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No effect of gender on lung mucociliary clearance in young healthy adults
Respiratory Medicine (1994) 88, 697-700
No effect of gender on lung mucociliary clearance in young healthy adults A. HASANIt, H. VORA, D. PAVIA,, J. E. ACNEW* AND S. W . CLARKE
Departments of Thoracic Medicine and *Medical Physics, Royal Free Hospital and School of Medicine, London NW3 2QG, U.K.
Lung mucociliary clearance (LMC) depends on age and it is adversely affected by cigarette smoking. When using the radioaerosol technique for measuring LMC the initial site of deposition of the radioaerosol within the lungs affects its rate of removal. Whether there is a difference in gender for LMC is still an open question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their lung mucociliary clearance measured using an objective, non-invasive radioaerosol technique. The male and female groups were closely matched for initial distribution of the radioaerosol. There was no statistical significant difference between males and females in the rate of clearance of inhaled radioaerosol over a 6 h observation period. When comparing the LMC of two groups although it is important to match them for age, smoking habits and initial topographical distribution of the tracer radioaerosol it does not seem essential to also match the two groups for gender.
Introduction
Lung mucociliary clearance (LMC) is one of the lung's host defence clearance mechanisms helping to keep it clean and sterile even when exposed to a polluted atmosphere (1). This mucus clearance mechanism is often impaired in lung disease and can be adversely affected by cigarette smoking, exposure to other pollutants and following certain pharmacological intervention (2). When comparing the L M C of one group of subjects with that from a control group it is therefore important that the two groups be comparable in smoking exposure. Furthermore, clearance of tracer radioaerosol, used in the measurement of LMC is strongly related to its initial deposition within the lungs and as such the groups to be compared need to be closely matched for initial radioaerosol deposition within the airways (3). It has been reported that LMC slows down with age (4,5) and therefore in any comparison of LMC Received 30 November 1993 and accepted in revised form 23 February 1994. tTo whom correspondence should be addressed at: Department of Thoracic Medicine, Royal Free Hospital, Pond Street, London, NW3 2QG, U.K. :~Present Address: Boehringer Ingelheim Ltd., Ellesfield Avenue, Bracknell, Berkshire RG12 8YS, U.K.
0954-6111/94/090697+04 $08.00/0
between two groups, age must be duly accounted for. Whether there is a difference in LMC between healthy females and males of similar age, smoking habits and initial radioaerosol deposition has yet to be determined (6,7). We report a study examining whether LMC is different between the sexes when the other variables that could affect clearance have been accounted for. Methods SUBJECTS
Forty-one healthy subjects (20 females, 21 males) volunteered to participate in a study of normal mucociliary clearance. The table gives the mean (SE) physical characteristics, pulmonary function indices and alveolar deposition for the females and males. All the subjects were free from chest infection for at least 4 weeks prior to the study and all were lifetime non-smokers. RADIOAEROSOLTECHNIQUE LMC was measured using a radioaerosol technique which has previously been described fully (8). Briefly, 5pro polystyrene particles labelled firmly w i t h 99mTc were inhaled under strictly controlled conditions via the mouth with the subjects seated and wearing a nose clip. Discrete breaths of 450 ml were 9 1994W. B. SaundersCompany Ltd
698
A. H a s a n i et al.
1001
o
~ 80
60 g ,.Q o
40
p
20
,
I 1
t
I 2
,
I 3
,
I 4
I
I 5
,
I ~',l 6
24
Time after inhalation of radioaerosol Fig. 1
Mean (SE) tracheobronchial retention curves for healthy non-smoking subjects [20 females (9 and 21 males (0)].
taken from approximately the resting level of the lungs followed by a 3-s breath holding pause to allow particles to deposit within the airways at the furthest point of entry (9). Subjects subsequently washed out their mouths and drank some water to clear the oesophagus. The initial radioaerosol lung burden and its subsequent clearance were monitored by two scintillation detectors suitably collimated and located anteroposteriorly to the midline of the chest (10). A count of lung radioactivity was made immediately after inhalation and at frequent intervals thereafter for the ensuing 6 h with a final count at 24 h. The 24-h counts taken were assumed to be representative of the initial lung burden reaching the nonciliated airways (alveolar deposition) and therefore unavailable for mucus clearance (11). PULMONARY FUNCTION
Pulmonary function tests were carried out prior to the inhalation of the tracer radioaerosol. A dry bellows spirometer (Vitalograph) and a Wright's peak flow meter were used to measure forced expiratory volume in 1 s (FEV~), forced vital capacity (FVC), maximum mid-expiratory flow rate (MMFR25 75) and peak expiratory flow rate (PEFR). The best out of three technically acceptable measurements was recorded and expressed as a percentage of the predicted value based on sex, age and height (12).
