TABLE A2.-Smoking and chronic obstructive pzclmonary disense s?/,,rpto,t,s'-percent p~c~~vzlenw (cont.) (Numbers ia pnrentheses represent total number of individuals in particular smoking group) SM = Smokers. NS = Nonsmokers. EX z Ex-smokers. Author, war, countiT, reference Number and type of population Cough Sputum production Breathlessness or dyspnea Chest illnesses Other Comments Wynder 315 male New York Citg et al., patients in NS .14.0 (44) 1965 New York City Pipe, cigar 33.0 (64) U.S.A. and 315 male Cigarettes: (298). patients in l-10 ..45.0 (44) California. 10-20 .46.0 (38) >20 . .67.0 (86) California NS . . ..22.0 (69) Pipe. cigar 30.0 (32) Cigarettes: l-10 ..45.0 (64) IO-20 . ..74.0 (91) >20 .14.0 (69) Fre0llr 1,055 randomly Cli~iical signs of et al., chosen males in bronchitis and 1966 Bordeaux 3s-70 rcspiratorU Fi-ZUlC.? years of age. insrcficienry (92). NS 25.4 (46) SM ._ 54.4 (4781 Haynes, 179 male Aacmgr number of Hea\ et al.. preparatory *cwrr rrugiratory StIlOkel- 1966 school illrfcsscs per 10 mure than U.S.A. students studcllts (adjuatcd 10 cign- (108). 14.-19 yeam for flw) rettes of nge. NS 0.36 per day. All smokers 2.30 Heavy SM 3.34 : TABLE A2.-Smoking and chronic obstructive pulmonary disease symptoms'-percent prevalence (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) SM = Smokers. NS = Nonsmokers. EX = Ex-smokers. Author, Y-S-. country, reference N,y;F$nd population Cough Sputum production Breathlessness or dyspnea Chest illnesses Other Comments Dellsen 6.313 male Post& Poetal Postal Dyspnea et al.. and 7,291 NS . . . 7.0 (903) 13.1 19.8 represented 1967, female postal Pipe. cigar 12.4 (628) 17.4 24.8 by Grade II U.S.A. and transit Cigarettes Only. (68). workers. only . .27.0(2,687) 28.9 31.7 Transit Transit Transit NS . .,... 6.4(1,012) 9.6 11.7 Pipe, cigar 10.6 (`766) 14.1 14.2 Cigarettes only . . ..23.6(3.'746) 23.7 21.9 Higgins 926 white NS . . . . ...16.4 (162) NS........... 31.1 NS . . . . . . . 6.0 et al., male resi- SM . . . . ...47.2 (613) SM _. . . 46.2 SM . . . .10.7 1968, dents of EX .19.3 (144) EX ,285 EX . . . . . . . . ...16.8 U.S.A. Marion (128). County, West Virginia, 26-69 years of age. Holland 9,786 male M&8 F`DJZ&?~ Males Ft3lWlt% and and female NS . . . . . . 3.8(1,900) 3.2t3.137) 2.4 2.1 Elliott. school SM . . . . 6.3(1,098) 6.3 (664) 6.1 8.3 1968. children. EX . . . . . 2.9(1,782) 4.3(1,161) 39 4.2 England 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . ..9.9(142) 18.8 TAULE A2 .-Smoking and chronic obstmutive pulmonary disease sZ/,)lpto,,rs'-percent pw~vzlence (cont.) (Numbera in parentheses represent total number of individuals in particular smoking group) SM = Smokers. NS = Nonsmokers. EX = Ex-smokers. Author, year, Number and Breathlessness country, type of Cough Sputum production or dyspnea Chest illnesses Other comments reference pORUlS2tiOZl Gandevia 762 male and M&8 Productive 1969 1,304 female NS . . .10.3 (234) cough upon Australia patients SM .61.3 (628) reuueat. (93). from 13 general Fslnd`S9 practices NS . . .10.6 (867) in all parts of SM . .31.4 (447) Australia. Rimington 41,729 male 1969 and 22,295 England female persons (199). participating in mass miniature radiography screening. Wilhelmsen 313 males et al., 6&64 years 1969, of age randomly Sweden S~lllDkd fro", (251). population of Gateborg. Age-adjusted total Cigarette prevalence of dosage chronic bronchitis gradient M&8 significant NS 5.1 (9.066) to P20 .20.6 Ft2?Mks NS _. 3.4(12.361) EX ., 3.8 (969) Pipe ._ 0.0 Cigarettes (8,986) 1.. 9 6.1 lo-19 10.6 >20 . .18.6 Chkric bronchitis NS ._ 1.0 (88) EX _. 3.0 (61) 1-14 grams/ day 6.0 (94) >16 . . ...17.0 (64) Author, Year, CountrY, reference Number and type of population Sputum production Breathlessness Chest illnesses or dyspnea .___- Lnmhert 9,975 malt I'( rxiatcjlt cough nnd phlegm and and female Alnlrs Reid, reslKmdrrs Rl ............... 27.7 27.7 16.8 Sriences Twin Pipe, ci!z?ar ............. 1.1 7.1 2.7 No ex-smoken included in C.mur, B analysis. The authors conclude that the data indicate R strong probability of a causal connection with smoking. Even Rwistty (of Group R: NS SM NS SM these symptoms. 