BRITISH MEDICAL JOURNAL
5 NOVEMBER 1977
normal group, although treatment with bromocriptine effectively suppressed circulating prolactin concentrations to below normal at all the dose levels studied. Life-tables'6 were used to calculate the cumulative conception rate because this method includes patients who cease treatment before the end of a study, and thus permits valid comparisons to be made between different studies. The cumulative conception rate reported here after bromocriptine treatment is dramatically different from the spontaneous conception rate obtained in a similar group of patients who were given no treatment.2 In the latter series only 43", of the patients conceived spontaneously in a period of eight years (10°, in the first year of follow-up, whereas 63°,, of the patients in this study conceived in 10 months). The conception rate after bromocriptine in these infertile women is still less than the reported rates for a normal population. " 22 At this stage it is premature to speculate about the direct or indirect effects of bromocriptine on follicular maturation and function of the corpus luteum. The role of prolactin in the regulation of reproduction in these women is undoubtedly complex,22 and may well be only loosely related to circulating prolactin concentrations.' Some mechanism apart from a mere reduction in plasma concentrations is needed to explain the resumption of menses in some euprolactinaemic women9 and not others.2 In our own series of ovulating women, the pregnancies that occurred were not among the patients with the highest prolactin concentrations, but were evenly distributed throughout the range of prolactin concentrations measured. Nonetheless, it seems most unlikely that the number of pregnancies obtained here in a group of women who normally are very difficult to treat successfully could be fortuitous and unrelated to bromocriptine administration. This new and apparently successful use of bromocriptine2; needs much careful research to establish not only the precise mode of action but also the type of ovulatory but infertile woman who is most likely to benefit
from it. We thank Miss L Brook for performing the luteinising hormone assays; Miss B McNeill for typing the manuscript; Sandoz Limited for financial support for one of us (EAL); and Mr A Singer for his co-operation in referring some of the patients.
1181 Requests for reprints should be addressed to Dr E A Lenton, University Department of Obstetrics and Gvnaecology, Jessop Hospital for Women, Sheffield S3 7RE.
References 2
Seki, K, and Scki, M, Journal of Clinical Endocrinology and Metabolism, 1974, 38, 508. Pepperell, R J, et al, British Journal of Obstetrics and Gynaecology, 1977,
84, 58. Seppala, M, et al, British Medical Journal, 1975, 2, 305. del Pozo, E, et al, in Ovulation in the Human, ed P G Crosignani and D R Mishell, p 297. London, Academic Press, 1976. Tyson, J E, et al, Amierican Journal of Obstetrics and Gynecology, 1975, 121, 375. Besser, G M, et al, British Medical Journal, 1972, 3, 669. Thorner, M 0, et al, British Medical Journal, 1974, 2, 419. 8 Thorner, M 0, et al, British Medical Journal, 1975, 4, 694. 9Tolis, G, and Naftolin, F, American Journal of Obstetrics and Gynecology, 1976, 126, 426. del Pozo, E, Varga, L, and Obolensky, W. Communication to Symposium on Ovulation in the Human. Freiburg, Germany, 10-12 September 1975. Corenblum, B, Pairandeau, N, and Shewchuk, A B, Obstetrics and Gynecology, 1976, 47, 486. 12 Cooke, I D, et al, Journal of Reproduiction and Fertility, 1977, 51, 203. 13 Lenton, E A, Adams, M, and Cooke, I D. In preparation. 4 Sherman, B M, and Korenman, S G,Journal of Clinical Endocrinology and Metabolism, 1974, 38, 89. 1 Reuter, A M, et al, International Journal of Nuclear Medical Biology, 1976, 3, 21. 1 Lamb, E J, and Cruz, A L, Fertility and Sterility, 1972, 23, 310. 1 Ehara, Y, et al, Amierican Journal of Obstetrics and Gynecology, 1973, 117, 962. 18 Franchimont, P, et al, Radioimnmunoassay of prolactin in health and disease, p 7. Brussels, Imprimerie Bietlot Freres, 1976. 1] Robyn, C, et al, in Human Prolactin, ed J P Pasteels and C Robyn, p 167. New York, Excerpta Medica, American Elsevier, 1973. 20 Lenton, E A, Weston, G A, and Cooke, I D, Fertility and Sterility, 1977. In press. 2l Diddle, A W, Jack, R W, and Pearse, R L, Anmerican journal of Obstetrics and Gynecology, 1947, 54, 57. 22 Tietze, C, Fertility anid Sterility, 1956, 7, 88. 23 Glass, M R, et al, British Medical3Journal, 1975, 3, 274. 24 McNatty, K P, Sawers, R S, and McNeilly, A S, Natuire, 1974, 240, 653. 2;5 British Medical Journal, 1977, 1, 863.
