Nasal peak inspiratory flow at altitude.

The present study investigated whether there are changes in nasal peak inspiratory flow (NPIF) during hypobaric hypoxia under controlled environmental conditions. During operation Everest III (COMEX '97), eight subjects ascended to a simulated altitude of 8,848 m in a hypobaric chamber. NPIF was recorded at simulated altitudes of 0 m, 5,000 m and 8,000 m. Oral peak inspiratory and expiratory flow (OPIF, OPEF) were also measured. Ambient air temperature and humidity were controlled. NPIF increased by a mean +/- SD of 16 +/- 12% from sea level to 8,000 m, whereas OPIF increased by 47 +/- 14%. NPIF rose by 0.085 +/- 0.03 L x s(-1) per kilometre of ascent (p<0.05), significantly less than the rise in OPIF and OPEF of 0.35 +/- 0.10 and 0.33 +/- 0.04 L x s(-1) per kilometre (p<0.0005). Nasal peak inspiratory flow rises with ascent to altitude. The rise in nasal peak inspiratory flow with altitude was far less than oral peak inspiratory flow and less than the predicted rise according to changes in air density. This suggests flow limitation at the nose, and occurs under controlled environmental conditions, refuting the hypothesis that nasal blockage at altitude is due to the inhalation of cold, dry air. Further work is needed to determine if nasal blockage limits activity at altitude.

Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350 m.

It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate. To evaluate the effect of L-arginine on the NO release in high altitude, 11 subjects were infused with L-arginine (0.5 g x kg(-1)) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The L-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. L-citrulline concentration, arterial oxygen saturation (Sa,O2), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion. The results showed that baseline L-citrulline was lower in hypoxia (p<0.05). L-arginine infusion increased L-citrulline concentration in both conditions. However, in hypoxia L-citrulline concentration remained lower than in normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In hypoxia, Sa,O2 increased from 15 min after the start of the infusion to 45 min (p<0.05). Blood pressure and heart rate were not affected by L-arginine infusion. Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with L-arginine. The decreased L-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in L-arginine availability. The improvement of arterial oxygen saturation by pretreatment with L-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.

Operation Everest III: role of plasma volume expansion on VO(2)(max) during prolonged high-altitude exposure.

We hypothesize that plasma volume decrease (DeltaPV) induced by high-altitude (HA) exposure and intense exercise is involved in the limitation of maximal O(2) uptake (VO(2)(max)) at HA. Eight male subjects were decompressed for 31 days in a hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal exercise was performed with and without plasma volume expansion (PVX, 219-292 ml) during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6, 000 m after 10-12 days) and after return to SL (RSL, 1-3 days). Plasma volume (PV) was determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by 26% (P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced DeltaPV was reduced both by PVX and HA (P < 0.05). Compared with SL, VO(2)(max) was decreased by 58 and 11% at HA and RSL, respectively. VO(2)(max) was enhanced by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at HA, the more VO(2)(max) was improved by PVX (P < 0.05). At exhaustion, plasma renin and aldosterone were not modified at HA compared with SL but were higher at RSL, whereas plasma atrial natriuretic factor was lower at HA. The present results suggest that PV contributes to the limitation of VO(2)(max) during acclimatization to HA. RSL-induced PVX, which may be due to increased activity of the renin-aldosterone system, could also influence the recovery of VO(2)(max).

Serial changes in spirometry during an ascent to 5,300 m in the Nepalese Himalayas.

