Acute Effects of Herbal Tea Dust Extracts on Lung Function

Acute Effects of Herbal Tea Dust Extracts on Lung Function* Eugenija Zuskin, M.D. ; Bozica Ko.nceljak , M.D.; Theodore J Witek, Jr., Pharm.D. ; and E. Neil Schachter, M.D. , F.C.C.P.

The acute effect of herbal tea dust extracts on lung function was studied in 15 of 25 healthy subjects responding to the inhalation of these extracts. Bronchial inhalation challenge was performed with tea extracts (sage, dog rose and gruzyan) and with normal saline solution as a control substance to assess their baseline airway reactivity to an isotonic aerosol. Lung function testing was performed before exposure and at 0, 15, 30, and 60 minutes after the cessation of exposure. The same subjects were also tested by cballenge with methacholine. Lung function was measured by recording FVC, FEV, FEFSO, FEF25, SGaw, and

Raw. Subjects were skin tested by the skin prick method and serum IgE levels were determined. The findings suggested that neither baseline nonspecific airway reactivity nor specific markers of immediate sensitivity to tea predict airway responses to tea extracts. Further evaluation of immunologic markers may help to explain the onset and progression of airway disease in workers. (Cheat 1989; 96:1321-31)

Tea is made from the young leaves and leaf buds of the tea plant, a species of evergreen. The principal chemical constituents of tea are caffeine, tannin and essential oil. One kilogram of tea may contain up to 30 g of caffeine. There are three main classes of tea: (1) fermented or black; (2) unfermented or green; and (3) the semifermented or oolong teas. Tea comes from practically the same plant in all countries, the differences in the various classes being due to methods of cultivation and manufacture, as well as local climatic and soil conditions. There are a few published reports on the effects of herbal teas on respiratory function. Several authors have listed tea as a cause of occupational asthma. 1· 3 Castellani and Chalmers4 described "tea factory cough" in workers occupationally exposed to tea dust. Uragoda5 reported a case of tea maker's asthma caused by inhalation of tea Huff. Attacks of allergic disease were described by Ebihara6 in two workers employed in a tea garden and Mackay7 described a high prevalence of respiratory diseases in tea garden workers. In our previous study of tea workers, a significantly higher prevalence of chronic respiratory symptoms was found in tea workers than in control subjects.~ Similarly, Uragoda9 found a prevalence of chronic bronchitis and asthma in tea workers higher than that expected in the general population. Pulmonary function in tea

workers was studied by Al-Zuhair and Cinkotai10 and by Castellan et al, 11 who reported across shift reductions for FEV 1 in tea workers related to tea dust exposure. In our study of tea workers, we found acute reductions of ventilatory capacity that were greater in workers with positive skin tests to different tea dust allergens than in those with negative skin tests. 12 Increased levels of IgE in tea workers (20.9 percent) have been interpreted as indicative of allergen-induced respiratory reactions. 13 In the present investigation, we studied the acute effect of the inhalation of different tea dust extracts on lung function in healthy subjects. The relationship of nonspecific airway reactivity to the response to tea dust inhalation was measured using methacholine provocation testing.

•From the Andrija Stampar School of Public Health, and the Institute for Medical Research and Occupational Medicine, Zagreb, Yugoslavia; and The Mount Sinai School of Medicine, New York. This study was supported in part by grant No SPCF-FIC-493 from the National Institutes of Health, and by the Henry and Catherine Gaissmao and the Miller Foundations, New York. Manuscript received December 28; revision acceJ::J April 4. Reprint requests: Dr. Schachter; Mt. Sinai Me · Center; One Gustave Levy Place, New York 10029

PD20FEF25 =provocative dose oE methacholine causing a ~ decrease in the FEFZS; CBE =cotton bract extract

SUBJECfS AND METHODS

The study was performed in 15 of 25 healthy subjects (five men and ten women) characterized as responders to tea dust (see bronchoprovocation with tea dust extracts); age range 18 to 23 years. All tested subjects had never been occupationally exposed to any dusts or fumes. They were healthy volunteers without any history of atopic disease recruited from a University student population in Zaghreb. All volunteers signed infOrmed consent as approved by the University institutional review board. Subjects were asked about respiratory and/or allergic symptoms, such as cough, phlegm, chest tightness, wheezing, shortness of breath, and allergy to dust , food, medication, metals, or insects. Before the bronchial challenge with tea extract, all subjects were asymptomatic and had normal lung function. Lung function measurements were performed using a body plethysmograph. Ventilatory capacity was measured by recording maximum expiratory Bow-volume (MEFV) curves from which the forced vital capacity (FVC), one-second forced expiratory volume (FEV,), and maximum expiratory Bow rates at 50 percent (FEF50) and at the last 25 percent (FEF25) of the vital capacity were read. In addition, airway resistance (Raw) and specific conductance CHEST I 96 I 6 I DECEMBER. 1989