9,oni) nvial- MZ .,, ., ., _. .._ 2.4 5.4 1.8 4.8 however, seem to be nhlr) nz ., 2.0 9.8 1.6 9.1 influenced by genetic factors. ' Data collected by either dirert interview, questionnaire, review of medical records and/or medical examination. TABLE A3.-Smoking and ventilatory function (Numbers in parcntheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. Author, ye==. country. reference Chivers, 1959, Enaland (52). Number and type of population MBC EFR FEV vc Miscellaneous COllllll~llt6 463 malr Height-in-inches iMean EFR employees Cigarettes/day: 64" 66" 68" 70" in liters of alkaline o-5 . t97(28) 91 (35) 108 (31) lOl(21) per minute. industry 6-20 . . .._ 89(50) xx (75) 101 (112) 109 (76) Regression plant. >20 ..t .._... 63 (6) 88.5 (9) 92.5 (9) 113(12) analysis of data revealed a significant re- lationship between smoking and de- creasing function. Higgins 773 males 25-94 55-a expressed et al., in various NS 145 (66) 101 (29) FEVO 75 as &an indirect 1959, occupations EX 143 (31) 89 (62) MBC. Enaland (25-34 and 1-14 gr*nls (116). 65-64 years .140(193) R7(167) of age). >lS mxms ,133 (89) 80(136) ___- Wilson 28 male RV/TLC et al., residents of NS 6.69 (14)NS . . . . . . 21.1 1960 Dallns, SM a4.44 (14)SM . . . . . 227.01 U.S.A. TtZX*?,, (232). former rural dwellers; matched for hody surface. a$?.?, and height. TABLE A3.-Smoking an,d ventilatorp function (cont.) (Numbers in parentheses represent total number of individusls in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. Author. Ye*=, Number and country, MBC reference type of EFR FEV oooulation vc Miscellaneous CO~llXtllts Ashford 4,014 male et al., gEsv* .o Data represent coal workers Age: SM results after 1961, at 3 Scottish <21-30 4.09(103) 3.96(280) correction for Scotland collieries. 21-30 .3.86(182) 3.77(665) (11). sitting height. 31-40 .3.44(138) 3.88(777) SM includes pipe 41-50 . 3.04 (110) 2.96 (756) smoker. 51-60 .2.71(102) 2.66(610) Data on ex-smoker >60 . ..2.38 (42) 2.21(237) not included. FEVl o found &&cant; lower for SM than NS. Fletcher 363 msle Mean mak EFR and London NS . . __. 670 (30) Tinker, transport 1-14 grams 637(166) 1961, employees. >I6 grams 6!28(116) England EX . . . . . 666 (61) (85). Franklin 213 male Hesvv smoker and factory J-vi .o "",o.;; y.;g Lowell. workers HWNY 2,670 3,611 Light `2,489 2,716 Light . . 3,703 (69) represents *n 1961, 40-60 years *2.666 `2.284 Heavy .`3,678(104) *mount equal to or more U.S.A. of age. than 30 pack (87). ye*lY. TABLE A3.-Smoking and wentilator~ function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. Author. Yew. Number and country, type of MBC reference population EFR FEV vc Miscellaneous Comments Balchum 1.451 male MMEFR et al.. employees NS 16.6 (38) 1962, in Pack/year: U.S.A. California 60 71.0 (24) 7.8(19) 8.0 6.0 12.0 24.0 26.0 40.0 45.0 62.0 Data for: MMEFR given as percent of individrmls with a value of <500 L/M; FEVl.O given as percent of individuals with value of <70 percent of expected. Goldsmith 3,311 active et al., or retired 1962, longshow- U.S.A. men. (95). MEFR NS . . . . . . ..313.63(260) Pipe, cigar 299.26 (126) EX . . 295.23(102) Cigarettes/day: crzo..... 309.73(144) 20-40 . 303.44(346) 240..... 307.63 (67) 2.80 2.84 2.89 2.91 2.90 Authors concluded that cigarette smoke WBS found to have B slight effect on pulmonary function. Martt. 73 healthy 1962. medic"1 per- DLCO Smokers defined U.S.A. sonnel with- NS . . . . . 33.10(30) asthosesmoki"g (162). out signifi- SM 20cigarettes' cant age 6-10 yesrs .328.20(10) day for varyi"a difference >lO years .624.90(25) periods. between smokers and nonsmokers. TABLE A3.-Smoking at&d uetitikLtOv:J function (cont.) (Numbers in parcntheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. .- Author. Ye=-, Number and c0untl-Y. type of MBC EFR FEV vc Miscellaneous Comme"ts reference population Revotskie 1,130 male FEV*.o Data presented et al.. and 1,813 M&8 FETMlt!S in terms of 1962, U.S.A. (192). Krumholz et al., 1964, U.S.A (140). female residents in Framing- ham par- ticipating in the pro- spcctive study. ~. 