A. Cogo, G. Fiorenzano

Annalisa Cogo, Giuseppe Fiorenzano

COPD patients at altitude

SUMMARY

Chronic Obstructive Pulmonary Disease (COPD) is a major health problem because of its high prevalence in the general population. Sometimes COPD patients ask their physicians about the possibility either to travel in mountain regions or to go by plane. The article reviews this possibility analyzing the characteristics of COPD, the high altitude environment, the adaptations of the respiratory system to high altitude and the recommendations for the patients. COPD is characterized by airflow obstruction not fully reversible, in response to exposure to noxious particles (cigarette smoke, professional exposures, pollution) in susceptible subjects. Symptoms of COPD are cough, sputum, progressive dyspnoea. Spirometry confirms the diagnosis and allows to assess the severity of obstruction. At altitude the climate is characterized by a progressive reduction of barometric pressure, with a reduction of inspired fraction of oxygen. Other findings are the decrease of air density, temperature and humidity, and a reduction of allergens and pollutants. In normal subjects, adaptation to high altitude is characterized by hyperventilation, pulmonary vasoconstriction and increased work of breathing. COPD patients have a reduction of the respiratory reserve, with a difficult adaptation to high altitude. The major problem is the gas exchange impairment. In COPD patients it is possible to predict the PaO2 at altitude using spirometry and gas analysis at sea level, so detecting the patients that require oygen supplementation at high altitude or during flights. Inspiration of drier and colder air may be beneficial for patients with mild symptoms, but dangerous for more impaired subjects. To evaluate the possibility for COPD patients to travel at high altitude an individual evaluation is needed, including spirometry, blood gas analysis and walking test. The results may be evaluated depending on: the living altitude, the altitude of destination, the rate of ascent, the duration of stay, the amount of exercise at altitude.

Keywords: COPD, altitude, mountaineering, hypoxia, flight

ZUSAMMENFASSUNG

Chronisch obstruktive Lungenerkrankungen (COPD) stellen aufgrund ihrer hohen Prävalenz in der Bevölkerung ein bedeutendes Gesundheitsproblem dar. Die betroffenen Patienten wünschen von den behandelnden Ärzten vielfach Auskunft über mögliche Probleme in der Höhe (Bergsport, Fliegen). Der vorliegende Beitrag gibt einen Überblick über COPD Merkmale, das Höhenklima, die Adaptationen des Atemsystems in der Höhe und die Empfehlungen für COPD Patienten. COPD ist eine obstruktive Atemwegserkrankung mit Flussbehinderung bei Schadstoffexposition (z.B. Zigarettenrauch, industrielle Schadstoffe), die nicht vollkommen reversibel ist. COPD Symptome sind Husten, verstärkte Schleimproduktion und zunehmende Atemnot. Lungenfunktionstests bestätigen die Diagnose und den Schweregrad der Erkrankung. Das Höhenklima ist durch die Reduktion des Luftdruckes und des Sauerstoffpartialdruckes charakterisiert. Außerdem nehmen mit der Höhe die Luftdichte, die Temperatur und die Luftfeuchtigkeit aber auch die Konzentration von Allergenen ab. Bei gesunden Personen ist die Höhenakklimatisation durch Hyperventilation, pulmonal-arterielle Vasokonstriktion und erhöhte Atemarbeit gekennzeichnet. COPD Patienten weisen eine Einschränkung der Atemreserve mit Schwierigkeiten der Höhenadaptation auf. Bei diesen Personen ist es möglich, den PaO2 in der Höhe anhand von Lungenfunktionstests und Blutgasen vorauszusagen. Die Einatmung von kalter und trockener Luft kann für Patienten mit leichter COPD günstig sein, ist aber gefährlich für jene mit schwerer COPD. Eine Beurteilung wird anhand der Lungenfunktion, Blutgasanalyse und eines „Walking Tests“ durchgeführt. Die Ergebnisse werden in Abhängigkeit folgender Faktoren beurteilt: absolute Höhe, Dauer des Höhenaufenthaltes, Anstiegsgeschwindigkeit und körperliche Belastung in der Höhe.

Schlüsselwörter: COPD, Höhe, Bergsport, Hypoxie, Fliegen

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) (1)

COPD is a chronic disease characterized by airflow limitation which is usually progressive and not fully reversible, associated with an abnormal inflammatory response of the lung to noxious particles or gases. Is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.

According to the airflow limitation, COPD is divided in 4 stages

Stage I: Mild FEV1/FVC < 0.70 80% predicted

Stage II: Moderate FEV1/FVC < 0.70 50% FEV1 80% predicted

Stage III:Severe FEV1/FVC < 0.70 30% FEV1 50% predicted

Stage IV:Very Severe FEV1/FVC < 0.70 FEV1 30% predicted or

FEV1 50% predicted plus chronic respiratory failure

COPD prevalence, morbidity, and mortality vary across countries but are worldwide increasing. In fact, COPD is a leading cause of morbidity and mortality worldwide and is projected to increase in next future due to continued exposure to COPD risk factors (GOLD) The main risk factors for COPD is the exposure to noxious particles such as tobacco smoke, occupational dusts, indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings and outdoor air pollution. Other risk factors are: genes, oxidative stress, respiratory infections, socioeconomic status and co-morbidities. Exposure to noxious agents leads to small airways disease, characterized by airway inflammation and remodeling and to parenchyma destruction causing loss of alveolar attachments and decrease of elastic recoil. A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease. The diagnosis should be confirmed by spirometry. A post-bronchodilator (400mcg of salbutamol in four separate doses) FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible. Another important point to be taken into account is the increased risk of COPD patients for comorbidities such as ischemic heart disease, osteoporosis, diabetes, lung cancer and respiratory infections which are responsible of COPD exacerbations.