(Accepted 1 Septemnber 1977)
Effects of sputum on pulmonary function G M COCHRANE, B A WEBBER, S W CLARKE British
Medical_Journal,
1977, 2, 1181-1183
Summary The specific airways conductance (SGAW) of 23 patients with copious sputum production and airflow obstruction was measured before and after physiotherapy to deterDepartment of Thoracic Medicine, New Cross Hospital, London SE14 5ER G M COCHRANE, MB, MRCP, consultant physician
Brompton Hospital, London B A WEBBER, MCSP, assistant superintendent, department of physiotherapy S W CLARKE, MD, FRCP, consultant physician
mine the effect of bronchial secretions on pulmonary function. Chest physiotherapy to remove these secretions had the effect of reducing airflow obstruction, as measured by SGAW. These findings suggest that sputum has a detrimental effect on pulmonary function and that physiotherapy can reduce airways obstruction. Introduction Although cough and sputum are the cardinal features of chronic bronchitis' and are also associated with bronchiectasis and cystic fibrosis, few studies have been undertaken to assess the effect on pulmonary function of liquid secretions within the bronchial tree. Moreover, previous studies have not given conclusive
1182
BRITISH MEDICAL JOURNAL
results.2 3Part at least of the airways obstruction seen in chronic bronchitis, bronchiectasis, or cystic fibrosis may be created by bronchial secretions that narrow the airway lumen and create a two-phase interaction between air and liquid during rapid or forced breathing.4 The present study was designed to measure the effect of bronchial secretions on pulmonary function before and after removal of these secretions by physiotherapy.
Patients and methods Twenty-three patients with chronic cough, sputum production, and airways obstruction (forced expiratory volume in 1 second (FEVy) forced vital capacity (FVC) < 70 % of predicted5 6) were studied before and after physiotherapy. They all produced at least 30 ml sputum per day and had less than a 150% improvement in FEVy after inhaling 150 tg of isoprenaline base. Their mean age was 49 years (18-62 years), and 10 patients were diagnosed as suffering from bronchiectasis, 11 from cystic fibrosis, and two from chronic bronchitis. The small proportion of patients with chronic bronchitis in this study was due to the comparatively large sputum volume, expectorated on a regular basis, that we determined as a minimum requirement to enter the study. We chose this large volume to increase the possibility of showing an effect on respiratory function before and after removing these secretions.
PULMONARY FUNCTION STUDIES
Thoracic gas volume (TGV), airways resistance (RAW) (body plethysmography performed with a Pulmostar SMB, Fenyves and Gut7 8), the derivative specific conductance (SGAW = 1/RAW x TGV), FEV,, and FVC (vitalograph) were measured at 9.00 am on the day of the study. SGAW was always determined first and three estimates of each variate were obtained. If the variation was greater than 5°O, the patient was excluded from the study. The patients had been fully instructed in the techniques on the previous day. The patient was then given physiotherapy for 20-30 minutes; this consisted of breathing exercises, chest vibration, and percussion in different postures.9 During this physiotherapy session sputum was collected and its volume measured and nature noted. In 16 of the 23 patients the sputum was considered to be mucopurulent and in the remaining seven mainly mucoid. No bacteriological studies were carried out on the sputum. No attempt was made to measure the sputum viscosity or elasticity, as this lay outside the scope of the present study. After physiotherapy 45-60 minutes lapsed to allow the patient to be in a
0
80-
70600
50 40
< n
0
' 307
OS.0
cr
, 20-
0 0
-0-
00 10
0
0
-
.00 0-02 0-06 0-10
-10I
0 14 0-18 0-22 SGAW (kPa/s) 0
-20-' 0
Percentage change in specific conductance (SGAW) against specific conductance after physiotherapy (@) and in four patients on a separate day who had no physiotherapy (Q).