18 physicians 24-37 years of age. NS . . .0.98 (65) Cigarettes/day: l-10 .0.9? (SO) IO-29 .0.91(163) >30 .0.90 (81) - MEFR NS ........ 680 (9) SM ........ `690 (9) 0.98(255) 0.99 (92) 0.93(157) 0.91 (22) ratio of observed to predicted values. - .-___ ~__ Mean DL NS SM Rest . . . . . . ...36 231 Exercise: 2 minutes .SO 341 4 minutes .60 '43 Zwi 20 medical MMEFR 3 minutes Dost exercise 39 '35 Authors found et al., 1964, U.S.A. (241). studentsor NS _.. 187 (10) graduate SM. .`193 (10) physicians. 4.34 `6.09 6.77 15.53 a sipnifirant difference betwrcn SM and NS for RV `TLC, complianre. and non- elastic resistance. Coates 1,342 male et al., and 242 Age: FEV1.0 Timed VC' FEVl.O/VC NS >SS &/day NS >.25/day NS >25/ahl 1965, female post 40-44 `2.99(186) 2.85 (69) 3.89 3.85 30.77 0.74 U.S.A. office 46-49 52.95(170) 2.64 (42) 3.92 3.83 30.74 0.70 (53). employees 60-64 '2.75(116) 2.62 (22) 3.71 3.74 '0.74 0.70 >40years 66-69 '2.64 (64) 2.44 (18) 3.54 3.61 so.74 0.68 of sge. 60-64 '2.35 (53) 2.30 (8) 3.30 3.33 '0.72 0.70 .- qQ?o! z3 . -. : . . gii :cB p- `d oi 2',0 : *. . . : : : : : : . . . I "F% Zm TABLE A3.-Smoking ad vmtilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. Author, Ye=-, Number and country, type of MBC reference population Edelman et al.. 1966, U.S.A. (79). 410 male community NS . . . . 164 ( 162 ) dwellers current ar- 103 cigarette years of smokers. . 6 161(118) *ge. EX . . . . . . . ., 167 (98, Pipe, cigar . 167 (47) EFR FEV vc Miscellaneous COllllll~!ltS 1.89 7.86 8.09 8.20 yp.0 12.64 2.80 2.91 vitai capacity 4.93 * 4.14 4.17 6.08 Ex-smokers of cigarettes only. Difference signifi- cant between NS and current cigarette smokers fit p26 . 8.30(160) 20-69 years of age. TABLE A3.-Smoking and wentilator~/ function (cont.) Author. (Numbers in parerltheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. year, Number and country. type of reference pornllation Sluis- 53Fwhite Cremrr malr and filrtory Sichel, workers 106X. over 35 South years of Africa REV. (208). MBC EFR FEV vc Miscellaneous J-44 45-54 >55 NY 553(106) 627(101) FEVf .o 444(27) ss-44 45-54 >a5 Crams/day: 3.70 3.22 2.76 l-14 557 (26) 619 (17) 410 (7) 3.64 3.31 2.24 15-24 532 (94) 446 (35) 401(13) 3.66 2.94 2.28 >?,S t52R (66) t494 (31) t380(10) 3.64 3.05 t2.12 Commrnts 1 cigarette: 1 gram. 1 ounce tobacco = 26 granls. 1 cigar = 2 to 5 grams. t Derived slopes found signifi- cantly different from 0. stanescu a7 malt bus F'EV. Nitrogen gradient et al.. drivers; ~ 1." _.. Yow1gcr Older YoNnger Older Younger Older 1963, 27 aged NS 4,470(14) 3,310(40) 6,125 4,290 1.63 2.49 Rumania 20-25, 60 SM 4,500(13) `3,200(20) `5.285 `4.290 11.47 5 3.77 (919). wed 40-60, all without respiratory symptoms. ___- - Dense" 5,287 male Fj:V. _-- FEV expressed as et al., 1969, U.S.A. (89). postal and 7,213 mnle transit workers in New York City. NS All cigarette <25 grams/day 225 awns/day Pos:~~ Wh itr. 3.29 (685) 3.11(2,340) 3.14 (1,292) 3.06 (1.038) Transit White 3.39 (620) 3.11(2.941) 3.15(1.929) 3.02(1,011) NS .................................... All cigarette ............................ <26 grams/dsy ......................... 225 grams/day ........................... - Non-zuhitc 3.05 (204) 2.94 (768) 2.96 (693) 2.93 (161) Now-white 3.08 (298) 2.99(1.041) 3.00 (891) 2.96 (149) standardized for specilied postal and transit workers at age 45 and at sitting height of 35 inches. Includes mixed smokers. TABLE A3.--Smoking md ventilatoq function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. -- Author, war. count.lY. Nutn$r;nd MRC EFR FEV vc Miscellaneous COltllll~llts reference Dopulation _ FEvl.O FEV expressed as NS _. .`97.6 (12) percent of SM _. 78.4 (58) predicted value for age, sex, and height. Rankin 60 male et al., and 10 1969, female Australia patients (190). with chronic alcoholism 26-66 years of age. Wilhelmsen 313 male et al.. residents 1969, of Giiteburg Sweden 50-54 years (231). of age. __~ Lefcoe 310 male and physicians w<1nna- of London. rott, Ontario. 1970, Canada (151). PEFR VC 1963 values only NS ........................... 525(M) 4.83 EX ........................... 539(67) 3.69 4.71 1-14 grams/day ................ 