113
Archives Internationales de Physiologie, de Biochimie et de Biophysique, 1992, 100, 113-1 19
Requ le 24 mars 1991.
The respiratory sensation a t high altitude BY
M.-J. DEL VOLGO and M.-C. NOEL-JORAND (Laboratoire de Physiologie, FacultP de MPdecine Secteur Nord, Marseille, France)
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
(6 figures)
The respiratory sensation was studied in Nepal at four different altitudes, 1377 m before and after the ascension, 2800 m, 3900 m and 530 m. Dyspnea was noted at each altitude for the nine subjects. They had to rate 4 external resistive loads between 2.5 and 13 cm H,O.l-'.s, presented in 2 pairs, a low and a high one. The discrimination between the loads i.e. the subject's sensitivity was obtained from Sensory Decision Analysis. These subjects were compared to six normal ones observed at sea level while breathing air, an hypoxic mixture (FIP, : 11 Yo) and air in a cold environment ( - 6°C). In these protocols, the load perception was not modified. The 2 populations exhibited a similar sensitivity when observed in normal conditions. At exertion and with altitude, the nine subjects demonstrated a progressive increase in dyspnea, rated with visual analog scales. At rest, the perception of the loads was not altered but slightly improved with altitude for 6 subjects. The other 3 subjects (2 subjects with clinical impairment, important dyspnea and pulmonary oedema) showed an impairment of the perception. The sensitivity to the loads was similar before and after the ascension for the well adapted subjects to altitude. In conclusion, the respiratory sensation is not impaired with altitude in well adapted subjects and transient hypoxia does not result in change in load perception. An impairment in load perception observed in some subjects is probably related to the secondary effects of chronic hypoxia, i.e. cerebral and/or pulmonary suboedema.
Introduction Well adapted subjects report an increase in dyspnea during exercise at altitude and breathing becomes dramatically discomfortable for climbers with pulmonary oedema. In this context and with reference et to our studies (BONNELet al., 1985, 1987; MATHIOT al., 1986) of resistive load perception at sea level, we were interested in studying the respiratory sensation of subjects from low altitude to high altitude. In normal subjects, the possible modifications in respiratory sensation at altitude could result from various factors, such as hypoxia, hypocapnia, an increase in low density air ventilation or a cold environment. The role of hypoxia in dyspnea is conflicting of 1985) and it was either direct or indirect effect (ALTOSE, studied in resistive load perception at rest at altitude. Unloading by heliox breathing results in an impairment et al., 1986) for a same of load perception (MATHIOT level of ventilation. Furthermore, in subjects with pulmonary or cerebral oedema, the modifications should be more important. In this difficult context, the chief purpose of the study was to observe how healthy subjects experience the respiratory sensation at altitude ranging from 1377 m to 530 m. In other words and more precisely, the
question being asked was : can the high altitude adapted subject discriminate between high and low loads as well as he can at low altitude or at sea level. The subject's sensitivity to resistive loads was obtained from Sensory Decision Analysis (GREEN& SWETS,1974). These subjects, familiar with altitude, were compared to normal subjects observed at sea level while breathing air, an hypoxic mixture and air in a cold environment.
Methods
Subjects : In Nepal, we studied 9 european subjects between 22 and 51 years of age (Table I), included two guides. These healthy subjects, without a history of cardiopulmonary or respiratory disease, were familiar with altitude and they were selected for this reason. They had volunteered for the experiment and been recruited in France where they were submitted to respiratory measurements at 1000 m (Table I). At sea level, the respiratory sensation of 8 volunteers, all normal and non smoking subjects, was studied in 2 experimental conditions consisting in the inhalation of an hypoxic mixture and breathing in a cold environment. Their ages ranged between 30 and
114
M.-J. DEL VOLGO AND M.-C.
NOEL-JOMND
TABLEI. Respiratory measures before the expedition in Nepal.
-----lT Subject
7
Age (YO
Weight (Kg)
Height (cm)
FEVl/VC
MET
(VO)
(S)
49 26 43
51 46 42 22 51
79 58 60 56 60 70 77 55 53
176 163 170 166 155 176 179 170 159
65 81 76 61 65 84 59 86 78
1.19 0.52 0.59 1.52 1.15 0.46 0.90 0.51 0.70
81 83 86 76 70 76 81 90 82
97 91 96 96 96 96 97 97 91
42 11
63 10
168 8
73 10
0.84 0.37
81 6
96.5 0.5
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
~~
CRE ANC NOE SIM vou* vou* CHA* MON BRO*
m SD
46
53 (mean = 42) with spirometry indices within their predicted normal range.