1327

(SGaw) were calculated. Measured values were compared with expected normal values of CECA" for FVC and FEV,. ofCherniack and Raber•• for FEF50 and FEF25, and of Ulmer et a)•• for Raw and SGaw. Bronclwprovocation and Skin Testing with Tea Dust Extracts

The present study was performed in 15 of 25 subjects selected because of their sensitivity to tea extracts. They were initially tested with tea extracts and with normal saline solution as a control substance. Two and one half milliliters of tea extract or normal saline solution was placed in a nebulizer which, with an airflow of 15 Umin, nebulized the fluid during inspiration only. The subjects continued to inhale the whole amount of the solution (tea extract or a placebo) during normal quiet breathing until the nebulizer was entirely empty. Each subject was challenged with all three tea extracts on separate days. Bronchoprovocation with tea extract and normal saline solution was performed at least one week apart. Tea extracts were prepared from three types of tea dust collected from operating machines in the work areas of industries previously studied.u The teas included in this study were sage, dog rose, and gruzyan. Aqueous extracts were prepared using 1 gof tea dust for 3 ml of sterile water. Tea dust was ground into a fine powder and extracted at room temperature. The extracted suspension was filtered initially through a coarse filter to remove particulates and subsequently through a micropore filter. The prepared extract was used fresh in the bronchoprovocation and skin testing studies. Lung function testing was performed before exposure and at 0, 15, 30, and 60 minutes after the cessation of exposure. Apositive response (characterizing responders) was defined as a 20 percent fall in FEV,. or a 25 percent fall in FEF50 or FEF25, or a 50 percent increase in Raw, or a 35 percent decrease in SGaw from the baseline at any measured point following tea allergen challenge. At each measurement, three breaths were performed and the best value was used for the purpose of analysis. Only subjects with a positive response to tea extract were studied. This represented 15 of 25 consecutive healthy volunteers. Subjects were skin tested with extracts of three different teas (gruzyan, sage, dog rose) using the standard skin prick test. These represent unfermented (green) teas. These are the teas which we observed to have the largest effect on the respiratory system in tea workers. Tea extracts were prepared from tea dust collected in the tea processing industry. The method ofSbeldon et al 17 was used for preparing the tea extracts. Skin prick testing with different tea allergens was performed using a dilution 1:500 of the tea extracts (0.02 ml of solution injected). In addition, skin testing was performed with histamine base (1 mglml) and a buffer as a control solution. The skin reactions were read after 20 minutes and were considered positive when the wheal was 3 mm greater than the control wheal. Serum levels of total lgE antibody were measured by PRIST, a direct radioimmunologic sandwich technique based on paper discs as a solid phase.•• Levels of lgE below 125 kUIL were considered normal.•• Nonspecific Bronchial Challenge

The same 15 subjects were tested for nonspecific bronchial reactivity by challenge with progressive concentrations of methacholine (3.0, 6.25, 12.5, 25.0, 50.0, 100.0 mglml). Five breaths of each concentration were inhaled. Lung function was measured in a body plethysmograph before and immediately after the inhalation of each concentration of methacholine. The FVC, FEV,. FEF50, FEF25, Raw, and SGaw were measured.

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StatiBtical Analysis

The mean peak decrements following the various tea provocations were compared to baseline values using the paired Student's t test. DifFerences in peak decrements among the three different teas were compared statistically by an analysis of variance.•

1328

Efl8cts ol Herbal Test Dust Extrac:ls on Lung {Zu$1dn et a/)

MEAN LUNG FUNCTION (FEF25 and SGawl CHANGES FOLLOWING BRONCHOPROVOCAiiON WITH 3 DIFFERENT TEA ALLERGENS IN 10 HEALTHY SUBJECTS

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TIME AFTER BRONCHOPROVOCATION (minutes) FIGURE 1. Mean relative changes of FEF25 and Gaw SE in 15 subjects following bronchoprovocation with three different tea dust extracts.

