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Pulmonary Function in Normal Subjects after Bronchoalveolar Lavage
Pulmonary Function in Normal SUbjects after Bronchoalveolar Lavage· Ching-Chi Lin, M.D., F.C.C.~;len-Liang Wu, M.D.; and Wen-Chu Huang, M.D., F.C.C.~
Twenty seven healthy individuals were divided randomly into three groups, The 6rst group of nine subjects received only a routine bronchoscopic examination. The second group of nine subjects was examined with the bronchoscope followed by bronchoalveolar lavage (BAL) with 200 mI of 25°C normal saline solution. The third group of nine subjects received a bronchoscopic examination followed by BAL, but with 200 ml of arc normal saline solution. Examination in all groups included arterial blood gas(ABC) analysis and pulmonary function test (PFT), both pre- and post-procedure. In group 1 there was no statistical difference in the pulmonary function test result after routine bronchoscopic examination except for decrease in PaO._
Several studies have shown that a fiberoptic bronchoscopic examination alone is associated with a small decline in FEV., FVC and PEFR, which can be prevented by the use of atropine prior to examination. 1-4 Similarly there were many observations indicating that bronchoalveolar lavage (BAL) with normal saline solution has no long-term physiologic effects in human subjects. However, transient acute hypoxemia with infiltrates seen on chest roentgenograms has been reported in normal subjects.P? Animal investigations have also disclosed no histologic change in lung lavage with less than 300 ml saline solution, but showed minor change in the lung histology and lung mechanics when large volumes of saline solution were used.v" In addition, however, acute observations have disclosed some alterations in ventilation/perfusion (V/¢J relationships and gas exchange." Many theories were used to explain exercise-induced asthma, and the most favored are the osmotic theory and the heat loss theory There were several factors affecting pulmonary function immediately after BAL, with the temperature of bronchoalveolar lavage fluid (BALF) one of the most important factors that has often been neglected. 5 The lack of data regarding the acute pathophysiologic consequences of BAL led us to undertake the present investigation of the acute effects of BAL and the different temperatures of BALF on the pulmonary function test (PFT) in a group of normal adults. *From the Chest Division, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. Manuscript received February 4; revision accepted October 5. Reprint requests: Dr. Lin, Chest Division, Department of Internal Medicine, Mackay Memorial Hospital, No. 92 Sec 21, Chung San North Road, Taipei, Taiwan ROC 10449
The results in group 2 showed a statistical difference in
both ABC and PFr data, especiaUy PaO., FEF 200-1200,
FEF25%-7S%, FEF25%, FEF5O%, and FEF7S%. In group 3, there was a significant decrease ofPaO. and no significant difference in PFT before and after BAL. From these data we conclude that BAL is a safe examination. However, the administration BAL 8uid (BALF) with !SOC normal saline solution can affect the results of the PFr signifiC8DtI~ Much of this adverse reaction can be minimized by using body temperature (3rC) saline solution. At 3rC, the ABG data showed a decrease in PaO., but pulmonary function was not affected signilicantl~
MATERIALS AND METHODS
Subjects The subjects for this study came from our out-patient clinic. they came into Mackay Hospital due to a variety of nonspecific minor complaints, such as chest tightness or foreign body sensation in the throat These patients bad no evidence of upper respiratory tract infection in the last two weeks prior to this investigation. All patients selected had less than five pack-years of smoking history and their physical esaminatson, chest radiograph~ and pulmonary function test results (simple spirometry), showed normal findings. If any patient were still concerned and requested further examination, we selected them for our experiment. Twenty seven young healthy individuals 25 to 35 years of age were selected for the study They were randomly divided into three groups, with nine in each group. Group 1 subjects received only a bronchoscopic examination, and they also served as the control group. Group 2 subjects received a bronchoscopic examination, followed by BAL using 200 ml of 25°C normal saline solution as lavage Iluid. Group 3 subjects also received a bronchoscopic examination followed by a BAL with 200 ml of 3rC normal saline solution. Originall~
Bronchoalveowr Lavage All subjects received intramuscular administration of 0.4 mg atropine, 40 mg of meperidine hydrochloride (Demerol), and topical lidocaine (Xyloeaine), The Olympus BF-B2 or BF-B3 fiberoptic bronchoscope was then administered transnasally and wedged in the subsegmental bronchial ori6ce of the right middle lobe or left lingular lobe. Each time an aliquot of 50 ml normal saline solution was infused and recovered using a gentle suction of less than 40 mm Hg. This was done four times, with a total of 200 ml of saline solution being used. The average BAL return rate was 55.8 ± 5.6 percent in group 2 and 59.2±5.1 percent in group 3.
