Diseases of the lung and/or respiratory pump affect the O2 and CO2 transport which is further impaired by altitude exposure. Prophylactic recommendations and measures require disease-specific evaluation of these patients prior to high altitude travel.
The British Thoracic Society (BTS) recommendations give detailed advice for doctors dealing with patients suffering from respiratory disorders who are planning air travel. Two billion passengers currently fly worldwide each year on commercial planes, about 5% having problems [13
Flying with no or partial compensation of the environmental barometric pressures at cruising altitudes should be known in advance as well as the intended and final altitude of the travel (landing place).
Previous episodes of complications (the need for supplemental oxygen, pulmonary hypertension, asthma attacks, emotional hyperventilation, thrombo-embolic and cardiac diseases), decompression and recompression symptoms during altitude travel (difficulties in ventilating the middle ear and the sinuses), previous pneumothorax, obstructive and restrictive ventilatory defects and other causes of respiratory impairment should be carefully evaluated (lung function tests and pulse oximetry) during the medical consultation.
The BTS-guidelines recommend the hypoxic altitude simulation test (HAST) breathing 15% FiO2 under normobaric conditions in patients with respiratory insufficiency, if they present at sea level with a SaO2 below 92% (PaO2 67-73 mm Hg) and/or additional risk factors (hypercapnia, FEV1 < 50% pred, cardiac disease), if a hypobaric chamber exposition (the ideal test) is not possible, which gives also information on possible barotraumata. We prefer in these patients to administer first supplemental O2 (primum nihil nocere) and to control the possibility to reach normal values of blood gases under normobaric conditions (Figures and ), if necessary in the sleep laboratory, to exclude critical hypoventilation at higher O2-flows and the need for non invasive ventilation. A one night supplemental O2 challenge test provides also more meaningful information than the HAST about the long term adaptation of hypoxic patients who intend to travel for extended periods by plane, car or train in hypoxic environments. It may be important to correct for anemia (Hb), because the O2-content of the blood is more informative for assessing O2 delivery to the tissues than SaO2 and PaO2-values. ECG recordings breathing supplemental nasal O2 (2 L/min) compared to the night without shows in many COPD-patients also a dramatic fall of hypoxia-induced ventricular premature beats (Figure ).
Figure 2 Polysomnography of a copd patient breathing 2 l/min nasal air at night. The patient shows a poor sleep quality due to frequent awakenings, and continuous hypercapnic (transcutaneous PCO2), hypoxic (transcutaneous PO2) and pulmonary hypertension (mean (more ...)
Figure 3 The same copd patient as in figure 2 breathing 2 l/min supplemental nasal O2 at night. Sleep quality and pulmonary hypertension are improved, arterial hypoxemia is normalized with unchanged hypercapnia. This patient could tolerate a 7 hour flight breathing (more ...)
Figure 4 Reduction of ventricuralr premature beats (vpbs) during 2 l/min O2 breathing at night in 13 copd patients. The ECG recordings during the night when breathing 2 litres nasal O2/min compared with the night breathing only air show a significant reduction (more ...)
Pneumothorax and other forms of "trapped air"
Air in the pleural cavity will expand during ascent and cause tension pneumothorax if it cannot escape through a chest tube, preferably equipped with a one-way valve (Figure ). Patients with residual "trapped air" after thoracic surgery or incompletely expanded lungs and captured air in pleural or other closed air-containing spaces in the body should not be exposed to rapid altitude changes.
Figure 5 Pneumothorax management fit for high altitude transport. Closed (non-ventilated) air spaces expand with increasing altitude (= closed pneumothorax) and shrink during descent. Therefore patients with pneumothorax need a chest tube with one way valve which (more ...)