5 NOVEMBER 1977
steady state before pulmonary function tests were repeated in the same sequence as before. Control studies-Four of the patients were again studied on a separate day but they had no physiotherapy and were allowed to expectorate normally. Eight of the patients were studied on another day when 150 ,tg of isoprenaline base by inhalation was given in place of physiotherapy. Four normal subjects (aged 19-46) with no sputum production or airways obstruction of any kind underwent a similar study of pulmonary studies and physiotherapy to ensure that any change in the respiratory values was not an effect of diurnal variation or of physiotherapy itself.
Results After physiotherapy SGAW improved in 17 of the 23 patients, was unchanged in two, and fell in four (see figure). The mean improvement was 18o% (Student's t test: 005 -P>0 02); the increase in FEVy was less striking (8 %; Student's t test: 0 1 >P 0-05). There was no relation between volume of sputum and improvement in SGAW, but in the four patients who were studied again on a day when they had no physiotherapy sputum volume was considerably reduced. They showed no significant change in SGAW (see figure). The normal subjects who were tested similarly showed no significant change in SGAW (P=0 2). Of the eight patients studied after inhaling isoprenaline, SGAW improved in five, was unchanged in two, and deteriorated in one. The mean change of +40% was not significant (0 2-P 0 1). FEV, improved in three patients, was unchanged in three, and deteriorated in two. The mean change was + 40% and, again, was not significant
(P = 02). Discussion Bronchial secretions together with mucosal oedema and smooth muscle spasm are usually considered to play some part in obstructing airflow in the bronchial tree in asthma, chronic bronchitis, and bronchiectasis. Although the role of smooth muscle spasm has been well defined, there are relatively few studies that have attempted to determine the role of secretions.2 This may in part reflect the difficulty of doing so. We chose to measure specific conductance because (even in patients) it reflects changes in the resistance of the large airways rather than the smaller airways,'0 and the secretions that physiotherapy may help to move are probably in the larger airways. SGAW also takes into account two factors that vary when the degree of airways obstruction changes-namely, airways resistance and functional residual capacity. For our purposes FEV, is a much cruder value and has the serious drawback that its measurement disturbs the bronchial "status quo" by shearing the secretions in a manner similar to coughing and probably by inducing reflex bronchoconstriction in patients with bronchial lability. The dynamics of coughing and forced expiratory manoeuvres are similar. We believe this criticism of the FEV, is supported by our data, which show a greater change in SGAW than in FEV,. We found no relation between SGAW and sputum volume. The distribution of sputum throughout the airways is probably more relevant in modifying airflow obstruction than is volume, viscosity, or character. Nevertheless, the nature of the bronchial disease, leading to either hypersecretion or airflow obstruction, or both, will also play a part in any changes detected. The control studies undertaken on normal subjects showed that there was no significant change in airway calibre after physiotherapy or diurnally. The possibility that the time in the morning could account for significant changes in SGAW in patients with sputum production but without physiotherapy was also excluded by studying four patients on the second day. The study of the eight patients who received isoprenaline indicated that although change in bronchial smooth-muscle tone after physiotherapy may have influenced our findings any effect was probably small and insignificant. The results suggest that bronchial secretions may account for
BRITISH MEDICAL JOURNAL
5 NOVEMBER 1977
a significant percentage of the airways obstruction (as determined by SGAW) in our patients and that this airways obstruction may be decreased by measures focused on bronchial clearance, such as physiotherapy. Additionally, our findings reinforce the value of chest physiotherapy in patients with a large volume of sputum production and airflow obstruction; objective data on its value has hitherto been sparse. We thank all the consultant physicians at the Brompton Hospital who kindly allowed us to study patients under their care and also Miss J M Wright for secretarial help. Dr G M Cochrane was supported by a grant from the Board of Governors of the National Heart and Chest Hospitals. Requests for reprints should be addressed to Dr G M Cochrane.