Pulmonary Function Test. The baseline pulmonary function tests and arterial blood gas levels were determined prior to bronchoscopic examination and premedication. "The second arterial blood gas determination was performed just before the end of the bronchoscopic examination or CHEST I 93 I 5 I MAY, 1988
1041
Table l-Changa in the Baulta of Spirometrr/ and Arterial Blood CGI after Bronclaoacopic EmrnintJlion in Group 1 Pulmonary FUnction Test
Before After Bronchoscopy Bronchoscopy (n == 9) (n==9)
FEVl ('II pred) FEVllFVC (%) FEF 200-1200 (If, pred) FEF25-75% (tJ pred) fEF251f, (II, pred) FEF5O% (If, pred) F~Fi5% (% pred) VC (If, pred) TLC (If, pred) By(If, pred) PaO.(mm Hg)
Difference in Results
93.17±6.74 81.33±5.91 86.42± 10.67
93.75±7.24 -0.58±2.31 81.91±8.51 -0.67±2.79 83.42± 10.99 3.00±2.98
85.42±9.35
82.17± 12.07
3.25±4.41
9O.46±9.57 0.88±2.65 ~1.34 ± 10.79 81.42±9.68 77.54±9.83 3.88±5.04 3.05±2.99 77.13±10.40 74.08± 12.18 94.5±7.87 92.83±7.36 1.67±2.64 96.42±7.32 92.41±7.41 4.01±7.36 98.47±9.32 101.43 ± 11.42 -2.96±12.36 94.42 ± 4.75- 85.50±7.488.92±3.38
-Paired , test == p
administered from one to two hours after we finished the bronchoscOpic examination and the bronchoalveolar lavage. The PIT was done using a Gould 5000 CPI computerized spirometer, The loop with the highest sum of FEV 1and FVC was analyzed. The FEV h FVC, FEV1/FVC ratio, FEF200-1200, FEF25If" FEF5O%, FEF75% were recorded, and a 80w rate at a constant volume at 50 and 75 percent of total lung capacity (Vso, V,J was derived and used as an indication of small airway dysfunction. The functio~ residual capacity (FRC) was measured by an open circult system multiple breath nitrogen washout test, while' we observed the N. display until the Nt concentration fell to below 1.4 percent, using a Gould 5000 CPI computerized spirometer. The ~dua1 volume (RV) and total lung capacity (TLC) were derived with the expiratQry reserve volume and vital capacity (VC) obtained from the CPI dry-rolling seal, volume displacement-type spirometer. The predictive equations of Lam et aI,8 were used for all spiro~etric tests. All pulmonary function tests are expressed as percent predicted.
Table !.-Charaga ita the Baulta ojSpiromet'1l and after BAL .".,h Saline Solution at Boom Temperaiure in Group 2
ArterialBlood CGI_ Pulmonary Fu~ction
. Test
FEV l (If, pred) FEVlFVC (%) FEF 200-1200 (% pred) FEF25-751f, ('II pred) FEF25% (If, pred) FEf~
(ti, pred) FEF75% (If, pred) VC ('II pred) TLC (If, pred) ~(% pred) PaO.(mm Hg)
After Lavage (0 ==9)
Difference in Results
89.67±6.90 SO.58±5.10 9O.09±8.49*
85.42±8.65 76.83±8.48 6O.42± 13.36-
4.25±3.90 3.75±4.37 29.67±5.83
86.43±9.32-
65.44 ± 12.24-
2O.99±4.46
9O.67±9.68-
64.50 ± 11.94-
26.17±4.34
84.33 ± 10.42-
6O.33± 14.49-
24.00±2.97
77.50± 10.56-
57.50± 12.35-
2O.00±5.48
Before Lavage (n == 9)
86.67±8.73 9O.50±6.81 97.54±7.82 94.37±5.82 96.32± 10.35- 114.35± 18.09* 95.42 ± 6.9266.98 ± 12.82-
.paired t test==p
3.83±3.87 -3.17±6.64 -18.03± 12.43 28.42±6.2
Table 3-Changes. in the Buults of Spirometry and ArterialBlood GaB after BAL with Saline Solution at Body Temperature in Group 3 Pulmonary Function Test FEV l (% pred) FEV/FVC (%) FEF 200-1200 (% pred) FEF25-75% (% pred) FEF25% (% pred) FEF5O% (II, pred) FEF75% (If, pred) VC ('II pred) PaO.(mm Hg)
Before Lavage (n==9)
After Lavage (3'rC) (n =9)
Difference in Results
95.38±6.43 82.42±6.98 88.50±8.36
91.42±7.08 SO.42±6.15 84.54±8.56
3.96±6.18 2.08±2.18 3.96±4.09
94.49± 10.13
9O.58± 12.77
3.91±2.83
93.33±9.71 84.47±9.81 76.17±7.94 95.50±8.41 92.33±5.54*
92.42± 12.65 SO. 75± 12.60 71.75 ± 14.74 94.33±8.30 77.42 ± 10.56-
0.92±3.29 3.72±5.38 4.42±4.10 1.17±2.42 14.92±5.04
-paired t test==p
There was no significant difference in PIT results before and after bronchoscopic examination in the control group (group 11 except for a decreased PaO! level after bronchoscopic examination (8.92 ± 3.38 mm Hg) as shown in Table 1. Table 2 demonstrates the results in group 2 before and after bronchoscopic examination with simultaneous BAL using 200 ml of 25°C normal saline solution. Although there was a decrease in FEV h FEV1/FVC, and FVC, these changes were of no statistical significance by paired ftest. On the other hand, changes in FEF 200-1200, FEF25-75%, FEF25%, 50%, 75% and Pa02' were of statistical significance . In group 3 subjects, 3rc of normal saline solution was used instead of 25°C normal saline solution, except for a decreased Pa02 in ABG where the results of the PIT showed no significant change, before and after lavage. Comparing groups 2 and 3, the changes in the pulmonary function before and after examination are presented in Table 4 and Figure 1. The changes in the pulmonary function tests especially in FVC, FEV1 and FEV/FVC, showed no statistical significance in groups 1, 2, and 3. While those representing respiratory midflow rates including FEF200-1200, FEF25-75%, FEF25%, FEF50%, FEF75%, etc and Pa02, demonstrated the changes that were of statistical significance in comparing group 2 to either group 1 or group 3, when the result of group 3 was compared with group Pulmonary FunctionIn Normal Subjects after SAL (Un, Wu, Huang)
Table 4-CompGrison of Changa in Baulta of Spirometry and ABC Determinatioru after Bronchoacopic Emmination, BAL with Saline Solution at Boom Temperature and at Body TempertJture Difference in Difference in Difference in Results, Results, ~C Results, 3rc Bronchoscope Saline BAL Saline BAL (n=9) (n=9) (n == 9) FEV! (% pred) FEVlFVC(%) FEF 200-1200 (% pred) FEF25-75% (% pred) FEF25% (% pred) FEF5O% (% pred) FEF75% (% pred) VC (% pred) Pa02 (mm Hg)