Exposure of patients to moderate altitude, (such as in Davos, Switzerland or Denver, US) breathing dry air without strenuous exercise tends to improve asthmatic symptoms, probably because of the lower allergen load. This is especially the case for house dust mite sensitive subjects, because the house dust mite cannot reproduce at altitude levels with low humidity. Acute exposure to higher altitudes or breathing cold air during exercise may trigger hyperventilation-induced or so-called exercise-induced asthma. Longer stays at altitudes of more than 4,000 m generally reduce the bronchial hyper-responsiveness of mildly asthmatic patients [15
Asthmatic subjects should maintain their pre-existing 'controller' medication and be equipped with an adequate supply of 'rescue' medications in the form of inhaled bronchodilators and oral steroids with appropriate instructions on their use. Breathing cold dry air through a face mask may help to humidify and warm the air entering the upper airways to BTPS-conditions and hence reduce broncho-constriction and airway inflammation.
It is not uncommon in non-asthmatic subjects, as a result of the increasing hypoxic drive, to develop clinical signs of an emotional hyperventilation syndrome without bronchial obstruction and/or a vocal cord dysfunction syndrome. It is possible to differentiate these "asthma" patients often clinically with the help of a stethoscope.
Pulmonary hypertension due to other lung diseases
HAPE is a consequence of hypoxic pulmonary vasoconstriction (HPV) and may be associated with other diseases that cause a significant reduction of the pulmonary vascular bed [16
]. These include interstitial and vascular lung diseases (primary forms of pulmonary hypertension and thromboembolic pulmonary diseases). Patients with lung diseases associated with pre-existing pulmonary hypertension (mean PAP > 25 mm Hg at rest) are advised against high altitude travel. If travel at altitudes above 2,500 m is unavoidable, supplemental oxygen should be administered in all patients who have pulmonary hypertension at sea level. The non-hypoxic component of pulmonary hypertension should be treated according to the therapy necessary for the specific lung disease under normobaric conditions. If the patient has no pre-existing pharmacotherapy for pulmonary hypertension they should be given as prophylaxis slow release nifedipine (20 mg b.i.d.) for the duration of the stay at altitude. Alternatives, depending on the underlying lung disease, include sildenafil, tadalafil and dexamethasone to reduce the hypoxic increase of pulmonary hypertension due to altitude exposure. The acute therapeutic response of phosphodiesterase-5 inhibitors, cortico steroids, calcium channel blockers and other pulmonary vasodilators (bosentan, iloprost) makes it impossible to predict the long-term effect of these drugs on pulmonary artery pressure either at sea level or at altitude (16).
The situation in which patients with COPD are most often exposed to altitude is when flying (Figure ), but some times they are also exposed as long-term residents. An important issue for them is the presence of bullous lung disease. In contrast to decompression in divers the expansion of these structures during altitude exposure does not appear to be a risk for pneumothorax. Increases of pulmonary artery pressure (pulmonary hypertension) are dependent on the initial pressure at departure level, the possibility of recruitment of the pulmonary vascular bed and the availability of oxygen to compensate the alveolar hypoxia induced vasoconstriction.
Figure 6 Mean pulmonary artery pressure (pap) above 30 mm hg excludes from flying without O2 increases in all 10 copd patients exposed to a cabin pressure equivalent to an altitude of 2,500 m above sea level. All patients increased their mean PAP far more than (more ...)
Since non-invasive pulmonary artery pressure measurements with ECHO are not easy to perform in COPD patients, spirometry is recommended. Patients with FEV1 < 1,5 L should be assessed with pulsoximetry and an arterial CO2 measurement. These allow to detect hypoxemia and hypercapnia today also non-invasively. If supplemental O2-breathing (2-4 L/min) does not lead to a sufficient O2 saturation of 94% (equivalent to 70-75 mm Hg PaO2) at the altitude level of assessment, the patient should not be recommended for hypoxic exposures above 2,500 m.