521(94) 3.62 4.33 >15 grams/day ................ 492 (64) 3.39 4.56 MMFR NS . . 4.09 (88) Cigarette smokers. 3.64(101) EX 3.99 (61) Pipe, cigar 4.17 (33) MMFR has been standardized for age and height. TABLE A3.-Smoking and ventilatorp function (cont.) Author, Year, country, reference (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers. EX = Ex-smokers. FEV Miscellaneous Comments Lundman, 1966. SWNkll (159). 31 MZ and 62 DZ twin pairs selected from Swedish Twin-Pair Registry. FE"1.0 Significant diflerences between smoking discordant twin pairs found for: 1. Group A MZ males and females. N2 washout gradient Significant differences between smoking dis- cordant twin pairs found for: Group B DZ males. MZ = monozygotic. DZ = dizygotie. The author concludes that the degree of ventilation as measured by Nz washout was correlated with cigarette consumption. The FEVleO was significantly lower for smokers and there was a correlation with cigarette consumption. Explanation of analyses for respiratory symptom prevalence: Group A analysis-using each firstborn twin aa one group in an unmatched relationship to each secondhorn twin. Group B analysis-using each twin set as matched pair. All comparisons in Group A and B are between smoking-discor- dant pairs. 2. Group B DZ males. 3. Group A DZ males. 1 Not significant (difference or trend) 2 p- ,)mptoms could not be explained by social class differences. (b) No overail association noted betwpen productive cough and air pollution. Coolev and Reid, 1970. England (58). Lambert and Reid, 1970, England (146). 10.X87 children G-10 years of ape from eon- trasting urban and rural areas. Illnesses considered included chronic cough, past bronchitis, blocked nose. (a) Every geographic area showed a clear gradient of in- creasing illness prevalence with decreasing social class. ,b) Social classes I, II, and III showed no urban:rural gradient while IV and V showed a clear excess in fre- quency of chest illnesses among urban residents over rural residents. 8,975 males and (a 1 The trend of increasing prevalence of bronchitic sump- females tams from rural to urban respondents was not negated responding by adjustment for smoking differencff. to questionnaire ib) After adJuetme"t for age and smoking habits. male S"I`VCY. respondents manifested a clear correlation of persistent cough and phlegm prevalence with increasing air pollu- tion. Correlation was not BS striking in females. (c) Although the proportionate rise in symptom preva- lence increased with air pollution similarly in each smok- ing group, the absolute differences in morbidity risk in- creased with increased cigarette consumption, suggffting synergistic influences of cigarette smoking and air pollu- tion. (d) In the absence of cigarette smoking, the correlation between the prevalence of persistent cough and phlegm and air pollution was slight. ' See GIossary of Terms: Bronrhopulmonary table A4. 217 TABLE A~.--E'l,idr?lriological st1idie.S ConCW?Ling the rehtionship of OCCUpatiOnal ezposwrc and smoking to chronic obstructive bonchopul~~~onary disease Author, Ye=-, c0u"tl-Y. reference Number and type of population Results Higgins 135 males Miners showed increased symptom prevalence (breathless- et al. (84nonminers. ness, cough, sputum). 1956, 101 miners) Miners showed increased prevalence of chronic bronchitis. England without pneumo- Miners showed decreased MBC.' (119). eoniosis. Differences in smoking between the two groups did not a~- count for above differences. Phillips 1.274 males None of the-industrial environments were associated wiz et al.. factory emplowes an increased prevalence of chronic cough. 1956, (coke and Cigarette smoking and age were directly correlated with U.S.A. electrolytic increased prevalence of chronic cough. (18.5). process 1. Higgins 325 males 25-34 Miners as compared to workers in non-dusty occupations: et al., years of age and 25-34 years of age-significantly increased prevalence of 1959, 401 males 55-64 chronic bronchitis and MBC abnormalities. England years of age in X-64 years of age-less significantly increased prevalence (116). various "ccupa- of chronic bronchitis and MBC abnormalities than in tions. 