Effect of cigarette smoking on maternal airway function during pregnancy

Effect of cigarette smoking on maternal airway function during pregnancy Tarun K. Das, PhD: Jean-Marie Moutquin, MD: and Jean-Guy Parent, MD b Quebec City, Quebec, Canada The effects of cigarette smoking on maternal airway function during pregnancy were investigated in a cross-sectional study of 97 smokers and 175 nonsmokers at different gestational ages. The groups were comparable in age, height, and weight. All subjects were healthy. Forced vital capacity, forced expiratory volume in 1 second, their ratio, the forced expiratory flow rates between 0.2 and 1.2 L, 25% and 75%, and 75% and 85%, and instantaneous flows at lung volumes of 25%, 50%, and 75% were measured. All spirometric tests were unaffected by gestational age. However, all parameters of spirometry were significantly less in smokers than in nonsmokers when cumulative data during pregnancy were compared. Forced vital capacity, forced expiratory volume in 1 second, and their ratio were minimally reduced (4%, p < 0.05; 8%, P < 0.001; and 4%, p < 0.001; respectively) in smokers as compared with nonsmokers. Larger reductions were noted in forced expiratory flow rates between 0.2 and 1.2 L (14%, P < 0.001) and between 25% and 75% (16%, P < 0.001), and in instantaneous maximum flows at lung volumes of 75% (11 %, P < 0.001) and 50% (13%, p < 0.001). Maximum reduction of forced expiratory flow rates between 75% and 85% (26%, p < 0.001) and in instantaneous flows at maximum lung volumes of 25% (23%, P < 0.001) suggests marked increases in small-airway resistance and early small-airway disease in smokers. The progression of small-airway disease is related to the level of cigarette exposure. The results of our study demonstrate that the bronchodilatory effect expected in pregnancy is not sufficient to overcome the deleterious effects of cigarette smoking. (AM J OBSTET GYNECOL 1991 ;165: 675-9.)

Key words: Cigarette smoke, pregnancy, airway function It has long been recognized that pregnancy can alter lung function and the natural history of certain pulmonary diseases. Although maximum flow rate and forced expiratory volume in 1 second (FEV,) are not measurably altered, I the reduced total pulmonary resistance and increased airway conductance" observed during pregnancy suggest a bronchodilatory effect. This improvement in respiratory function is attributed to an increased concentration of progesterone, which is known to have a marked smooth-muscle-relaxing effect. 3 Indeed, progesterone has been given therapeutically to patients with obesity hypoventilation syndrome,' asthma,' and chronic obstructive pulmonary disease. 6 It could be hypothesized that the deleterious effects of smoking on airway function may be decreased during pregnancy, especially during the third trimester when progesterone levels are highest. Although cigarette smoking can cause airflow limitation in nonpregnant women,' little information is available on its efFrom the Department of Obstetrics and Gynecology" and the Division of Respiratory Physiology, Department of Medicine,' Saint-Fran(ois D'Assise Hospital, Laval University. Supported by a Laval University postdoctoral fellowship (T.K.D.) and Club des Services Sociaux, Quebec. Received for publication June 28, 1990; revised March 11, 1991; accepted March 15, 1991. Reprint requests: Jean-M. Moutquin, MD, Saint-Fran(ois D'Assise Hospital, 10 Rue I'Espinay, Quebec City, Quebec, Canada GIL 3L5. 611 /29607

fects on maternal airway function during pregnancy. This study was designed to assess the effects of cigarette smoking on airway function in normal pregnant women and to determine whether these effects are related to gestational age.

