Lack of Effect of Hydration on Sputum Production in Chronic Bronchitis

Lack of Effect of Hydration on Sputum Production in Chronic Bronchitis

Lack of Effect of Hydration on Sputum Production in Chronic Bronchitis Chang Shim, M.D., F.C.C.P.;* Malcolm King, Ph.D.;t and M. Henry Willia1lUJ, J1:...

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Lack of Effect of Hydration on Sputum Production in Chronic Bronchitis Chang Shim, M.D., F.C.C.P.;* Malcolm King, Ph.D.;t and M. Henry Willia1lUJ, J1:, M.D., F.C.C.P.*

Patients with chronic lung disease productive of sputum are generally encouraged to drink a large amount of ftuid to facilitate sputum production. This clinical practice has not been tested systematically. Twelve outpatients with chronic obstructive pulmonary disease in clinically stable condition who had daily sputum production were asked in random sequence: 1) to drink one glass of ftuid every waking hour after supper and upon waking the next morning (hydration), 2) to drink no ftuid after supper and upon waking the next

morning (dry), and 3) to drink ftuid ad lib (ad lib). Each morning sputum collection was started upon waking and continued for four hours. The differences in volume, elasticity of sputum, respiratory symptoms, and ease of expectoration were not significant. We conclude that moderate hydration and dehydration have no effect on volume expectorated, the elasticity of sputum, respiratory symptoms or forced expiratory volume in one second.

patients with chronic lung disease productive of sputum are generally encouraged to drink large amounts of fluid to facilitate sputum production. It is believed that large amounts of fluid would result in thinning of sputum and facilitate its expectoration. 1 This clinical practice based on intuition has not been systematically tested. We carried out a prospective study of 12 patients With chronic obstructive pulmonary disease (COPD) in clinically stable condition who had daily sputum production.

total of four hours. Oral medication was withheld for 17 hours after supper when the fluid regimens began. Two patients who were taking sustained-release theophylline withheld the evening and the morning dose. Twopuffsof beta-agonist aerosol from a metered-dose inhaler were allowed in the morning. The patients presented to the laboratory at 8:30 AM. Pulmonary function was tested and inquiry was made about respiratory symptoms when the sputum collection was completed in the laboratory. Each patient was specifically asked about ease ofexpectoration as compared to his usual experience prior to enrolling in the study. The patients were asked to state whether it was easier, the same as or worse than usual on each fluid regimen. Urine was collected in the laboratory to determine its specific gravity (SG)to assess patient compliance with the regimen. Sputum volume was measured and its color and consistency were noted. An aliquot was frozen immediately and shipped to the sputum laboratory for the measurement of viscoelastic properties. The viscoelastic properties of the sputum samples were determined on the thawed specimens by the magnetic microrheometer technique." This technique used a magnetically oscillating steel microsphere in a drop of mucus as a mechanical probe. The image of the sphere is magnified and projected onto a pair of photocells, whose current is proportional to the displacement of the sphere (strain). The magnetic force driving the sphere (stress) is proportional to the excitation current in the electromagnet coil. Aplot of the photocell current vs the excitation current in the magnet yields an ellipse, from which viscoelastic data can be computed. Tworheologic parameters are reported in this study: G*, the ratio of stress amplitude to strain amplitude, and tan 8, the tangent of the phase lag between stress and strain. Both parameters were measured at frequencies of1, 10, and 100radians per second. G* is a measure of the overall capacity of the sample to resist deformation at a given frequency; tan 8 corresponds to the ratio of viscous to elastic deformation. Both parameters correlate negatively with mucocillary clearance in the frog palate model system."