25-34 years of age group. No smoking information available. Chivers, 1959, England (5%). 463 males in No significant differences in PEFR' between dusty and non-dusty and non-dusty Pl`""PS. dusty occupations Cigarette smoking (especially in those >40 years of age) (lime and soda was associated with decreased PEFR values. ash exposure). Higgins 300 male miners Miners showed increased prevalence of symptoms and de- and and 300 male creased MBC values which remained even after standard. Cochrane, nonminers 35-64 ization for smoking habits. 1961, yeal of age. Total dust exposure was not directly correlated with these England findings. (115). Wives of miners showed similar symptom and test change. as compared with wives of nonminers. Brinkman and Coates. 1962, U.S.A. (42). 1.31'7 males 40-65 years of age with various silica exposure histories. Increased silica exposure was associated with an increased prevalence of chmnic bronchitis. Highest prevalence of chronic bronchitis was noted in the non-exposed group; and this group was noted to have the highest number of smokers and highest consumption. Hyatt et al., 1964. U.S.A. (1.28). 261 male miners and ex-miners 4s55years of age. Increased history of underground work was associated with an increased broncbopulmonarv symptom prevalence and decreased pulmonary function values. The impairment of pulmonary function associated with underground work was separate from effect of smoking; but smoking and underground work did show additive effects. ElW""d et al., 1965. Ireland (77). 2,525 male and female flax workers over 35 years of age. Preparing room workers who manifested byssinosis symp- tams also showed an increased prevalence of chronic bronchitis independent of age or smoking when compared with non-preparing room workers. Female workers manifested a significant association be- tween byssinosis symptoms and smoking while msle work- ers did not. Sluis-Cremer 827 miners and et al., nonminers over 1967. 35 years of age. South Africa (ZO9). Those smokers exposed to gold mine dust manifested more symptoms of CQPD 1 than did non-dust exposed smokers. while prevalence of symptoms, among nonsmokers. was similar for the two groups. 218 TABLE A7.-Epidemiological studies concerning the relationship of occupational exposure and smoking to chronic obstructive bronchopulmonary disease (cont.) Author, Ye==. countlY, reference Number and tYDe Of population Results Sluis-Cramer X27 miners and The dose relationship of cigarettes and COPD 1 symptoms et al., 1967, nonminers over wss much more noticeable among those exposed to dust. South Africa 35 years of age. Thr authors stressed the synergistic actions of cigarette (2OY). (cont.) smoking and dust exposure. Bouhuys et al., 1969, U.S.A. (39). 455 male cotton Those exposed to dust manifested a significantly greater textile workers prevalence of byssinosis symptoms than nonexposed. (214 exposed to Smokers manifested a significantly greater prevalence of dust in carding byssinosis symptoms than nonsmokers. and spinning No significant differences in Monday morning FEV' values rooms, 241 not were observed between smokers and nonsmokers. exposed) Prevalence of byssinosis symptoms did not show any re- lationship to length of employment. Bouhuys et al,. 1969, U.S.A. (38). 216 male hemp Hemp workers (especially the older ones) were noted to workers and 247 have different smoking habits from control group--fewer workers in other heavy smokers. more light smokers, more ex-smokers due industries in to doctor's orders. ssme region, Aged 20-49 - a. No difference in FEV1.9' values. between 20-69 year?, controls and hemp workers in any smok- of sge. ing category. b. No difference in FEV1.o values between men in different smoking categories. Aged 59-69 - 3. Hemp workers manifested decreased FEV1.9 values in all smoking groups except for heaviest smokers. Ex-smok- ers had lowest FEVI.o values. h. Those smoking most had lower FEVI.9 values as compared with light and non- smokers. The authors conclude that: There appears to be no synergism between smoking and hemp exposure as to effect on FEV,.o although the selection process whereby those with symptoms have o greater tendency to stop smoking may obscure such a relationship. Chester et al., 1969. U.S.A. (49). 