Respiratory function measurements The spirometric values of the subjects studied in Nepal were obtained in France, from electrical integration of the flow signal (HP4780A; Hewlett-Packard) (Table I). The spirometric characteristics of the other 8 subjects were determined with a Pulmonet I11 Gould. For all subjects, measurements of arterial gases and SaOz were achieved with an ABL 330 Radiometer analyser and an OSM2 oxymeter respectively.
Loaded breathing apparatus The subjects, comfortably seated, wore a nose-clip and mouth piece connected to a Rudolph valve (no 1400). A rigid plastic tube (internal diameter : 3 cm; length : 70 cm) was interposed between the inspiratory side of the Rudolph valve and a 4-way stopcock with the latter placed on the back of the chair so as to be hidden from the subject's view. The additional resistors consisted of brass cylinders drilled to different diameters connected to the stopcock. At sea level, the basal circuit resistance was 1.6 cmHZO.l-'.s and the resistances of the added loads were 2.5 (Ll), 4 (L2), 4.5 (L3) and 13 (L4) cmHzO.l-'.s at an airflow rate of 1 1 . P . The values were 1.4; 2.6; 2.9 and 7.4 respectively at an airflow rate of 0.5 1.s-'. The subjects had to rate the loads in pairs, a low with L1 and L2 and a high pair, with L3 and L4.
General procedure The subject was connected to the circuit and breathed for 2 min without the added resistor in order to adapt to the apparatus and to its minimal resistance. After familiarization with the apparatus and the environment, the loads and their values were presented to the subject. He was instructed that the inspiratory side of the circuit would be loaded only and that during
each experimental session, the load would have two different values : either low (L1 and L2) or high (L3 and L4). Before the experimental sessions, a minimum number of training trials were performed with each of the loads. Each load was presented for a single breath and the rating experiment consisted in asking the subject to quantify his sensation after each load presentation by using a five point scale : 1) very slight intensity, 2) slight intensity, 3) moderate intensity, 4) important intensity, 5) very important intensity. During the test procedure, the subjects underwent two sessions of 100 trials blocked into two halves, in order to induce a contrast effect by pairing an intermediate value (L2) out of the four selected loads with a lower one (Ll), and the next intermediate value (L3) with a higher value (L4). One half consisted of 25 L1 and 25 L2 trials, the other half, 25 presentations each of L3 and L4. Each load was selected by turning the handle of the stopcock during the expiration preceding the tested inspiration. The subject's answer was given immediately and no abstention was permitted. During each half, the order of the load presentation was random. Which of the two pairs was chosen in the first half of each session was also randomly determined.
Specific procedures At altitude The experiment started in Kathmandou (1377 m, 860 mb) and was carried out at 3 different altitudes, 2800 m (720 mb), 3900 m (632 mb), 5300 m (525 mb) and again on return at 1377 m. For each experiment, the subjects were observed in the first hours (between 12 and 36) of their reaching these altitudes. From Kathmandou, they walked with light loads and arrived at 2800 m one day later, at 3900 m 4 days later and at 5300 m 6 days later. They returned to Katmandou 22 days after their departure. Before the specific experiment of respiratory sensation, breathing frequency and pulse rate were obtained.
115
RESPIRATORY SENSATION AND ALTITUDE
The load perception was carried out in the most comfortable environment in guest-houses. After this experiment, the subjects performed a physical exercise (20 leg-flexions) and they were asked to rate their breathing discomfort with a visual analog scale, i.e. an horizontal line of 10 cm, from no breathing discomfort to very important breathing discomfort.
.mtn-l
90
80
80
At sea level (below 200 m)
70
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
60
The load perception was carried out with six subjects in 2 different experimental conditions. (1) While breathing a hypoxic ( 0 2 : 11070 and N2) mixture or air from a compressed origin in order to obtain the same experimental installation. The humidified gases were collected in a Douglas bag. The loads were interposed by means of plastic tubes between the issue of the bag and the stopcock. (2) In 7 subjects, the respiratory sensation was tested in 2 ambient temperature conditions, moderate (24°C) and cold ( - 6°C). The 2 conditions of each protocol were randomly determined for each subject.