METHODS

Patients with COPD attending our Chest Clinic who had a history of chronic sputum production were asked to participate in the study. Those who had a history of heart disease, obstructive uropathy, or renal failure, or a clinical diagnosis of bronchiectasis were excluded from the study. The study protocol was approved by the institutional Committee of Clinical Investigation. Those who consented to participate were given a sputum cup and were asked in random sequence to follow one of three different regimens: 1. To drink one glass of fluid (approximately 250 ml) every waking hour after supper and upon waking the next morning (hydration regimen). Alcoholic drinks were disallowed. Otherwise, the nature of the fluid was not restricted so that the patients could choose whatever fluid they wished. Most chose to drink tap water. 2. To drink no fluid after supper or upon waking the next morning (dry regimen). Dry toast was allowed for breakfast in the morning but they were not allowed to drink any fluid including coffee, tea or milk. 3. To drink fluid as desired (ad lib regimen). Each morning sputum collection was started at home upon waking, between 6 and 7:30 AM and continued in the laboratory for a *Professor of Medicine, Albert Einstein College of Medicine, Bronx Municipal Hospital Center, Bronx, NY. t Associate Professor Medicine, Pulmonary Defense Group, University of Alberta, Edmonton, Alberta, Canada. Supported in part by Medical Research Council, Canada and Irving D. Karpas Fund in Medicine. Manuscript received January 12; revision accepted March 12. Reprint requests: Dr. Shim, Bronx Municipal Hospital Center, Van Etten Hospital, Rm 3A4, Bronx 10461

RESULTS

Six men and six women patients ranging in age between 56 and 70 years participated in the study. They had a diagnosis of COPD for seven years or longer, Most had chronic stable air flow obstruction of moderate to severe degree on routine spirometry CHEST / 92 / 4 / OClOBER. 1987

879

Table l-Blaeologic Properties of Sputum

35

Tan &(l)t

G*(l), dynlsq em* Patient

1 2 3 4 5 6 7 8 9 10 11 Mean

30

15

SD

Dry Hydration Ad Lib Dry Hydration Ad Lib 45 46

41 66 191 316 68 117 389 66 52 127 120

178 60 49 112 158 347 245 72 302 23 87 148 lOS

174 69 59 47 162 47 SOl 195 355 34 380 183 160

0.32 0.35 0.21 0.29 0.39 0.24 0.24 0.15 0.19 0.29 0.19 0.26 0.07

0.20 0.30 0.27 0.20 0.24 0.30 0.29 0.36 0.43 0.15 0.25 0.27 O.OS

0.28 0.24 0.22 0.28 0.49 0.17 0.18 0.13 0.19 0.36 0.29 0.26 0.10

*G*(l), dynlsq em-s-mucus elasticity at 1 radian/sec. tTan &(l)-viscosity-elasticity ratio.

o DRY FIGURE.

HYD

AD LIB

Expectorated sputum volume on three regimens. Short

bars represent the mean values.

carried out at their regular clinic visits. All12 were exsmokers. Most had been told to drink plenty of fluid in the past by the physicians encountered in the course of their illness, but only four claimed to drink large amounts of fluid regularly, at least several glasses of water daily, before entering this study. All 12 patients completed the three fluid regimens. Most of them claimed to have drunk 1,800 to 2,400 ml of fluid, mostly tap water, on the hydration day and 500 to 1,()()() ml on the ad lib day and no fluid on the dry day. Patient compliance with the fluid regimens assessed by urine specific gravity was excellent. Specific gravity ranged from 1.020 to 1.027 on the dry day and from 1.004 to 1.009 on the hydration day and from 1.008 to 1.020 on ad lib day. None of the patients complained of excessive dryness on. the dry day regimen and they were willing to. wait to the end of the study to drink fluid, 'The only complaints on the hydration regimen were of frequent visits to the bathroom. Seven patients inhaled two puffs of beta-agonist aerosol from a metered-dose inhaler upon waking in the morning before reporting to the laboratory. Five took no medication at all on the morning of the study. 'The means and standard deviations of volumes of expectorated sputum for the 12 patients were 9.6 ± 7.8 ml, 9.8 ± 7.6 ml, and 9.3 ± 8.0 ml on the dry, hydration and ad lib regimens, respectively (Fig I). 'The differ880