RESULTS

Table 1 shows anthropometric, immunologic, and baseline lung function data in the 15 healthy subjects tested. Since changes in FEV1 following methacholine were minimal for this healthy group, nonspecific airway responsiveness was measured by the provocative dose of methacholine required to reduce the FEF25 from baseline (PD20FEF25) by 20 percent. The data for PD20FEF25 are listed in Table 1. The results of skin prick testing demonstrated that four subjects (26.7 percent) reacted to dog rose and three of them had increased lgE (> 1000 kUIL; 500 kU/L; 145 kU/L). One subject (6.7 percent) reacted to gruzyan tea and had a normal lgE value. Two subjects had increased serum IgE levels with negative skin reactions to the tested teas (880 kU/L; 500 kU/L). The results of the acute effects of different tea allergens on lung function in 15 subjects for FEF25 and SGaw are presented in Figure 1. In Table 2, the data are analyzed as the maximum decrement over the ~minute challenge for each individual and expressed as mean± SD. There were statistically significant mean acute decreases in all lung function parameters following inhalation of sage, dog rose, and gruzyan tea (p<0.001). The largest tnean maximal acute reductions were recorded for SGaw (sage: -35.6 ~rcent; dog rose: -35.4 percent; gruzyan: -37.4 J)ercent), followed by FEF25 (sage: -26.3 percent; dog rose: -27.7 percent; gruzyan: -25.0 percent), and FEF50 (sage: -19.6 percent; dog rose: -24.1

percent; gruzyan: -25.0 percent) (Table 3). There were no differences in the degree of bronchoconstriction between the three types of tea extracts. There was no association between the baseline PD20FEF25 and the maximal acute reduction in FEF25 following all three types of tea allergens Table 2-Lung Function lbrometen Before and After Inhalation of Three lea &tract3 (mean :t: SD) Sage Pre

Post•

5.28 4.81 +1.06 +0.88 p <0.002 FEV,,L 4.53 4.04 ±0.72 ±0.59 p <0.001 FEF50, Us 5.83 4.69 ±1.08 ±1.04 p 0.003 FEF25, Us 3.27 2.41 +0.73 +0.62 p <0.001 Raw, cmH10/l/s o.i4 0.20 +0.03 ±0.07 p <0.001 SGaw, cmH10/s 2.05 1.32 0.40 0.45 p <0.001 FVC,L

Dog Rose Pre

.Post

5.31 4.90 +0.98 ±0.97 <0.001 4.54 4.00 +0.67 ±0.67 <0.001 5.94 4.51 ±1.26 ±0.86 <0.001 2.37 3.28 ±0.69 ±0.70 <0.001 0.14 0.19 ±0.03 ±0.06 <0.001 2.06 1.33 0.32 0.42 <0.001

Gruzyan Pre

Post

5.32 4.85 ±0.97 ±0.92 <0.001 4.52 3.89 ±0.73 ±0.53 <0.001 5.81 4.36 ±1.20 ±1.14 <0.001 3.37 2.35 ±0.75 ±0.82 <0.001 0.13 0.21 ±0.04 ±0.09 <0.001 2.11 1.32 0.35 0.49 <0.001

*Post values represent the peak decrement recorded during a 50minute period. CHEST I 98 I 6 I DECEMBER. 1989

1329

Table 3-Compariron of Mean ( ± SD) Maximal Decnmrent in .Wng Function Following Inhalation of Various Tea Extracts

FVC, L FEV,,L FEFSO, Us FEF25, Us

Sage

OogRose

Gruzyan

91.33 ±6.85

91.93 ±4.46 p=0.920 88.33 +7.49 p=0.568 77.47 + 14.48 p=0.632 72.93 + 16.70 p=0.695 140.73 ±30.90 p=0.409 65.00 + 13.56 p=0.702

91.13 ±5.18

89.67 :t 7.51 81.87 :t 14.85 75.07 +15.09

Raw, cmH10/l/s

143.13 +26.67

SGaw, cmH10/s

65.47 +14.89

86.67 ±8.04 76.93 :t 16.74 70.00 :t 16.93

154.53 ±31.76 61.00 :t 18.79

*Expressed as percent of baseline.