139 male chlorine Chlorine-exposed group manifested no difference in symp- plant workers toms and a decreased MBC value when compared with (55 with history non-exposed group. ofsevereex- Smokers in chlorine-exposed group had significantly de- posure). creased MBC and FEV values as compared with non- smokers in non-exposed group. Greenberg 121 workers in et al., washing powder Sensitized group manifested lower FEV1.o/FVC' values as compared with nonsensitized group even after smok- 1970. factory (48 found ing habits w'ere controlled for. England to be sensitized (97). to product, 73notj. Tokuhat" et al., 1910, U.S.A. (218). 801 male miners Increased mine exposure was associated with residual vol- "me and FEV abnormalities even after adjustments for age and smoking. A systematic exposure-impairment relationship wss noted only among smokers while relatively few nonsmokers showed COPD impairment, Smoking miners manifffted more X-ray alterations and COPD symptoms than nonsmokers. regardless of num- ber of years of underground exposure. r See Glossary of Terms in Bronchopulmonary table A4. 219 Author. sea=, countrY. reference Animal Results Freeman and Haydon. 1964 U.S.A. (90). Spi-agUe-DaWleY rats. 23 p.g.m.: (a, after 37-41 days-moderate hypertrophy and hyper- plasitl uf bronchial anil bmnchiolar egithelium. (b) after 146-157 days-[ 1) Advanced hypertrophy and hyperplasia of bronchial and bronchi&x epithelium. (2) Increased lung volume. (3) Proliferation of Connective tissue. HlWd@ll et al.. 1965 U.S.A. (107). Haydon et al.. 1967 U.S.A. (106). Sprague-Dawley rats. 12.~ p.p.m. to death: !a) Mrpertrophy and occasional metaplasia of bronchial and hronchiolar epithelium. (b) Increase in number of actively secreting goblet cells. -- ___lll Albino rabbits. g-12 p.p.m. for 4 months: ia) Abnormal dilatation of peripheral air spaces. (b) Decreased density of alveolar walls. (c) Hrpertrophy and hyperDlasia of bronchial epithelium (especially terminal bronchiolar) (d) Increase in size of alveolar ducts. le) Increased elastic tissue staining. (f ) Increased alveolar size. Freeman et al.. 1968. U.S.A. (91). Sprague-Dawley rats. 0.8 p.p.m.-2 p.pm. for entire lifespan: (a) Alveolar distention. (b) Reduction in number of cilia. (c) Epithelial inactivity ("dormancy"). Freeman et al., 1968. U.S.A. (89). Spra!qx-Dawley rats. 18 p.p.m. (a.1 5 days-terminal bronchiolar rpithelial hypertrophy. (b) 4 weeks- ( 1) Widespread bronchiolar epithelial hy- pertrophy. (2) Non-necrotizing emphysema. Blair et al., 1969, U.S.A. (32). Female Swiss Albino mice. Kleinerman, Male Syrian Golden 1970. hamsters. U.S.A. (136). 0.5 p.p.m.: la) 6 hours'dav for 3 months-pneumonitis. (b) 24 hours/day for 3 months- (1) Respiratory bronchi- alar obstruction. (2) Alveolar expansion and brnnchiolar inflammation con- sistent with early focal emphysema. 100 p.p.m. for 5'2 hours: (a) thymidine autoradiography-intense burst of prolif. eration of epithelium returning to normal in 4 days (more persistent distally). (b) electron microscope-( 1) Decreased number of se- cretory cells + secretory granules. (2) Increased number of lyso- somal structures. (3 ) No change in number of ciliated cells. 220 TARLE AlS.---Experimrxts concerning the effect of cigarette smoke or its constituents upon ciliary function Author, ye==, countrr, reference System Method ' Results Mendenhall In vitro: Cigarette smoke ControlsPciliary activity depressed spproxi- and Calf trachea. by direct appli- mateI\. 4 percent. Shreeve. cation or in Experimental&ciliary activity depressed a~- 1937, solution. proximately 40 percent. U.S.A. (164). Rakieten In vitro: I. Nicotine in I. Ciliary activity depressed only upon ea- et al.. (a) rabbit Locke-Ringers posui-e to 100 mg. percent solution. 