S T A T I S T I C A L ANALYSIS
The Student's two-tailed t-test was used for the analysis of the data and statistical significance was accepted at the P<0.05 level. Informed written consent was obtained from all the volunteer subjects. Approval for the study was granted by the Hospital's Ethical Practices Subcommittee.
Results
The female and male groups were comparable in age; the females were significantly shorter than the males. Although all the pulmonary function indices for both groups were within the normal range nevertheless the female group had statistically significantly higher values for % predicted FEV 1 and PEFR. Alveolar deposition was similar between the two groups. Figure 1 shows the mean (sE) tracheobronchial retention curves. There was no statistically significant difference in the amount of radioaerosol present in the lungs at any time post inhalation between the two groups (although on average the females appeared to clear somewhat slower than the males). The mean (sw) areas under the tracheobronchial retention curve between 0 and 3 h (AUCo_3) and 0 and 6 h (AUC o 6) were: 156 (10) vs. 147 (7) % h and 210 (19) vs. 196 (14) % h for the females
No gender effect on tracheobronchial clearance
699
Table 1 Mean (SE)physical characteristics, pulmonary function and alveolar deposition for 20 females and 21 males
Age (yr) Height (m) % Predicted FEV l % Predicted FVC %Predicted PEFR Predicted MMFR2s_75 Alveolar Deposition (%)
Females
Males
P
24-4(1-3) 1.64(0.01) 123(4) 115(3) 104(4) 103(9) 55(2)
26-7(1-4) 1.76(0.02) 111(3) 109(3) 94(3) 101(6) 54(2)
Ns <0.0001 <0.03 NS <0.05 NS NS
NS, not significant. and males respectively; there was no significant difference between them. The females studied were clearly significantly shorter than the males (Table 1). In order to check whether height might significantly influence LMC we selected two subgroups, eight from each of the female and male groups, with similar heights [1.70 (0.01) and 1"69 (0"02) m for female and male respectively]. These subgroups, once again, were similar in age [23 (2) and 28 (2) years for female and male respectively] and initial distribution of the tracer radioaerosol [59 (3) and 54 (3) % for female and male respectively]. The clearance pattern between the two sexes was similar to that of the bigger groups with no significant difference between the two subgroups. A similar comparison was made between four males and eight females with comparable FVCs: 4-55 (0.12) and 4.31 (0.07)1 respectively. Once again, the clearance pattern between the two sexes was similar to that reported for the bigger groups. Discussion On theoretical grounds faster clearance might be expected in females when compared to males because of the somewhat smaller lungs and therefore shorter transit path along the ciliated airways for the deposited radioaerosol to be transported and cleared from the lungs. If women had faster clearance than men this might decrease risks to them from exposure to hazardous airborne particulates (in the workplace or elsewhere). In recent years increasing attention has been paid to sections of the public at large who might be at greater than average risk from exposure to airborne radioactivity. Relatively little attention has been paid to differing deposition in women as opposed to men with the notable exception of the work by Pritchard and associates (13) and even less to possible differing rates of clearance. Yeates and associates (6) reported
no difference in tracheal transport rates between 32 men and 10 women. On the other hand, Garrard and associates (7) reported a slower proximal mucociliary clearance in a group of nine men compared to four women. In this study we specifically took account of body stature in terms of matching male and female subgroups (a) for height and (b) for FVC. Our study shows that there is no significant difference in LMC between healthy non-smoking females and males. It is possible that this study did not have the power to detect the small difference in clearance between the two sexes. However, we have previously reported (14) that in healthy non-smoking volunteers the intersubject coefficient of variation for the 6-h tracheobronchial clearance is 13% and 35% for AUC o 6. The actual net difference at 6-h between females and males was 4% and that for the AUCo_6 14 % h. Using the same methodology we have reported that 129 chronic bronchitic patients would be needed in order to detect a 5% difference in 6-h tracheobronchial clearance with an 80% statistical power in a crossover study. In the present study using parallel groups this number on one hand might need to be bigger and on the other hand smaller since the inter-subject coefficient of variation in healthy subjects is approximately one third that for chronic bronchitic (14). This small, non-significant difference in clearance between the sexes can be considered as unimportant. As such we propose that when comparing clearances between two groups of subjects the need to match for sex although preferable does not seem necessarily to be essential. References 1. Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir Dis' 1977; 116:73 i25. 2. Pavia D. Lung mucociliary clearance. In: Clarke SW, Pavia D, eds. Aerosols and the Lung. London: Butterworth, 1984; 127-155.