ences were not significant (analysis of variance). 'The patients noted no symptomatic difference in regard to ease of expectoration of sputum, chest congestion or breathing. Each patients sputum appeared similar in color and consistency on the three regimens. Some patients always expectorated thick, tenacious sputum that was difficult to transfer from the cup to a test tube. Sputum viscoelasticity (Table I) was measured on specimens from 11 patients only. One of the sample tubes was broken in transit. Values for G* {1}-mucus elasticity at 1 radian/sec, were 127± 120, 148± 108, and 183 ± 160 dyn/em" on the dry, hydration, and ad lib regimens, respectively. The respective values fo~ tan 8 (l}-viscosity-elasticity ratio, were 0.26 ± 0.07, 0.27±0.08, and 0.26±0.10 respectively. 'The differences in elasticity were not significant, nor were the differences in tan 8. Viscoelastic measurements at 10 and 100 radians/sec led to the same conclusions. Variations in sputum rheology from patient to patient are always large, and this study is no exception. 'The mean interpatient coefficient of variation in G*, expressed in log units, was 0.38 or 140percent. However, Table !-Forcstl E.,-Gtory Volume ita One Second Patient

1 2 3 4 5 6 7 8 9 10 11 12 Mean

SD

Predicted

Dry

Hydration

Ad Lib

2.56 2.94 2.35 2.76 2.42 1.83 2.29 2.20 2.18 2.76 2.47 2.42

0.60 1.73 0.76 1.67 0.57 0.50

0.60 1.63 0.73 1.78 0.53 0.59 0.91 1.38 0.86 0.96 1.37 0.75 0.93 0.49

0.60 1.65 0.74 1.75

0.97

1.28 0.90 1.16 1.38 0.70 0.94 O.SO

0.50 0.54 0.85 1.~

0.75 1.13 1.38 0.70 0.91 0.50

LackmHydrationand Sputum ProducIIon in Chronic Bronchitis (Shim, King, _ems)

the variations in the viscoelastic properties within individual patients on the three regimens were considerably smaller (0.22 log units or 65 percent), suggesting that differences in G* between patients are real. Seven of the 11 patients had reasonably stable sputum rheology over the course of the study. Forced expiratory volume in one second (FEV J was a mean of 0.94, 0.93, and 0.91 L on the dry, hydration and ad lib regimens (no significant difference in analysis of variance), respectively (Table 2). DISCUSSION

Most of our patients produced only modest amounts of sputum daily. Some patients claimed to produce sputum only in the morning. Most patients claim that morning sputum is the most troublesome for its expectoration and its effect on breathing. Since this was an outpatient study in which complete collection of sputum could not be assured over a 24-h period, we elected to collect it only for four hours with emphasis on complete collection partly under our observation. In general, sputum collection was completed within the first two hours of waking in the morning. The hydration and relative dehydration regimens employed in this study were not vigorous, but we reasoned that three levels of hydration and dehydration were clinically realistic. The effect of extreme hydration and dehydration on sputum production, although interesting physiologically, would not be clinically relevant. Bang and Bang, 4 for example, demonstrated that severe dehydration in chickens (withholding water for 17 to 72 h) resulted in progressive deterioration of nasal mucociliary function, most likely due to abnormally viscid or noncompliant mucus. This dysfunction was readily reversed with spontaneous rehydration. Chopra et alS found that in anesthetized dogs, intravenous saline increased tracheal clearance rate. However, Marchette et al" showed recently that, i~ conscious allergic sheep, systemic hydration of 35 mllkg did not significantly alter baseline tracheal mucociliary clearance, and this same degree of hydration actually led to a worsening of the already compromised clearance function following antigen challenge. Our hydration and dry regimens lasted around 16to 17 hours. We do not know if this was a sufficient interval to affect the viscoelasticity of bronchial mucus. It could have been possible to prolong the hydration regimen but it would have been impractical to prolong the dry regimen. After all, the patients would not have allowed themselves to go dry for a longer period in real life. We would have liked to have withheld bronchodilators altogether during the study, since they may affect mucociliary clearance, 7-9 but some of our patients have a great deal of respiratory distress every morning and they felt that they could not have complied with