1942, and rat solution. II. Ciliary activity dwressed after 15-20 min- U.S.A. trachael II. Cigarette smoke utes exposure depending on concentration (188). rings. in solution. of smoke in solution. (b) human nasal Ill"C"llS membrane Kordik III vitro: Nicotine in Locke's Nicotine at 1O--5 g,:cc had no effect on CiliarY et al., Rabbit solution. 1952, trachea England (137). Hilding, In vitro: Cigarette smoke 1956. Cow trachea (direct U.S.A. exposure). (120). Krueger and Smith, 1958, U.S.A. (139). In viuo: Rabbit trachea Cig.arette smoke. Dalhamn, 111 uiz.0: Cigarette smoke. 1959, I. Rat Sweden trachea (59). In t&-o: II. Rabbit trachea III. Humafi ciliated lll"~"SZl &lk In vitro: Cigarette smoke. et al.. Rat and rabbit 1959 tracheal U.S.A. epithelium. (80). Railenger, In i.itro: Cigarette smoke 1960, H11mall in solution. U.S.A. bronchial (25). and tracheal epithelium obtained during anesthesia. activity. All tracheas showed depressed or absent ciliary activity. Cigarette smoke decreased ciliary activity by approximately 200 beats/minute. I. T/10 showed cessation of ciliaw activity after one exposure. II. 6:lO showed cessation of ciliary activity after one exposure. III. fi/T showed cessation of ciliary activity after one cigarette exposure. Decreased ciliary activity noted on exposure to cigarette smoke: (a) Repetitive exposure was associated with persistence of response over longer periods of time. (b f "Tar"-rich cigarette was more inhibitory than "tar'`-poor. (P) Filtered smoke was less inhibitory than unfiltered. Ciliary activity was fully inhibited within 5-28 minutes of exposure depending upon concen- tration <,I smoke in solution. 221 TABLE A13.-Eeperiments concerning the effect of cagarette smoke or its constituents upon diary function (cont.) Author, year. country, reference system Method 1 Results Wynder et al., 1963, U.S.A. (236). In viva: Cigarette smoke; Unfiltered cigarette smoke--eiliastaais by 2ud- Fresh water and its fractions 5th puff. ItlUSSd in solution. Acid (phenolic) fraction solution-immediate ciliated ciliastasis. epithelium. Whole extract fraction solution-no cilia&& Neutral fraction solution-no ciliastasis. 1 percent phenol solution-immediate ciliast+ sis. Dalhamn In viva: Cigarette smoke. Unfiltered cigarettes-ciliastasis in 3/S cati and Cat trachea. after 5 cigarettes. Rylander. Filtered cigarettes-no ciliastasis after 8 cig+ 1964, rettes (5 cats). Sweden Controls-no ciliastasis (5 eats). (61). Ballenger In vitro: Nicotine in solution. Initial stimulation of activity followed by de- et al., Human cline and complete ciliastasis after 12-24 1965, ciliated hours of exposure. U.S.A. tracheal (26). epithelium obtained during. anesthesia. Dslhamn In viva: Cigarette smoke. The longer the time interval between expo- and cat tracklea. sures, the more puffs were required to cause Rylander, ciliastasis. 1965, Sweden (62). Wynder In vim: Various compounds Formic, acetic, propionic, benzoic acids all et al., Fresh water in solution. more ciliatoxic than phenol. 1965, mussel Oxalic acid lass ciliatoxic than phenol. U.S.A. ciliated Formaldehyde, acrolein more ciliatoxic than (235). epithelium phenol. C!XSO" In viva: Cigarette smoke. Percent decrease in ciliamy activity et al.. Cat trachea. Control . . . . 0 1966, Unfiltered smoke . . . 53 U.S.A. cell"lose acetate filter . . 46 (44). Carbon cellulose acetate filter . . 30 Dalhamn. h viva: Cigarette smoke. Mean number of puffs required to produce 1966, Cat trachea. ciIiastiai8 Sweden No filter ................................ 91 (60). Charcoal filter .......................... 170 Commercial cellulose acetate filter ........ 194 Charcoal and acetate filter .............. 512 Cambridge filter ........................ 600 Kensler In vioo: Cigarette smoke Rabbit trachea-Total smoke condensate of 3 and Rabbit and components cigarettes. gas phase condensate of 7 ciga- Battista, trachea, in Tyrode's rettes caused similar ciliastasis. 1966. cat trachea, solution. Other species--All found sensitive to ciliastatic U.S.A. dog trachea, components of cigarette smoke. Bulk of ac- (lS5). monkey tivity noted in gas phase (HCH. formalde- trachea. hyde, acrolein) rat trachea. 222 TABLE A13.