Data analysis In each experiment, the data were treated for individual subjects by means of a direct plot of mean numerical rating (from 1, very slight intensity) against load values. Another technique was also used for each pair by means of the conventional ‘Receiver Operating Characteristic’ (7)’ which was fully described by the present authors (2). Briefly, an ROC describes the relation between the proportion of true positive and false positive decisions mapped by changes in the subject’s decision criterion. In the present discrimination experiment, the lower load of each pair was assimilated to ‘noise’ and the higher to ‘signal’ alternative. The subject’s ratings were treated as separate binary cut-offs, each of which being used to map the subject’s judgment into ‘positive’ and ‘negative’ decisions. This simulated the use of four distinct criteria for making positive decisions, from very stringent (‘very important intensity’ versus all lower categories) to very lax (all categories versus ‘very slight intensity’). This procedure yielded four points on the ROC curve for each experimental session. The non-parametric sensitivity index, P (A), corresponds to the area under each ROC curve; its expected values vary between 0.5 or less and 1.0 as detection improves from chance level or bad perception to perfect. In the present experiment, P (A) reflects the subject’s ability to discriminate between the two loads in each pair. This index is independent of response bias from the subject. For statistical analysis, we used the non parametric Mann-Whitney U test and Wilcoxon signed rank Ttest. Correlation were tested with r or Spearman R coefficient; P values of 0.05 or less were considered significant.
60
L P
HP
FIG.1. Discrimination index (P(A))for low (LP) and high (HP)pair,
pulse rate, PaO, and SaO, (mean and SE) while breathing normoxic and hypoxic (FI02 :I 1 %) mixtures in 6 subjects at sea level.
Results Cardiorespiratory function results Four subjects out of the nine observed at altitude exhibited bronchial obstruction at 1000 m, expressed by low ratio FEVl/VC (Table I). The mean external temperature during each experiment was 20°C in Kathmandou; 12°C at 2800 m; 8°C at 3900 m; 3°C at 5300 m and 18°C on return at 1377 m. At rest, breathing frequency and pulse rate were increased with altitude from respectively 14.3 f 3.4 and 7 4 f 6 min-’ at 1377 m to 17.2k4.3 and 94+ 14 min-’ at 5300 m. This was more obvious for pulse rate ( R = .63; n = 30; P < 0.01) than for breathing frequency ( R = 0.39; n = 34; P
Archives Internationales de Physiologie, de Biochimie et de Biophysique, 1992, 100, 113-1 19
Requ le 24 mars 1991.
The respiratory sensation a t high altitude BY
M.-J. DEL VOLGO and M.-C. NOEL-JORAND (Laboratoire de Physiologie, FacultP de MPdecine Secteur Nord, Marseille, France)
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
(6 figures)
The respiratory sensation was studied in Nepal at four different altitudes, 1377 m before and after the ascension, 2800 m, 3900 m and 530 m. Dyspnea was noted at each altitude for the nine subjects. They had to rate 4 external resistive loads between 2.5 and 13 cm H,O.l-'.s, presented in 2 pairs, a low and a high one. The discrimination between the loads i.e. the subject's sensitivity was obtained from Sensory Decision Analysis. These subjects were compared to six normal ones observed at sea level while breathing air, an hypoxic mixture (FIP, : 11 Yo) and air in a cold environment ( - 6°C). In these protocols, the load perception was not modified. The 2 populations exhibited a similar sensitivity when observed in normal conditions. At exertion and with altitude, the nine subjects demonstrated a progressive increase in dyspnea, rated with visual analog scales. At rest, the perception of the loads was not altered but slightly improved with altitude for 6 subjects. The other 3 subjects (2 subjects with clinical impairment, important dyspnea and pulmonary oedema) showed an impairment of the perception. The sensitivity to the loads was similar before and after the ascension for the well adapted subjects to altitude. In conclusion, the respiratory sensation is not impaired with altitude in well adapted subjects and transient hypoxia does not result in change in load perception. An impairment in load perception observed in some subjects is probably related to the secondary effects of chronic hypoxia, i.e. cerebral and/or pulmonary suboedema.