1183
References ILancet, 1965, 2, 776. 2March, H, Archives of Physical Medicine and Rehabilitation, 1971, 51, 528. 3Pham, Q T, et al, Bulletin de Physio-Pathologie Respiratoire, 1973, 9, 293. Clarke, S W, Jones, J G, and Oliver, D R, Journal of Applied Physiology, 1970, 29, 464. Cotes, J E, Lung Function, 2nd edn. Oxford, Blackwell Scientific, 1968. 6 Cotes, J E, et al, British Medical Journal, 1966, 1, 1016. Dubois, A B, et al, Journal of Clinical Investigation, 1956, 35, 322. 8 Dubois, A B, Botello, S Y, and Comroe, J H, jun, J1ournal of Clinical Investigation, 1956, 35, 327. 9 Gaskell, D V, and Webber, B A, Brompton Hospital Guide to Chest Physiotherapy, 3rd edn. London, Blackwell, 1977. Macklem, P T, American Journal of Medicine, 1972, 52, 721.
(Accepted 31 August 1977)
Rapid increases in plasma prostaglandin concentrations after vaginal examination and amniotomy M D MITCHELL, A P F FLINT, J BIBBY, J BRUNT, J M ARNOLD, A B M ANDERSON, A C TURNBULL Britishl Medical journal, 1977, 2, 1183-1185
Summary Peripheral plasma concentrations of 13,14-dihydro-15keto prostaglandin F (PGFM) were measured in three groups of women after the 37th week of pregnancy. Samples were taken before and five minutes after (a) amniotomy, (b) vaginal examination with sweeping of the fetal membranes, or (c) vaginal examination without sweeping of the membranes. Each procedure significantly raised the circulating PGFM levels, although amniotomy and vaginal examination with membrane sweep were more potent stimuli than vaginal examination alone. These findings suggest that there is a considerable potential for rapid increases in prostaglandin production during late pregnancy and provide a possible explanation for the fact that amniotomy and vaginal examination with membrane sweep often initiate labour.
Introduction It is well known that in late pregnancy both amniotomy and vaginal examination when the membranes are swept off the lower uterine segment may initiate labour, although the mechanisms responsible have not been elucidated. Recent Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU M D MITCHELL, MA, DPHIL, medical research fellow A P F FLINT, BSC, PHD, senior biochemist (now senior scieintific officer, department of physiology, ARC Institute of Animal Physiology, Babraham, Cambridge) BIBBY, MB, MRCOG, clinical research assistant J BRUNT, BSC, research assistant J M ARNOLD, MB, BCH, senior house officer (now senior house officer, Royal United Hospital, Bath) A B M ANDERSON, MD, PHD, lecturer A C TURNBULL, MD, FRCOG, Nuffield professor of obstetrics and
gynaecology
evidence has shown that parturition in most species, including primates, is associated with raised concentrations of prostaglandins in intrauterine tissues, plasma, or amniotic fluid,1-3 and this has focused attention on the possibility that prostaglandins may be released in response to disruption of intrauterine tissues such as decidua4 or fetal membranes. 6 Recent work from this department7 has shown that amniotic fluid concentrations of the primary prostaglandin PGF -and its major circulating metabolite 13,14-dihydro-1 5-ketoprostaglandin F (PGFM) are significantly higher in samples obtained by amniotomy than at amniocentesis. We suggested7 that this may relate to the increased disruption at amniotomy of the membranes that contain prostaglandin synthesising enzymes," or it may be a process analagous to that found in pregnant sheep,8 ' where marked PGF release into the uterine vein occurs within minutes of vaginal and cervical stimulation. Since amniotomy both stimulates the upper genital tract (vagina and cervix) and disrupts the membranes, and since these two procedures might theoretically stimulate increased intrauterine prostaglandin production, it became clear that we had to examine the effect of these procedures separately. We therefore studied the effects of (a) stimulating the upper genital tract (vaginal examination); (b) disrupting the attachment of part of the fetal membranes by separating them from the lower uterine segment (vaginal examination plus membrane sweep); and (c) puncturing the membranes vaginally to induce labour (amniotomy). The availability of a sensitive and specific radio-immunoassay for PGFM allowed us to study circulating concentrations of this metabolite in the peripheral plasma in response to these procedures.