-Experiments concerning the effect of cigarette smoke or its constituents upon diary function (cont.) Author, Y-r, countrY. reference system Method 1 Dalhamn In viva: Cellulose aeetate- and Cat trachea. filter cigarettes Rylander, with varying 1967. amounts of Sweden "tar" but simi- C-55). lar gas phases. D*lh*"ln In viva: and Cat trachea. Rylander, 1968, Sweden (64). Unfiltered and Cambridge-filter cigarettes. Resu1t.s Increased amounts of tar were associated with decreased number of puffs required to inhibit eiliary sctivity. Whole smoke found to be markedly more toxic to ciliary activity than volatile (gas) phase at lower dosages (puff volume). This differ- ence diminishes with increasing puff volume. Kaminski In viva: Whole and filtered Wet chamber adsorption significantly reduced et al.. Cat trachea. cigarette smoke the ciliastatic activity of whole smoke, but 1968, exposed or unex- did not affect the ciliastatic activity of smoke U.S.A. posed to "wet previously filtered by Cambridge or charcoal (183). chamber" made filters. to stimulate oral mueosa and saliva. Krahl In viva: Cigarette smoke Significant ciliastasis. reversible. and Common dissolved in Buhnash. molluek sea water. 1969. ciliated U.S.A. epithelium. (188). Battista In vitro: Cigarette smoke The authors observed that: and Chicken or HCN in (1) The more diluted smoke required more Kensler, tracheal TYrode'e puffs to cause ciliastasis. 1970, epithelium. solution. (2) Activated charcoal filtered smoke was U.S.A. less ciliastatic than cellulose acetate filtered (2.3). smoke and also contained less HCN and acrolein. (3) HCN alone was ciliastatic but recovery was more rapid than after cigarette smoke alone. They conclude that the gas phase components are more related to ciliastasis (as particulate matter is not significantly decreased by char- coal filtration while HCN and acrolein are). Battista In viva: Cigarette smoke. The authors observed that: and Hen trachea. (1) Whole smoke acutely depressed ciliarv Kensler, activity in 4-6 puffs. 1970. (2) Gas phase was only slightly less depres- U.S.A. sant than whole smoke. (99). (3) Chronic exposure (1 cigarette/day for 32 days) to smoke resulted in no apparent permanent defect in ciliary activity (al- though mucous production was signifi- cantly increased). 223 TABLE Al.?.-Ezperi~uexts comerning the effect of cigarette smoke or its consLitzcents upon ciliary function (cont.) __- Author. year. country, reference system Method 1 Results Dalhamn In viva: Unfiltered cigarette Average mmzber of pufis required to arve.qt and Cat trachea. and cigar smoke. ciliatu activity Rylander, 1970, Cigarette smoke 13) (p<:o,ol) Cigar smoke . .114J Sweden The authors note that cigar smoke is of a (65). different pH and that it contains more iso- prene, acetone, toluene. and acetonitrile. Kennedy In viva: Mainstream Electron microscopic observations: and Protozoan cigarette smoke. (1) After 7 minutes exposure-alteration of Elliott, (ciliated) mitochondrial structure. 1970. (2) After 42 minutes exposure-destruction U.S.A. of internal mitochondrial membrane atrw- (134). ture. (3) Gas phase alone, while ciliatoxic, did cause mitoehondrial swelling but no dis- ruption of membrane structure. `Unless otherwise stated, method entailed the direct observation of ciliarv activity using markers. 224 TABLE A14.-Experiments concerning the effect of cigarette smoke on pzclmonavy surfactmt aml swfacc tcnsiot? Author, year, country. system Method Results refwence __~ Miller and Rat lung extracts Cigarette smoke: (1) Exposure to cigarette smoke was associated with decreased surface tension in lung extract. Bondurant, (1) Applied to (2) Surface tinsion of rats (lung extracts) exposed to'cigarette smoke was decreased 1962, extract. as compared with those not exposed. U.S.A. (2) Exposure (165) of rats. Cook 40 subjects undergoing Surface tension and Webb hronchoscopy: VdUfS of lrurfactnnt 1966, 14 normal 20 100 Stability in&z (reflectn t Values significantly U.S.A. 1 nonsmokers with percent pcrccnt sxrfactnnt activity) different from (57) pulmonary disease area ama values of normals 19 smokers with and Normal . . 6.6 GO.0 1.61 at p