Introduction Well adapted subjects report an increase in dyspnea during exercise at altitude and breathing becomes dramatically discomfortable for climbers with pulmonary oedema. In this context and with reference et to our studies (BONNELet al., 1985, 1987; MATHIOT al., 1986) of resistive load perception at sea level, we were interested in studying the respiratory sensation of subjects from low altitude to high altitude. In normal subjects, the possible modifications in respiratory sensation at altitude could result from various factors, such as hypoxia, hypocapnia, an increase in low density air ventilation or a cold environment. The role of hypoxia in dyspnea is conflicting of 1985) and it was either direct or indirect effect (ALTOSE, studied in resistive load perception at rest at altitude. Unloading by heliox breathing results in an impairment et al., 1986) for a same of load perception (MATHIOT level of ventilation. Furthermore, in subjects with pulmonary or cerebral oedema, the modifications should be more important. In this difficult context, the chief purpose of the study was to observe how healthy subjects experience the respiratory sensation at altitude ranging from 1377 m to 530 m. In other words and more precisely, the
question being asked was : can the high altitude adapted subject discriminate between high and low loads as well as he can at low altitude or at sea level. The subject's sensitivity to resistive loads was obtained from Sensory Decision Analysis (GREEN& SWETS,1974). These subjects, familiar with altitude, were compared to normal subjects observed at sea level while breathing air, an hypoxic mixture and air in a cold environment.
Methods
Subjects : In Nepal, we studied 9 european subjects between 22 and 51 years of age (Table I), included two guides. These healthy subjects, without a history of cardiopulmonary or respiratory disease, were familiar with altitude and they were selected for this reason. They had volunteered for the experiment and been recruited in France where they were submitted to respiratory measurements at 1000 m (Table I). At sea level, the respiratory sensation of 8 volunteers, all normal and non smoking subjects, was studied in 2 experimental conditions consisting in the inhalation of an hypoxic mixture and breathing in a cold environment. Their ages ranged between 30 and
114
M.-J. DEL VOLGO AND M.-C.
NOEL-JOMND
TABLEI. Respiratory measures before the expedition in Nepal.
-----lT Subject
7
Age (YO
Weight (Kg)
Height (cm)
FEVl/VC
MET
(VO)
(S)
49 26 43
51 46 42 22 51
79 58 60 56 60 70 77 55 53
176 163 170 166 155 176 179 170 159
65 81 76 61 65 84 59 86 78
1.19 0.52 0.59 1.52 1.15 0.46 0.90 0.51 0.70
81 83 86 76 70 76 81 90 82
97 91 96 96 96 96 97 97 91
42 11
63 10
168 8
73 10
0.84 0.37
81 6
96.5 0.5
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
~~
CRE ANC NOE SIM vou* vou* CHA* MON BRO*
m SD
46
53 (mean = 42) with spirometry indices within their predicted normal range.
Respiratory function measurements The spirometric values of the subjects studied in Nepal were obtained in France, from electrical integration of the flow signal (HP4780A; Hewlett-Packard) (Table I). The spirometric characteristics of the other 8 subjects were determined with a Pulmonet I11 Gould. For all subjects, measurements of arterial gases and SaOz were achieved with an ABL 330 Radiometer analyser and an OSM2 oxymeter respectively.
Loaded breathing apparatus The subjects, comfortably seated, wore a nose-clip and mouth piece connected to a Rudolph valve (no 1400). A rigid plastic tube (internal diameter : 3 cm; length : 70 cm) was interposed between the inspiratory side of the Rudolph valve and a 4-way stopcock with the latter placed on the back of the chair so as to be hidden from the subject's view. The additional resistors consisted of brass cylinders drilled to different diameters connected to the stopcock. At sea level, the basal circuit resistance was 1.6 cmHZO.l-'.s and the resistances of the added loads were 2.5 (Ll), 4 (L2), 4.5 (L3) and 13 (L4) cmHzO.l-'.s at an airflow rate of 1 1 . P . The values were 1.4; 2.6; 2.9 and 7.4 respectively at an airflow rate of 0.5 1.s-'. The subjects had to rate the loads in pairs, a low with L1 and L2 and a high pair, with L3 and L4.
General procedure The subject was connected to the circuit and breathed for 2 min without the added resistor in order to adapt to the apparatus and to its minimal resistance. After familiarization with the apparatus and the environment, the loads and their values were presented to the subject. He was instructed that the inspiratory side of the circuit would be loaded only and that during
each experimental session, the load would have two different values : either low (L1 and L2) or high (L3 and L4). Before the experimental sessions, a minimum number of training trials were performed with each of the loads. Each load was presented for a single breath and the rating experiment consisted in asking the subject to quantify his sensation after each load presentation by using a five point scale : 1) very slight intensity, 2) slight intensity, 3) moderate intensity, 4) important intensity, 5) very important intensity. During the test procedure, the subjects underwent two sessions of 100 trials blocked into two halves, in order to induce a contrast effect by pairing an intermediate value (L2) out of the four selected loads with a lower one (Ll), and the next intermediate value (L3) with a higher value (L4). One half consisted of 25 L1 and 25 L2 trials, the other half, 25 presentations each of L3 and L4. Each load was selected by turning the handle of the stopcock during the expiration preceding the tested inspiration. The subject's answer was given immediately and no abstention was permitted. During each half, the order of the load presentation was random. Which of the two pairs was chosen in the first half of each session was also randomly determined.