Patients and methods In all patients pregnancy had progressed beyond 37 weeks of gestation from the first day of the last menstrual period. There was no difference among the groups studied in the mean length of gestation, age or parity of the patients, or cervical "ripeness." The pregnancies were considered to be uncomplicated with no major maternal or fetal pathology. All patients were subsequently delivered vaginally of single healthy live born infants, who were considered to be "mature" with
5 NOVEMBER 1977
normal group, although treatment with bromocriptine effectively suppressed circulating prolactin concentrations to below normal at all the dose levels studied. Life-tables'6 were used to calculate the cumulative conception rate because this method includes patients who cease treatment before the end of a study, and thus permits valid comparisons to be made between different studies. The cumulative conception rate reported here after bromocriptine treatment is dramatically different from the spontaneous conception rate obtained in a similar group of patients who were given no treatment.2 In the latter series only 43", of the patients conceived spontaneously in a period of eight years (10°, in the first year of follow-up, whereas 63°,, of the patients in this study conceived in 10 months). The conception rate after bromocriptine in these infertile women is still less than the reported rates for a normal population. " 22 At this stage it is premature to speculate about the direct or indirect effects of bromocriptine on follicular maturation and function of the corpus luteum. The role of prolactin in the regulation of reproduction in these women is undoubtedly complex,22 and may well be only loosely related to circulating prolactin concentrations.' Some mechanism apart from a mere reduction in plasma concentrations is needed to explain the resumption of menses in some euprolactinaemic women9 and not others.2 In our own series of ovulating women, the pregnancies that occurred were not among the patients with the highest prolactin concentrations, but were evenly distributed throughout the range of prolactin concentrations measured. Nonetheless, it seems most unlikely that the number of pregnancies obtained here in a group of women who normally are very difficult to treat successfully could be fortuitous and unrelated to bromocriptine administration. This new and apparently successful use of bromocriptine2; needs much careful research to establish not only the precise mode of action but also the type of ovulatory but infertile woman who is most likely to benefit
from it. We thank Miss L Brook for performing the luteinising hormone assays; Miss B McNeill for typing the manuscript; Sandoz Limited for financial support for one of us (EAL); and Mr A Singer for his co-operation in referring some of the patients.
1181 Requests for reprints should be addressed to Dr E A Lenton, University Department of Obstetrics and Gvnaecology, Jessop Hospital for Women, Sheffield S3 7RE.
References 2
Seki, K, and Scki, M, Journal of Clinical Endocrinology and Metabolism, 1974, 38, 508. Pepperell, R J, et al, British Journal of Obstetrics and Gynaecology, 1977,
84, 58. Seppala, M, et al, British Medical Journal, 1975, 2, 305. del Pozo, E, et al, in Ovulation in the Human, ed P G Crosignani and D R Mishell, p 297. London, Academic Press, 1976. Tyson, J E, et al, Amierican Journal of Obstetrics and Gynecology, 1975, 121, 375. Besser, G M, et al, British Medical Journal, 1972, 3, 669. Thorner, M 0, et al, British Medical Journal, 1974, 2, 419. 8 Thorner, M 0, et al, British Medical Journal, 1975, 4, 694. 9Tolis, G, and Naftolin, F, American Journal of Obstetrics and Gynecology, 1976, 126, 426. del Pozo, E, Varga, L, and Obolensky, W. Communication to Symposium on Ovulation in the Human. Freiburg, Germany, 10-12 September 1975. Corenblum, B, Pairandeau, N, and Shewchuk, A B, Obstetrics and Gynecology, 1976, 47, 486. 12 Cooke, I D, et al, Journal of Reproduiction and Fertility, 1977, 51, 203. 13 Lenton, E A, Adams, M, and Cooke, I D. In preparation. 4 Sherman, B M, and Korenman, S G,Journal of Clinical Endocrinology and Metabolism, 1974, 38, 89. 1 Reuter, A M, et al, International Journal of Nuclear Medical Biology, 1976, 3, 21. 1 Lamb, E J, and Cruz, A L, Fertility and Sterility, 1972, 23, 310. 1 Ehara, Y, et al, Amierican Journal of Obstetrics and Gynecology, 1973, 117, 962. 18 Franchimont, P, et al, Radioimnmunoassay of prolactin in health and disease, p 7. Brussels, Imprimerie Bietlot Freres, 1976. 1] Robyn, C, et al, in Human Prolactin, ed J P Pasteels and C Robyn, p 167. New York, Excerpta Medica, American Elsevier, 1973. 20 Lenton, E A, Weston, G A, and Cooke, I D, Fertility and Sterility, 1977. In press. 2l Diddle, A W, Jack, R W, and Pearse, R L, Anmerican journal of Obstetrics and Gynecology, 1947, 54, 57. 22 Tietze, C, Fertility anid Sterility, 1956, 7, 88. 23 Glass, M R, et al, British Medical3Journal, 1975, 3, 274. 24 McNatty, K P, Sawers, R S, and McNeilly, A S, Natuire, 1974, 240, 653. 2;5 British Medical Journal, 1977, 1, 863.