-0.58±2.31 4.25±3.90 -0.67±2.79 3.75±4.37 3.00±2.98* 29.67 ± 5.83*
3.96±6.18 2.08±2.18 3.96±4.09*
3.25±4.41* 20.99 ± 4.46*
3.91±2.83*
0.88 ± 2.65* 3.88±5.04* 3.05±2.99* 1.67±2.64 8.92±3.38*
26.17 ± 4.34* 0.92±3.29* 24.00±2.97* 3.72±5.38* 20.00 ± 5.48* 4.42±4.10* 3.83±3.87 1.17±2.42 28.42±6.2* 14.92± 5.04*
*ANOVA test and Scheffe test p
1, there is no statistical significance except for the changes in the amount of Pa02 • DISCUSSION
Bronchoalveolar lavage is a relatively new diagnostic method. Although it is generally considered to be a safe procedure, a bronchoscopic examination alone and a BAL have been known to induce acute physiologic changes (such as bronchospasm or hypoxia) in normal persons. Some studies have shown that pulmonary mechanical changes that were induced by fiberoptic bronchoscopic examinations could be prevented by prior administration of atropine. 1-4 However, the effectiveness of this method in preventing acute pulmonary changes during and after BAL is still not clear With this in mind, the authors began to explore other preventative methods. In retrospect, there might be several factors that could affect changes in the respiratory physiology such as the technique, the amount and the recovery percentage of BALF, and the condition of the patients lungs prior to the examination.P''" Given these probable factors, the temperature of the BALF seems to have been the one factor that has been overlooked. In this study we found that a fiberoptic bronchoscopic examination with BAL could be performed safely on normal subjects. We specifically use 200 ml of normal saline solution in our BAL because it usually seemed to be sufficient for this kind of procedure. 14-15 A larger amount of BALF has been reported to cause more serious lung function abnormalities." This has been alluded to by many other researchers. 14-15 In the control study we found that bronchoscopic examination with prior administration of atropine produced no significant change in the patients pulmonary function or respiratory physiology However, it did significantly decrease the PaO! at the 0.05 level.
When 25°C normal saline solution was administered during the BAL, there was a significant decrease in the mid-flow rates (FEF25-75%, FEF25%, 50%, 75%) and PaO~b but no significant change was noticed in the FEV., FVC, and TLC. When 3'rC normal saline solution was employed in performing the BAL, the results showed only a signficant decrease ofPa02 while the other pulmonary function test showed no significant change in comparing with the control group. In contrast, when 25°C normal saline solution was administered during BAL, the effect on PITs was much more substantial when comparing with the group using 37°C normal saline solution. These results are similar to the findings of Rankin et al. 12 They used 300 ml of room temperature (0.9% NaCI) solution to perform lavage in 12 healthy nonsmoking volunteers. After the BAL, they found a small decrease in the mean FVC and FEVI , but it was not statistically significant. However, the drop in Vmax (50%) was seen as highly significant. Unfortunately they did not use 3rC saline solution to perform lavage in the normal volunteers, and therefore, did not gain the same results as we did. In contrast, Bums et al5 performed a very detailed study of the physiologic consequences of saline lobar
a
•
b
c
-
-
FEV 1 ~
0
•
PErl
L-.J
f
d
I HHErR I
L:.--J
~
control croup BAl. by rouill temperature .a11ne
BAL by bod/' temper-1ture .allne
FIGURE 1. Mean percentage of decrement in FEV h PEFR, MMEFR, VC and PaOt 1-2 h post-lavage, for normal subjects who underwent either room temperature saline (slanted line bars) or body temperature saline (solid bars) solution lavage compared to controlled subjects (open bars), Significant decrements in PEFR, MMEFR and PaOloccurred in the room temperature lavage group. (a, b, c, d, e. f: p
1011
lavage in healthy adults. They used a 6beroptic bronchoscope with a cuff that could be inHated when placed in the right lower lobe to perform lavage in normal volunteers. These subjects underwent lavage with 1,000 ml of room and body temperature saline solutions. They found that the subjects who underwent lavage with room temperature saline solution had a 20 percent decline in TLC and an elevated R~ The FEF 25-75% and the vital capacity were significantly reduced. However, the airway resistance (Raw) did not signi6cantly increase. On the contrary the subjects who had lavage with body temperature saline solution experienced only a significant elevation of the R~ but no statistically significant change occurred in the TLC, VC, FEVIt Ra~ etc. In terms of changes in Pa02 , the results of this study were very different from those of Bums et ale In our study the control group, who received only a bronchoscopic examination, experienced a decrease of 8.92±3.38 mm Hg. Group 2, which had lavage with room temperature saline solution, demonstrated a very serious decrease in Pa02 of 28.42 ± 6.2 mm Hg. Group 3, who received the 37°C saline solution, experienced only a moderate decrease of 14.92 ± 5.04 mm Hg. On the other hand, all of the patients of Bums et al, whether they were treated with a bronchoscope or BAL, exhibited a substantial and very serious decrease in Pa02 