Fat-free-mass-and-spirometric-changes-during-high-altitude- by asafwewe


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                                   Annalisa Cogo

    Department of Clinical and Experimental Medicine, Section of Respiratory
                      Diseases, University of Ferrara Italy


It is well known that exposure to high altitude is associated with changes in body
fluid compartments. In particular, the subjects can face with both dehydration and
peripheral oedema while spirometric changes, suggestive for extra vascular lung
fluid accumulation, can appear (17). With regard to the first point, the very low
absolute humidity at high and very high altitude can frequently cause dehydration.
This is mainly due to the fact that water loss through sweating is increased during
exercise as well as the insensible water loss induced by ventilation. Increased
ventilation is a common adaptation feature of high altitude and the level of
ventilation may be very high especially during exercise; furthermore the
hyperventilation of dry and cold air increases the water loss. Peripheral oedema is
common in newcomers at high altitude, is most frequently localized at the fingers
and the face and is due to an increase in extra cellular fluid. Both exercise and
hypoxia have been reported to have an additive effect on body fluid shift (17). With
regard to the second point (extra vascular lung fluid accumulation), the exposure to
high altitude is known to induce changes in spirometry, including an increase in
flow rates, and a fall in vital capacity (VC) and forced vital capacity (FVC). After
the first observation made by Angelo Mosso in 1897 (10) who observed a mean
11% decrease in VC at 4559m as compared to sea level, in many papers the
reduction of FVC and of flows at the last part of FVC has been reported (1, 6, 8, 9,
13). The potential explanation for reduced forced vital capacity and vital capacity at
high altitude can be summarized as follows: an increase in pulmonary blood
volume; the development of interstitial lung oedema; respiratory muscles weakness.

The presence of interstitial lung oedema is supported by many data, especially the
increase in closing volume, indicating small airways compression by extra vascular
lung fluid accumulation, which has been reported in 74% of ~250 recreational
climbers at 4559 (2). According to this paper, increased pulmonary extra vascular
lung fluid would track centrally along major pulmonary vessels and airways.
Peribronchial fluid accumulating in this way would be expected to compress
airways increasing the volume at which airways close. An increased permeability of
capillary endothelium could at least in part explain the increase of interstitial lung
fluid. Actually a growing number of papers have shown that hypoxia increases
capillary endothelial permeability both in vivo and in vitro (4, 7, 11, 16). We aimed
to answer to the following questions: at which altitude does the lung interstitial
oedema appear? Does it appear also in elite climbers? Is endothelial permeability a

Material and Methods
We studied 18 subjects: 9 recreational climbers (Nepal 2003) and 9 elite climbers
(Everest 2004) during two different studies with similar study design and similar
ascent profile. None suffered from AMS.
Nepal 2003: We studied 9 recreational climbers, 4 females and 5 males with a mean
age 35,2 at different altitudes during the trekking to the Pyramid Laboratory
(5050m). The subjects have been studied at sea level, 3500m and 5050m the first
day after the arrival. Forced expiration curve and oscillatory resistances have been
assessed to detect early peripheral airways obstruction and urinary proteins, as an
indirect signs of endothelial permeability, have been measured. Subjects collected
urines for 24 hours in a rest day to avoid the effect of exercise on urinary proteins.
Everest 2004: We studied 9 elite climbers, all males with a mean age 39,8. The
subjects have been studied at sea level, and at 5200m (Everest North base camp) the
first day after the arrival and after 10 days. Between the 1° and 10° day all subjects
climbed up to 6500-7000m.
Slow and forced spirometry has been performed. Furthermore in order to test the
presence of abnormalities in the small airways, maximal and partial expiration flow
volume curves have been assessed. . In fact the effects of deep inhalation on airway

calibre are believed to reflect the distensibility of intraparenchimal airways. After 2
min. of regular tidal breathing the subjects are asked to expire forcefully from 70%
FVC to empty the lungs and to inspire immediately to full the lungs and to expire
again forcefully and completely. The Maximal to Partial (M/P) ratio is considered
an index of the effect of deep inhalation: in particular, M/P = 1 no effect of deep
inhalation on airway calibre;       M/P < 1 bronchoconstrictor effect; M/P > 1
bronchodilator effect (12).
To test the hypothesis that increased endothelial permeability can contribute to lung
fluid accumulation urinary micro albumin (overnight urine collection 8pm-8am) as
an indirect index of endothelial permeability has been measured.

