trigger a cascade of signaling events that leads to adaptation to high altitudes. The generation of reactive oxygen species is included in these signaling events that may cause adaptive responses. Excess production of reactive oxygen species may result in impaired muscle function and reduced capillary perfusion at high altitudes, which may contribute to more serious health events.^1,3–5

Oxygen saturation decreases in healthy subjects at altitudes above sea level as a result of low atmospheric pressure.^6–8 Oxygen saturation is defined as the fraction of hemoglobin bound to oxygen relative to total hemoglobin. Hemoglobin is responsible for supplying the tissues with oxygen, which is consumed partially through aerobic metabolism.^9,10 At high altitudes, increased red blood cell production (polycythemia) can occur in compensation for inadequate tissue oxygenation. ¹¹ The bodies of long-term residents of high-altitude areas have shown to possess genetic adaptations to the hypoxic conditions found there. In these people, the development of polycythemia mainly depends on two factors: the adaptation of the body to high altitude, and the altitude level, which can be classified into three categories: high altitude, 4900–11,500 ft above sea level; very high altitude, 11,500–18,000 ft above sea level; and extreme altitude, more than 18,000 ft above sea level.^8,12

Many studies have recorded the health problems related to living in or travelling to high altitudes, and have discussed the oral features of living at high altitudes,^13,14 including periodontal inflammation,^15,16 saliva production, ¹⁷ dental pain and anesthesia, ¹⁸ inflammatory mediators and bleeding index, ¹⁹ and dental fluorosis. ²⁰ However, studies covering the effect of high altitudes on the oral cavity are relatively fewer, and many of them lack conclusive findings or require more detailed investigation. This review summarizes the major published findings relating to the oral pathology of living in and travelling to high-altitude areas.

Toothache and Anesthesia

Barodontalgia refers to oral symptoms that result from pressure change when travelling to high altitudes.^21,22 Barodontalgia is classified into direct and indirect forms. The former refers to a flare-up of existing oral conditions caused by changes in barometric pressure. Direct barodontalgia can be produced by certain dental pathologies, such as caries, defective restorations, pulpitis, pulp necrosis, apical periodontitis, periodontal pockets, impacted teeth, and dental cysts. Radiographic assessments for direct barodontalgia may show any of the following findings: pulpal caries, restoration near the pulp, periapical radiolucency, and, in some cases, inadequate endodontic obturation. ²¹ In contrast, indirect barodontalgia may be caused by barosinusitis or barotitis media. It presents as toothache in the upper premolar and molar regions with no signs of dental lesions, but the radiograph shows opacity (fluid) in the maxillary sinus.^21,23 However, some studies reported that it is difficult to diagnose barodontalgia because barometric pressure changes are difficult to reproduce in the clinic, especially if the patient has diffuse pain and multiple carious or filled teeth. ²⁴ One study suggested that changes in barometric pressure influence the appearance of painful oral conditions. ²³ This is frequently seen in aircraft crew and much-travelled passengers, and awareness of its correct management is important. Misunderstanding the cause of the pain, often through failure to take an adequate history, may lead to inappropriate management.

Some reports have described the need to modify anesthetic application techniques because anesthesia may take effect more slowly at higher altitudes. They recommended waiting for 3–10 min instead of the usual waiting period of 2–4 min at sea level.^18,25 This advice needs more investigation with larger sample sizes at different altitudes to reach reliable conclusions. In practice, many factors can delay the effect of anesthesia, such as taking medication, patient weight, age, degree of inflammation in the area, dose, route of administration, injection rate, and vascularity of the injection site. ²⁶

Dental Barotrauma

Barotrauma refers to the pathological response to changes in barometric pressure. Boyle’s law states that the gas volume at steady temperature varies inversely with the surrounding pressure. Any change in atmospheric pressure causes changes in the volume of gas inside the body’s rigid cavities and can cause several adverse effects in dental tissue, including dental barotrauma.^21,27,28 Dental barotrauma can present as tooth fracture, restoration fracture, or reduced retention of the prosthetic device. There have been several reports of dental barotrauma relating to high-altitude flying during military operations, mainly from the first half of the 20th century. These describe loss of restoration, failing crowns, tooth fracture, and multiple emergency dental visits. ²⁷