of around 30 mm Hg. They also exhibited hypoxemia. The reasons for the discrepancies in our respective studies could be attributed to the different procedures and methods employed. We used a bronchoscope that was wedged in the subsegmental bronchus of the right middle lobe or the left lingular lobe. We also used 200 ml of saline solution when we performed lavage. In contrast, Bums et al used a cuffed bronchoscope that was placed in the right lower lobe and then used 1,000 ml of normal saline solution for lavage. In reviewing the literature" and the results of this study it was shown that BAL will lead to changes in respiratory physiology of patients. These changes are due mainly to obstruction of the respiratory tract and not just the replacement of air when the BALF is inserted. Possibly another and more compelling reason is that cold saline solutions seem to induce bronchospasm similar to those caused by cold air, exercise and/or hyperventilation. 16 Researchers have indicated that bronchospasm may be related to osmolality 17.18 This can be discounted in this studg for the osmolality of normal saline solution is the same as the human body Therefore, temperature still seems to play a significant role. In retrospect, one bafBing question remains to be answered: why does it take one to two hours for BAL to cause bronchospasm when exercise-related asthma usually occurs within 20 minutes? The most probable 1012
reason is that BALF and cold air have different physical-chemical characteristics, and subsequently have different delaying effects. 5 This has been observed especially when room temperature saline solution is used in the BAL. This often seems to lead to interstitial edema and the invasion of inHammatory cells. 19--21 This local change in the middle lobe could affect the rest of the lung through the neurologic reflexes or the release of mediators or both. 18 Room temperature BALF may also cause more serious change in pulmonary function as represented by the How rate. Consequently the V/Q will decrease, which may possibly lead to more serious hypoxemic complications. 22 In conclusion, it seems that BAL is a safe procedure in normal subjects. Also, it is important to remember that certain pulmonary function will be affected when administering BAL. However, many of the effects on the pulmonary system may be minimized by using body temperature saline solution. REFERENCES 1 Belen J, Neuhaus A, Markowitz D, Rotman HH. Modification of the effect of fiberoptic bronchoscopy on pulmonary mechanics. Chest 1981; 79:516-19 2 Neuhaus A, Markowitz D, Rotman HH. The effects of fiberoptic bronchoscopy with and without atropine premedication on pulmonary function in humans. Ann Thorac Surg 1978; 25:39398
3 Albertini RE, Harrell JH, Kurihara N. Arterial hypoxemia induced by fiberoptic bronchoscopy JAMA 1974; 230:1666-67 4 Zavala DC, Godsey K, Bedell GN. The response to aerosol and intramuscular atropine sulfate given to patients undergoing fiberoptic bronchoscopy. Am Rev Respir Dis 1978; 117:96 5 Burns DM, Shure D, Francoz R, Kalafer M, Harrell J, Wifztum K, et al. The physiologic consequences of saline lobar lavage in healthy human adults. Am Rev Respir Dis 1983; 127:695-701 6 Cole ~ Burton C, Lanyon H, Collins J. Bronchoalveolar lavage for the preparation of free cells technique and complications. Br J Dis Chest 1980; 74:273-78 7 Huber GL, Edmunds LH, Finley TN. Effects of experimental saline lavage on pulmonary mechanics and morphology Am Rev Respir Dis 1971; 104:334-37 8 Francoz RA, Konopka R, Sgroi ~ Moser KM. Changes in ventilation and perfusion in anesthetized dogs following lobar lavage with saline solution. Chest 1978; 74:552-58 9 Lam KK, Pang SC, Allan WGL. A survey of ventilatory capacity in Chinese subjects in Hong Kong. Ann Human BioI 1982; 9:459-72 10 Strumpf IJ, Feld MK, Cornelius MJ, Keogh BA, Crystal RG. Safety of fiberoptic bronchoalveolar lavage in evaluation of interstitial lung disease. Chest 1981; 80:268-71 11 Bechtel J}, Starr III 'I: Dantzker DR, Bower JS. Airway hyperreactivity in patients with sarcoidosis. Am Rev Respir Dis 1981; 124:759-61 12 Rankin )A, Snyder PE, Schachter EN, Matthay RA. Bronchoalveolar lavage: Its safety in subjects with mild asthma. Chest
1984;85:723-28
13 Tilles OS, Guldenheim PO, Ginns ic, Hales CA. Pulmonary function in normal subjects and patients with sarcoidosis after bronchoalveolar lavage. Chest 1986; 89:244-48 14 Davis CS, Giancola MS, Costanza MC. Analyses of sequential bronchoalveolar lavage samples from healthy human volunteers. Am Rev Respir Dis 1982; 126:611-16 Pulmonary function In Normal Subjects after BAL (Un, Wu, Huang)
15 Gotoh 1: Ueda S, Nakayama 1: 18kishitaY, Yasuoka S, Tsubura E. Protein components of bronchoalveolar lavage fluids from non-smokers and smokers. Eur J Respir Dis 1983; 64:369-77 16 O·Cain CF: Dowling NB, Slutsky AS. Airway elrects ofrespiratory heat loss in normal subjects. J Appl Physiol 1980; 49:87580
17 Deal EC, McFadden ER, Ingram RH, Jaeger JJ. Esophageal temperature during exercise in asthmatic and non-asthmatic subjects. J Appl Physioll979; 46:484-90 18 Godfrey S. Exercise-induced asthma. In: Clark 11H, Godfrey S, eds. Asthma, 2nd ed. London: Chapman and Hall, 1983:5778
19 Innen eR, Terry PS, 1taystman RJ, Menkes RA. Collateral ventilation and the middle lobe syndrome. Am Rev Respir Dis