Material and methods This was a cross-sectional study of women in each of the three trimesters of pregnancy who were recruited after written informed consent. The study was performed at the antenatal clinic of Saint-Fran<;:ois D' Assise Hospital, a tertiary care teaching hospital associated with Laval University in Quebec City. Included in the study were women with nulliparous or multiparous singleton pregnancies who had no evidence of cardiopulmonary or obstetric disorders. Smokers had to abstain from smoking for 2::2 hours before the test. Subjects were excluded if satisfactory measurements could not be taken because of a lack of cooperation or an inability to perform the tests. Ex-smokers were retrospectively excluded because this group was too small to permit meaningful analysis. The study groups consisted of 97 pregnant smokers and 175 pregnant nonsmokers. Patients were grouped into three categories on the basis of gestational age: Group A (first trimester, 7 to 13 weeks) included 59 nonsmokers and 28 smokers; group B (second trimester, 14 to 26 weeks) included 56 nonsmokers and 35 smokers; group C (third trimes-

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September 1991 Am J Obstet Gyneeol

Table I. Anthropometric and cigarette smoking data of pregnant women Nonsmokers (n = 175)

Age (yr) Height (cm) Weight (kg) Cigarettes/ day Years of smoking Data are presented as mean

28.0 ± 3.52 161.7 ± 5.39 64.4 ± 11.06

±

Smokers (n = 97)

27.3 160.8 64.2 16.0 10.4

;±

± ± ± ±

p Value

NS NS NS

4.26 ,Uni 11.56 6.55 3.76

SD. NS, Not significant.

Table II. Forced expiratory spirography in nonsmokers during pregnancy

Variable

Age (yr) Height (em) FVe (L) FEV (L) FEV \! FEFo2-l2 (LI sec) FEF25 \f.75% (L/ sec) FEF 75 \f.859f (Lisee) Vmax 75% (Lisee) Vmax 50% (Llsec) Vmax 25% (Llsec) j j

Data are presented as mean ± SD.

Group A: First trimester (n = 59)

27.66 161.33 3.90 3.34 85.75 6.52 3.77 1.41 6.11 4.31 1.90

± ± ± ± ± ± ± ± ± ± ±

3.22 5.66 0.51 0.42 4.09 1.27 0.71 0.36 0.87 0.81 0.44

Group B: Second trimester (n = 56)

27.89 162.06 3.89 3.33 85.75 6.70 3.81 1.39 6.13 4.33 1.93

± ± ± ± ± ± ± ± ± ± ±

3.97 5.47 0.54 0.41 4.54 1.21 0.72 0.37 1.07 0.97 0.49

Group C: Third trimester (n = 60)

28.48 161.68 4.00 3.41 85.47 6.87 3.90 1.37 6.21 4.40 1.92

± ± ± ± ± ± ± ± ± ± ±

3.36 5.11 0.45 0.34 3.82 1.16 0.64 0.33 1.24 0.68 0.50

P Value of all parameters between trimesters not significant. FVC, Forced vital capacity.

ter, 27 to 40 weeks) included 60 nonsmokers and 34 smokers. Each subject was studied as a member of only one gestational group. Spirometric tests were conducted with a wedge bellow spirometer (Vitalograph Medical Instruments Ltd., Buckingham, England). Standard test methods were adhered to, with the patient in a standing position as recommended by the American Thoracic Society.8 The spirometer was calibrated against a known volume of air with a precision syringe. s. 9 Specific measurements of forced expiratory spirogram included forced vital capacity, FEV h FEV! expressed as a percentage of forced vital capacity (FEV!%), maximum expiratory flow rate (FEF o2 .1. 2 L), maximum midexpiratory flow rate (FEF 25 %.75%), maximum end-expiratory flow rate (FEF m1 .85 %), and instantaneous flow (Vmax) at 75%, 50%, and 25% of remaining forced vital capacity. The expiratory efforts were maintained in most trials for 6 seconds. The best effort of three values within 5% or 100 ml of each other was used for the analysis. The maximum forced vital capacity and FEV values were recorded, and flow rates were calculated from the curve with the greatest sum of forced vital capacity and FEV!. All values were corrected for body temperature and pressure saturated with water vapor. For each of the spirometric tests in both smokers and nonsmokers, the difference between means ( ± SD) was evaluated with the unpaired Student t test. One-way analysis of variance was also used for comparisons inj

volving more than two groups. The relationship between smoking habit and lung function was assessed with multiple regression analysis. The alpha error for a significant test was set at the 5% level. The percentage of difference between the smoking and nonsmoking groups was assessed for each of the spirometric tests. Results