Nepal 2003 (Table 1)
Expiratory flows in the first part of forced expiration are significantly increased at
altitude. The forced vital capacity and the flows at the last part of the expiration
curve (FEF75%) are decreased at 3500m but the difference is not statistically
significant while at 5050m the difference is significant as compared to sea level.
FEV1 did not show any significant change and the ratio FEV1/VC was always
>70%. Oscillatory resistances (Rs) are significantly reduced at 3500m while at
5050m there is a tendency to rise with an intermediate value between sea level and
3500m. On the other hand the reactance (Xrs) is significantly lower already at
3500m and further decreases at 5050m. The urinary proteins are significantly
increased at 3500m and 5050m as compared to sea level.
Everest 2004 (Table 2)
Peak expiratory flows at altitude are significantly higher than at sea level. The slow
and forced vital capacity is significantly reduced at base camp 1 with no difference
between maximal and partial curve (M/P = 1.09). Urinary micro albumin is
significantly increased. At base camp 2 all values are similar to sea level but the
M/P ratio is significantly lower.
Conclusion and Discussion

Nepal 2003
High altitude exposure induces changes in lung volume and flow rates. The
mechanisms of these changes are multi factorial in origin. The increase of
expiratory flows, in particular peak expiratory flow, and the decrease of airway
resistance at 3500m, are expected and are due to the reduced density of the air.
Hypoxia exposure induces an endothelial permeability increase, which is already
evident at 3500m, an altitude at which the mean oxygen saturation is 90%. The
spirometric changes, as detected by forced expiration curve, become evident only at
5050m as shown by the significant decrease of FEF75% and the lack of further
decrease of oscillatory resistance. If only these values would be taken into account it
could result that extra vascular lung fluid accumulation does not immediately follow
the increased capillary permeability during exposure to high altitude. Really a very
interesting result has been found with the measurement of oscillatory resistances
and reactance. In fact a significant reduction of reactance (but not increase of
resistance) has been found at 3500, suggesting that changes in the mechanical
properties of the lungs are already present. In fact, it has been recently reported that
the reactance of the respiratory system can predict transpulmonary resistance more
accurately than can resistance of the respiratory system (5). We can therefore
conclude that the early changes in endothelial permeability and in lung function
(indicating distal airways obstruction probably due to extra vascular lung fluid
accumulation) are already present at 3500m and become more evident at higher
Everest 2004
The significant reduction of flows at the last part of Forced Vital Capacity after the
first night > 5000m, with no difference between Maximal and Partial expiration, can
be interpreted as narrowing of the “small airways” (14, 15). The narrowing of the
small airways could be due to the compressing effect of extra vascular lung fluid
accumulation. Increased endothelial permeability can contribute to extra vascular
lung fluid accumulation. After 9 days at altitudes above 5200m (climbing up to
6500-7000m), a deep inhalation induces a reduction of expiratory flows simulating
a “bronchoconstrictor effect”. Two hypothesis could explain these result: 1)

climbing to very high altitude while breathing cold dry air might have altered the
airway cytokine profile inducing airway inflammation. This is supported by a recent
study (3). Lung elastic recoil decreases more than airway recoil and this could be
due to increased airway wall stiffness probably due to a small but still present
airway wall oedema. Further studies are requested to better understand this
High altitude exposure induces significant changes in lung function. The
mechanisms of these changes are multi factorial in origin but the development of
interstitial oedema can play a role. From our research we can summarize that these
changes affect both elite and recreational climbers, are evident starting from 3500m
(an altitude at which hypoxemia becomes evident); are more pronounced at 5000m;
decrease after 7 days but in any case don’t preclude a successful climbing at
extreme altitudes.

                  Italian Institute for the Mountain and EV-K2-CNR Committee
                               for financial and logistic support

NEPAL 2003                                                           EVEREST 2004
Daniela Bonardi                                                      Luciano Bernardi
Federica Campigotto                                                  Elisa Paolucci
Alfredo Donnaloja                                                    Luca Pomidori
Marco Farinatti                                                      Annette Schneider
Valter Fasano
Annalisa Fioretti                                                    All Climbers
Alessandra Gennari
Luca Pomidori
Fabrizio Tagliavini,
Gabriele Valli


1. Cogo A, Legnani D, Allegra L. Respiratory function at different altitudes.
   Respiration. 1997;64(6):416-21.

2. Cremona, G, Asnaghi R, Baderna P, Brunetto A, Brutsaert T, Cavallaro C,
   Clark TM, Cogo A, Donis R, Lanfranchi P, Luks A, Novello N, Panzetta S,
   Perini L, Putnam M, Spagnolatti L, Wagner H, and Wagner PD. Pulmonary
   extravascular fluid accumulation in recreational climbers: a prospective
   study. Lancet 359: 303-309, 2002.

