Journal of Applied Physiology Millar Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 104: 1583-1593, 2008. First published April 24, 2008; doi:10.1152/japplphysiol.00079.2008
8750-7587/08 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
104/6/1583    most recent
00079.2008v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ofir, D.
Right arrow Articles by O'Donnell, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ofir, D.
Right arrow Articles by O'Donnell, D. E.

Sex differences in the perceived intensity of breathlessness during exercise with advancing age

Dror Ofir,1 Pierantonio Laveneziana,1 Katherine A. Webb,1 Yuk-Miu Lam,2 and Denis E. O'Donnell1

1Respiratory Investigation Unit, Department of Medicine; and 2Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada

Submitted 25 January 2008 ; accepted in final form 18 April 2008


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40–80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (VO2) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (VE), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (VT) to dynamic inspiratory capacity (IC) (all P < 0.05). These changes were quantitatively similar in women (n = 39) and in men (n = 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished (P = 0.05), as exercise ventilation increased relative to capacity (P = 0.013) and as the VT/IC ratio increased (P = 0.003) during exercise. Older women (60–80 yr old, n = 23) reported greater (P < 0.05) intensity of exertional breathlessness at a standardized VO2 and VE than age-matched men (n = 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on VT expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve.

dyspnea; aging; inspiratory capacity

CARDIOVASCULAR FACTORS are widely accepted as a proximate limit to maximal oxygen uptake (VO2) during weight-bearing exercise in healthy humans (42, 48). By contrast, the respiratory system is regarded as relatively "overbuilt" and less likely to contribute to exercise limitation except in elite athletes at very high power outputs (15, 21). However, it is recognized that in sedentary older individuals, intolerable exertional breathlessness may contribute to exercise limitation even before physiological maxima are attained (39). A number of studies have reported that more than 30% of the elderly (>65 yr) experience breathlessness during activities of daily living (23, 24, 30, 47). The nature and mechanisms of exertional breathlessness in older healthy humans are poorly understood. While the physiological effects of aging on the respiratory system are well established (14, 25, 40), the interaction between these changes in respiratory system compliance, muscle function, and ventilation/perfusion (V/Q) matching and the perceptual responses to physical exertion is largely unknown. Psychophysical studies of external mechanical loading have indicated that sensory thresholds for imposed external load detection are increased in the elderly compared with youth (40, 46), but the impact of aging on magnitude estimation of respiratory sensation during a variety of physiological perturbations (including exercise) is uncertain. This information becomes important if we are to improve the evaluation and management of exertional breathlessness in the healthy elderly or in patients with chronic cardiopulmonary conditions, many of whom are elderly.

The complaint of activity-related breathlessness appears to be more common in older women than in older men (5, 47). Women report greater intensity of breathlessness at a given power output during incremental cycle exercise (28). Population studies in patients with various cardiopulmonary conditions have similarly indicated that, when matched for disease severity, women experience greater levels of respiratory difficulty, greater exercise intolerance, and poorer perceived health status than their male counterparts (13, 20, 51). The mechanisms underlying the propensity for women to experience more disabling symptoms than men with similar disease staging are unknown.

This is the first study to explore potential mechanisms underlying sex differences in exertional breathlessness in health. Our objective was to determine if possible sex differences in the nature or degree of age-related respiratory impairment accounted for differences in respiratory sensation at a standardized exercise stimulus. We wished to determine if the increased intensity of exertional breathlessness in elderly women compared with age-matched men was associated with greater dynamic mechanical constraints during exercise secondary to relatively reduced inspiratory capacity and static inspiratory muscle strength in women. We hypothesized that, regardless of any sex differences in the progressive respiratory impairment of aging, the relatively reduced baseline ventilatory capacity in women would mean more pronounced negative effects on subjective breathlessness during exercise compared with age-matched men.

We undertook a cross-sectional study to compare the effects of aging on perceptual and ventilatory responses to incremental treadmill exercise in healthy male and female participants whose age ranged from 40 to 80 yr. We completed within- and between-sex comparisons of: 1) age-related changes in resting pulmonary function and skeletal (ventilatory and peripheral) muscle strength, and 2) age-related changes in expiratory flow limitation, breathing pattern, operating lung volumes, and pulmonary gas exchange during exercise. We conducted correlative analyses to determine the main independent contributory factors to exertional breathlessness and examined the interaction between the effects of age and sex on symptom perception.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Subjects

Subjects were recruited by advertising for research volunteers in the community. Men and women between 40 and 80 yr of age were included if they had normal spirometry [forced expiratory volume in 1 s (FEV1) ≥ 80% predicted, ratio between FEV1 and forced vital capacity (FEV1/FVC) > 70%] and no evidence of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or bronchial asthma. Subjects were excluded if they had: 1) a medical condition that could cause or contribute to breathlessness, i.e., metabolic or cardiovascular disease; or 2) other disorders that could interfere with exercise testing such as neuromuscular or musculoskeletal disorders. Subjects were divided into four groups based on sex and age: the younger female [40–59 yr old (YF)], younger male [40–59 yr old (YM)], older female [60–80 yr old (OF)], and older male [60–80 yr old (OM)] group.

Study Design

This was a controlled, cross-sectional study in which informed consent was obtained from all subjects and ethical approval was received from the University and Hospital Health Sciences Human Research Ethics Board. Subjects attended the laboratory once for a 4- to 6-h visit. Medical, smoking, and symptom histories were obtained by questionnaire. Chronic activity-related dyspnea was assessed using the Medical Research Council (MRC) dyspnea scale, Baseline Dyspnea Index (BDI), and an oxygen cost diagram (16, 31, 32). Habitual physical activity was assessed as either "active" (exercised at least twice per week on a regular basis) or "sedentary" (exercised less than twice per week on a regular basis) at the time of questionnaire completion. Procedures at this visit included anthropometric measurements (height, weight, circumferences, skinfold thicknesses), complete pulmonary function tests, symptom-limited incremental treadmill test, and, after an appropriate recovery period of 60–90 min, peripheral muscle strength tests.

