Respiratory Travel Medicine

Article history: International tourist arrivals continue to increase over time due to global economic growth, increasing middle class in developing countries, technological advances, innovative business concepts, cost-effective travel, and facilitation of visas. The increase in tourist visits has resulted in health problems due to the trips. Respiratory tract infections are the main reason tourists seek medical care. Respiratory infections occur in 20% of all tourists, almost the same as the incidence of diarrhea. The majority of international inbound tourism involved air travel. Though physiological changes happen in everyone while air travel, people with lung disease are at high risk for significant complications and necessitate a specific risk assessment strategy. A preflight evaluation is conducted if there is any uncertainty regarding the patient's fitness for flight and the effect of eligibility to fly. This literature review summarized the important aspect of travel medicine from the respiratory medicine point of view. passengers to the rupture of a


INTRODUCTION
Global economic growth, an increasing number of middle-class people in developing countries, technological developments, innovative business concepts, affordable travel costs, and visa facilitation have led to an increase in international tourist arrivals. According to the preliminary United Nations World Tourism Organization (UNWTO) figures, foreign tourist arrivals (overnight visitors) were still 72% lower than in the pre-pandemic year of 2019. 2020 was the worst year for tourism, with overseas arrivals falling by 73%.
Increased immunization rates and better coordination are required for recovery. 1 Travel medicine has developed rapidly as more and more people travel to unusual and remote places. It has also gotten more complicated due to dynamic developments in the global epidemiology of infectious diseases, change in drug resistance patterns, and a rise in the number of travelers suffering from chronic illnesses. Nearly one billion tourists cross international borders every year. Nevertheless, previous studies showed that few travelers sought health advice before traveling (pretravel). Many got pre-travel advice from less competent practitioners to provide current and accurate information. 2 *Corresponding author: niwayancandrawati@gmail.com that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious

LITERATURE REVIEW
Everyone planning a trip must know the health risks that can occur and how to protect themselves, therefore they can minimize the risk of contracting the disease. Travelers who plan to visit a destination are strongly advised to consult a health professional before traveling. Consultation is conducted at least 4-8 weeks before the trip. It includes information about possible health risks, vaccinations, and medications that the tourists may need. 1 Respiratory tract infections are the main reason tourists seek medical care. Respiratory infections occur in 20% of all tourists, almost the same as the incidence of diarrhea. Upper respiratory tract infections occur more often than lower respiratory tract infections. Anamnesis about travel history is necessary to evaluate patients with respiratory infections. 3 This literature review discussed respiratory travel medicine before the COVID-19 pandemic.

Risk Factors for Health Problems in Travelers
Some factors used to determine the risks that can occur to tourists are the type of transportation used, tourist destinations, duration and season of travel, accommodation standards, sanitation, and tourist health status. The mode of transportation and length of travel are crucial factors in determining the risk of infectious disease exposure and the requirement for particular immunizations. The duration of the trip also determines the possibility of tourists experiencing disturbances caused by altitude, temperature, and humidity. 4 Direct physical interaction, droplet dispersion, and minuscule suspended particles are all possible pathways for transmission. The congregation of huge groups of people at airports, cruise ships, and hotels can also help spread respiratory diseases. Inflammation of the respiratory tract, exacerbations of asthma and chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia are all linked to poor air quality at destinations and exposure to SO2, NO2, CO, and ozone.
Children, the elderly, and travelers with comorbidities such as asthma and COPD are at a higher risk of contracting respiratory tract infections. 3