There are many predisposing factors, such as the presence of preexisting leaking restorations or hidden secondary caries underlying restoration in the affected tooth at the time of exposure to barometric change. ²¹ In addition, it has been reported that using either zinc phosphate cement or glass ionomer cement in a prosthetic device’s cementation can cause significant reduction in the crown or bridge retention in approximately 90% and 50% of cases, respectively. The cause is considered to be pressure change in microtubules of the cement layer under the prosthetic device, leading to microleakage and impairing retention. Using resin cement is preferred as this is not associated with such microleakage.^21,28

Acute deterioration, characterized by barodontalgia and dental barotrauma, has been reported in association with abrupt reduction in barometric pressure related with aircraft travelling. It is important however that persons subjected to barometric pressure changes related to high altitudes and their dentists maintain awareness of the possibility of dental deterioration, so that dental management of such cases is appropriate. ²¹

Dental Fluorosis

Over the last two decades, multiple studies have attempted to identify the underlying relationships and improve understanding of the increase in the incidence of dental fluorosis in high-altitude residents. Many studies support the finding that the high-altitude state is a risk factor for dental fluorosis.^29–32 One study compared the prevalence and severity of dental fluorosis in residents of high-altitude and low-altitude areas. The findings showed a significant increase in the prevalence and severity of dental fluorosis by 22.2% in residents of high-altitude areas compared with those in low-altitude areas. ²⁹

In one study conducted at three different high-altitude areas (>6560 ft above sea level) in Mexico, all of which were naturally fluoridated areas, the participants showed a high prevalence of dental fluorosis. Approximately 8 out of 10 adolescents showed evidence of fluorosis, indicating a dental public health problem. That study also assessed the relationship between the concentration of fluoride in water and the incidence of dental fluorosis in each area and concluded that communities living in high-altitude areas might show a higher prevalence and severity of dental fluorosis by 83.8% than communities living at sea level. ³⁰

Another recent study aimed to measure the effect of living at different altitudes on the fractional urinary fluoride excretion and total daily fluoride retention in young residents living at low and high altitudes in Nepal. The findings of that study revealed that altitudes have a small and nonsignificant effect on the total daily fluoride retention level. However, residents at lower altitudes showed a significantly higher level of fractional urinary fluoride excretion, indicating substantial bodily retention of fluoride at high altitudes, which may increase the risk of dental fluorosis. ³¹

The findings of the cited studies were consistent. However, the severity of dental fluorosis depends on many factors, such as the altitude, the natural fluoride concentration in the drinking water, and the socioeconomic status of such community (which may influence the type of water consumed, whether factory-filled bottled water or naturally available water).

Saliva Production and Characteristics

Several studies have investigated the effect of altitudes on saliva production and composition. Changes in the normal saliva production levels or its normal characteristics and composition can result in an increase in the incidence of new caries.^17,33 One study aimed at assessing salivary pH after exercise under hypoxic conditions, which resembled a high-altitude condition. The results showed a significantly strong effect of such exercise on saliva alkalinization, with the salivary pH being significantly higher than that recorded after exercise under normoxic conditions. This effect can threaten tooth health and may preclude the maintenance of sound caries-free teeth. ³³

Another study conducted in India compared salivary production and the incidence of dental caries in Indian Army troops over a six-month period of residence in a high-altitude area. The findings showed that such residence had an adverse effect on the troops’ health, with the participants exhibiting low water intake, low fresh food intake, high carbohydrate intake, ignorance of oral hygiene, and a stressful lifestyle. This led indirectly to low salivary production and increased the incidence of caries. ¹⁷

An important study on the salivary proteome, investigating salivary biomarkers for any changes occurring because of hypoxia at high altitudes, revealed significant changes in protein expression. Some proteins, such as apoptosis, inducing factor 2, cystatin S, cystatin SN, and carbonic anhydrase 6, were upregulated. In contrast, other proteins, such as polymeric immunoglobulin receptor, alpha-enolase, and prolactin-inducible protein, were downregulated. These results suggest that changes in the salivary proteome can be used as an indicator of oxidative stress caused by hypoxia in high-altitude areas. ³⁴

The studies summarized above suggest direct and indirect effects of high altitudes, reducing salivary flow. This finding needs further investigation as other factors may contribute to reduction in saliva production or to changes in saliva protein expression in people residing in high-altitude areas.