Pulmonary Function Testing

Routine spirometry, constant-volume body plethysmography, single-breath diffusing capacity for carbon monoxide (DLCO), and maximum inspiratory and expiratory mouth pressures [PImax and PEmax; measured at functional residual capacity (FRC) and total lung capacity (TLC), respectively] were performed using an automated pulmonary function testing system (6200 Autobox DL or Vmax229d; SensorMedics, Yorba Linda, CA) in accordance with recommended techniques (1, 29, 34, 50). Pulmonary function measurements were expressed as percentages of predicted normal values (8, 10, 35); predicted normal inspiratory capacity (IC) was calculated as predicted TLC minus predicted FRC.

Peripheral Muscle Strength

Peripheral muscle strength was assessed using a computerized isokinetic dynamometer (LIDO Active System; Loredan Biomedical, West Sacramento, CA). Maximal knee and elbow torques were measured in the sitting position, with movement patterns ranging from 90° of flexion to full extension, at an angular velocity of 60°/s. Mid-upper arm and thigh circumference were measured to account for muscle mass.

Cardiopulmonary Exercise Testing

Symptom-limited exercise tests were conducted on an electronically controlled treadmill (MedTrack ST55; Quinton Instrument, Bothell, WA) using a metabolic cart (Vmax229 Cardiopulmonary Exercise Testing Instrument; SensorMedics). Exercise tests were performed using an incremental protocol (3): either a Bruce, modified Bruce, or modified Naughton protocol was selected depending on individual body size and level of fitness. Exercise tests were terminated at the point of symptom limitation (i.e., peak exercise) or if participants were unable to maintain the treadmill speed. A maximal effort was confirmed on the basis of accepted criteria (2). Cardiopulmonary exercise test parameters were collected on a breath-by-breath basis while subjects breathed through a mouthpiece with nasal passages occluded by a noseclip. Pulse oximetry using a finger sensor (SatTrak; SensorMedics) and electrocardiographic monitoring (Q710; Quinton Instrument, Bothell, WA) were carried out continuously, and blood pressure was measured at rest and at regular intervals throughout exercise testing.

Symptom evaluation.   Exertional breathlessness was defined as "the sensation of labored or difficult breathing" and leg discomfort as "the level of leg difficulty/discomfort experienced during exercise." Before exercise testing, subjects were familiarized with the modified Borg scale (7), and its endpoints were anchored such that zero represented "no breathlessness (leg discomfort)" and 10 was "the most severe breathlessness (leg discomfort) that they had ever experienced or could imagine experiencing." By pointing to the Borg scale, subjects rated the magnitude of their perceived breathlessness and leg discomfort at rest, every 2–3 min and at the peak exercise. On exercise cessation, subjects were also asked to verbalize their main reason for stopping exercise (i.e., breathlessness, leg discomfort, both breathing and legs, or other), and this reason was documented. In addition, the sensory aspects of perceived breathing discomfort at peak exercise were described by completion of a questionnaire modified from Simon and coworkers (43).

Breathing pattern and operating lung volumes.   Breathing pattern (timing, flow, and volume measurements) and dynamic IC were measured using the SensorMedics Vmax229 system as previously described (38). Operating lung volumes and their changes during exercise were derived from measurements of dynamic IC that were performed at rest, within the last 30-s period of each increment of exercise, and at peak exercise. Assuming that TLC remained constant (44, 45), changes in IC reflect changes in end-expiratory lung volume (EELV = TLC – IC), and changes in inspiratory reserve volume (IRV = IC – VT) reflected changes in end-inspiratory lung volume (EILV = TLC – IRV). This has been found to be a reliable method of tracking acute changes in lung volumes (37, 52). Tidal flow-volume curves at baseline, at each stage during testing, and at peak exercise were constructed for each patient and placed within their respective maximal flow-volume envelopes using the coinciding IC measurements. Estimates of expiratory flow limitation were made from these flow-volume loops using a previously described method (26).

Exercise endpoints.   Exercise variables were measured and averaged in 30-s intervals throughout each test stage and at peak exercise; peak exercise was defined as the last 30 s of loaded exercise. The ventilatory threshold (VTh) was detected individually using the V-slope method (4) and verified by combining three methods (19). Relationships between VT and ventilation (VE) were examined, and a point of inflection was determined for each subject (22). We compared our measurements of peak VO2 with predicted normal values accounting for sex, age, height, and weight; a correction factor of 1.09 was applied to estimate the difference between predicted values obtained with cycle vs. treadmill ergometry since treadmill testing results in higher values for peak VO2 (6). Other exercise parameters were compared with the predicted normal values of Jones (27). Maximum ventilatory capacity (MVC) was estimated as FEV1 multiplied by 35 (17).

Statistical Analysis

A sample size of 16 provides the power (80%) to detect a significant difference in dyspnea intensity (Borg Scale) measured at a standardized workload during incremental treadmill exercise based on a relevant difference in Borg ratings of ±1; a SD of 1 for Borg ratings changes found at our laboratory, {alpha} = 0.05; and a two-tailed test of significance. Values are reported as means ± SD unless otherwise specified. The conventional level of statistical significance of 0.05 was used for all analyses.

Qualitative descriptors of breathlessness were analyzed as frequency statistics; group comparisons were made using Pearson's chi-square test. Borg dyspnea ratings, cardiorespiratory parameters, metabolic parameters, breathing pattern, and operating lung volumes were compared at rest, at peak exercise, and at a standardized VO2 during exercise (the highest equivalent VO2 achieved for comparison between the female age groups and between the 60- to 80-yr-old groups was 20 ml·kg–1·min–1; a VO2 of 25 ml·kg–1·min–1 was used for comparisons between the male age groups). Exercise response slopes were studied using linear regression analysis of data sets from each individual. Summary statistics were compared using a 2 x 2 ANOVA for sex and age differences between the four groups. In case of a significant interaction between age and sex from the 2 x 2 ANOVA, four pairwise comparisons (YF vs. OF, YM vs. OM, YF vs. YM, and OF vs. OM) were performed using the post hoc multiple comparison approach; Bonferroni adjustment was applied to adjust the P values for these four comparisons.