The characteristics of the pregnant women are presented in Table I. The groups were comparable for age, height, and weight. Among smokers the daily consumption was 16.0 ± 6.55 (mean ± SD) cigarettes for a duration of 10.4 ± 3.76 (mean ± SD) years. Table II illustrates the forced expiratory spirogram during the various trimesters for nonsmoking pregnant women. Forced vital capacity, FEV Io FEV!%, FEF o.2 .1. 2 L, FEF 25 %.75%' FEF 75 %.85%' and 75% Vmax, 50% Vmax, and 25% Vmax were not affected by advancing gestational age. This was also the case in the smoking group (Table III). When cumulative data during pregnancy were compared, the values of all spirometric parameters were significantly less among smokers as compared with nonsmokers (Table IV). More marked differences between groups were noted in both FEF and Vmax than in forced vital capacity, FEV Io and FEV!%. The greatest differences were observed in FEF 75 %.85% and 25% Vmax (26% and 23%, respectively; p < 0.001). The dose-response relationship between the level of

Airway function in pregnant smokers

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677

Table III. Forced expiratory spirography in smokers during pregnancy Group A: First trimester (n = 28)

Variable

Age (yr) Height (em) Cigarettes I day Years of smoking FVC (L) FEV I (L) FEVI% FEF 02 .1.2L (Lisee) FEF 25 %.75% (Lisee) FEF 75 %.S5% (Lisee) Vmax 75% (Lisee) Vmax 50% (Lisee) Vmax 25% (Lisee) Data are presented as mean

27.85 161.02 16.20 10.90 3.75 3.04 81.04 5.60 3.06 0.98 5.35 3.60 1.48 ±

Group B: Second trimester (n = 35)

± 4.26 ± 5.49

± ± ± ± ± ± ± ± ± ± ±

26.71 161.16 17.20 10.30 3.88 3.17 81.82 6.05 3.22 1.07 5.69 3.70 1.46

6.69 4.39 0.51 0.45 7.09 1.44 0.75 0.32 1.34 0.97 0.56

Group C: Third trimester (n = 34)

± 3.78 ± 4.64 ± 6.81

27.50 160.34 15.10 10.00 3.72 3.07 83.27 5.59 3.33 1.01 5.26 3.94 1.48

± 3.60 ± ± ± ± ± ± ± ± ±

0.52 0.46 6.32 1.42 0.84 0.40 1.28 0.92 0.48

± 4.75 ± 5.75 ± 6.17

± 3.41

± 0.62 ± 0.45

± 5.32 ± 0.89 ± 0.68 ± 0.32 ± 0.81

± 0.79 ± 0.46

SD. P Value of all parameters between trimesters not significant.

Table IV. Forced expiratory spirography during pregnancy Variable

FVC (L) FEV I (L) FEV I% FEF 0.2-1.2 L (L I sec) FEF 25%-75% (LI sec) FEF759!_S5% (Lisee) Vmax 75% (Lisee) Vmax 50% (Lisee) Vmax 25% (Lisee)

Nonsmokers (n = 175)

3.93 3.36 85.65 6.70 3.85 1.39 6.15 4.35 1.91

0.49 0.39 4.13 1.22 0.69 0.35 ± 1.07 ± 0.82 ± 0.47 ± ± ± ± ± ±

Smokers (n = 97)

3.78 3.09 82.10 5.76 3.21 1.03 5.44 3.76 1.47

± 0.55 ± ± ± ± ±

± ± ±

0.45 6.23 1.27 0.76 0.35 1.16 0.89 0.49

Difference (%)