3. Davis MS, Malayer JR, Vandeventer L, Royer CM, McKenzie EC,
   Williamson KK. Cold weather exercise and airway cytokine expression. J
   Appl Physiol. 2005 Jun;98(6):2132-6.

4. Hansen JM, Olsen NV, Feldt-Rasmussen B, Kanstrup IL, Dechaux M,
   Dubray C, Richalet JP. Albuminuria and overall capillary permeability of
   albumin in acute altitude hypoxia. J Appl Physiol 1994;76(5):1922-7.

5. Johnson MK et al Use of reactance to estimate transpulmonary resistance.
   Eur Respir J, 25, 1061-1069, 2005.

6. Jaeger JJ, Sylvester JT, Cymerman A, Berberich JJ, Denniston JC, Maher
   JT. Evidence for increased intrathoracic fluid volume in man at high altitude.
   J Appl Physiol. 1979 Oct;47(4):670-6.

7. Lewis DM, Bradwell AR, Shore AC, Beaman M, Tooke JE. Capillary
   filtration coefficient and urinary albumin leak at altitude. Eur J Clin Invest
   1997; 27(1):64-8.
8. Mansell A, Powles A, Sutton J. Changes in pulmonary PV characteristics of
   human subjects at an altitude of 5,366 m. J Appl Physiol. 1980 Jul;49(1):79-

9. Mason, NP, Barry PW, Pollard AJ, Collier DJ, Taub NA, Miller MR, and
   Milledge JS. Serial changes in spirometry during an ascent to 5,300 m in the
   Nepalese Himalayas. High Alt Med Biol 1: 185-195,2002.

10. Mosso A. Fisiologia dell’uomo sulle Alpi. Treves, Torino 1897.

11. Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D.
    Hypoxia modulates the barrier and coagulant function of cultured bovine
    endothelium. Increased monolayer permeability and induction of
    procoagulant properties. J Clin Invest 1990; 85(4):1090-8.

12. Pellegrino R, Sterk PJ, Sont JK, Brusasco V. Assessing the effect of deep
    inhalation on airway calibre: a novel approach to lung function in bronchial
    asthma and COPD. Eur Respir J. 1998 Nov;12(5):1219-27

13. Wilson CM, Bakewell SE, Miller MR, Hart ND, McMorrow RC, Barry PW,
    Collier DJ, Watt SJ, Pollard AJ. Increased resting bronchial tone in normal
    subjects acclimatised to altitude. Thorax. 2002 May;57(5):400-4.

14. PT Macklem The physiology of small airways Am J Respir Crit Care Med
    157, S181-S183, 1998.

15. AJ Woolcock Effect of drugs on small airways. Am J Respir Crit Care Med
    157, S203-S207, 1998.

16. Yan SF, Ogawa S, Stern DM, Pinsky DJ. Hypoxia-induced modulation of
    endothelial cell properties: regulation of barrier-function and expression of
    interleukin-6. Kidney Int; 51(2):419-25, 1997.

17. Ward MP, Milledge JS, West JB. High Altitude Medicine and Physiology
    Chapman and Hall , London, 2001.

Data obtained in recreational climbers
Results of respiratory function test are expressed as % of sea level value. Results of
urinary protein, oscillatory resistances and reactance are expressed as absolute

                         sl                       3500m                5050m
PEF                      100                      120,2(2)**           132,3(3,3)**
FVC                      100                      94,50 ± 3,49**       90,97 ± 2,46**
FEF75                    100                      90,2(1)              92,6(1,9)
OR 6-10 Hrz              2,13(.2)                 1,7(.2)**            2,02(.15)
Xrs                      0,39 (.13)               -0,54 (.2)**         -0,89 (.15)**
Urin Prot (mg/dl)        5                        27,4(3)**            24,3(4)**

**=p<.05 compared to sea level


Data obtained in elite climbers (Everest 2004).

Results of respiratory function test are expressed as % of sea level value. Results of
urinary microalbumin and oxygen saturation are expressed as absolute value.

                              SL                5200m 1°day        5200m 10°day
FVC                           100               75,5(3,3)**        94,1(1,2)
FEF75                         100               70 (5,1)**         86(4,8)
M/P40                         1,024(0,06)       1,09(0,08)         0,79(0,06)**
urin.alb. mcg/min             3,7(0,7)          8,8(1)**           5(1,4)
SpO2%                    99                     69,3(1)**          79(1)** ^^
**=p<.05 compared to sea level


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