Pre-Travel Assessment
Patient evaluation before travel includes fitness assessment or travel contraindications (such as preexisting disease, fit to fly), evaluation of travel itinerary or risk assessment (such as previous activities, travel to People with a history of experiencing substantial symptoms following a previous flight or whose doctor is concerned about their condition -rural or urban areas), relevant medical history (such as vaccination history, allergies, chronic illness, mental health history, and medication), good mental health screening, and ability to deal with stress in a hostile environment. 2 Travelers who have plans to visit developing countries are advised to consult a medical professional before traveling. Consultation should be conducted at least 4-8 weeks before the trip and preferably can be completed sooner if traveling for a long period. The consultation includes information about possible health risks, determining the need for vaccinations, and other medical items that may be needed during the trip. All travelers are strongly advised to seek adequate travel insurance. 4 Medical emergencies occur in 1 in 604 flights and 1 in 30,000 passengers. 5,6 Respiratory diseases accounted for about 12% of in-flight problems. Other conditions include syncope (37.4%), symptoms of heart disease (7.7%), stroke (2%), and cardiac arrest (0.3%). At altitudes above 3,048 m (10,000 ft), hypoxemia becomes more evident, and oxygen saturation drops to 89% in healthy people. 7,8 Another possible risks of air travel include low relative humidity and gas expansion due to altitude in enclosed lung parenchymal spaces according to Boyle's law. At an altitude of 2,438 (8,000 ft), a 38% expansion of the humidified gas occurs. 9 A pre-flight assessment is conducted if there is any doubt about the patient's medical condition for air travel and the effect of comorbidities on the patient's health condition. Patients should generally be stable and have been cured from exacerbations before traveling. 9 Table 2. The conditions listed below are classified as contraindications for air travel: 9 No. Condition 1 Ventilatory failure that has not been treated 2 Pneumothorax that has not been treated 3 Respiratory infections that can pose a threat to others, such as tuberculosis, severe acute respiratory syndrome, middle east respiratory syndrome, COVID-19 4 Bronchogenic cyst. Cerebral air embolism has been reported in airplane passengers due to the rupture of a bronchogenic cyst.

5
The highest fixed flow rate typically accessible on commercial airplanes is 4 L/min, therefore severe hypoxemia patients who need >4L/min oxygen while flying are traditionally urged not to fly. This limit is no longer applicable due to the presence of POCs that have been approved for a flight that supply a variety of flow rates that are continuous and intermittent. The highest flow rate is limited by the technology present during in-flight oxygen delivery. Pulse-dose delivery devices, on the other hand, can make determining the flow provided more difficult and might not be properly accepted. Breathing through the mouth, talking, snoring, and/or sleeping should all be considered. On commercial airplanes, high-flow nasal oxygen (HFNO) could not be provided.
In addition, it is advised for a diver to avoid flying

Disability
If the traveler is generally healthy, physical disability is usually not a contraindication. Airlines have policies regarding passengers with disabilities who require support from someone that can provide comprehensive assistance to passengers. 4

Pre-Existing Disease
Travelers suffering from chronic diseases must consult a doctor before preparing for a trip.

Management of Respiratory Disease Patients Planning Air Travel
Although all people experience physiological changes during flight, people with lung disease are at a higher risk of significant complications and require a specific risk assessment strategy. Respiratory complaints are the second most common medical issue while flying after syncope or presyncope. 10 Without cabin pressure, passengers can be exposed to hypoxic conditions because the partial pressure of oxygen at an altitude of over 45,000 feet is about ⅙ the pressure at sea level. The aircraft cabin is pressurized at an altitude of 8,000 feet, corresponding to breath 15.1% oxygen at sea level. 10 Partial arterial pressure of oxygen (PaO2) at an altitude of 8,000 feet (2,438 m) in healthy passengers is affected by age and minute ventilation but decreases to 60-75 mmHg and oxygen saturation (SpO2) 88-94%, which is measured by pulse oximetry. This situation does not cause symptoms in healthy people. Altitude exposure can worsen hypoxemia in passengers with lung disease. The physiological compensation for acute hypoxemia is triggering peripheral chemo-receptors in carotid bodies that stimulate mild to moderate hyperventilation with increased tidal volume, which is influenced by increasing minute ventilation to maximize alveolar oxygen pressure (PAO2) and PaO2. There was a decrease in carbon dioxide artery pressure (PaCO2) due to hyperventilation, but hypoxia neutralized the effects of cerebral vasoconstriction and maintained oxygen transport to the brain. Tachycardia causes an increase in cardiac output, which helps to maintain blood flow and oxygen transport. 11 Pulmonary disease patients who will travel should have their primary doctor/pulmonologist/specialist evaluate them before flying, pack medication and therapeutic devices in carry-on baggage with extra supplies (batteries, infusion pumps/tubing, and many more), and notify the airline in advance if special accommodations are required. Advice for more specific requests differs based on the disease. Table 1 lists the patient factors that need to be evaluated further to determine if supplementary oxygen is required. 12 FEV1 and SpO2 are important markers for severity. However, in patients with pulmonary diseases, this marker cannot accurately predict the occurrence of hypoxemia or complications during or after the flight. 13 It is recommended that doctors must evaluate preceding flight information, flight duration and destination, and also the time of last exacerbation in patients with the risk of hypoxemia or other problems due to air travel. Patient care routines, such as bronchodilators, must be optimized before traveling. 11 Patients with medical needs that often air travel can obtain a Frequent Traveler's Medical Card (FREMEC) that records essential medical details and replace the forms required for each flight. After being registered, medical support may be provided whenever the patient travels. FREMEC is issued by various airlines. If a patient travels on a different airline, they must verify the validity with the new airline. 11 The patient factors that need to be evaluated further to determine if supplementary oxygen is required according to various health organization are described in Table 3.