700
A. Hasani et al.
3. Agnew JE, Bateman JRM, Watts M, Paramananda V, Pavia D, Clarke SW. The importance of aerosol penetration for lung mucociliary clearance studies. Chest 1981; 80: 843-846. 4. Goodman RM, Yergin BM, Landa JF, Golinvaux MH, Sackner MA. Relationship of smoking history and pulmonary function tests to tracheal mucous velocity in non-smokers, young smokers, ex-smokers, and patients with chronic bronchitis. Am Rev Respir Dis 1978; 117: 205-214. 5. Puchelle E, Zahm JM, Bertrand A. The influence of age on bronchial mucociliary transport. Scand J Respir Dis" 1979; 60: 307-313. 6. Yeats DB, Aspin N, Levison H, Jones MT, Bryan AC. Mucociliary tracheal transport rates in man. J Appl Physiol 1975; 39: 487495. 7. Garrard CS, Gerrity TR, Yeates DB. The relationship of aerosol deposition, lung size, and the rate of mucociliary clearance. Arch Environ Hlth 1986; 41:11-15. 8. Pavia D, Sutton PP, Agnew JE, Lopez-Vidriero MT, Newman SP, Clarke SW. Measurements of bronchial
9. 10. 11. 12. 13. 14.
mucociliary clearance. Eur J Respir Dis 1983; 64: 41-56. Newman SP, Pavia D, Moren F, Sheahan NF, Clarke SW. Deposition of pressurised aerosols in the human respiratory tract. Thorax 1981; 36:52 55. Thomson ML, Pavia D. Long-term tobacco smoking and nmcociliary clearance. Arch Environ Hlth 1973; 26: 86-89. Camner P, Philipson K. Human alveolar deposition of 4~tm Teflon particles. Arch Environ Hlth 1978; 36: 181 185. Cotes JE. Lung function: assessment and application in medicine. Fourth edn. Oxford: Blackwell, 1979. Pritchard JN, Jefferies SJ, Black A. Regional deposition of 2.5 to 5.0/~m polystyrene microspheres inhaled by women. Ann Occup Hyg 1988; 32: 939-946. Del Donno M, Pavia D, Agnew JE, Lopez-Vidriero MT, Clark SW. Variability and reproducibility in the measurement of tracheobronchial clearance in healthy subjects and patients with different obstructive lung disease. Eur Respir J 1988; 1: 613-620.
No effect of gender on lung mucociliary clearance in young healthy adults A. HASANIt, H. VORA, D. PAVIA,, J. E. ACNEW* AND S. W . CLARKE
Departments of Thoracic Medicine and *Medical Physics, Royal Free Hospital and School of Medicine, London NW3 2QG, U.K.
Lung mucociliary clearance (LMC) depends on age and it is adversely affected by cigarette smoking. When using the radioaerosol technique for measuring LMC the initial site of deposition of the radioaerosol within the lungs affects its rate of removal. Whether there is a difference in gender for LMC is still an open question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their lung mucociliary clearance measured using an objective, non-invasive radioaerosol technique. The male and female groups were closely matched for initial distribution of the radioaerosol. There was no statistical significant difference between males and females in the rate of clearance of inhaled radioaerosol over a 6 h observation period. When comparing the LMC of two groups although it is important to match them for age, smoking habits and initial topographical distribution of the tracer radioaerosol it does not seem essential to also match the two groups for gender.
Introduction
Lung mucociliary clearance (LMC) is one of the lung's host defence clearance mechanisms helping to keep it clean and sterile even when exposed to a polluted atmosphere (1). This mucus clearance mechanism is often impaired in lung disease and can be adversely affected by cigarette smoking, exposure to other pollutants and following certain pharmacological intervention (2). When comparing the L M C of one group of subjects with that from a control group it is therefore important that the two groups be comparable in smoking exposure. Furthermore, clearance of tracer radioaerosol, used in the measurement of LMC is strongly related to its initial deposition within the lungs and as such the groups to be compared need to be closely matched for initial radioaerosol deposition within the airways (3). It has been reported that LMC slows down with age (4,5) and therefore in any comparison of LMC Received 30 November 1993 and accepted in revised form 23 February 1994. tTo whom correspondence should be addressed at: Department of Thoracic Medicine, Royal Free Hospital, Pond Street, London, NW3 2QG, U.K. :~Present Address: Boehringer Ingelheim Ltd., Ellesfield Avenue, Bracknell, Berkshire RG12 8YS, U.K.