The aims of the present study were to determine the changes in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and peak expiratory flow (PEF), during an ascent to 5,300 m in the Nepalese Himalayas, and to correlate the changes with arterial oxygen saturation measured by pulse oximetry (SpO2) and symptoms of acute mountain sickness (AMS). Forty-six subjects were studied twice daily during an ascent from 2,800 m (mean barometric pressure 550.6 mmHg) to 5,300 m (mean barometric pressure 404.3 mmHg) during a period of between 10 and 16 days. Measurements of FVC, FEV1, PEF, SpO2, and AMS were recorded. AMS was assessed using a standardized scoring system. FVC fell with altitude, by a mean of 4% from sea level values [95% confidence intervals (CI) 0.9% to 7.4%] at 2,800 m, and 8.6% (95% CI 5.8 to 11.4%) at 5,300 m. FEV1 did not change with increasing altitude. PEF increased with altitude by a mean of 8.9% (95% CI 2.7 to 15.1%) at 2,800 m, and 16% (95% CI 9 to 23%) at 5,300 m. These changes were not significantly related to SpO2 or AMS scores. These results confirm a progressive fall in FVC and increase in PEF with increasing hypobaric hypoxia while FEV1 remains unchanged. The increase in PEF is less than would be predicted from the change in gas density. The fall in FVC may be due to reduced inspiratory force producing a reduction in total lung capacity; subclinical pulmonary edema; an increase in pulmonary blood volume, or changes in airway closure. The absence of a correlation between the spirometric changes and SpO2 or AMS may simply reflect that these measurements of pulmonary function are not sufficiently sensitive indicators of altitude-related disease. Further studies are required to clarify the effects of hypobaric hypoxia on lung volumes and flows in an attempt to obtain a unifying explanation for these changes.

Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude.

The aim of this study was to determine the frequency of cough and the citric acid cough threshold during hypobaric hypoxia under controlled environmental conditions. Subjects were studied during Operation Everest 3. Eight subjects ascended to a simulated altitude of 8,848 m over 31 days in a hypobaric chamber. Frequency of nocturnal cough was measured using voice-activated tape recorders, and cough threshold by inhalation of increasing concentrations of citric acid aerosol. Spirometry was performed before and after each test. Subjects recorded symptoms of acute mountain sickness and arterial oxygen saturation daily. Air temperature and humidity were controlled during the operation. Cough frequency increased with increasing altitude, from a median of 0 coughs (range 0-4) at sea level to 15 coughs (range 3-32) at a simulated altitude of 8,000 m. Cough threshold was unchanged on arrival at 5,000 m compared to sea level (geometric mean difference (GMD) 1.0, 95% confidence intervals (CI) 0.5-2.1, p=0.5), but fell on arrival at 8,000 m compared to sea level (GMD 3.3, 95% CI 1.1-10.3, p=0.043). There was no relationship between cough threshold and symptoms of acute mountain sickness, oxygen saturation or forced expiratory volume in one second. Temperature and humidity in the chamber were controlled between 18-24 degrees C and 30-60%, respectively. These results confirm an increase in cough frequency and cough receptor sensitivity associated with hypobaric hypoxia, and refute the hypothesis that high altitude cough is due to the inhalation of cold, dry air. The small sample size makes further conclusions difficult, and the cause of altitude-related cough remains unclear.

Treatment of cancer of the exocrine pancreas.

BACKGROUND: The incidence of cancer of the exocrine pancreas varies among populations, being the fourth or fifth cause of cancer death in the West. Outcome remains poor and opinions remain divided over the optimal management of the condition. METHOD: A computer literature search was made of the MEDLINE database from January 1990 to December 1997 and selected other studies. RESULTS: Indications and contraindications for surgery, indications for stenting, indications for resection, the technique of palliative procedures and of resection, chemotherapy, radiotherapy, and combined treatments and other treatments are discussed and recommendations made. CONCLUSIONS: Irrespective of tumor size or spread, resection if feasible gives the best survival rates. Careful patient selection is required, however, to exclude those patients for whom surgical resection has no benefit. Nonsurgical procedures including endoscopic stenting in patients with high operative risk or short survival expectancy can significantly improve quality of life. The place of adjuvant therapies remains controversial and further controlled trials are required to demonstrate their efficacy.

Operation Everest III (COMEX '97). Effects of prolonged and progressive hypoxia on humans during a simulated ascent to 8,848 M in a hypobaric chamber.