1978; 118:30)..10 20 Cohen AD, Batra GK. Bronchoscopy and lung lavage induced bilateral pulmonary neutrophil inftux and blood leukocytosis iB dogs and monkeys. Am Rev 8espir Dis 1980; 122:239-47 21 Widdicombe JG. Respiratory reSses from the luns. Dr Med Bull 1963; 19:15-20 22 Bogen RM, Saidon J~ Shelburne J, Neigh JL, Shuman JF: 1lmtum ICIl Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. N Engl J Med 1972; 286:1230-33
Plan to Attend 54th Annual SclenUflc Assembly Anaheim October 3·7, 1988
CHEST I 83 I 5 I MAY, 1_
__
Twenty seven healthy individuals were divided randomly into three groups, The 6rst group of nine subjects received only a routine bronchoscopic examination. The second group of nine subjects was examined with the bronchoscope followed by bronchoalveolar lavage (BAL) with 200 mI of 25°C normal saline solution. The third group of nine subjects received a bronchoscopic examination followed by BAL, but with 200 ml of arc normal saline solution. Examination in all groups included arterial blood gas(ABC) analysis and pulmonary function test (PFT), both pre- and post-procedure. In group 1 there was no statistical difference in the pulmonary function test result after routine bronchoscopic examination except for decrease in PaO._
Several studies have shown that a fiberoptic bronchoscopic examination alone is associated with a small decline in FEV., FVC and PEFR, which can be prevented by the use of atropine prior to examination. 1-4 Similarly there were many observations indicating that bronchoalveolar lavage (BAL) with normal saline solution has no long-term physiologic effects in human subjects. However, transient acute hypoxemia with infiltrates seen on chest roentgenograms has been reported in normal subjects.P? Animal investigations have also disclosed no histologic change in lung lavage with less than 300 ml saline solution, but showed minor change in the lung histology and lung mechanics when large volumes of saline solution were used.v" In addition, however, acute observations have disclosed some alterations in ventilation/perfusion (V/¢J relationships and gas exchange." Many theories were used to explain exercise-induced asthma, and the most favored are the osmotic theory and the heat loss theory There were several factors affecting pulmonary function immediately after BAL, with the temperature of bronchoalveolar lavage fluid (BALF) one of the most important factors that has often been neglected. 5 The lack of data regarding the acute pathophysiologic consequences of BAL led us to undertake the present investigation of the acute effects of BAL and the different temperatures of BALF on the pulmonary function test (PFT) in a group of normal adults. *From the Chest Division, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. Manuscript received February 4; revision accepted October 5. Reprint requests: Dr. Lin, Chest Division, Department of Internal Medicine, Mackay Memorial Hospital, No. 92 Sec 21, Chung San North Road, Taipei, Taiwan ROC 10449
The results in group 2 showed a statistical difference in
both ABC and PFr data, especiaUy PaO., FEF 200-1200,
FEF25%-7S%, FEF25%, FEF5O%, and FEF7S%. In group 3, there was a significant decrease ofPaO. and no significant difference in PFT before and after BAL. From these data we conclude that BAL is a safe examination. However, the administration BAL 8uid (BALF) with !SOC normal saline solution can affect the results of the PFr signifiC8DtI~ Much of this adverse reaction can be minimized by using body temperature (3rC) saline solution. At 3rC, the ABG data showed a decrease in PaO., but pulmonary function was not affected signilicantl~
MATERIALS AND METHODS
Subjects The subjects for this study came from our out-patient clinic. they came into Mackay Hospital due to a variety of nonspecific minor complaints, such as chest tightness or foreign body sensation in the throat These patients bad no evidence of upper respiratory tract infection in the last two weeks prior to this investigation. All patients selected had less than five pack-years of smoking history and their physical esaminatson, chest radiograph~ and pulmonary function test results (simple spirometry), showed normal findings. If any patient were still concerned and requested further examination, we selected them for our experiment. Twenty seven young healthy individuals 25 to 35 years of age were selected for the study They were randomly divided into three groups, with nine in each group. Group 1 subjects received only a bronchoscopic examination, and they also served as the control group. Group 2 subjects received a bronchoscopic examination, followed by BAL using 200 ml of 25°C normal saline solution as lavage Iluid. Group 3 subjects also received a bronchoscopic examination followed by a BAL with 200 ml of 3rC normal saline solution. Originall~
Bronchoalveowr Lavage All subjects received intramuscular administration of 0.4 mg atropine, 40 mg of meperidine hydrochloride (Demerol), and topical lidocaine (Xyloeaine), The Olympus BF-B2 or BF-B3 fiberoptic bronchoscope was then administered transnasally and wedged in the subsegmental bronchial ori6ce of the right middle lobe or left lingular lobe. Each time an aliquot of 50 ml normal saline solution was infused and recovered using a gentle suction of less than 40 mm Hg. This was done four times, with a total of 200 ml of saline solution being used. The average BAL return rate was 55.8 ± 5.6 percent in group 2 and 59.2±5.1 percent in group 3.