Relationships between exertional dyspnea intensity (Borg ratings at a standardized VO2) and possible physiological contributors (concurrent exercise measurements and baseline pulmonary function) were determined by Pearson correlations. To test the possibility of a different relationship between the dependent variable and the independent variable across groups, an interaction term was incorporated into the regression model.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Subjects

A total of 73 subjects completed the study: YF (n = 16), OF (n = 23), YM (n = 18), and OM (n = 16). Subject characteristics are summarized in Table 1. There were no significant differences in the baseline characteristics of the four study groups, other than size differences between men and women. Cigarette smoking history and current smoking status are reported in Table 1. The majority of subjects were never smokers or were remote ex-smokers, although one subject in the YM group was a current smoker with a 13-pack-yr smoking history. No subjects with a smoking history had clinical or spirometric evidence of COPD. Chronic activity-related dyspnea measured by the BDI focal score was significantly (P < 0.05) lower by approximately one unit in OF compared with either YF or age-matched males (OM). Physical activity levels were similar (P = 0.42) across groups with the majority (79–100%) of subjects in each group participating in some form of regular activity.


View this table:
[in this window]
[in a new window]

  		Table 1. Baseline subject characteristics and activity-related dyspnea questionnaires

 
Resting pulmonary function measurements for all groups were in keeping with their normal predicted values and are summarized in Table 2. There were significant age-related changes in maximal expiratory flows, lung volumes, diffusing capacity, and respiratory muscle strength measurements. Across age groups, measurements were also consistently greater in men than women. However, there were no interaction effects between age and sex, i.e., age-related declines in pulmonary function were similar across sexes.


View this table:
[in this window]
[in a new window]

  		Table 2. Pulmonary function and muscle strength

 
The mean forced expiratory flow between 25 and 75% (FEF25–75%)/FVC ratio was used as an index of dysanapsis, a term referring to a dissociation between airway size and lung size (33). There was a significant age-related decrease in this ratio (P = 0.001) with no sex-related effect or interaction between age and sex: in the older subgroups, the FEF25–75%/FVC ratio reached a similar value of 0.62 ± 0.21 and 0.59 ± 0.05 in women and men, respectively.

Significant age-related decreases in maximal torque measurements for the knee and elbow were found in both men and women (Table 2). As expected, knee and elbow torque measurements were significantly (P < 0.0005) greater in men than women for both age groups. There was no interaction between aging and sex-related effects in these measurements.

Exertional Breathlessness

The primary reasons for stopping exercise are summarized in Table 3. Breathing discomfort was identified as the primary reason for stopping exercise in 57% of the OF group (P = 0.006). Within each of the YF, YM, and OM groups, the selection frequency of reasons for stopping exercise was not significantly different. At peak exercise, Borg ratings of breathlessness and perceived leg discomfort were not different across all groups.


View this table:
[in this window]
[in a new window]

  		Table 3. Measurements at peak exercise and at the ventilatory threshold

 
Breathlessness/VO2 slopes showed a significant aging effect (P < 0.05) with no significant sex-related effect: slopes were greater in OF compared with YF (P < 0.05) but not in OM compared with YM (P = 0.29) (Fig. 1). Likewise, Borg ratings of breathlessness intensity at a standardized VO2 of 20 ml·kg–1·min–1 showed a significant age effect (P = 0.003), as well as a significant interaction between aging and sex-related effects (P = 0.041), i.e., the age-related increase in breathlessness ratings was greater in women. Ratings of breathlessness were significantly (P < 0.05) greater by >1 Borg unit on average at a standardized VO2 in the 60- to 80-yr-old group compared with the 40- to 59-yr-old group in both men and women. Analysis of breathlessness/VE slopes indicated a significant sex-related effect only (P = 0.037) such that women had steeper slopes than men (Fig. 1): slopes were 0.11 ± 0.05, 0.08 ± 0.06, 0.08 ± 0.05, and 0.06 ± 0.03 Borg units/(l/min) in OF, OM, YF, and YM, respectively. There were no significant sex or age effects for breathlessness/VE slopes when VE was expressed as a percentage of estimated MVC.


Figure 1
View larger version (11K):
[in this window]
[in a new window]

  		Fig. 1. Breathlessness/oxygen uptake (VO2) slopes showed a significant aging effect (P < 0.05) with no significant sex-related effect: slopes were greater in 60- to 80-yr-old women [old female (OF) group] compared with 40–59-yr-old women [young female (YF) group] (P < 0.05) but not in 60–80-yr-old men [old male (OM) group] compared with 40–59-yr-old men [young male (YM) group]. Breathlessness/ventilation (VE) slopes showed a significant (P < 0.05) sex-related effect only, such that women had steeper slopes than men. *Ratings of dyspnea intensity at a standardized VO2 of 20 ml·kg–1·min–1 showed a significant age effect (P = 0.003), as well as a significant interaction between aging and sex-related effects (P = 0.041): the age-related increase in dyspnea ratings was greater in women. Values are means ± SE for measurements at rest, during each stage of exercise, and at peak exercise.

 
At the end of symptom-limited exercise, shallow breathing was the only descriptor of breathing discomfort that was significantly (P < 0.05) different across the four groups: this descriptor was chosen by 39% of the OF group, by 31% of the YF group, and by only one subject in each of the OM and YM groups. Rapid breathing was reported by 75% of OM compared with 43% of OF group (P = 0.051).