-4 -8 -4

-14 -16 -26 -11 -13 -23

p Value

<0.05 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

Data are presented as mean ± SD. FVC, Forced vital capacity. cigarette consumption and lung function is shown in Table V. The number of cigarettes smoked per day was directly related to the difference between the groups. This relationship was also confirmed by multiple regression analysis when adjustments were made for confounding variables such as age, height, and duration of smoking. Comment

Airway function during pregnancy could be influenced by anatomic, hormonal, or biochemical factors. Progressive enlargement of the gravid uterus, mainly in the third trimester, may produce a restrictive effect. The reported reduction in alveolar Pco 2 in pregnancy, which is responsible for bronchial smooth-muscle constriction, can cause obstruction in airway function by increasing airway resistance. 10. II Our observation in both the nonsmoking and smoking groups showed no significant alteration in forced vital capacity, FEV 1, FEF, and Vmax at different lung volumes as pregnancy advanced; therefore there may be other mechanisms operating in pregnancy to oppose the expected alteration of airway function. Alternatively, those factors may have insufficient influence to modify the respiratory function as measured.

The results concerning forced vital capacity, FEV I, and FEV I%during the three trimesters in nonsmoking pregnant women are in agreement with previous studies in which serial measurements were performed. 12,13 FEF and V max at different lung volumes have not been fully studied during pregnancy. In two studies,!' 14 FEF 25 %_75%, 50% Vmax, and 25% Vmax were measured and found to be unaltered during pregnancy; there were similar findings in our study. FEFo2 _1.2 L, FEF 75 %_S5%, and 75% Vmax were also unchanged. There was no relationship between any of the studied parameters and gestational age. Preservation of airway function in the second half of pregnancy in spite of the enlarged gravid uterus may be caused by bronchodilating effects. Progesterone is known to have a widespread smooth-muscle-relaxing effect' and an increased l3-adrenergic activity. 1, The relative mobility of the thoracic cage I6 may also be responsible for preserving forced vital capacity. This is the first report of a significant decrease in airway function among pregnant smokers as compared with pregnant nonsmokers. Maximum reductions were seen in tests reflecting small-airway function. The decrease in forced vital capacity (4%, p < 0.05) could be explained by a narrowing or closure of the small air-

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Das, Moutquin, and Parent

September 1991 Am J Obstet Gynecol

Table V. Effect of amount of cigarette smoking on forced expiratory spirography in pregnancy Vmax25% (L/ sec)

Group 1: Non- 3.88 ± 0.48 33.3 ± 0.39 6.78 ± 1.26 3.87 ± 0.73 1.43 ± 0.36 6.13 ± l.l8 4.36 ± 0.88 1.99 ± 0.49 smokers (n = 77)

Group 2: Light 3.76 ± 0.51 3.15 ± 0.37 5.91 ± 0.98 3.45 ± 0.63 l.l1 ± 0.32 5.56 ± 0.92 4.06 ± 0.73 1.57 ± 0.42 smokers* (n = 59)

Group 3: Heavy smokerst (n = 38)

Group 1 vs 2 Group 1 vs 3 Group 2 vs 3

3.82 ± 0.61 3.01 ± 0.55 5.53 ± 1.62 2.85 ± 0.81 0.89 ± 0.36 5.25 ± 1.46 3.28 ± 0.92 1.33 ± 0.57

p < 0.05 P < 0.001 P < 0.001

p < 0.001 P < 0.001 P < 0.05

NS NS NS

NS P < 0.001 NS

Data are presented as mean ± SD. FVe, Forced vital capacity; NS *1 to 15 cigarettes per day for 10.3 years. t 16 to 30 cigarettes per day for 10.5 years.