Pulmonary Function Test. The baseline pulmonary function tests and arterial blood gas levels were determined prior to bronchoscopic examination and premedication. "The second arterial blood gas determination was performed just before the end of the bronchoscopic examination or CHEST I 93 I 5 I MAY, 1988
1041
Table l-Changa in the Baulta of Spirometrr/ and Arterial Blood CGI after Bronclaoacopic EmrnintJlion in Group 1 Pulmonary FUnction Test
Before After Bronchoscopy Bronchoscopy (n == 9) (n==9)
FEVl ('II pred) FEVllFVC (%) FEF 200-1200 (If, pred) FEF25-75% (tJ pred) fEF251f, (II, pred) FEF5O% (If, pred) F~Fi5% (% pred) VC (If, pred) TLC (If, pred) By(If, pred) PaO.(mm Hg)
Difference in Results
93.17±6.74 81.33±5.91 86.42± 10.67
93.75±7.24 -0.58±2.31 81.91±8.51 -0.67±2.79 83.42± 10.99 3.00±2.98
85.42±9.35
82.17± 12.07
3.25±4.41
9O.46±9.57 0.88±2.65 ~1.34 ± 10.79 81.42±9.68 77.54±9.83 3.88±5.04 3.05±2.99 77.13±10.40 74.08± 12.18 94.5±7.87 92.83±7.36 1.67±2.64 96.42±7.32 92.41±7.41 4.01±7.36 98.47±9.32 101.43 ± 11.42 -2.96±12.36 94.42 ± 4.75- 85.50±7.488.92±3.38
-Paired , test == p
administered from one to two hours after we finished the bronchoscOpic examination and the bronchoalveolar lavage. The PIT was done using a Gould 5000 CPI computerized spirometer, The loop with the highest sum of FEV 1and FVC was analyzed. The FEV h FVC, FEV1/FVC ratio, FEF200-1200, FEF25If" FEF5O%, FEF75% were recorded, and a 80w rate at a constant volume at 50 and 75 percent of total lung capacity (Vso, V,J was derived and used as an indication of small airway dysfunction. The functio~ residual capacity (FRC) was measured by an open circult system multiple breath nitrogen washout test, while' we observed the N. display until the Nt concentration fell to below 1.4 percent, using a Gould 5000 CPI computerized spirometer. The ~dua1 volume (RV) and total lung capacity (TLC) were derived with the expiratQry reserve volume and vital capacity (VC) obtained from the CPI dry-rolling seal, volume displacement-type spirometer. The predictive equations of Lam et aI,8 were used for all spiro~etric tests. All pulmonary function tests are expressed as percent predicted.
Table !.-Charaga ita the Baulta ojSpiromet'1l and after BAL .".,h Saline Solution at Boom Temperaiure in Group 2
ArterialBlood CGI_ Pulmonary Fu~ction
. Test
FEV l (If, pred) FEVlFVC (%) FEF 200-1200 (% pred) FEF25-751f, ('II pred) FEF25% (If, pred) FEf~
(ti, pred) FEF75% (If, pred) VC ('II pred) TLC (If, pred) ~(% pred) PaO.(mm Hg)
After Lavage (0 ==9)
Difference in Results
89.67±6.90 SO.58±5.10 9O.09±8.49*
85.42±8.65 76.83±8.48 6O.42± 13.36-
4.25±3.90 3.75±4.37 29.67±5.83
86.43±9.32-
65.44 ± 12.24-
2O.99±4.46
9O.67±9.68-
64.50 ± 11.94-
26.17±4.34
84.33 ± 10.42-
6O.33± 14.49-
24.00±2.97
77.50± 10.56-
57.50± 12.35-
2O.00±5.48
Before Lavage (n == 9)
86.67±8.73 9O.50±6.81 97.54±7.82 94.37±5.82 96.32± 10.35- 114.35± 18.09* 95.42 ± 6.9266.98 ± 12.82-
.paired t test==p
3.83±3.87 -3.17±6.64 -18.03± 12.43 28.42±6.2
Table 3-Changes. in the Buults of Spirometry and ArterialBlood GaB after BAL with Saline Solution at Body Temperature in Group 3 Pulmonary Function Test FEV l (% pred) FEV/FVC (%) FEF 200-1200 (% pred) FEF25-75% (% pred) FEF25% (% pred) FEF5O% (II, pred) FEF75% (If, pred) VC ('II pred) PaO.(mm Hg)
Before Lavage (n==9)
After Lavage (3'rC) (n =9)
Difference in Results
95.38±6.43 82.42±6.98 88.50±8.36
91.42±7.08 SO.42±6.15 84.54±8.56
3.96±6.18 2.08±2.18 3.96±4.09
94.49± 10.13
9O.58± 12.77
3.91±2.83
93.33±9.71 84.47±9.81 76.17±7.94 95.50±8.41 92.33±5.54*
92.42± 12.65 SO. 75± 12.60 71.75 ± 14.74 94.33±8.30 77.42 ± 10.56-
0.92±3.29 3.72±5.38 4.42±4.10 1.17±2.42 14.92±5.04
-paired t test==p
There was no significant difference in PIT results before and after bronchoscopic examination in the control group (group 11 except for a decreased PaO! level after bronchoscopic examination (8.92 ± 3.38 mm Hg) as shown in Table 1. Table 2 demonstrates the results in group 2 before and after bronchoscopic examination with simultaneous BAL using 200 ml of 25°C normal saline solution. Although there was a decrease in FEV h FEV1/FVC, and FVC, these changes were of no statistical significance by paired ftest. On the other hand, changes in FEF 200-1200, FEF25-75%, FEF25%, 50%, 75% and Pa02' were of statistical significance . In group 3 subjects, 3rc of normal saline solution was used instead of 25°C normal saline solution, except for a decreased Pa02 in ABG where the results of the PIT showed no significant change, before and after lavage. Comparing groups 2 and 3, the changes in the pulmonary function before and after examination are presented in Table 4 and Figure 1. The changes in the pulmonary function tests especially in FVC, FEV1 and FEV/FVC, showed no statistical significance in groups 1, 2, and 3. While those representing respiratory midflow rates including FEF200-1200, FEF25-75%, FEF25%, FEF50%, FEF75%, etc and Pa02, demonstrated the changes that were of statistical significance in comparing group 2 to either group 1 or group 3, when the result of group 3 was compared with group Pulmonary FunctionIn Normal Subjects after SAL (Un, Wu, Huang)
Table 4-CompGrison of Changa in Baulta of Spirometry and ABC Determinatioru after Bronchoacopic Emmination, BAL with Saline Solution at Boom Temperature and at Body TempertJture Difference in Difference in Difference in Results, Results, ~C Results, 3rc Bronchoscope Saline BAL Saline BAL (n=9) (n=9) (n == 9) FEV! (% pred) FEVlFVC(%) FEF 200-1200 (% pred) FEF25-75% (% pred) FEF25% (% pred) FEF5O% (% pred) FEF75% (% pred) VC (% pred) Pa02 (mm Hg)