Exposure to high altitude induces physiological or pathological modifications that are not always clearly attributable to a specific environmental factor: hypoxia, cold, stress, inadequate food. The principal goal of hypobaric chamber studies is to determine the specific effect of hypoxia. Eight male volunteers ("altinauts"), aged 23 to 37 were selected. They were first preacclimatized in the Observatoire Vallot (4,350 m) before entering the chamber. The chamber was progressively decompressed down to 253 mmHg barometric pressure, with a recovery period of 3 days at 5,000 m in the middle of the decompression period. They spent a total of 31 days in the chamber. Eighteen protocols were organized by 14 European teams, exploring the limiting factors of physical and psychological performance, and the pathophysiology of acute mountain sickness (AMS). All subjects reached 8,000 m and 7 of them reached the simulated altitude of 8,848 m. Three altinauts complained of transient neurological symptoms which resolved rapidly with reoxygenation. Body weight decreased by 5.4 kg through a negative caloric balance. Only four days after the return to sea-level, subjects had recovered 3.4 kg, i.e. 63% of the total loss. At 8,848 m (n = 5), PaO2 was 30.6 +/- 1.4 mmHg, PCO2 11.9 +/- 1.4 mmHg, pH 7.58 +/- 0.02 (arterialized capillary blood). Hemoglobin concentration increased from 14.8 +/- 1.4 to 18.4 +/- 1.5 g/dl at 8,000 m and recovered within 4 days at sea-level. AMS score increased rapidly at 6,000 m and was maximal at 7,000 m, especially for sleep. AMS was related to alteration in color vision and elevation of body temperature. VO2MAX decreased by 59% at 7,000 m. The purpose of this paper is to give a general description of the study and the time course of the main clinical and physiological parameters. The altinauts reached the "summit" (for some of them three consecutive times) in better physiological conditions than it would have been possible in the mountains, probably because acclimatization and other environmental factors such as cold and nutrition were controlled.

Cough frequency and cough-receptor sensitivity are increased in man at altitude.

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher. 2. Cough frequency, monitored in ten subjects, increased from a median of 0 coughs at sea level (range 0-1) to 5 coughs at 5000 m (range 0-13) and to over 60 coughs in subjects ascending to 7000 m. Citric acid cough threshold, measured in 42 subjects, was unchanged on arrival at 5300 m compared with sea level (geometric mean difference 1.26, 95% confidence intervals 0.84-1.89, P = 0.25), but was significantly reduced after 6 days, or more, at altitude compared with sea level (geometric mean difference 2.2, 95% confidence intervals 1.54-3.15, P = 0.0002). Cough threshold was not related to symptoms of acute mountain sickness, oxygen saturation, carbon dioxide tension or lung function. 3. These results indicate an increase in cough and cough-receptor sensitivity after some days at altitude. This may be due to respiratory tract damage from breathing cold dry air at increased ventilatory rates. Other explanations, such as sub-clinical pulmonary oedema or an effect on the cough centre of acclimatization to altitude, cannot be excluded.

Hypoxia, hypocapnia and spirometry at altitude.

