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/I ~ ~~ ~/~ i/j 7 , PEENYI, - METHYL - 07CADIAZOLE (Pt40) hS A TOBACCO~ADDZTIPE' Clinical and spirometric evaluation after six weeks smoking. Bg St'nre Bevegird andiTore 3Ia'1hamn From the Department of Clinical Physiology, Sodersjukhuaet,. 100 64 Stockholm 38 and the Institute of Hygiene, University of Uppsala. .

2 Phenyl-Methyl - Oxadiazole (PMO) has in extensive tosting on animals showed:oonsiderable anti-infl'amnatorr properties on the upper air-ways. Longt'esm~oral admini.stration of the drug to man has not revealed any toxic effects. The anti-inflammatory properties of PMO could thus be of clinical value for treatment of patients with upper air-way'disease, such as chronic bronchitis. In a recent study (Bevegdrd and h+h1hamn, 1976) the effects of inhalation of PMO'and:menthol on pulmonary function we.s evaluated. Inhalation of PMO per se caused no changes in pulmonary function as evaluated from dynamic spirometri and blood gases determined in arterial'ized blood. In ths present study Y,:O has been used as a:tobacco additive and its clinical and spirometric effects has been studied on ten healthy cigarette smokers. Ten healthy cigarette smokers constituted a control group. Material- Twenty healthy subjects, all cigarette smokers, were included in the study. There were eleven women and 9 men in the group. Ten subjects smoked cigarettes containing PMO and ten subjects smoked non-prepared cigarettes during a period of six weeks. dll subjects were smokers and smoke&between sixty and two hundred and fifty cigarettes per week. L

I4ethods and procedure: All subjects were examined with dynamic spirometri before ~ and after the six week period of smoking. The tests were performed on an Ohio-842 spirometer. Each subject was questioned about subjective symptomaduring the smoking period. Each subject got a week supply of cigarettes in advance and all the fag-ends were colleoted for later analysis of remaining PP10 content and as a check of the cigarette consumption6 Results: Effect sn s irome~ tric v~alue~s:'All subjects except two in the control group had essentially normal spirometria values both before and after the smoking period. In the control group case number 15 and 20 had a slight to moderate ventilatory restriction of restrictive type. The values for vital capacity, expiratory and inspiratory flows and maximal voluntary ventilation are given in table I. There were no significant differences concerning the spirometric values before and after the six week period of smoking cigarettes containing Pt40: In the control group the vital capacity, the FEV1.0 and the M9V 40 were slightly higher after the smoking period. The differences were small. Subjective s toms: Some subjects felt improved after the six week aaavs~aa~aa~ period both in the PMO and in the control group. Some subjects noted that the cigarettes had a bad taste but there was no difference between the PNlO and control group. In general there was no difference concerning subjective remarks between the Pi40 and control group.

4 uonotusions. In a group of ten subjects smoking cigarettes containing PM0 for six weeks (~70 to 201 cigarettes per week) there wera no significant differences concerning subjective symptoms or spirometric values before and after the period. In the control group of ten subjects smoking non-prepared cigarettes (60 - 253 cigarettes per week),vital capacity, FEP1.0 an&r1FV40 were slightly higher at the endiof the periods. In such a small material the occurrence of a slight upper air-way infection at the first occation could easily have such effects on the spiromet'ric values. There were no significant differences concerning subjective symptoms.

I /(,m Ltm Case no. 9C m 1.0 FEV% FIV 1,0 YIV% M7v 40 Mvv free With YMO B A~A B A B A B A B A B A B A 1. I.S. 3.40 3.80 3.00 2.92 86 77 3.10 2.53 89 67 92 94 86 1o6 2. J.K. 4.70 4.98 3.90 3.80 83 77 3.90 4.13 83 83 125 117 120 128 3. A.G. 4.68 4.89 3.96 3.91 .84 80 4.18 4.62 88 94 133 139 161 147 4. R.B. 3.91 4.57 3.08 3.47 79 76 3.08 4.48 79 98 116 117 116 132 5. J.K-E. 4.75 4.95 4.25 3.74 89 76 4.50 4.18 95 84 125 121 118 130 6. W,K. .5,42 5.83 4.20 4.51 77 77 5.05 5.61 93 96 158 177 185 179 7. A.U. 4.55 4.84 4.05 4.24 89 87 4.50 4.79 99 98 129 147 139 144 8. B.M. 4.51 3.69 3.36 3.47 75 83 4.07 3.47 9o 83 108 93 116 T01 a 9. B.A-C. 3.85 4.02 3.25 3.30 84 82 3.74 3.69 84 92 107 103 123 103 1o.,A.A. Mean 5.90 4.57 6.33 4.80 4.50 4.73 3.76 3.81 76 82.2 74 78.9 5.50 5.67 4.16 4.32 93 89.3 89 88.4 131 162 122.4 127.0 176 134.0 178 134.8 SD 0.74 0.85 0.54 0,56 5.18 4.01 0.77 0.95 6.06 9.56 18.0 28.5 31•0 2a.I B-A -0.23 -0.05 3.30 -0,16 0.90 -4.nq -0.80 SD 0.40 0.26 5.56 0.59 11.22 14-13 13.92 t -1.81 -0.66 1.88 -0.82 0.25 -.1.03 -0.18 n.a. n.s. n.s. n.s. n,s. n.s. n.s. I eVC9soou 2