-0.58±2.31 4.25±3.90 -0.67±2.79 3.75±4.37 3.00±2.98* 29.67 ± 5.83*
3.96±6.18 2.08±2.18 3.96±4.09*
3.25±4.41* 20.99 ± 4.46*
3.91±2.83*
0.88 ± 2.65* 3.88±5.04* 3.05±2.99* 1.67±2.64 8.92±3.38*
26.17 ± 4.34* 0.92±3.29* 24.00±2.97* 3.72±5.38* 20.00 ± 5.48* 4.42±4.10* 3.83±3.87 1.17±2.42 28.42±6.2* 14.92± 5.04*
*ANOVA test and Scheffe test p
1, there is no statistical significance except for the changes in the amount of Pa02 • DISCUSSION
Bronchoalveolar lavage is a relatively new diagnostic method. Although it is generally considered to be a safe procedure, a bronchoscopic examination alone and a BAL have been known to induce acute physiologic changes (such as bronchospasm or hypoxia) in normal persons. Some studies have shown that pulmonary mechanical changes that were induced by fiberoptic bronchoscopic examinations could be prevented by prior administration of atropine. 1-4 However, the effectiveness of this method in preventing acute pulmonary changes during and after BAL is still not clear With this in mind, the authors began to explore other preventative methods. In retrospect, there might be several factors that could affect changes in the respiratory physiology such as the technique, the amount and the recovery percentage of BALF, and the condition of the patients lungs prior to the examination.P''" Given these probable factors, the temperature of the BALF seems to have been the one factor that has been overlooked. In this study we found that a fiberoptic bronchoscopic examination with BAL could be performed safely on normal subjects. We specifically use 200 ml of normal saline solution in our BAL because it usually seemed to be sufficient for this kind of procedure. 14-15 A larger amount of BALF has been reported to cause more serious lung function abnormalities." This has been alluded to by many other researchers. 14-15 In the control study we found that bronchoscopic examination with prior administration of atropine produced no significant change in the patients pulmonary function or respiratory physiology However, it did significantly decrease the PaO! at the 0.05 level.
When 25°C normal saline solution was administered during the BAL, there was a significant decrease in the mid-flow rates (FEF25-75%, FEF25%, 50%, 75%) and PaO~b but no significant change was noticed in the FEV., FVC, and TLC. When 3'rC normal saline solution was employed in performing the BAL, the results showed only a signficant decrease ofPa02 while the other pulmonary function test showed no significant change in comparing with the control group. In contrast, when 25°C normal saline solution was administered during BAL, the effect on PITs was much more substantial when comparing with the group using 37°C normal saline solution. These results are similar to the findings of Rankin et al. 12 They used 300 ml of room temperature (0.9% NaCI) solution to perform lavage in 12 healthy nonsmoking volunteers. After the BAL, they found a small decrease in the mean FVC and FEVI , but it was not statistically significant. However, the drop in Vmax (50%) was seen as highly significant. Unfortunately they did not use 3rC saline solution to perform lavage in the normal volunteers, and therefore, did not gain the same results as we did. In contrast, Bums et al5 performed a very detailed study of the physiologic consequences of saline lobar
a
•
b
c
-
-
FEV 1 ~
0
•
PErl
L-.J
f
d
I HHErR I
L:.--J
~
control croup BAl. by rouill temperature .a11ne
BAL by bod/' temper-1ture .allne
FIGURE 1. Mean percentage of decrement in FEV h PEFR, MMEFR, VC and PaOt 1-2 h post-lavage, for normal subjects who underwent either room temperature saline (slanted line bars) or body temperature saline (solid bars) solution lavage compared to controlled subjects (open bars), Significant decrements in PEFR, MMEFR and PaOloccurred in the room temperature lavage group. (a, b, c, d, e. f: p
1011
lavage in healthy adults. They used a 6beroptic bronchoscope with a cuff that could be inHated when placed in the right lower lobe to perform lavage in normal volunteers. These subjects underwent lavage with 1,000 ml of room and body temperature saline solutions. They found that the subjects who underwent lavage with room temperature saline solution had a 20 percent decline in TLC and an elevated R~ The FEF 25-75% and the vital capacity were significantly reduced. However, the airway resistance (Raw) did not signi6cantly increase. On the contrary the subjects who had lavage with body temperature saline solution experienced only a significant elevation of the R~ but no statistically significant change occurred in the TLC, VC, FEVIt Ra~ etc. In terms of changes in Pa02 , the results of this study were very different from those of Bums et ale In our study the control group, who received only a bronchoscopic examination, experienced a decrease of 8.92±3.38 mm Hg. Group 2, which had lavage with room temperature saline solution, demonstrated a very serious decrease in Pa02 of 28.42 ± 6.2 mm Hg. Group 3, who received the 37°C saline solution, experienced only a moderate decrease of 14.92 ± 5.04 mm Hg. On the other hand, all of the patients of Bums et al, whether they were treated with a bronchoscope or BAL, exhibited a substantial and very serious decrease in Pa02 of around 30 mm Hg. They also exhibited hypoxemia. The reasons for the discrepancies in our respective studies could be attributed to the different procedures and methods employed. We used a bronchoscope that was wedged in the subsegmental bronchus of the right middle lobe or the left lingular lobe. We also used 200 ml of saline solution when we performed lavage. In contrast, Bums et al used a cuffed bronchoscope that was placed in the right lower lobe and then used 1,000 ml of normal saline solution for lavage. In reviewing the literature" and the results of this study it was shown that BAL will lead to changes in respiratory physiology of patients. These changes are due mainly to obstruction of the respiratory tract and not just the replacement of air when the BALF is inserted. Possibly another and more compelling reason is that cold saline solutions seem to induce bronchospasm similar to those caused by cold air, exercise and/or hyperventilation. 