1. Both hypoxia and hypocapnia can cause broncho-constriction in humans, and this could have a bearing on performance at high altitude or contribute to altitude sickness. We studied the relationship between spirometry, arterial oxygen saturation and end-tidal carbon dioxide (ETCO2) concentration in a group of healthy lowland adults during a stay at high altitude, and then evaluated the response to supplementary oxygen and administration of a beta 2 agonist. 2. We collected spirometric data from 51 members of the 1994 British Mount Everest Medical Expedition at sea level (barometric pressure 101.2-101.6 kPa) and at Mount Everest Base Camp in Nepal (altitude 5300 m, barometric pressure 53-54.7 kPa) using a pocket turbine spirometer. A total of 205 spirometric measurements were made on the 51 subjects during the first 6 days after arrival at Base Camp. Further measurements were made before and after inhalation of oxygen (n = 47) or a beta 2 agonist (n = 39). ETCO2 tensions were measured on the same day as spirometric measurements in 30 of these subjects. 3. In the first 6 days after arrival at 5300 m, lower oxygen saturations were associated with lower forced expiratory volume in 1 s (FEV1; P < 0.02) and forced vital capacity (FVC; P < 0.01), but not with peak expiratory flow (PEF). Administration of supplementary oxygen for 5 min increased oxygen saturation from a mean of 81%-94%, but there was no significant change in FEV1 or FVC, whilst PEF fell by 2.3% [P < 0.001; 95% confidence intervals (CI) -4 to -0.7%]. After salbutamol administration, there was no significant change in PEF, FEV1 or FVC in 35 non-asthmatic subjects. Mean ETCO2 at Everest Base Camp was 26 mmHg, and a low ETCO2 was weakly associated with a larger drop in FVC at altitude compared with sea level (r = 0.38, P < 0.05). There was no correlation between either ETCO2 or oxygen saturation and changes in FEV1 or PEF compared with sea-level values. 4. In this study, in normal subjects who were acclimatized to hypobaric hypoxia at an altitude of 5300 m, we found no evidence of hypoxic broncho-constriction. Individuals did not have lower PEF when they were more hypoxic, and neither PEF nor FEV1 were increased by either supplementary oxygen or salbutamol. FVC fell at altitude, and there was a greater fall in FVC for subjects with lower oxygen saturations and probably lower ETCO2.

Nasal mucociliary transport is impaired at altitude.

There have been a number of anecdotal reports of rhinitis and nasal obstruction occurring at altitude. To quantify these reports, we investigated nasal obstruction and mucociliary transport in a group of healthy volunteers trekking to Mount Everest Base Camp, Nepal, altitude 5,300 m. Nasal obstruction was estimated by subjective scoring and mucociliary transport was determined by the saccharin method. Subjective assessment showed that nasal obstruction was increased on arrival at 5,300 m in 23 out of 54 subjects, unchanged in 24, and decreased in seven (McNemar's test: chi 2 = 7.5; p < 0.01). The median saccharin time at sea level was 11 min (95% confidence interval (95% CI) 8-17 min) and increased to 60 min (95% CI 27-60 min) on arrival at 5,300 m. Compared to sea level, the saccharin time was prolonged in 25 out of 33 subjects (McNemar's test: chi 2 = 14.7; p < 0.01), and remained prolonged after 2 weeks at altitude (median 60 min; 95% CI 38-60 min). These results confirm the subjective feelings of nasal obstruction and show that nasal mucociliary transport times are increased at altitude. The mechanisms of these findings are not clear, but nasal obstruction may impede breathing and adversely affect performance at altitude.

Effect of altitude on spirometric parameters and the performance of peak flow meters.

BACKGROUND: Portable peak flow meters are used in clinical practice for measurement of peak expiratory flow (PEF) at many different altitudes throughout the world. Some PEF meters are affected by gas density. This study was undertaken to establish which type of meter is best for use above sea level and to determine changes in spirometric measurements at altitude. METHODS: The variable orifice mini-Wright peak flow meter was compared with the fixed orifice Micro Medical Microplus turbine microspirometer at sea level and at Everest Base Camp (5300 m). Fifty one members of the 1994 British Mount Everest Medical Expedition were studied (age range, 19-55). RESULTS: Mean forced vital capacity (FVC) fell by 5% and PEF rose by 25.5%. However, PEF recorded with the mini-Wright peak flow meter underestimated PEF by 31%, giving readings 6.6% below sea level values. FVC was lowest in the mornings and did not improve significantly with acclimatisation. Lower PEF values were observed on morning readings and were associated with higher acute mountain sickness scores, although the latter may reflect decreased effort in those with acute mountain sickness. There was no change in forced expiratory volume in one second (FEV1) at altitude when measured with the turbine microspirometer. CONCLUSIONS: The cause of the fall in FVC at 5300 m is unknown but may be attributed to changes in lung blood volume, interstitial lung oedema, or early airways closure. Variable orifice peak flow meters grossly underestimate PEF at altitude and fixed orifice devices are therefore preferable where accurate PEF measurements are required above sea level.