ALTITUDE

Before considering how patients suffering from chronic obstructive pulmonary disease can cope with altitude, a revision of the environmental changes at high altitude affecting the respiratory system as well as its compensatory responses is needed (2, 3). The main environmental characteristic is the progressive, nonlinear decrease in barometric pressure with increasing altitude. The main consequence of this reduction is the progressive decrease of the so called “oxygen cascade”: alveolar, arterial and tissue oxygen tension (Pa,O2) values. Ambient temperature also decreases (around 1°C every 150m) as well as the air density and the absolute humidity. The consequence is that at high altitude colder and drier air is breathed, as compared to sea-level; this fact favours the loss of water through the airways especially during exercise induced hyperventilation. Allergen and outdoor pollution exposure is usually reduced or absent in the mountain so decreasing the inflammatory stimulus to the airways.

RESPIRATORY RESPONSES TO ALTITUDE

The lung is the gate between the environmental oxygen and the metabolic machinery of the body and immediately responds to hypoxia by increasing ventilation (the so called hypoxic ventilatory response) in order to improve oxygen saturation. Hyperventilation is obtained at expense of a higher respiratory work. In healthy subjects, the increase in ventilation is at beginning obtained with an increase in tidal volume while respiratory rate increases only at higher altitude (2, 4).

PULMONARY VASCULAR SYSTEM

The second immediate response to hypoxia exposure is the pulmonary vasoconstriction. In fact, a level of alveolar hypoxia ≤70mmHg triggers hypoxic pulmonary vasoconstriction and a subsequent increase in pulmonary arterial pressure which is variable among healthy subjects.

PULMONARY MECHANICS

Various changes in pulmonary mechanics have been described at high altitude. The decreased density of the air reduces respiratory resistance and increases the flows. In many studies a decrease in forced vital capacity and slow vital capacity has been reported. These change can be due to different factors: an increase in pulmonary vascular blood, mild interstitial oedema and decreased respiratory muscle strength. As regards FEV1, conflicting results are reported:

decrease, increase or no change. These conflicting results may me due to the fact that several studies are different in the altitude at which are performed, in the rate of ascent (and the level of acclimatization). Moreover, small numbers of subjects are usually studied in each research (3, 4).

RESPIRATORY PATHOPHYSIOLOGY OF COPD

The airflow limitation and the progressive derangement of lung architecture induce several problems in COPD patients such impairment of gas exchange, increased ventilator requirements, pulmonary hypertension, respiratory muscle weakness. All of them can be affected by high altitude.

Bronchial obstruction

The reduced density of the air should reduce airflow resistance. This could be a favourable factor for mild COPD patients. For more severe patients we should also take into account the possibility that both hypoxemia and the reduced temperature of inhaled air could worsen the bronchoconstriction.

Gas exchange

The key question is to define the level of PaO2 at altitude: is the COPD patient able to maintain an adequate PaO2 or does he need supplemental oxygen? In other words, is PaO2 expected to fall below the thresholds stated by British Thoracic Society and Aerospace Medical Association guidelines of 50-55mmHg (5, 6)? Most of the available studies have examined this question during either hypoxia simulation test or during commercial flights (7-18). Only one study reports data directly obtained in the mountain (19). In any case, no data are available at altitudes above 3000m. It seems possible to predict the level of hypoxemia at altitude, combining sea-level FEV1 values with the sea-level PaO2: PaO2, Alt = (0.5196PaO2,SL)+(11.856 FEV1)–1.76 (9-12). Subjects with a predicted PaO2 with supplemental O2. (5, 6). = 50– 55 mmHg should travel to high altitude

Altitude SL PaO2 Alt PaO2 References

1900m 66 54 7

1524 68 55 19

2348 72 55 19

3048 72 50 13

As en example, we also report the data from some studies: However, it is important to note that all studies examined small numbers of patients with an average FEV1 of 1–1.5 L and without hypercapnia. No information is available for patients with more severe disease or evidence of hypercapnia.

Pulmonary hypertension

Patients with severe COPD and baseline hypoxaemia often develop pulmonary hypertension at sea level. The exposure to altitude and the relative more severe hypoxemia is expected to worsen pulmonary hypertension so putting the patients at risk for the development of high altitude pulmonary oedema or acute right heart failure These patients should be advised to avoid altitude exposure. If this is not possible, they should assume both oxygen and a prophylactic therapy (nifedipine SR 20mg b.i. d). through the duration of their stay at altitude (3).

RECOMMENDATIONS

Patients who only present with symptoms or mild airway obstruction can take advantage of the lower density and the lower humidity of the inhaled air and the reduction in air pollutants. COPD patients whose baseline FEV1 is ≤1.5 L should be assessed prior to highaltitude travel to determine the need for supplemental oxygen.

Assessment of COPD patients prior to high-altitude exposure

•Spirometry to assess the level of bronchial obstruction •Blood Gas Analysis to assess the efficiency of gas exchange •Six minute walking distance to detect the presence of oxygen desaturation during exercise at sea level Some specific questions should be asked: •The living altitude •The altitude of destination •The sleeping altitude •The rate of ascent (by cable car, bus, walking) •The duration of stay •The amount of exercise at high altitude?

In fact, the possibility to develop acute mountain sickness and to suffer from adverse events is directly related to the severity of hypoxemia which further deteriorates during sleeping (due to the onset/worsening of sleep apnoea at altitude) and exercise (3, 4).

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