0954-6111/94/090697+04 $08.00/0
between two groups, age must be duly accounted for. Whether there is a difference in LMC between healthy females and males of similar age, smoking habits and initial radioaerosol deposition has yet to be determined (6,7). We report a study examining whether LMC is different between the sexes when the other variables that could affect clearance have been accounted for. Methods SUBJECTS
Forty-one healthy subjects (20 females, 21 males) volunteered to participate in a study of normal mucociliary clearance. The table gives the mean (SE) physical characteristics, pulmonary function indices and alveolar deposition for the females and males. All the subjects were free from chest infection for at least 4 weeks prior to the study and all were lifetime non-smokers. RADIOAEROSOLTECHNIQUE LMC was measured using a radioaerosol technique which has previously been described fully (8). Briefly, 5pro polystyrene particles labelled firmly w i t h 99mTc were inhaled under strictly controlled conditions via the mouth with the subjects seated and wearing a nose clip. Discrete breaths of 450 ml were 9 1994W. B. SaundersCompany Ltd
698
A. H a s a n i et al.
1001
o
~ 80
60 g ,.Q o
40
p
20
,
I 1
t
I 2
,
I 3
,
I 4
I
I 5
,
I ~',l 6
24
Time after inhalation of radioaerosol Fig. 1
Mean (SE) tracheobronchial retention curves for healthy non-smoking subjects [20 females (9 and 21 males (0)].
taken from approximately the resting level of the lungs followed by a 3-s breath holding pause to allow particles to deposit within the airways at the furthest point of entry (9). Subjects subsequently washed out their mouths and drank some water to clear the oesophagus. The initial radioaerosol lung burden and its subsequent clearance were monitored by two scintillation detectors suitably collimated and located anteroposteriorly to the midline of the chest (10). A count of lung radioactivity was made immediately after inhalation and at frequent intervals thereafter for the ensuing 6 h with a final count at 24 h. The 24-h counts taken were assumed to be representative of the initial lung burden reaching the nonciliated airways (alveolar deposition) and therefore unavailable for mucus clearance (11). PULMONARY FUNCTION
Pulmonary function tests were carried out prior to the inhalation of the tracer radioaerosol. A dry bellows spirometer (Vitalograph) and a Wright's peak flow meter were used to measure forced expiratory volume in 1 s (FEV~), forced vital capacity (FVC), maximum mid-expiratory flow rate (MMFR25 75) and peak expiratory flow rate (PEFR). The best out of three technically acceptable measurements was recorded and expressed as a percentage of the predicted value based on sex, age and height (12).
S T A T I S T I C A L ANALYSIS
The Student's two-tailed t-test was used for the analysis of the data and statistical significance was accepted at the P<0.05 level. Informed written consent was obtained from all the volunteer subjects. Approval for the study was granted by the Hospital's Ethical Practices Subcommittee.
Results
The female and male groups were comparable in age; the females were significantly shorter than the males. Although all the pulmonary function indices for both groups were within the normal range nevertheless the female group had statistically significantly higher values for % predicted FEV 1 and PEFR. Alveolar deposition was similar between the two groups. Figure 1 shows the mean (sE) tracheobronchial retention curves. There was no statistically significant difference in the amount of radioaerosol present in the lungs at any time post inhalation between the two groups (although on average the females appeared to clear somewhat slower than the males). The mean (sw) areas under the tracheobronchial retention curve between 0 and 3 h (AUCo_3) and 0 and 6 h (AUC o 6) were: 156 (10) vs. 147 (7) % h and 210 (19) vs. 196 (14) % h for the females
No gender effect on tracheobronchial clearance
699
Table 1 Mean (SE)physical characteristics, pulmonary function and alveolar deposition for 20 females and 21 males
Age (yr) Height (m) % Predicted FEV l % Predicted FVC %Predicted PEFR Predicted MMFR2s_75 Alveolar Deposition (%)
Females
Males
P
24-4(1-3) 1.64(0.01) 123(4) 115(3) 104(4) 103(9) 55(2)
26-7(1-4) 1.76(0.02) 111(3) 109(3) 94(3) 101(6) 54(2)
Ns <0.0001 <0.03 NS <0.05 NS NS