Pre-Flight Assessment
Pulse oximetry is the first and easiest screening test. Previously, it was thought that people with oxygen saturation >95% at rest at sea level did not need oxygen while flying. 9 Patients with a resting saturation of <92%

Walk Tests
People who can walk 50 meters or climb 10-12 stairs without shortness of breath are believed to have adequate cardiopulmonary reserves for flight. The capacity to enhance minute ventilation and cardiac output during exercise is an excellent test for assessing cardiopulmonary reserve. However, recent data shows that the 50 m walk test is not sensitive for assessing fitness to fly, although it is sometimes still used as a reference by airlines and aviation authorities. A pulmonologist has experience with other walking tests, for example, the 6-or 12-minute walk test (6MWT or 12MWT) and the shuttle walk test (SWT). Baseline walk test values (6MWT and SWT) could not predict in-flight hypoxemia under various respiratory conditions but changes in SpO2 at 6MWT and SWT are correlated with hypoxic challenge testing (HCT) outcomes in ILD, COPD, and chest wall deformities. The walk test could not estimate in-flight oxygen demand but can tell which person requires further testing. 9,11 A walk test may determine whether or not HCT is necessary. HCT and inflight oxygen should not be required for persons with COPD who undertake SWT or 6MWT, and the saturation did not fall below 84%. 9 A study by Edvardsen, et al. implied that it is fair to prescribe oxygen at 2 L/min during flight without proceeding to HCT if SpO2 is between 92 and 95% at rest and falls below 84% but has no signs of CO2 retention. HCT will be needed to estimate the flow rate of oxygen if there are issues with CO2 retention. 9,16 6MWT interpretation is described in Table 4.

Predictive Equations
For predicting which patients may require oxygen supplementation while flying, a number of predictive models have been presented. These equations have the advantage of being simple and easy to employ during an office visit. 10 Predictive equations might be a less expensive and time-consuming alternative to an HCT, especially in primary care, but they substantially underestimate the requirement of in-flight O2 in the vast majority of patients. 17 PaO2 is calculated using the following equations