the request to avoid bronchodilators for the entire 17-h study period. Sputum production on the three fluid regimens was similar whether or not the patient inhaled beta-agonist aerosol in the morning. Sputum volume, appearance and viscoelasticity did not change on the three regimens. Although many of our patients, prior to the study, had expressed concern over their ability to expectorate sputum on the dry regimen they stated after the study that there was no difference in ease of expectoration on the three regimens. Our sputum collection obviously missed the mucus that was cleared from the tracheobronchial tree by the mucociliary transport mechanism and swallowed. Forced expiratory volume in one second values were also similar on the three regimens. Undoubtedly there were some sampling problems in selecting small amounts of sputum from a clinical specimen of sputum. Although the patients had been cautioned to collect only sputum, and most of the samples appeared homogeneous to the naked eye, there must have been contamination with saliva. Even sputum samples obtained by tracheobronchial suctioning of intubated patients often do not appear homogeneous. The vaues of G* and tan 8 are comparable to those reported for canine tracheal mucus" and for fresh sputum from cystic fibrosis patients," using the same rheologic testing equipment. However, the fact that in this study the sputum specimens were frozen and then thawed means that we cannot be certain that the absolute values reported here can be fairly compared with those reported previously. The method of freez . . ing, storing and thawing of the sputum was similar to that described by Charman and Reid," who reported that freezing and storing of sputum at - 70°C, followed by rapid warming at room temperature prevented degradation of the sputum, as far as viscosity is concerned. A second analysis of nine aliquots of sputum in our study showed a nonsignificant decrease in G* ofO.19±0.29 log units at 1 radian/second but no change at 100 radian/second (O.OI±O.20), suggesting that elasticity may be more sensitive to degradation than viscosity. Nevertheless, the changes in viscoelasticity associated with freezing and thawing are modest with respect to the overall variations in viscoelasticity between patients, and it is felt that despite any uncertainty in absolute values, the conclusion that there were no significant differences between treatment regimens is entirely valid. In summary, our results do not support the clinical practice of encouraging vigorous hydration for patients with chronic sputum production. Drinking a glass of fluid, approximately 250 ml, hourly did not have an effect on sputum production. We do not know whether hydration has an effect on sputum production in other pulmonary disease such as asthma, bronchiectasis, CHEST I 92 I 4 I OC108ER, 1987

881

pneumonia or cystic fibrosis, or in patients in an Intensive Care Unit setting. ACKNOWLEDGMENTS: The rheology measurements were performed at the Meakins Christie Labs, McGill University, Montreal. The authors would like to thank Mrs. Anne Wright for assisting in the analysis. . REFERENCES

1 American Lung Association pamphlet. Help yourself to better breathing, 1982:6, 20 2 King M, Macklem zr The rheological properties of microliter quantities of normal mucus. J Appl Physiol1977; 42:797-802 3 King M. Relationship between mucus viscoelasticity and ciliary transport in guaran gel/frog palate model system. Biorheology 1980; 17:249-54 4 Bang BG, Bang FB. Responses of upper respiratory mucosae to dehydration and infection. Ann NY Acad Sci 1963; 106:625-30 5 Chopra SK, 'Iaplin G~ Simmons DH, Robinson GD, Elam D, Coulson A. Effects of hydration and physical therapy on tracheal

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transport velocity. Am Rev Respir Dis lOTI; 115:1009 6 Marchette LC, Marchette BE, Abraham WM, Wanner A. The effect of systemic hydration on normal and impaired mucociliary function. Pediatr Pulmonoll985; 1:107-11 . 7 Saclmer MA, Yergin BM, Brito M, Januszkiewicz A. Effect of adrenergic agonists on tracheal mucus velocity. Bull Eur Physiopathol Respir 1979; 15:505-11 8 Yeates DB, Aspin N, Levison H, Jones Ml: Bryan AC. Mucociliary tracheal transport rates in man. J Appl Physiol 1975; 39: 487-95 9 Pavia D, Bateman JRM, Clarke SW Deposition and clearance of inhaled particles. Bull Eur Physiopathol Respir 1980; 16:335-66 10 King M. Interrelation between mechanical properties of mucus and mucociliary transport: effect Qfpharmacologic interventions. Biorheology 1979; 16:57-68 11 King M. Is cystic &brosis mucus abnormal? Pediatr Res 1981; 15: 120-22 12 Charman J, Reid L. The effect of freezing, storing and thawing on the viscosity of sputum. Biorheology 1973; 1~:295-~1

Lack of Hydrationand Sputum Production in Chronic Bronchitis(Shim, King, Wi/Hams)