Table 4-Compariron of Largest Change in .Wng Function Following Tea Extracts in Subjects With arid Without Specific Reactions to Tea Extracts* Subject FEV1 FEFSO FEF25 1 3 9 12 13 14 15 i

so 2 4 5 6 7 8 10

11 i

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-18 -19 -6 -20 -21 -31 -9 -18 ±8.2 -9 -13 -17 -14 -15 -10

-11 -14 -13 ±2.7

-20 -33 -33 -40 -32 -60 -21 -34 :t 13.4 -12 -46 -7 -31 -50 -20 -19 -29 -27 :t 15.3

-24 -31 -33 -48 -45 -61 -26 -38 :t 13.5 -26 -56 -30 -28 -55 -15 -34 -43 -38 :t 14.4

Raw +206 +155 +160 + 181 +172 +150 +178 +172 :t 19.1 +107 +223 +127 +138 +169 +160 +207 +170 +163 ±39.1

SGaw IgE Skin Test -39 -34 -42 -68 -65 -38 -45 -48 :t 12.8 -23 -56 -30 -31 -44 -39 -61 -61 -43 :t 14.9

+ + + + + +

+ + + +

*Expressed as percent change from baseline.

(p>0.05) using the rank correlation test. We also examined the relationship between specific sensitivity to tea antigens (ie, positive skin tests) or the presence of elevated IgE and the response to inhaled extract. The results are summarized in Table 4. There is no difference between the two subgroups. DISCUSSION

The potential health hazards of different herbal tea have been described by several authors. 1•21 •22 Grammer and Patterson,3 and Brooks2 listed tea as a possible cause of occupational immunologic disease. Acase of anaphylactic reaction to camomile tea was described by Benner and Lee. 23 Our data demonstrated that inhalation of sage, dog rose, and gruzyan tea extracts in healthy subjects may cause a significant acute decrease in lung function. These data are comparable to the results obtained in tea workers occupationally exposed to sage, dog rose, and gruzyan tea. 8 Immunologic studies in tea workers, however, demonstrated higher prevalences of positive skin reactions than in volunteers to extracts such as sage (45 percent), gruzyan (40 percent), mint (35 percent), and dog rose (10 percent). 11 Serum levels of total igE were increased in 27 percent of these tea workers. In this study, seven out of 15 healthy subjects sensitive to tea inhalation by lung function changes complained of acute symptoms following tea allergen inhalation. Castellan et al 11 reported that 7 percent of workers in an herbal tea factory complained of a firstday-back to work pattern of chest tightness. This is similar to the findings in our study of tea workers in which 10 percent of the workers reported acute chest 1330

tightness more intense at the beginning of the work week or on return to work after a period of absence. 8 However, the number of workers complaining of this symptom pattern is considerably lower than among textile workers (20 to 40 percent)24 or coffee workers (15 percent). 25 The frequency with which our healthy nonexposed volunteers responded to the extract is high (60 percent). It is nonetheless comparable to our experience with challenge with cotton bract extract. Since the exact biochemical nature of the irritant is unknown, it is not possible, at this time, to quantitatively compare occupational and laboratory challenges. Nevertheless, as with CBE, our experience with tea dust extract may lead to useful physiologic and pharmacologic information. 26 The mechanism by which the tea dust may act to produce airway obstruction has been postulated to be either nonimmunologic (reflex, inflammatory or pharmacologic) or immunologic (immediate hypersensitivity response). The present study does not allow us to definitively characterize this question, although the fact that nonspecific reactivity in our subjects does not correlate with responsiveness to tea extracts suggests that nonspecific airway irritability may not be an initiating factor in this occupational disease. Experience from our previous study in tea workers suggests that specific skin sensitivity to tea may predict the severity of the airway response. 12 Nevertheless, in the current study among the five subjects with evidence of immediate skin sensitivity (Thble 4), no increased airway reactivity was documented. This suggests that pre-existing skin sensitivity to tea extract does not Elfects of Herbal Test Oust Extracts on Lung (Zuskln et a/)

predict the severity of ailway reactivity to this occupational agent. Lam et al27 suggested that nonspecific bronchial hyperreactivity is likely to be the consequence rather than the predisposing factor in occupational asthma. Our current study suggests this to be the case for airway disease due to tea dust exposure. Further study of this question by routine methacholine inhalation testing during the pre-employment examination of workers entering industries known to give rise to occupational asthma along with regular follow-up examinations may help to answer this question, specifically for tea-related ailway disease. This current study extends our previous observations in tea workers. A large proportion of naive subjects never exposed in the industry to tea dust displays significant degrees of bronchoconstriction following challenge with tea extracts. The degree of nonspecific airway reactivity in these healthy subjects does not appear to influence the severity of this reaction. Similarly, specific reactivity to skin testing with tea extract as well as the measurement of serum lgE does not appear to predict those individuals with more pronoonced reactions. These data suggest that in the case of respiratory disease induced by occupational exposure to tea dust, nonspecific airway hyperreactivity as well as specific sensitivity to tea antigens is a result of employment in the industry rather than a risk factor for occupational asthma. REFERENCES