Physiological Responses to Exercise

Measurements at peak exercise are provided in Table 3. All groups reached a peak VO2 that corresponded well with the normal predicted value of Blackie et al. (6) (with a 9% correction for treadmill). At peak exercise, significant (P < 0.05) age and sex effects were found for VO2, VE, VE/VCO2, and VT. However, peak differences in VO2, VE, and VT disappeared once variables were expressed as a percentage of their respective predicted capacity. There was a significant (P = 0.031) age effect for peak heart rate, but this also disappeared when evaluated as a percentage of predicted maximum. Minimal hypoxemia was noted during exercise: mean reductions in oxygen saturation (SpO2) of 2–4% were shown within each group, while one OM and two YF had an SpO2 that fell to transient nadir of 87% at end exercise. All groups reached a similar minimal IRV at the end of exercise; therefore differences in absolute VT during exercise could be explained by differences in IC. There was no interaction between aging and sex-related effects for any measured variable at peak exercise.

Ventilatory responses to exercise are shown in Fig. 2. At a standardized VO2, there was a significant (P ≤ 0.01) aging effect for VE, VE/VCO2, and PETCO2; a significant (P ≤ 0.01) sex effect was also found for VE/VCO2 and PETCO2. Slopes of VE over VCO2 showed significant age (P < 0.0005), sex (P = 0.034), and interaction (P = 0.023) effects: the age-related increase in these slopes was greatest in women. A significant (P < 0.01) age- and sex-related increase was also found for VE/VCO2 at the VTh (Table 3). Although there was a significant age-related decline in the absolute VO2 at the VTh in both men and women, this difference disappeared when VO2 was expressed as a percentage of actual peak VO2.


Figure 2
View larger version (17K):
[in this window]
[in a new window]

  		Fig. 2. Ventilatory responses to incremental treadmill exercise in adult men and women show significant (P < 0.05) age-related increases in VE, the ratio of VE to carbon dioxide production (VCO2), and partial pressure of end-tidal carbon dioxide (PETCO2). *Significant (P < 0.05) difference at a standardized VO2 of 25 and 20 ml·kg–1·min–1 within men and women, respectively. Values are means ± SE for measurements at rest, during each stage of exercise, and at peak exercise.

 
Breathing pattern and operating lung volume responses to exercise are shown in Fig. 3. There were no significant sex-related, age-related, or interaction effects for slopes of VT over VE; however, women had significantly (P < 0.0005) greater slopes of breathing frequency (F) over VE than men. An inflection in the VT/VE relationship occurred when IRV had reached a similarly reduced level in all groups: at this point, mean IRV ranged from 0.55 to 0.75 liter, or 8–12% TLC. There were also no age- or sex-related differences across groups in dyspnea intensity at this inflection point. However, there were significant age- (P < 0.01) and sex-related (P < 0.0005) decreases in the absolute VO2, VE, and VT where this inflection occurred. Similar to the breathlessness intensity differences, these breathing pattern differences disappeared when measurements were expressed as percentages of their respective capacity, i.e., VO2 as a percentage of predicted maximum, VE as a percentage of estimated MVC, and VT as a percentage of predicted VC (Fig. 4). Breathing pattern and operating volume measurements at a standardized VO2 showed significant age-related decreases in IRV (P < 0.0005) and IC (P < 0.0005); increases in VT/IC (P < 0.0005) and increases in F (P = 0.014); significantly smaller IRV (P < 0.0005) and IC (P < 0.0005); and greater F (P = 0.002) in women compared with men with no significant interaction between aging and sex-related effects.


Figure 3
View larger version (17K):
[in this window]
[in a new window]

  		Fig. 3. Breathing pattern and operating volume measurements are shown as ventilation increased during exercise in the YF, OF, YM, and OM groups. Significant (P < 0.05) age-related reductions in tidal volume (VT), inspiratory reserve volume (IRV), and inspiratory capacity (IC) were shown in both men and women. There were also significant (P < 0.05) sex-related effects for peak VT and IC and for slopes of breathing frequency (F) over ventilation. Values are means ± SE for measurements at rest, the first 2 stages of exercise, the VT/ventilation inflection point, and peak exercise. TLC, total lung capacity. Gray arrows show the direction of age-related effects.

 

Figure 4
View larger version (16K):
[in this window]
[in a new window]

  		Fig. 4. There were no age or sex differences found when measurements of VT and IRV were normalized for age and sex [i.e., expressed as percentages of predicted vital capacity (VC) and TLC, respectively] and plotted against ventilation as a fraction of maximal ventilatory capacity (MVC). Similarly, exertional breathlessness intensity was not different across groups when expressed against ventilation/MVC or against IRV.

 
Examination of tidal vs. isovolume maximal expiratory flows at rest showed no evidence of expiratory flow limitation (EFL) in the YF or YM groups. In contrast, EFL at rest was evident in 6 (26%) and 4 (25%) subjects from the OF and OM groups, respectively. At the peak of exercise when ventilations were high, EFL was evident in 12 (52%) of the OF group, 11 (67%) of the OM group, 5 (31%) of the YF group, and 12 (69%) of the YM group. There was a significant age (P = 0.013) and sex (P = 0.010) effect in the VE at which the onset of EFL was noted in these subjects: the onset of EFL by this method occurred at a greater VE in the younger vs. older groups, and in men vs. women. The magnitude of dynamic hyperinflation (reduction in IC) from rest to peak exercise was similar across all groups (Table 3). Representative samples of flow-volume loops during exercise in each group are shown in Fig. 5.


Figure 5
View larger version (15K):
[in this window]
[in a new window]

  		Fig. 5. Tidal flow-volume loops at rest, the ventilatory threshold (VTh), and at peak exercise are plotted within the respective maximal loops in representative subjects from each group. IC decreases with increasing age, thereby reducing IRV and limiting the VT response to exercise. This mechanical restriction is greater in women, i.e., reduced resting IC. Dynamic pulmonary hyperinflation is shown by a decrease in IC during exercise. The IRV is shown at VTh (heavy line on the volume axis) when the relative exercise intensity was comparable across groups.