16 Researchers have indicated that bronchospasm may be related to osmolality 17.18 This can be discounted in this studg for the osmolality of normal saline solution is the same as the human body Therefore, temperature still seems to play a significant role. In retrospect, one bafBing question remains to be answered: why does it take one to two hours for BAL to cause bronchospasm when exercise-related asthma usually occurs within 20 minutes? The most probable 1012
reason is that BALF and cold air have different physical-chemical characteristics, and subsequently have different delaying effects. 5 This has been observed especially when room temperature saline solution is used in the BAL. This often seems to lead to interstitial edema and the invasion of inHammatory cells. 19--21 This local change in the middle lobe could affect the rest of the lung through the neurologic reflexes or the release of mediators or both. 18 Room temperature BALF may also cause more serious change in pulmonary function as represented by the How rate. Consequently the V/Q will decrease, which may possibly lead to more serious hypoxemic complications. 22 In conclusion, it seems that BAL is a safe procedure in normal subjects. Also, it is important to remember that certain pulmonary function will be affected when administering BAL. However, many of the effects on the pulmonary system may be minimized by using body temperature saline solution. REFERENCES 1 Belen J, Neuhaus A, Markowitz D, Rotman HH. Modification of the effect of fiberoptic bronchoscopy on pulmonary mechanics. Chest 1981; 79:516-19 2 Neuhaus A, Markowitz D, Rotman HH. The effects of fiberoptic bronchoscopy with and without atropine premedication on pulmonary function in humans. Ann Thorac Surg 1978; 25:39398
3 Albertini RE, Harrell JH, Kurihara N. Arterial hypoxemia induced by fiberoptic bronchoscopy JAMA 1974; 230:1666-67 4 Zavala DC, Godsey K, Bedell GN. The response to aerosol and intramuscular atropine sulfate given to patients undergoing fiberoptic bronchoscopy. Am Rev Respir Dis 1978; 117:96 5 Burns DM, Shure D, Francoz R, Kalafer M, Harrell J, Wifztum K, et al. The physiologic consequences of saline lobar lavage in healthy human adults. Am Rev Respir Dis 1983; 127:695-701 6 Cole ~ Burton C, Lanyon H, Collins J. Bronchoalveolar lavage for the preparation of free cells technique and complications. Br J Dis Chest 1980; 74:273-78 7 Huber GL, Edmunds LH, Finley TN. Effects of experimental saline lavage on pulmonary mechanics and morphology Am Rev Respir Dis 1971; 104:334-37 8 Francoz RA, Konopka R, Sgroi ~ Moser KM. Changes in ventilation and perfusion in anesthetized dogs following lobar lavage with saline solution. Chest 1978; 74:552-58 9 Lam KK, Pang SC, Allan WGL. A survey of ventilatory capacity in Chinese subjects in Hong Kong. Ann Human BioI 1982; 9:459-72 10 Strumpf IJ, Feld MK, Cornelius MJ, Keogh BA, Crystal RG. Safety of fiberoptic bronchoalveolar lavage in evaluation of interstitial lung disease. Chest 1981; 80:268-71 11 Bechtel J}, Starr III 'I: Dantzker DR, Bower JS. Airway hyperreactivity in patients with sarcoidosis. Am Rev Respir Dis 1981; 124:759-61 12 Rankin )A, Snyder PE, Schachter EN, Matthay RA. Bronchoalveolar lavage: Its safety in subjects with mild asthma. Chest
1984;85:723-28
13 Tilles OS, Guldenheim PO, Ginns ic, Hales CA. Pulmonary function in normal subjects and patients with sarcoidosis after bronchoalveolar lavage. Chest 1986; 89:244-48 14 Davis CS, Giancola MS, Costanza MC. Analyses of sequential bronchoalveolar lavage samples from healthy human volunteers. Am Rev Respir Dis 1982; 126:611-16 Pulmonary function In Normal Subjects after BAL (Un, Wu, Huang)
15 Gotoh 1: Ueda S, Nakayama 1: 18kishitaY, Yasuoka S, Tsubura E. Protein components of bronchoalveolar lavage fluids from non-smokers and smokers. Eur J Respir Dis 1983; 64:369-77 16 O·Cain CF: Dowling NB, Slutsky AS. Airway elrects ofrespiratory heat loss in normal subjects. J Appl Physiol 1980; 49:87580
17 Deal EC, McFadden ER, Ingram RH, Jaeger JJ. Esophageal temperature during exercise in asthmatic and non-asthmatic subjects. J Appl Physioll979; 46:484-90 18 Godfrey S. Exercise-induced asthma. In: Clark 11H, Godfrey S, eds. Asthma, 2nd ed. London: Chapman and Hall, 1983:5778
19 Innen eR, Terry PS, 1taystman RJ, Menkes RA. Collateral ventilation and the middle lobe syndrome. Am Rev Respir Dis
1978; 118:30)..10 20 Cohen AD, Batra GK. Bronchoscopy and lung lavage induced bilateral pulmonary neutrophil inftux and blood leukocytosis iB dogs and monkeys. Am Rev 8espir Dis 1980; 122:239-47 21 Widdicombe JG. Respiratory reSses from the luns. Dr Med Bull 1963; 19:15-20 22 Bogen RM, Saidon J~ Shelburne J, Neigh JL, Shuman JF: 1lmtum ICIl Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. N Engl J Med 1972; 286:1230-33
Plan to Attend 54th Annual SclenUflc Assembly Anaheim October 3·7, 1988
CHEST I 83 I 5 I MAY, 1_
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