ways, because 20% of forced vital capacity is thought to be related to these structures. 17 Loss of the elastic recoil pressure of the lung may also cause forced vital capacity to fall. The reductions in FEV 1 (8%, P < 0.001) and FEV 1% (4%, P < 0.001) seen among smokers suggest an overall airway obstruction, although neither bronchoconstriction, compliance, nor recoil was actually measured. Because FEV 1 is a measure of flow rate during the first second of forced expiratory spirography, it includes sufficient flows at lower lung volumes to reflect smallairway changes in addition to large-airway changes. The decreased flow at large lung volumes, such as FEFo2 . L2 L (14%, P < 0.001) and 75% Vmax (11%, P < 0.00 i) may be caused by either an increase in large airway resistance or a decrease in effort, inasmuch as these flows are largely effort dependent. Although subjects performed tests using maximum effort, a decrease in the expiratory muscle power among smokers cannot be entirely ruled out. In contrast, FEF25 %.75% and FEF 75 %.S5% are independent of effort and are important to detect small-airway patency, particularly an airway with a diameter <2 mm. In smokers the contribution of small-airway resistance to total-airway resistance normally increases at low lung volumes, even when FEV 1 is not clinically abnormal. In the smoking group there was marked deterioration in both FEF 25 %.75% (16%, P < 0.001) and FEF75%85% (26%, P < 0.001). A 25% reduction in FEF75%85% is considered to be clinically abnormap s ; however, the sensitivity of FEF25 %.75% to dysfunction is not necessarily greater than that of FEV 1 because the FEF 25 %.75% has higher withinand between-individual variability.19 Although direct airway resistance and elastic recoil pressure or lung compliance were not measured, it is assumed that the observed decrease in flow rates at low

=

p < 0.01 P < 0.001 NS

p< P<

0.05 0.001 P < 0.001

p < 0.001 P < 0.001 P < 0.01

p < 0.05 P < 0.001 NS

not significant.

lung volumes is caused by increased resistance to flow rather than a decrease in driving force. Alteration in lung elastic recoil after smoking cannot be entirely ruled out; however, in normal pregnant women lung elastic recoil should not be altered because lung compliance has been shown to remain unchanged during pregnancy compared with the postpartum period. 2 The measurement of Vmax showed significant reductions in smokers. The maximum percentage of diffrence between smokers and nonsmokers was seen in 25% Vmax, suggesting early small-airway disease in smokers even though the subjects were asymptomatic. The relationship between the progression of small-airway dysfunction and smoking habits is confirmed by a direct relationship between the level of cigarette exposure and the degree of lung function loss. Further, there is a nicotine-induced increase in oxygen consumption with a reduced oxygen supply caused by carbon monoxide in smokers.20 These factors could lead to a reduced supply of oxygen to the fetus. This reduced oxygen supply could contribute to intrauterine growth retardation. In summary, changes in airway function in smokers during pregnancy were similar to those observed in nonpregnant smokers.7 It can be concluded that the bronchodilatory effect expected in pregnancy is not sufficient to overcome the deleterious effect of cigarette smoking. We thank Dr. William Fraser, MD, for his fruitful comments and Carmen Lindsay, BSc, Micheline Cote, RN, and Helene Rolland for their assistance. REFERENCES 1. Gazioglu K, Kaltreider NL, Rosen M, Yu PN. Pulmonary

function during pregnancy in normal women and in patients with cardiopulmonary disease. Thorax 1970; 25:445-50.

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2. Gee JBL, Packer BS, Millen JE, Rubin ED. Pulmonary mechanics during pregnancy. J Clin Invest 1967;46:94552. 3. H ytten FE, Leitch I. The physiology of human pregnancy. 2nd ed. Oxford: Blackwell Scientific, 1971:189. 4. Sutton FD Jr, Zwillich CW, Creagh CE, Pierson DJ, Wiel Jv. Progesterone for outpatient treatment of pickwickian syndrome. Ann Intern Med 1975;83:476-9. 5. Beynon HLC, Garbett ND, Barnes PJ. Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone. Lancet 1988;2:370-2. 6. Tyler JM. The effect of progesterone on respiration of patients with emphysema and hypercapnia. J Clin Invest 1960;39:34-41. 7. White JR, Froeb HF. Small airways dysfunction in nonsmokers chronically exposed to tobacco smoke. N Engl J Med 1980;302:720-3. 8. American Thoracic Society. Snowbird workshop on standardization of spirometry. Am Rev Respir Dis 1979; 119:831-8. 9. Vitalograph Medical Instruments Ltd. Technical manual with operation instructions. Buckingham, England, Maids Moreton House, 1982. 10. Boutourline-Young H, Boutourline-Young E. Alveolar carbon dioxide levels in pregnancy, parturient and lactating subjects. J Obstet Gynaecol Br Emp 1956;63:50928. 11. Newhouse MT, Becklake MR, Macklem PT, McGregor M.