 
Correlates of Exertional Breathlessness

Correlates of breathlessness intensity at a standardized VO2 during exercise are provided in Table 4. In women, the strongest correlates of breathlessness intensity at the highest standardized VO2 (20 ml·kg–1·min–1) were VT/IC and VT expressed as a percentage of predicted VC; these relationships were similar across age groups. In men, the strongest correlates of breathlessness intensity at the highest standardized VO2 (25 ml·kg–1·min–1) were VT/IC and IRV expressed as a percentage of predicted TLC; these relationships were consistent across age groups. Within all older (60–80 yr old) subjects, the strongest correlates of breathlessness intensity at a standardized VO2 of 20 ml·kg–1·min–1 were VT/IC and VT expressed as percentage of predicted VC; there was no effect of sex difference on these relationships in this age group. Across all groups, breathlessness ratings also correlated with VE (partial r = 0.33, P = 0.005) and VE/MVC (partial r = 0.26, P = 0.032) at a standardized VO2. Standardized Borg ratings of intensity of breathlessness and perceived leg discomfort also correlated across groups with PImax (partial r = 0.22, P = 0.05) and maximal knee torque (partial r = 0.41, P = 0.010), respectively.


View this table:
[in this window]
[in a new window]

  		Table 4. Pearson correlation coefficients for variables measured at a standardized VO2 during exercise and tested against concurrent breathlessness intensity ratings (Borg scale)

 
Relationships between Borg ratings of breathlessness intensity and IRV (%predicted TLC) or VE/MVC were superimposed for all groups: breathlessness increased as IRV decreased or as VE/MVC increased (Fig. 4).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
The main findings of this study are as follows: 1) perceptual responses to incremental treadmill exercise were similar in men and women in the 40- to 59-yr-old groups; 2) breathlessness intensity ratings were higher at a standardized metabolic load during exercise in the 60- to 80-yr-old compared with the 40- to 59-yr-old age groups in both men and women; 3) in both sexes, the higher levels of exertional breathlessness with advancing age were associated with reduced static inspiratory muscle strength, greater ventilatory mechanical constraints, and higher ventilatory demand during exercise; and 4) ratings of breathlessness intensity at a standardized metabolic load were higher in 60- to 80-yr-old women (OF group) than age-matched men (OM group), reflecting the interaction of the increased ventilatory constraints of aging and the relatively reduced baseline ventilatory capacity in women.

During incremental treadmill testing, all four groups reached their predicted peak VO2 without apparent ventilatory limitation but nevertheless experienced significant exertional symptoms. The intensity of breathlessness and the cardiopulmonary responses throughout incremental exercise were similar in men and women in the 40- to 59-yr-old age groups. However, women in this age group were more likely to report the qualitative descriptor "shallow" at end exercise than men. In women of this age range, small differences in breathing pattern responses (i.e., lower VT) to exercise and in the ventilatory demand/capacity ratio (i.e., higher at a given VO2) are likely explained by their anatomically smaller lungs, airways, and respiratory musculature.

In the OF group compared with the YF group, the intensity of breathing discomfort was higher at a standardized VO2 during exercise (by 1.5 Borg units at 20 ml·kg–1·min–1), and breathlessness/VO2 slopes were, on average, ~40% steeper (P < 0.05) (Fig. 1). In the OM group, exertional breathlessness intensity was greater than in the YM group only at higher metabolic loads (≥25 mlO2·kg–1·min–1); breathlessness/VO2 slopes were not significantly different. The following potential contributors to increased exertional breathlessness in the 60- to 80-yr-old group of both sexes were considered: 1) greater age-related muscular weakness and mechanical ventilatory constraints during exercise; 2) increased ventilatory demand during exercise reflecting greater ventilation/perfusion mismatching and metabolic alterations; and 3) a combination of these factors.

Age-Related Abnormalities in Ventilatory Mechanics

Cross-sectional comparison (within both sexes) of resting pulmonary function parameters between the 60- to 80-yr-old and the 40- to 59-yr-old groups confirmed the expected age-related reductions in FEV1, FVC, IC, DLCO, and maximal respiratory pressures. The magnitude of change in these parameters was similar in male and female participants.

Age-related changes in cardiopulmonary responses to treadmill exercise were quantitatively similar in men and women. In the 60- to 80-yr-old groups, symptom-limited peak VO2 and VE were reduced by an average of 33% and 19% in the OF group and by 22% and 17% in the OM group compared with their respective younger groups. It is noteworthy that in the 60- to 80-yr-old group, the resting IC, which represents the operating limit for VT expansion during exercise in the presence of EFL, was reduced by an average of 15% compared with the 40- to 59-yr-old group. The IC reduction was the result of a combination of variable increases in FRC (particularly in men) and a reduction in TLC, possibly due to age-related reductions in height and PImax or both in combination. During exercise, the rest-to-peak decreases in IC, reflecting the extent of air trapping secondary to EFL, were similar in the 40- to 59-yr-old group and the 60- to 80-yr-old group and averaged –0.3 liter. The oldest groups appeared to have greater EFL as crudely assessed by the VT overlap method during flow-volume loop analysis. Greater "restrictive" mechanical constraints were evident during exercise in the 60- to 80-yr-old group by the relatively higher VT/IC ratios and the reduced dynamic IRV at lower metabolic rates compared with the 40- to 59-yr-old group. In the OF group the lower baseline resting IC (reduced by 14% compared with the YF group) with further reduction during exercise resulted in a relatively more rapid and shallow breathing pattern compared with the YF group. Such age-related differences in breathing pattern responses to exercise were less evident in the OM compared with the YM group, likely reflecting the relatively larger lung volume reserve in men.