The same evaluation criteria can be applied to patients with cystic fibrosis
Patients with hypercapnic ventilatory failure (global respiratory insufficiency) at sea level are generally not able to sustain the increased hypoxic drive at altitude without additional oxygen breathing. Often they need also ventilatory support (non invasive ventilation). An optimal antiobstructive inhalation therapy with tiotropium bromide, indacaterol, topical steroids and possibly oral theophylline, which has also a positive effect on AMS, should be established [18
Interstitial lung diseases (ILD)
ILD generally present with hypoxemia and normoor hypocapnia. If at rest and during exercise supplemental oxygen breathing restores normal arterial pO2
values at sea level, these patients can travel to moderate altitudes without problems as long as they do not also suffer from pulmonary hypertension. In contrast to obstructive lung diseases the response of pulmonary artery pressures on O2
-breathing is more limited in patients with ILD than in those with COPD (Figure ). The restriction of the vascular bed in ILD patients is generally less functional (alveolar hypoventilation induced) but more structural. Pulmonary vasodilators (nifedipine, sildenafil) other than supplemental O2
have limited therapeutic potential, but if it can be demonstrated in an acute setting that one or a combination of these drugs lowers pulmonary hypertension, they should be administered especially for short altitude exposures [19
Figure 7 Dependency of mean pulmonary artery pressure (pap) response on O2-breathing as a function of residual volume (rv) and airway resistance (raw) % predicted. Legenda: open circles: baseline at; full circles: on oxygen. A: The response of mean PAP on O2-breathing (more ...)
Pulmonary thromboembolic disease
Patients with known thromboembolic complications, including smoking females with underlying coagulopathy and/or oral contraceptive use, are at increased risk during long distance flights or bus travel or other activities with a high degree of immobility. Restricted leg movement, venous occlusion (backpacking) and dehydration should be avoided. Any anticoagulant therapy started at sea level should be continued at altitude together with all other drugs prescribed to reduce pulmonary hypertension and disease-specific symptoms. There are anecdotal reports that lung emboli after thoracic surgery are less frequent if the operation is performed above 1,800 m compared to in lowland hospitals.
Respiratory pump disorders
Few studies have examined patients with respiratory pump disorders. Patients needing non-invasive ventilation (NIV) as a consequence of pump failure, alone or in combination with lung diseases and respiratory muscle fatigue, are generally not fit for travelling to altitudes above 2,500 m. They should also avoid long distance flights without supplemental O2-breathing and the support of a mechanical ventilator.
Patients with this syndrome are at risk of cor pulmonale and hence acute right heart failure under an additional hypoxic stress at altitude inducing more pulmonary vasoconstriction. Nocturnal hypoxemia (especially during REM sleep) due to obesity induced hypoventilation predisposes to both AMS and HAPE. Pulmonary artery pressures at altitude increase in proportion to the body mass index (BMI > 30 kg/m2, PaCO2 during the day > 45 mm Hg). Patients without daytime pulmonary hypertension who need only continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) at night can travel to moderate altitudes with their devices, but should also get prophylactic drug therapy as needed.
Obstructive and/or central sleep apnea
Patients with OSAS develop already subclinical HAPE at moderate altitudes of 2,500-3,000 m [19
]. Their symptoms of AMS benefit from 750 mg/d acetazolamide as well as fluid retention and systemic blood pressure elevation. Pulmonary gas exchange improved during the verum compared to the placebo night [20
]. Patients with pulmonary hypertension and/or day time hypoxemia at sea level need slow release nifedipine 20 mg b.i.d. with supplemental oxygen at night.
Carotid surgery and control of breathing
The hypoxemic ventilatory response is reduced in patients who have undergone endarterectomy with damage to the carotid body. These patients may show no increase of ventilation under hypoxic stress and therefore they have a high risk of developing AMS and HACE. If these patients need to travel at altitude, they should be first tested for their hyperoxic ventilatory response, to verify if there is a supplemental O2-induced hypoventilation.
Neuromuscular diseases and thoracic malformations
Patients with muscular dystrophies, diaphragmatic paralysis, amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome or severe kyphoscolioses have limited ability to increase their ventilation as required for altitude adaptation. Often they first hypoventilate during sleep at night and later during day time at sea level and need non-invasive ventilation (NIV) or bi-level positive airway pressure (BiPAP). Any prior treatment with BiPAP or NIV should be continued at altitude. Nocturnal or even 24 hour supplemental O2-breathing may be indicated to avoid at altitude an additional alveolar hypoxia-induced pulmonary vasoconstriction. Patients with kyphoscoliosis and pulmonary hypertension need additional oxygen combined with slow release nifedipine 20 mg b.i.d. In patients with bilateral diaphragmatic paralysis NIV is already indicated during moderate altitude exposure.