12. 13. 14. 15. 16. 17. 18. 19. 20.

Effect of alteration of end tidal CO 2 tension on flow resistance. J Appl Physiol 1964;19:745-9. Alaily AB, Carrol KB. Pulmonary ventilation in pregnancy. Br J Obstet Gynaecol 1978;85:518-24. Milne JA, Mills RJ, Howie AD, Pack AI. Large airways function during normal pregnancy. Br J Obstet Gynaecol 1977;84:448-51. Baldwin GR, Moorthi DS, Whelton JA, MacDonnell KF. New lung functions and pregnancy. AM J OBSTET GyNECOL 1977; 127:235-9. Raz S, Zeigler M, Caine M. The effect of progesterone on the adrenergic receptors of the urethra. Br J Urol 1973;45:131-5. Thomson KJ, Cohen ME. Studies on the circulation in pregnancy. II. Vital capacity observations in normal pregnant women. Surg Gynecol Obstet 1938;66:591-603. Woolcock AJ, Macklem PT, Hogg JC, et al. Effect of vagal stimulation on central and peripheral airways in dogs. J Appl Physiol 1969;26:806-13. Morris JF, Koski A, Breese JD. Normal values and evaluation of forced end-expiratory flow. Am Rev Respir Dis 1975; III :755-62. Buist AS. Tests of small airways function. Respir Care 1989;34:446-54. Noble PW, Lavee AE,Jacobs MM. Respiratory diseases in pregnancy. Obstet Gynecol Clin North Am 1988;15:391428.

Effectiveness of antibiotic prophylaxis in preventing bacteriuria after multichannel urodynamic investigations: A blind, randomized study in 124 female patients Kevin R. Baker, MD, Harold P. Drutz, MD, and Mary D. Barnes, RN, BA Toronto, Ontario, Canada One hundred twenty-four women with chronic, persistent lower urinary tract symptoms who had been scheduled for elective urodynamic investigations at Mount Sinai's Urodynamic Investigative Unit were divided into two blind, randomized groups, receiving either a placebo or prophylactic antibiotic. At the time of urodynamic testing, the rate of unsuspected urinary tract infection was 8.1 %. There was no statistically significant decrease in postinstrumentation infection rate in the group who received prophylactic antibiotics. We conclude that, given in the fashion described in the study, prophylactic antibiotics are not effective in preventing urinary tract infections caused by urodynamic testing. (AM J OSSTET GYNECOL 1991 ;165: 679-81.)

Key words: Prospective, randomized, prophylactic antibiotics, complex multichannel urodynamic investigation From the Gynecological Urology and Urodynamic Investigative Unit, Mount Sinai Hospital, and the Section of Urogynecology, Department of Obstetrics and Gynecology, University of Toronto. Received for publication July 9, 1990; revised March 1, 1991 .. acceptedMarch 15,1991. Reprint requests: Harold P. Drutz, MD, Head, Section of Urogynecology, Suite 1221, Mount Sinai Hospital, 600 Universi~~ Avenue, Toronto, Ontario, Canada M5G 1X5.

6/1 /29603

Recent cases of bacteriuria after urodynamic investigations performed in the urogynecology unit at Mount Sinai Hospital prompted us to review the current literature and to question whether routine prophylactic antibiotics should be given after urodynamic testing. Previously, antibiotic prophylaxis was not routine in our investigative laboratory. Previous reports

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