Mechanical/Muscular Factors and Exertional Breathlessness

Ventilatory muscle strength diminished with advancing age in both men and women. This likely reflects generalized skeletal muscle weakness with aging, as peripheral muscle strength was reduced in tandem. Thus the effort expended to drive both muscle groups must represent a higher fraction of their maximal possible effort in the older groups. Indeed, exertional symptom intensity correlated significantly (albeit weakly) with muscle strength measurements across groups: breathlessness increased as PImax decreased and perceived leg discomfort increased as leg strength decreased. The neurophysiological basis of exertional breathlessness (and perhaps also leg discomfort) in this circumstance is thought to be increased central motor command output with increased central corollary discharge to the somatosensory cortex (9, 12, 18).

At the highest standardized VO2 for both sexes, indexes of volume restriction such as high VT/IC ratios and reduced dynamic IRV correlated well with breathlessness intensity ratings. Breathlessness/IRV relationships were superimposed in the 60- to 80-yr-old groups and 40- to 59-yr-old groups of both sexes. However, at a standardized VO2, breathlessness intensity was significantly higher and the dynamic IRV was proportionately diminished in the older groups compared with their younger counterparts. The relatively lower dynamic IRV at a given VO2 in the older groups points to a higher operating position of the VT on the upper reaches of the respiratory system's pressure-volume relationship where there is increased elastic loading and functional weakness of the inspiratory muscles.

Increased Ventilatory Demand and Exertional Breathlessness

Ventilation was increased significantly by ~30% for any given submaximal VO2 in the 60- to 80-yr-old groups of both sexes compared with the 40- to 59-yr-old groups. Consistent with previous studies (14, 41), VE/VCO2 ratios were significantly elevated before and at the ventilatory threshold in the 60- to 80-yr-old groups (at a point where PETCO2 was stable) in both sexes compared with their younger counterparts. In both sexes, the finding of a significant reduction in DLCO in the 60- to 80-yr-old group compared with the younger groups is also in keeping with the well-described age-related decreases in the alveolar/capillary surface area for gas exchange and increased V/Q nonuniformity (49). However, ventilatory inefficiency in the elderly was not of sufficient magnitude to compromise CO2 elimination or result in significant arterial O2 desaturation, even at the peak of symptom-limited exercise. Ventilatory thresholds, heart rate/VO2 slopes, peak heart rate reserve, and peak VO2 remained within the predicted normal range for these older participants, essentially excluding significant peripheral skeletal muscle deconditioning and/or impaired cardiac function as additional sources of ventilatory stimulation.

To what degree did the small increases in VE seen in the 60- to 80-yr-old groups contribute to greater exertional breathlessness intensity compared with the 40- to 59-yr-old groups? Certainly, younger healthy individuals can tolerate increases in exercise VE during dead space loading that are comparable to the age-related increases in this study with minimal or no increase in breathing discomfort (36). However, we cannot exclude the possibility that even small increases in ventilatory demand (and therefore muscular effort) of this magnitude, in the setting of progressive age-related decline in respiratory muscle strength and dynamic mechanical restriction, may lead to greater respiratory difficulty in the elderly. At a VO2 of 20 ml·kg–1·min–1, age-related increases in breathlessness intensity were associated with increases in VE and the VE/MVC ratio across groups.

Sex Differences in Perceived Breathlessness in the Older Age Group

The effect of aging on breathlessness/VO2 and VE/VCO2 slopes was greater in women than men. Breathlessness was also more frequently reported as the primary exercise-limiting symptom in the OF group. These findings are in keeping with previous reports on sex-related influences on symptom perception in both health and cardiopulmonary disease (5, 13, 20, 23, 24, 47, 51). As expected, women in the OF group, whose average height was 12 cm less than age-matched men, had significantly smaller (in absolute terms) lung volumes, maximal expiratory flow rates, DLCO, and static inspiratory muscle strength. The question arises whether the intrinsically smaller airway size relative to lung volume in women (i.e., dysanapsis), described by Mead (33), predisposes them to greater exertional breathlessness with advancing age. In our study, there was an age-related decline in the ratio of FEF25–75% to FVC (a surrogate measure of dysanapsis) but with no significant sex-related effect. Older men and older women had similar such ratios and showed no differences in measured expiratory flow limitation during exercise to account for differences in breathlessness. Moreover, we were unable to demonstrate that the increased breathlessness in elderly women compared with age-matched men was the result of greater derangements of dynamic mechanics (related to reduced IC), reduced inspiratory muscle strength, or abnormal pulmonary gas exchange. Future studies that compare the effect of manipulation of ventilatory mechanics (bronchodilators, helium/oxygen, or increased chemostimulation) on breathlessness in men and women are likely to provide greater insights into the relative importance of such mechanical factors in causation.

While the age-related respiratory muscle weakness and dynamic ventilatory constraints were broadly similar in men and women, the sensory consequences of these changes were proportionately greater in the oldest female group, who had the lowest estimated MVC of all four subgroups. It is noteworthy that the increase in breathlessness at any given VE or VO2 in the OF group compared with the OM group disappeared when these variables were expressed as percent MVC and percent predicted, respectively. It follows that in the OF group, the ventilation required to support any physical task represents a higher fraction of their MVC than age-matched men, with attendant proportionate increases in relative contractile muscle effort and perceived breathlessness.

We acknowledge that our study did not address the important question of whether gender differences in subjective responses to exercise could be accounted for by nonphysiological factors (psychological, sociocultural and environmental) that are known to shape the expression of breathlessness on an individual basis (5, 11).