NS, not significant. and males respectively; there was no significant difference between them. The females studied were clearly significantly shorter than the males (Table 1). In order to check whether height might significantly influence LMC we selected two subgroups, eight from each of the female and male groups, with similar heights [1.70 (0.01) and 1"69 (0"02) m for female and male respectively]. These subgroups, once again, were similar in age [23 (2) and 28 (2) years for female and male respectively] and initial distribution of the tracer radioaerosol [59 (3) and 54 (3) % for female and male respectively]. The clearance pattern between the two sexes was similar to that of the bigger groups with no significant difference between the two subgroups. A similar comparison was made between four males and eight females with comparable FVCs: 4-55 (0.12) and 4.31 (0.07)1 respectively. Once again, the clearance pattern between the two sexes was similar to that reported for the bigger groups. Discussion On theoretical grounds faster clearance might be expected in females when compared to males because of the somewhat smaller lungs and therefore shorter transit path along the ciliated airways for the deposited radioaerosol to be transported and cleared from the lungs. If women had faster clearance than men this might decrease risks to them from exposure to hazardous airborne particulates (in the workplace or elsewhere). In recent years increasing attention has been paid to sections of the public at large who might be at greater than average risk from exposure to airborne radioactivity. Relatively little attention has been paid to differing deposition in women as opposed to men with the notable exception of the work by Pritchard and associates (13) and even less to possible differing rates of clearance. Yeates and associates (6) reported
no difference in tracheal transport rates between 32 men and 10 women. On the other hand, Garrard and associates (7) reported a slower proximal mucociliary clearance in a group of nine men compared to four women. In this study we specifically took account of body stature in terms of matching male and female subgroups (a) for height and (b) for FVC. Our study shows that there is no significant difference in LMC between healthy non-smoking females and males. It is possible that this study did not have the power to detect the small difference in clearance between the two sexes. However, we have previously reported (14) that in healthy non-smoking volunteers the intersubject coefficient of variation for the 6-h tracheobronchial clearance is 13% and 35% for AUC o 6. The actual net difference at 6-h between females and males was 4% and that for the AUCo_6 14 % h. Using the same methodology we have reported that 129 chronic bronchitic patients would be needed in order to detect a 5% difference in 6-h tracheobronchial clearance with an 80% statistical power in a crossover study. In the present study using parallel groups this number on one hand might need to be bigger and on the other hand smaller since the inter-subject coefficient of variation in healthy subjects is approximately one third that for chronic bronchitic (14). This small, non-significant difference in clearance between the sexes can be considered as unimportant. As such we propose that when comparing clearances between two groups of subjects the need to match for sex although preferable does not seem necessarily to be essential. References 1. Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir Dis' 1977; 116:73 i25. 2. Pavia D. Lung mucociliary clearance. In: Clarke SW, Pavia D, eds. Aerosols and the Lung. London: Butterworth, 1984; 127-155.
700
A. Hasani et al.
3. Agnew JE, Bateman JRM, Watts M, Paramananda V, Pavia D, Clarke SW. The importance of aerosol penetration for lung mucociliary clearance studies. Chest 1981; 80: 843-846. 4. Goodman RM, Yergin BM, Landa JF, Golinvaux MH, Sackner MA. Relationship of smoking history and pulmonary function tests to tracheal mucous velocity in non-smokers, young smokers, ex-smokers, and patients with chronic bronchitis. Am Rev Respir Dis 1978; 117: 205-214. 5. Puchelle E, Zahm JM, Bertrand A. The influence of age on bronchial mucociliary transport. Scand J Respir Dis" 1979; 60: 307-313. 6. Yeats DB, Aspin N, Levison H, Jones MT, Bryan AC. Mucociliary tracheal transport rates in man. J Appl Physiol 1975; 39: 487495. 7. Garrard CS, Gerrity TR, Yeates DB. The relationship of aerosol deposition, lung size, and the rate of mucociliary clearance. Arch Environ Hlth 1986; 41:11-15. 8. Pavia D, Sutton PP, Agnew JE, Lopez-Vidriero MT, Newman SP, Clarke SW. Measurements of bronchial
9. 10. 11. 12. 13. 14.
mucociliary clearance. Eur J Respir Dis 1983; 64: 41-56. Newman SP, Pavia D, Moren F, Sheahan NF, Clarke SW. Deposition of pressurised aerosols in the human respiratory tract. Thorax 1981; 36:52 55. Thomson ML, Pavia D. Long-term tobacco smoking and nmcociliary clearance. Arch Environ Hlth 1973; 26: 86-89. Camner P, Philipson K. Human alveolar deposition of 4~tm Teflon particles. Arch Environ Hlth 1978; 36: 181 185. Cotes JE. Lung function: assessment and application in medicine. Fourth edn. Oxford: Blackwell, 1979. Pritchard JN, Jefferies SJ, Black A. Regional deposition of 2.5 to 5.0/~m polystyrene microspheres inhaled by women. Ann Occup Hyg 1988; 32: 939-946. Del Donno M, Pavia D, Agnew JE, Lopez-Vidriero MT, Clark SW. Variability and reproducibility in the measurement of tracheobronchial clearance in healthy subjects and patients with different obstructive lung disease. Eur Respir J 1988; 1: 613-620.