(Accepted 1 Septemnber 1977)
Effects of sputum on pulmonary function G M COCHRANE, B A WEBBER, S W CLARKE British
Medical_Journal,
1977, 2, 1181-1183
Summary The specific airways conductance (SGAW) of 23 patients with copious sputum production and airflow obstruction was measured before and after physiotherapy to deterDepartment of Thoracic Medicine, New Cross Hospital, London SE14 5ER G M COCHRANE, MB, MRCP, consultant physician
Brompton Hospital, London B A WEBBER, MCSP, assistant superintendent, department of physiotherapy S W CLARKE, MD, FRCP, consultant physician
mine the effect of bronchial secretions on pulmonary function. Chest physiotherapy to remove these secretions had the effect of reducing airflow obstruction, as measured by SGAW. These findings suggest that sputum has a detrimental effect on pulmonary function and that physiotherapy can reduce airways obstruction. Introduction Although cough and sputum are the cardinal features of chronic bronchitis' and are also associated with bronchiectasis and cystic fibrosis, few studies have been undertaken to assess the effect on pulmonary function of liquid secretions within the bronchial tree. Moreover, previous studies have not given conclusive
1182
BRITISH MEDICAL JOURNAL
results.2 3Part at least of the airways obstruction seen in chronic bronchitis, bronchiectasis, or cystic fibrosis may be created by bronchial secretions that narrow the airway lumen and create a two-phase interaction between air and liquid during rapid or forced breathing.4 The present study was designed to measure the effect of bronchial secretions on pulmonary function before and after removal of these secretions by physiotherapy.
Patients and methods Twenty-three patients with chronic cough, sputum production, and airways obstruction (forced expiratory volume in 1 second (FEVy) forced vital capacity (FVC) < 70 % of predicted5 6) were studied before and after physiotherapy. They all produced at least 30 ml sputum per day and had less than a 150% improvement in FEVy after inhaling 150 tg of isoprenaline base. Their mean age was 49 years (18-62 years), and 10 patients were diagnosed as suffering from bronchiectasis, 11 from cystic fibrosis, and two from chronic bronchitis. The small proportion of patients with chronic bronchitis in this study was due to the comparatively large sputum volume, expectorated on a regular basis, that we determined as a minimum requirement to enter the study. We chose this large volume to increase the possibility of showing an effect on respiratory function before and after removing these secretions.
PULMONARY FUNCTION STUDIES
Thoracic gas volume (TGV), airways resistance (RAW) (body plethysmography performed with a Pulmostar SMB, Fenyves and Gut7 8), the derivative specific conductance (SGAW = 1/RAW x TGV), FEV,, and FVC (vitalograph) were measured at 9.00 am on the day of the study. SGAW was always determined first and three estimates of each variate were obtained. If the variation was greater than 5°O, the patient was excluded from the study. The patients had been fully instructed in the techniques on the previous day. The patient was then given physiotherapy for 20-30 minutes; this consisted of breathing exercises, chest vibration, and percussion in different postures.9 During this physiotherapy session sputum was collected and its volume measured and nature noted. In 16 of the 23 patients the sputum was considered to be mucopurulent and in the remaining seven mainly mucoid. No bacteriological studies were carried out on the sputum. No attempt was made to measure the sputum viscosity or elasticity, as this lay outside the scope of the present study. After physiotherapy 45-60 minutes lapsed to allow the patient to be in a
0
80-
70600
50 40
< n
0
' 307
OS.0
cr
, 20-
0 0
-0-
00 10
0
0
-
.00 0-02 0-06 0-10
-10I
0 14 0-18 0-22 SGAW (kPa/s) 0
-20-' 0
Percentage change in specific conductance (SGAW) against specific conductance after physiotherapy (@) and in four patients on a separate day who had no physiotherapy (Q).