In summary, the intensity of breathlessness during weight-bearing exercise in men and women in the 40- to 59-yr-old groups were similar. Cross-sectional comparisons within each sex revealed that participants in the 60- to 80-yr-old groups experienced greater breathing difficulty at a standardized VO2 than their younger counterparts and occurred more consistently in women. Although the origin of breathlessness is multifactorial, correlative analysis identified age-related ventilatory muscular/mechanical constraints and higher ventilatory requirements as potential contributory factors in the oldest groups. The impact of the progressive age-related decline in respiratory function on perceived exertional symptoms was most pronounced in the OF group whose baseline maximal ventilatory capacity was, by nature, relatively diminished compared with their male counterparts.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by the William Spear Endowment Fund, Queen's University.


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. O'Donnell, 102 Stuart St., Kingston, Ontario K7L 2V6, Canada (e-mail: odonnell{at}queensu.ca)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. American Thoracic Society/European Respiratory Society. ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 166: 518–624, 2002.[Free Full Text]
  2. American Thoracic Society/American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 167: 211–277, 2003.[Free Full Text]
  3. Balady GJ, Berra KA, Golding LA, Gordon NF, Mahler DA, Myers JN, Sheldahl LM. ACSM's Guidelines for Exercise Testing and Prescription. Baltimore, MD: Lippincott Williams and Wilkins, 2000.
  4. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol 60: 2020–2027, 1986.[Abstract/Free Full Text]
  5. Becklake MR, Kauffmann F. Gender differences in airway behaviour over the human life span. Thorax 54: 1119–1138, 1999.[Free Full Text]
  6. Blackie SP, Fairbarn MS, McElvaney GN, Morrison NJ, Wilcox PG, Pardy RL. Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age. Am Rev Respir Dis 139: 1424–1429, 1989.[Web of Science][Medline]
  7. Borg GA. Psychophysical basis of perceived exertion. Med Sci Sports Exerc 14: 377–381, 1982.[Web of Science][Medline]
  8. Burrows B, Kasik JE, Niden AH, Barclay WR. Clinical usefulness of the single-breath pulmonary diffusing capacity test. Am Rev Respir Dis 84: 789–806, 1961.[Web of Science][Medline]
  9. Chen Z, Eldridge FL, Wagner PG. Respiratory-associated thalamic activity is related to level of respiratory drive. Respir Physiol 90: 99–113, 1992.[CrossRef][Web of Science][Medline]
  10. Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volumes in healthy nonsmoking adults. Bull Eur Physiopath Respir 18: 419–425, 1982.[Web of Science][Medline]
  11. Dale RE, Spitzer WO, Schechter MT, Suissa S. The influence of psychological status on respiratory symptom reporting. Am Rev Respir Dis 139: 1459–1463, 1989.[Web of Science][Medline]
  12. Davenport PW, Friedman WA, Thompson FJ, Franzen O. Respiratory-related cortical potentials evoked by inspiratory occlusion in humans. J Appl Physiol 60: 1843–1848, 1986.[Abstract/Free Full Text]
  13. de Torres JP, Casanova C, Hernandez C, Abreu J, Aguirre-Jaime A, Celli BR. Gender and COPD in patients attending a pulmonary clinic. Chest 128: 2012–2016, 2005.[CrossRef][Web of Science][Medline]
  14. DeLorey DS, Babb TG. Progressive mechanical ventilatory constraints with aging. Am J Respir Crit Care Med 160: 169–177, 1999.[Abstract/Free Full Text]
  15. Dempsey JA, Hanson PG, Henderson KS. Exercise-induced arterial hypoxaemia in healthy human subjects at sea level. J Physiol 355: 161–175, 1984.[Abstract/Free Full Text]
  16. Fletcher CM, Elmes PC, Fairbairn AS, Wood CH. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J 2: 257–266, 1959.[Free Full Text]
  17. Gandevia B, Hugh-Jones P. Terminology for measurements of ventilatory capacity: a report to the Thoracic Society. Thorax 12: 290–293, 1957.[Free Full Text]
  18. Gandevia SC, Macefield G. Projection of low-threshold afferents from human intercostal muscles to the cerebral cortex. Respir Physiol 77: 203–214, 1989.[CrossRef][Web of Science][Medline]
  19. Gaskill SE, Ruby BC, Walker AJ, Sanchez OA, Serfass RC, Leon AS. Validity and reliability of combining three methods to determine ventilatory threshold. Med Sci Sports Exerc 33: 1841–1848, 2001.[CrossRef][Web of Science][Medline]
  20. Han MK, Postma D, Mannino DM, Giardino ND, Buist S, Curtis JL, Martinez FJ. Gender and chronic obstructive pulmonary disease: why it matters. Am J Respir Crit Care Med 176: 1179–1184, 2007.[Abstract/Free Full Text]
  21. Harms CA, Wetter TJ, St Croix CM, Pegelow DF, Dempsey JA. Effects of respiratory muscle work on exercise performance. J Appl Physiol 89: 131–138, 2000.[Abstract/Free Full Text]
  22. Hey EN, Lloyd BB, Cunningham DJ, Jukes MG, Bolton DP. Effects of various respiratory stimuli on the depth and frequency of breathing in man. Respir Physiol 1: 193–205, 1966.[CrossRef][Web of Science][Medline]
  23. Ho SF, O'Mahony MS, Steward JA, Breay P, Buchalter M, Burr ML. Dyspnoea and quality of life in older people at home. Age Ageing 30: 155–159, 2001.[Abstract/Free Full Text]
  24. Horsley JR, Sterling IJ, Waters WE, Howell JB. Respiratory symptoms among elderly people in the New Forest area as assessed by postal questionnaire. Age Ageing 20: 325–331, 1991.[Abstract/Free Full Text]
  25. Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am Rev Respir Dis 143: 968–977, 1991.[Web of Science][Medline]
  26. Johnson BD, Weisman IM, Zaballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop. Chest 116: 488–503, 1999.[CrossRef][Web of Science][Medline]
  27. Jones NJ. Clinical Exercise Testing. Philadelphia, PA: Saunders, 1988.