Hypoxic Challenge Testing (HCT)
Hypoxic challenge testing/HCT (sometimes referred to as High Altitude Simulation Test or HAST) is conducted using a 15% oxygen-enriched inspired gas mixture, which produces an approximation comparable to inspired oxygen pressure (PO 2) as inhaling air at the highest cabin pressure allowed (2,438m or 8,000 ft).
HCT is commonly conducted in a specialized respiratory physiology unit. 9,10 Pre-flight evaluation of individuals with chronic airflow obstruction and restrictive respiratory disease using HCT is described in Figures 1 and 2. Hypobaric hypoxia results from an inverse correlation between the partial pressure of oxygen and altitude, which cause a drop in alveolar partial oxygen pressure (PaO2) during ascent and lower arterial blood oxygenation. Euphoria, headache, tiredness, lassitude, and dizziness are all symptoms of hypobaric hypoxia, which, if left untreated, can cause unconsciousness and even death. 18 Increased minute ventilation, heart rate, and cardiac output compensate in healthy individuals; therefore, most people experience no physiological influence at typical cabin altitudes. People with a history of pulmonary disease, particularly hypoxemia at sea level, might be unable to adapt to the lower PO2 at altitude by utilizing these processes, resulting in hypoxia of the alveolar and tissue. 19 Lung mechanics may be harmed by changes in breathing patterns, which may be exacerbated by gas expansion, vital capacity reduction, and increased residual volume. 9 HCT determines whether or not travelers with respiratory conditions require oxygen during flying and at what flow rate. It does not determine fitness for flight, despite the name "fitness to fly" examination. 9 In otherwise healthy people, HAST testing can also predict in-flight hypoxemia rather accurately. 10 The results of the HCT do not predict respiratory problems when flying.
Such symptoms appear to be caused by bad respiratory mechanics and a diminished respiratory reserve affecting the response to hypoxemia rather than hypoxemia itself.
Those who have more severe dyspnea at sea level are more prone to develop symptoms. By using in-flight oxygen, individuals whose oxygen saturation falls during HCT and who have a history of respiratory symptoms while air travel can prevent this. Anxiety related to flying might also cause symptoms. 9 HCT procedure is as follows: for 20 minutes, patients sit at rest and inhale a 15% oxygen gas mix through a Douglas bag with a non-rebreathe valve and mouthpiece or a nitrogen-driven gas combination through a 40% venturi mask. SaO 2 level is monitored during the test, which will be called off if it goes below 86%. Before and after the test, arterial blood gas tensions are measured. 20 BTS recommendations for the results of HCT are: 9 -In-flight oxygen is not required if PaO2 is ≥6.6 kPa (≥50 mm Hg) or SpO2 is ≥85% -In-flight oxygen is required if PaO2 is <6.6 kPa (<50 mm Hg) or SpO 2 is <85% -Oxygen titration is conducted to maintain PaO2 ≥6.6 kPa or SpO2 ≥ 85% in adults and SpO2 90% in children aged more than one year, as needed -If there is a history of hypercapnia, keep an eye on pH and pCO 2 -When PaO2 is kept at ≥ 6.6 kPa and SpO2 is ≥ 85%, consider recommending against air travel if pH drops to <7.35 and PCO2 rises by more than 1 kPa (7.5 mm Hg) from baseline Flowchart of patient selection for HCT to evaluate individuals with chronic airflow obstruction ( Figure 1) and restrictive respiratory disease (Figure 2).

Emergency Response during Flight
When a passenger has a respiratory problem on a flight, intervention choices are limited. The following actions should be followed in the first assessment and management of passengers who experience difficulty breathing or increased work of breathing: 12 -Examine vital signs and give oxygen supplementation if necessary -Check for breath sounds and evaluate for deviation of the trachea -If necessary, request that the pilot descend to a lower altitude and consult a ground medical consultant if one is available Patients with dyspnea need to be managed more specifically, which will be determined by their overall clinical picture. 12

Post-Travel Evaluation
A medical examination is usually unnecessary upon returning home after a routine trip for short periods.
Except for particular populations like refugees and foreign adoptees, the Centers for Disease Control and Prevention (CDC) has no established recommendations for screening international travelers who do not display any disease symptoms. 3

Figure 2.
Pre-flight evaluation of individuals with restrictive respiratory disease. HCT, hypoxic challenge test; LTOT, long-term oxygen therapy; 6MWT, 6-minute walk test; SWT, shuttle walk test (incremental); *, data is limited in this group and pulsed delivery oxygen may not be suitable for some patients, therefore they should be assessed on case-by-case basis. If in doubt, HCT should be considered. 9 Travelers should seek a medical evaluation when they return if: 4 -Returning from a country where malaria is or might be found with a fever, to rule out malaria as the source of their ailment -If they have a chronic disease like cardiovascular disease, diabetes mellitus, chronic respiratory disease, or have been on anticoagulants -In the weeks after they return home, they may become ill, especially if they have a fever, chronic diarrhea, vomiting, jaundice, urinary abnormalities, skin disease, or genital infection -They were treated for malaria while on the trip -While traveling, they could have been exposed to a deadly infectious disease -Have stayed in a developing country for more than three months Returning tourists frequently experience respiratory problems, which are usually caused by common respiratory viruses. The most prevalent vaccinepreventable disease linked to overseas travel is influenza.
The majority of post-travel diseases can be treated as outpatients, but certain patients, particularly those with systemic febrile disorders, may require hospitalization. 3

SUMMARY
Everyone planning a trip must know the health risks that can occur and how to protect themselves, therefore they can minimize the risk of contracting the disease. Patient evaluation before travel includes fitness assessment or travel contraindications, evaluation of travel itinerary or risk assessment, relevant medical history, good mental health screening, and ability to deal with stress in a hostile environment. When a respiratory emergency happens during a flight, intervention options are limited. A medical examination is usually not necessary when returning home after routine travel for short periods. Except for particular populations like refugees and foreign adoptees, the CDC has no established recommendations for screening international travelers who do not display any disease symptoms.