5 NOVEMBER 1977
steady state before pulmonary function tests were repeated in the same sequence as before. Control studies-Four of the patients were again studied on a separate day but they had no physiotherapy and were allowed to expectorate normally. Eight of the patients were studied on another day when 150 ,tg of isoprenaline base by inhalation was given in place of physiotherapy. Four normal subjects (aged 19-46) with no sputum production or airways obstruction of any kind underwent a similar study of pulmonary studies and physiotherapy to ensure that any change in the respiratory values was not an effect of diurnal variation or of physiotherapy itself.
Results After physiotherapy SGAW improved in 17 of the 23 patients, was unchanged in two, and fell in four (see figure). The mean improvement was 18o% (Student's t test: 005 -P>0 02); the increase in FEVy was less striking (8 %; Student's t test: 0 1 >P 0-05). There was no relation between volume of sputum and improvement in SGAW, but in the four patients who were studied again on a day when they had no physiotherapy sputum volume was considerably reduced. They showed no significant change in SGAW (see figure). The normal subjects who were tested similarly showed no significant change in SGAW (P=0 2). Of the eight patients studied after inhaling isoprenaline, SGAW improved in five, was unchanged in two, and deteriorated in one. The mean change of +40% was not significant (0 2-P 0 1). FEV, improved in three patients, was unchanged in three, and deteriorated in two. The mean change was + 40% and, again, was not significant
(P = 02). Discussion Bronchial secretions together with mucosal oedema and smooth muscle spasm are usually considered to play some part in obstructing airflow in the bronchial tree in asthma, chronic bronchitis, and bronchiectasis. Although the role of smooth muscle spasm has been well defined, there are relatively few studies that have attempted to determine the role of secretions.2 This may in part reflect the difficulty of doing so. We chose to measure specific conductance because (even in patients) it reflects changes in the resistance of the large airways rather than the smaller airways,'0 and the secretions that physiotherapy may help to move are probably in the larger airways. SGAW also takes into account two factors that vary when the degree of airways obstruction changes-namely, airways resistance and functional residual capacity. For our purposes FEV, is a much cruder value and has the serious drawback that its measurement disturbs the bronchial "status quo" by shearing the secretions in a manner similar to coughing and probably by inducing reflex bronchoconstriction in patients with bronchial lability. The dynamics of coughing and forced expiratory manoeuvres are similar. We believe this criticism of the FEV, is supported by our data, which show a greater change in SGAW than in FEV,. We found no relation between SGAW and sputum volume. The distribution of sputum throughout the airways is probably more relevant in modifying airflow obstruction than is volume, viscosity, or character. Nevertheless, the nature of the bronchial disease, leading to either hypersecretion or airflow obstruction, or both, will also play a part in any changes detected. The control studies undertaken on normal subjects showed that there was no significant change in airway calibre after physiotherapy or diurnally. The possibility that the time in the morning could account for significant changes in SGAW in patients with sputum production but without physiotherapy was also excluded by studying four patients on the second day. The study of the eight patients who received isoprenaline indicated that although change in bronchial smooth-muscle tone after physiotherapy may have influenced our findings any effect was probably small and insignificant. The results suggest that bronchial secretions may account for
BRITISH MEDICAL JOURNAL
5 NOVEMBER 1977
a significant percentage of the airways obstruction (as determined by SGAW) in our patients and that this airways obstruction may be decreased by measures focused on bronchial clearance, such as physiotherapy. Additionally, our findings reinforce the value of chest physiotherapy in patients with a large volume of sputum production and airflow obstruction; objective data on its value has hitherto been sparse. We thank all the consultant physicians at the Brompton Hospital who kindly allowed us to study patients under their care and also Miss J M Wright for secretarial help. Dr G M Cochrane was supported by a grant from the Board of Governors of the National Heart and Chest Hospitals. Requests for reprints should be addressed to Dr G M Cochrane.