I I Case no. VC FEV 1.0 Fm FIV 1.0 Y.[V% Mw 40 Mvvfree Without PMO B A B A B A B A B A B A B A 11. M.G 5.78 6.00 4.84 4.84 81 78 5.83 6.11 98 98 156 159 172 173 12. s.R-M. 4.30 4.73 3.30 3.47 75 72 4.10 4.46 93 93 105 116 114 111 13. S.c. 4.65 4.95 3.80 4.02 82 81 4.40 4.73 95 96 120 130 119 130 14. B.K. 3.85 4.29 3.36 3.41 85 79 3.85 4.07 97 95 116 117 125 125 15. A.N. 3.30 3.30 2.30 2.26 70 68 2.45 1.93 74 58 75 75 87 86 16. K.L. 4.90 5.45 4.00 4.32 84 79 4.70 4.95 96 91 123 127 117 126 17. E.B. 3.63 4.48 3.30 3.41 91 76 2.20 3.19 61 71 103 102 122 111 18. A.M-L. 4.46 4.68 3.14 3.63 70 78 4.13 4.26 93 91 116 123 125 131 19. R.rf. 4.07 4.62 3.74 3.82 87 83 4.13 3.93 96 85 1o9 114 131 121 20. B.E. 2.60 2.64 1.70 1.71 64 58 2.30 1.93 87 66 52 61 55 52 Mean 4.15 4.51 3.35 3.49 78.9 75.2 3.81 3.96 89.0 84.4 107.5 112.4 116.7 116.7 SD 0.89 0.97 0.87 0.92 8.72 7-.44 1.17 1.31 12.1 14.2 28.0 27.9 30.06 31.48 ~ B-A -0.36 -0.14 3.70 -0.15 4.60 -4.90 0.10 SD 0.26 0.16 5.66 0.43 9•07 4.25 7.29 t -4.41 -2.71 2.07 -1.08 1.60 -3.64 0.04 nc x n.e. n.e. n.s. xoc n.s. 11 6vE96v00

PMO 2fl1 st/vecka 0 problem {{AA-o Marita Boberg Annie-Britt Dr~ 1 Mot.Aof hs~ t rr"f 4 k 'i munnen ~~.~ ~~ ur ~ «*r+~-u 70 st/ve'dka SvedA 1 mun och c~h hals ~ 4-c~ u~ . c vd •T 76 st/vecka _Andningen lattare 140 st/vecka -0-problem i . 68 st/vecka ,pV,7+IJ2.,~ Torr "~ ha1 en Rethosta eft 175 st/ve a Smakar brand film 133 st~ka2 v Sveda pa tungan forsta veckorna. Rokhosta forsta veckorna. ju r wvy ~+s.~-y a, -f vw.~.,t f., `~ yvax~. . 181 ~st~/veAa l Dalig doft av fimparna. Smaken bra. Oftare roksugen. Rokhosta som tidigare aret okat. Cig. gar att av. kbe R ~ .. ', ~~tx[~ ?~- ' 179 st/vecka fc.k EcSr"! SvArfimpade. Hostan pa morgonen uteblivit. Mindre slem i halsen. Dc_ V~Q F . EV ,~rue-d ~,v~pc~ ,v~Cuu,e_ 1` r U -/

,,. . 0-,gr-uP2en_ i 1. Mona-Lisa Andersson 179st/vecka ~ • ' " Smakar parfym. IngPn rokbaksmalla . 2. Lena Karrdal ~- ,Svarf impade. Ln1kta ~ i~, RCikt m~era.' ~~ /`~ ~ er~- : No rro~w~ r"!~4 129 st/vecka . Nils Andersson Smakar illa. Rethosta (efter 8.l.i.) 163 st/vecka Luxtar e) Ztta. Tungbrostaa'. smakar battre men lukta (vectk~ 4). Askan ramlar av. ~,._. :f---~---~ . Gunilla Sandler 129 st/vecka T 5. Rose-Marie Sigrell Y . Ketty Berger ~ 7. Elof Bjorkman Y a '1' kl ' 1 k d kh t t K t Torr~ h~ps~ta bland (efter d.l.i.) ~ vf f A"/ Ihf .` 164 st/veck a Latt rethosta sista veckan 60 st/vecka 0 problem 140 st/vecka Bnl. frun bA'ttrg jraga om rokhosta Birdie Hasselstr8m 84 st/vec?fa ' 6 veckors torrhosta. Smakar ej tobak. orr i halsen. Magen p$verkad (diarrd i tre dagar) A..ic-74,,vd l-.tt. . Goran Melinder 253 st/vecka Otack mak i munnen• - Y 101. Marianne Rosander 175 st/vecka aen e ro os . Fami jen agar pa u en. vars Latt illamaende_ Mindre torr i munnen. Smakar pyton. Inf. i tandkottet. ~- ~