1 Ridkers PM. Toxic effects of herbal tea. Arch Environ Health 1987; 42:133-36 2 Brooks SM . Occupational asthma. In: Weiss EB, Segal MS, Stein M, eds. Bronchial asthma. Boston: Little, Brown and Company, 1985:461-93 3 Grammer LC, Patterson R. Occupational immunologic lung disease. Ann Allergy 1987; 58:151-59 4 Castellani A, Chalmers A. A manual of tropical medicine. 3rd ed. New York: William Wood and Co, 1919 5 Uragoda CG. Tea maker's asthma. Br J Ind Med 1970; 27:18182 6 Ebihara I . Study on the inhalative allergy of ciliae of leaves: inhalative allergy of the ciliae of tea leaves. J Sci Labour 1975; 51:661-65

7 Mackay DM. Disease patterns in tea garden in Bangladesh. J Occup Med 1977; 19:469-72 8 Zuskin E, Skuric Z. Respimtory function in tea workers. Br J lnd Med 1984; 41 :88-93 9 Uragoda CG. Respiratory disease in tea workers in Sri Lanka. Thorax 1980; 35:114-17 10 AI-Zuhair YS, Cinkotai FF. Ventilatory function in workers exposed to tea and wood dust. IRCS, Med Sci Microbiol 1977; 5:190 11 Castellan RM, Boehlecke BA, Petersen MR, Thedell TD, Merchant JA. Pulmonary function and symptoms in herbal tea workers. Chest 1981; 79:81-85 12 Zuskin E , Kanceljak B, Skuric Z, lvankovic D. Immunological and respimtory changes in tea workers. Int Arch Occup Environ Health 1985; 56:57-65 13 Zuskin E, Duncan PG, Douglas J. The pharmacological characterization of aqueous extracts of vegetable dusts. Lung 1983; 161:301-06 14 Commission des Communautes Europeenes, CECA (1971) Aide memoire pour Ia pmtique de I'examen de Ia function ventilatoire per Ia spirographie. Collection D'Hygiene et de medicine du tmvail, No. 11, Luxembourgh 15 Cherniack RM, Raber MB. Normal standards for ventilatory function using an automated wedge spiromete. Am Rev Respir Dis 1972; 106:38-46 16 UlmerWT, Reichel G, Nolte D. Die Lungenfunktion. Stuttgart: Georg Thieme Verlag, 1976 17 Sheldon JM, Lowe) RG, Mathews KP. A manual of clinical allergy. Philadelphia: WB Saunders Company, 1967:507-31 18 Wide L, Pomth J. Radioimmunoassay of proteins with the use of Sephadex coupled antibodies. Biochim Biophys Acta 1966; 130:257-60 19 Johansson SGO. Serum IgND levels in healthy children and adults. Intern Arch Allergy 1968; 34:1-4 20 Snedecor GW, Cochran WG. Statistical methods. ed 6 . Ames, lA: Iowa State Press, 1974 21 Siegel RH . Herbal intoxication: psychoactive effects from herbal cigarettes, tea, and capsules. JAMA 1976; 236:473-76 22 Segelman AB, Segelman FP, Karliner J, Sofia RD . Sassafras and herb tea: potential health hazards. JAMA 1976; 236:477 23 Benner MH, Lee HJ. Anaphylactic reaction to camomile tea. J Allergy Clio lmmunol1973; 52:307-08 24 Zuskin E. Valic F, Bohuys A. Byssinosis and airway responses due to exposure to textile dust. Lung 1976; 154:17-24 25 Zuskin E, Valic F, Skuric Z. Respimtory function in coffee workers. Br J Ind Med 1979; 36:117-22 26 Schachter EN, Buck MG, Zuskin E, Witek TJ, Beck GJ, Tyler D . Airway reactivity and cotton braxct induced bronchial obstruction. Chest 1985; 97:51-55 27 Lam S, Wong R, Yeung M. Nonspeci6c bronchial reactivity in occupational asthma. J Allergy Clio Immunol1979; 63:28-34

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