  28. Killian KJ, Summers E, Jones NL, Campbell EJ. Dyspnea and leg effort during incremental cycle ergometry. Am Rev Respir Dis 145: 1339–1345, 1992.[Web of Science][Medline]
  29. MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 26: 720–735, 2005.[Abstract/Free Full Text]
  30. Mahler DA, Baird JC. Dyspnea in the elderly. In: Dyspnea Mechanisms, Measurement, and Management, edited by Mahler DA, O'Donnell DE. Boca Raton, FL: Taylor and Francis Group, 2005, p. 19–28.
  31. Mahler DA, Weinberg DH, Wells CK, Feinstein AR. The measurement of dyspnea. Contents, interobserver agreement, and physiologic correlates of two new clinical indexes. Chest 85: 751–758, 1984.[CrossRef][Web of Science][Medline]
  32. McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability, and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J 2: 241–243, 1978.[Abstract/Free Full Text]
  33. Mead J. Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am Rev Respir Dis 121: 339–342, 1980.[Web of Science][Medline]
  34. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of spirometry. Eur Respir J 26: 319–338, 2005.[Abstract/Free Full Text]
  35. Morris JF, Koski A, Temple WP, Claremont A, Thomas DR. Fifteen-year interval spirometric evaluation of the Oregon predictive equations. Chest 93: 123–127, 1988.[CrossRef][Web of Science][Medline]
  36. O'Donnell DE, Hong HH, Webb KA. Respiratory sensation during chest wall restriction and dead space loading in exercising men. J Appl Physiol 88: 1859–1869, 2000.[Abstract/Free Full Text]
  37. O'Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 158: 1557–1565, 1998.[Abstract/Free Full Text]
  38. O'Donnell DE, Revill SM, Webb KA. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164: 770–777, 2001.[Abstract/Free Full Text]
  39. Ofir D, Laveneziana P, Webb KA, Lam YM, O'Donnell DE. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I COPD. Am J Respir Crit Care Med 177: 622–629, 2008.[Abstract/Free Full Text]
  40. Pride NB. Ageing and changes in lung mechanics. Eur Respir J 26: 563–565, 2005.[Free Full Text]
  41. Prioux J, Ramonatxo M, Hayot M, Mucci P, Prefaut C. Effect of ageing on the ventilatory response and lactate kinetics during incremental exercise in man. Eur J Appl Physiol 81: 100–107, 2000.[CrossRef][Web of Science][Medline]
  42. Saltin B, Calbet JA. Point: In health and in a normoxic environment, VO2 max is limited primarily by cardiac output and locomotor muscle blood flow. J Appl Physiol 100: 744–745, 2006.[Free Full Text]
  43. Simon PM, Schwartzstein RM, Weiss JW, Fencl V, Teghtsoonian M, Weinberger SE. Distinguishable types of dyspnea in patients with shortness of breath. Am Rev Respir Dis 142: 1009–1014, 1990.[Web of Science][Medline]
  44. Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in normal males. J Appl Physiol 49: 506–510, 1980.[Abstract/Free Full Text]
  45. Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J Appl Physiol 49: 511–515, 1980.[Abstract/Free Full Text]
  46. Tack M, Altose MD, Cherniack NS. Effects of aging on sensation of respiratory force and displacement. J Appl Physiol 55: 1433–1440, 1983.[Abstract/Free Full Text]
  47. Tessier JF, Nejjari C, Letenneur L, Filleul L, Marty ML, Barberger GP, Dartigues JF. Dyspnea and 8-year mortality among elderly men and women: the PAQUID cohort study. Eur J Epidemiol 17: 223–229, 2001.[CrossRef][Web of Science][Medline]
  48. Wagner PD. A theoretical analysis of factors determining VO2 max at sea level and altitude. Respir Physiol 106: 329–343, 1996.[CrossRef][Web of Science][Medline]
  49. Wagner PD, Laravuso RB, Uhl RR, West JB. Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100% O2. J Clin Invest 54: 54–68, 1974.[Web of Science][Medline]
  50. Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, MacIntyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G. Standardisation of the measurement of lung volumes. Eur Respir J 26: 511–522, 2005.[Abstract/Free Full Text]
  51. Watson L, Vestbo J, Postma DS, Decramer M, Rennard S, Kiri VA, Vermeire PA, Soriano JB. Gender differences in the management and experience of chronic obstructive pulmonary disease. Respir Med 98: 1207–1213, 2004.[CrossRef][Web of Science][Medline]
  52. Yan S, Kaminski D, Sliwinski P. Reliability of inspiratory capacity for estimating end-expiratory lung volume changes during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 156: 55–59, 1997.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
A. W. Sheel, J. A. Guenette, R. Yuan, L. Holy, J. R. Mayo, A. M. McWilliams, S. Lam, and H. O. Coxson
Evidence for dysanapsis using computed tomographic imaging of the airways in older ex-smokers
J Appl Physiol, November 1, 2009; 107(5): 1622 - 1628.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
P. G. Camp, D. E. O'Donnell, and D. S. Postma
Chronic Obstructive Pulmonary Disease in Men and Women: Myths and Reality
Proceedings of the ATS, September 15, 2009; 6(6): 535 - 538.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
J Smith, P Albert, E Bertella, J Lester, S Jack, and P Calverley
Qualitative aspects of breathlessness in health and disease
Thorax, August 1, 2009; 64(8): 713 - 718.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
D. Jensen, K. A. Webb, G. A. L. Davies, and D. E. O'Donnell
Mechanical ventilatory constraints during incremental cycle exercise in human pregnancy: implications for respiratory sensation
J. Physiol., October 1, 2008; 586(19): 4735 - 4750.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
104/6/1583    most recent
00079.2008v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ofir, D.
Right arrow Articles by O'Donnell, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ofir, D.
Right arrow Articles by O'Donnell, D. E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.