Specific procedures At altitude The experiment started in Kathmandou (1377 m, 860 mb) and was carried out at 3 different altitudes, 2800 m (720 mb), 3900 m (632 mb), 5300 m (525 mb) and again on return at 1377 m. For each experiment, the subjects were observed in the first hours (between 12 and 36) of their reaching these altitudes. From Kathmandou, they walked with light loads and arrived at 2800 m one day later, at 3900 m 4 days later and at 5300 m 6 days later. They returned to Katmandou 22 days after their departure. Before the specific experiment of respiratory sensation, breathing frequency and pulse rate were obtained.
115
RESPIRATORY SENSATION AND ALTITUDE
The load perception was carried out in the most comfortable environment in guest-houses. After this experiment, the subjects performed a physical exercise (20 leg-flexions) and they were asked to rate their breathing discomfort with a visual analog scale, i.e. an horizontal line of 10 cm, from no breathing discomfort to very important breathing discomfort.
.mtn-l
90
80
80
At sea level (below 200 m)
70
Archives of Physiology and Biochemistry Downloaded from informahealthcare.com by McMaster University on 11/24/14 For personal use only.
60
The load perception was carried out with six subjects in 2 different experimental conditions. (1) While breathing a hypoxic ( 0 2 : 11070 and N2) mixture or air from a compressed origin in order to obtain the same experimental installation. The humidified gases were collected in a Douglas bag. The loads were interposed by means of plastic tubes between the issue of the bag and the stopcock. (2) In 7 subjects, the respiratory sensation was tested in 2 ambient temperature conditions, moderate (24°C) and cold ( - 6°C). The 2 conditions of each protocol were randomly determined for each subject.
Data analysis In each experiment, the data were treated for individual subjects by means of a direct plot of mean numerical rating (from 1, very slight intensity) against load values. Another technique was also used for each pair by means of the conventional ‘Receiver Operating Characteristic’ (7)’ which was fully described by the present authors (2). Briefly, an ROC describes the relation between the proportion of true positive and false positive decisions mapped by changes in the subject’s decision criterion. In the present discrimination experiment, the lower load of each pair was assimilated to ‘noise’ and the higher to ‘signal’ alternative. The subject’s ratings were treated as separate binary cut-offs, each of which being used to map the subject’s judgment into ‘positive’ and ‘negative’ decisions. This simulated the use of four distinct criteria for making positive decisions, from very stringent (‘very important intensity’ versus all lower categories) to very lax (all categories versus ‘very slight intensity’). This procedure yielded four points on the ROC curve for each experimental session. The non-parametric sensitivity index, P (A), corresponds to the area under each ROC curve; its expected values vary between 0.5 or less and 1.0 as detection improves from chance level or bad perception to perfect. In the present experiment, P (A) reflects the subject’s ability to discriminate between the two loads in each pair. This index is independent of response bias from the subject. For statistical analysis, we used the non parametric Mann-Whitney U test and Wilcoxon signed rank Ttest. Correlation were tested with r or Spearman R coefficient; P values of 0.05 or less were considered significant.
60
L P
HP
FIG.1. Discrimination index (P(A))for low (LP) and high (HP)pair,
pulse rate, PaO, and SaO, (mean and SE) while breathing normoxic and hypoxic (FI02 :I 1 %) mixtures in 6 subjects at sea level.
Results Cardiorespiratory function results Four subjects out of the nine observed at altitude exhibited bronchial obstruction at 1000 m, expressed by low ratio FEVl/VC (Table I). The mean external temperature during each experiment was 20°C in Kathmandou; 12°C at 2800 m; 8°C at 3900 m; 3°C at 5300 m and 18°C on return at 1377 m. At rest, breathing frequency and pulse rate were increased with altitude from respectively 14.3 f 3.4 and 7 4 f 6 min-’ at 1377 m to 17.2k4.3 and 94+ 14 min-’ at 5300 m. This was more obvious for pulse rate ( R = .63; n = 30; P < 0.01) than for breathing frequency ( R = 0.39; n = 34; P