Periodontal Inflammation and Inflammatory Mediators

Hypoxia related to high altitudes has been proven to be the cause of accumulative changes at the molecular level, which later affect an individual’s health. It has also been proven to affect oral tissue health. This section focuses on the adverse effects of hypoxia on the inflammation process and inflammatory mediators. One study found that the defense genes present in oral bacteria of communities living in high-altitude areas are somewhat different from those of oral bacteria of communities living at sea level. This suggests that hypoxic conditions at high altitudes play a major role in oral bacterial biodiversity and host immune response. ³⁵ Chronic exposure to hypoxia at high altitudes is believed to be a risk factor for periodontitis. One study found that an increase in oxidative stress with a lower antioxidant capacity in the submandibular gland and periodontal and gingival tissues might indicate a deleterious effect of chronic hypoxia on oral health. This was shown by increased alveolar bone loss, altered periodontal ligament height, and decreased salivary flow. ¹⁵

Chronic exposure to hypoxia induced the expression of high levels of inflammatory mediators such as prostaglandin E2, decreased immunoreactivity of hypoxia-inducible factor 1α, and the presence of apoptotic nuclei and irregular secretion granules in oral tissue, indicating the damaging role of these inflammatory mediators during hypoxia. ³⁶ Another study used a rat periodontitis model in a simulated high-altitude hypoxic environment to measure the association of cytokines and clinical periodontal parameters under hypoxic conditions and compare the findings with those obtained in normal conditions. The results showed an increase in tumor necrosis factor α and prostaglandin E2, and a decrease in interleukin-8 levels in the gingival crevicular fluid of the hypoxia group in relation to increased attachment loss, pocket depth, plaque index, and bleeding index. ³⁷

Rats exposed to hypoxia have been shown to exhibit an advanced degree of periodontitis, and the microbial community in their gingival crevicular fluid is also affected. ³⁸ In addition, the levels of alkaline phosphatase and prostaglandin E2 are elevated under hypoxic conditions. Thus, low oxygen status can cause modifications in the composition of the gingival crevicular fluid to facilitate its adaptation to the hypoxic environment. These changes are mainly related to the inflammatory process in periodontal diseases. ³⁹

Articles about the effects of hypoxia at high altitudes on periodontal status and the inflammatory process suggest that these go well beyond the direct effects of hypoxia in the oral cavity. The effects include deterioration in oral bacterial biodiversity, reduced host immune response, and alteration in the expression of inflammatory mediators in the oral cavity. The overall conclusion is that prolonged exposure to hypoxic conditions adversely affects periodontal inflammatory processes and the oral bacterial flora.

Conclusion

In this review, the effects of high altitude on oral tissue health have been addressed. Changes in barometric pressure may cause aggravation of dental pain and barotrauma and may influence the efficacy of dental anesthesia, but more research is needed to explore the relationship between changes in barometric pressure and dental deterioration. In addition, the prevalence of dental fluorosis has been shown to be higher among residents of high-altitude areas. Moreover, it is clear from the literature that hypoxia at high altitudes affects most aspects of oral health, including the levels of inflammatory mediators and periodontal inflammation parameters. Because of the capacity of the body to adapt at high altitudes, the changes in oral health of people living there, such as dental fluorosis, altered salivary flow, and periodontal inflammation, are cumulative. However, acute deterioration characterized by barodontalgia and dental barotrauma, which result from abrupt reduction in barometric pressure, appears to affect solely people who travel to high altitudes. Most of publications in regard to the acute deterioration related to travelling to high altitude is reported in the first half of the 20th century which is considered as a limitation. More studies on the effect of high altitude on oral tissue health in different high-altitude areas are essential to optimize the significant changes and plan appropriate treatment options. In view of all these findings, it is important to consider living at and travelling to high altitudes as risk factors for oral disease, and both patients and dentists need clear guidelines, encouraging awareness, and advice on appropriate dental practice.