1183
References ILancet, 1965, 2, 776. 2March, H, Archives of Physical Medicine and Rehabilitation, 1971, 51, 528. 3Pham, Q T, et al, Bulletin de Physio-Pathologie Respiratoire, 1973, 9, 293. Clarke, S W, Jones, J G, and Oliver, D R, Journal of Applied Physiology, 1970, 29, 464. Cotes, J E, Lung Function, 2nd edn. Oxford, Blackwell Scientific, 1968. 6 Cotes, J E, et al, British Medical Journal, 1966, 1, 1016. Dubois, A B, et al, Journal of Clinical Investigation, 1956, 35, 322. 8 Dubois, A B, Botello, S Y, and Comroe, J H, jun, J1ournal of Clinical Investigation, 1956, 35, 327. 9 Gaskell, D V, and Webber, B A, Brompton Hospital Guide to Chest Physiotherapy, 3rd edn. London, Blackwell, 1977. Macklem, P T, American Journal of Medicine, 1972, 52, 721.
(Accepted 31 August 1977)
Rapid increases in plasma prostaglandin concentrations after vaginal examination and amniotomy M D MITCHELL, A P F FLINT, J BIBBY, J BRUNT, J M ARNOLD, A B M ANDERSON, A C TURNBULL Britishl Medical journal, 1977, 2, 1183-1185
Summary Peripheral plasma concentrations of 13,14-dihydro-15keto prostaglandin F (PGFM) were measured in three groups of women after the 37th week of pregnancy. Samples were taken before and five minutes after (a) amniotomy, (b) vaginal examination with sweeping of the fetal membranes, or (c) vaginal examination without sweeping of the membranes. Each procedure significantly raised the circulating PGFM levels, although amniotomy and vaginal examination with membrane sweep were more potent stimuli than vaginal examination alone. These findings suggest that there is a considerable potential for rapid increases in prostaglandin production during late pregnancy and provide a possible explanation for the fact that amniotomy and vaginal examination with membrane sweep often initiate labour.
Introduction It is well known that in late pregnancy both amniotomy and vaginal examination when the membranes are swept off the lower uterine segment may initiate labour, although the mechanisms responsible have not been elucidated. Recent Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU M D MITCHELL, MA, DPHIL, medical research fellow A P F FLINT, BSC, PHD, senior biochemist (now senior scieintific officer, department of physiology, ARC Institute of Animal Physiology, Babraham, Cambridge) BIBBY, MB, MRCOG, clinical research assistant J BRUNT, BSC, research assistant J M ARNOLD, MB, BCH, senior house officer (now senior house officer, Royal United Hospital, Bath) A B M ANDERSON, MD, PHD, lecturer A C TURNBULL, MD, FRCOG, Nuffield professor of obstetrics and
gynaecology
evidence has shown that parturition in most species, including primates, is associated with raised concentrations of prostaglandins in intrauterine tissues, plasma, or amniotic fluid,1-3 and this has focused attention on the possibility that prostaglandins may be released in response to disruption of intrauterine tissues such as decidua4 or fetal membranes. 6 Recent work from this department7 has shown that amniotic fluid concentrations of the primary prostaglandin PGF -and its major circulating metabolite 13,14-dihydro-1 5-ketoprostaglandin F (PGFM) are significantly higher in samples obtained by amniotomy than at amniocentesis. We suggested7 that this may relate to the increased disruption at amniotomy of the membranes that contain prostaglandin synthesising enzymes," or it may be a process analagous to that found in pregnant sheep,8 ' where marked PGF release into the uterine vein occurs within minutes of vaginal and cervical stimulation. Since amniotomy both stimulates the upper genital tract (vagina and cervix) and disrupts the membranes, and since these two procedures might theoretically stimulate increased intrauterine prostaglandin production, it became clear that we had to examine the effect of these procedures separately. We therefore studied the effects of (a) stimulating the upper genital tract (vaginal examination); (b) disrupting the attachment of part of the fetal membranes by separating them from the lower uterine segment (vaginal examination plus membrane sweep); and (c) puncturing the membranes vaginally to induce labour (amniotomy). The availability of a sensitive and specific radio-immunoassay for PGFM allowed us to study circulating concentrations of this metabolite in the peripheral plasma in response to these procedures.
Patients and methods In all patients pregnancy had progressed beyond 37 weeks of gestation from the first day of the last menstrual period. There was no difference among the groups studied in the mean length of gestation, age or parity of the patients, or cervical "ripeness." The pregnancies were considered to be uncomplicated with no major maternal or fetal pathology. All patients were subsequently delivered vaginally of single healthy live born infants, who were considered to be "mature" with
