10% TABLE A2.—Smoking and chronic obstructive pulmonary disease syniptoms'—percent prevalence (cont.) (Numbers 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 Other Comments reference population Wynder 315 male New York City et al., patients in NS........14.0 (44) 1965 New York City Pipe, cigar 33.0 (64) U.S.A. and 315 male Cigarettes: (288). patients in 1-10 ...45,.0 (44) California. 10-20 ...46.0 (88) >20 ....67.0 (85) California NS wo... 22.0 (69) Pipe, cigar 30.0 (32) Cigarettes: 1-10 ...45.0 (54) 10-20 ...74.0 (91) >20 = ....74.0 (69) Freour 1,055 randomly Clinical signs of et al., chosen males in bronchitis and 1966 Bordeaux 30-70 respiratory France years of age. insufficiency (92). NS ...... 25.4 (45) SM ......54.4 (478) Haynes, 179 male Average number of Heavy et al., preparatory severe respiratory smoker— 1966 school illnesses per 10 more than U.S.A. students students (adjusted 10 ciga- (108). 14-19 years for age) rettes of age. NS) ....... 0.36 per day. All smokers 2.30 Heavy SM 3.34 20z 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, year, Number and Breathlessness country, type of Cough Sputum production or dyspnea Chest illnesses Other Comments reference population Densen 5,313 male Postai Postal 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 IT U.S.A. and transit Cigarettes only. (68). workers. only ....27,0(2,687) 28.9 317 Transit Transit Transit NS ....... 6.4(1,012) 9.6 11.7 Pipe, cigar 10.5 (765) 14.1 14.2 Cigarettes only ....23.5(3,746) 23.7 21.9 Higgins 926 white NS ....... 15.4 (162) NS ........... 811 NS ........... 5.0 etal., male resi- SM .......47.2 (518) SM ...........46.2 SM ........... 10.7 1968, dents of EX ....... 19.3 (144) EX .........., 28.5 EX ...........16.8 U\S.A. Marion (118). County, West Virginia, 26-69 years of age. Holland 9,786 male Malea Females Males Females and and female NS ....... 3.8 (1,900) 3.2 (3,137) 2.4 2.1 Elliott, school SM ....... 6.3 (1,098) 6.3 (554) 6.1 8.3 1968, children, EX ....... 2.9(1,782) 4.3(1,151) 3.9 42 England
  • 20 ..... 20,6 Females NS ...... 3.4(12,861) EX ...... 38 (959) Pipe .... 0.0 Cigarettes (8,985) 1-9 1... BI 10-19... 10.6 D>20 oo. eee 18.5 Wilhelmsen 313 males Chronic bronchitis et al., 50-54 years NS ...... 1.0 (88) 1969, of age randomly EX 2.2... 3.0 (67) Sweden sampled from 1-14 grams/ (281). population day ... 5.0 (94) of Goteborg. D165 1... 17.0 (64) $02 TABLE A2.—Smoking and chronic obstructive pubnonary 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, year, Number and Breathlessness country, type of Cough Sputum production or dyspnea Chest illnesses Other Comments reference pepulation Lambert 9,975 male Persistent cough and phlegm and and female Males Reid, responders dlge Age Age Age 1970, to a postal 85 45 45-55 55-65 65-69 England survey NS « 1(227) 6 (200) 11(171) T (61) (146). (4,688 males KX . 7(803) 11(358) 15 (335) 18(148) and 5,287 <20 ....15 (521) 22 (488) 30(490) 37 (189) females 20 ». 23 (191) 28 (204) 32 (149) 38 (37) 35-69 years >20 --27(148) 28 (136) 42(121) 25 (12) of age). Females NS . 8(500) 4(637) 5 (925) 6 (21) EX ..... 3(127) 8(128) 7 (94) 7 (Al) <20 . 9(602) 13 (472) 16 (306) 11 (65) 20 .16 (128) 27 (122) 31 (77) 14. (7) 20 . 23 (22) 26 (39) 43 (7) (1) Lefcoe 310 male Age-standardized rates Excluded from and physicians of chronic reapiratory ex-smokers Wonnacott, in London disease are those 1970, and Ontario, NS .......... 1.0 (88) cigarette Canada 25-74 years EX «. 5.0 (61) smokers who (151). of age. SM 34.0 (101) now smoke Pipe, cigar ..12,0 (388) pipes or cigars. ‘Data collected by either direct interview, questionnaire, review of medical records and/or medical examination. soz TABLE A2a.—Smoking and chronic obstructive pulmonary disease symptoms'—percent prevalence (Numbers in parentheses represent total number of individuals in particuar smoking group) SM = Smokers. NS = Nonsmokers. EX = Ex-smokers. Author, year, Number and country, type of Cough Bronchitis Comments reference popuation Cederlof 9,319 twin Observed/ Observed Explanation of analyses for All ex-smokers included et al., pairs expected Hypermorbidity expected Hypermorbidity respiratory symptom with smokers. 1966, registered Group A: cases ratio cases ratio prevalence: MZ—monozygotic Sweden in Sweden Males ........393/151.9 2.6 157/50.8 3.1 Group A analysis—using each pairs (46). of 12,889 Females 186/ 49.4 2.8 43/11.2 3.8 firstborn twin as one group DZ—dizygotic pairs available. Group B SM/NS: in an unmatched relationship Author concludes that MZ Males .... 14.6/7,.7 1.9 6.6/ 1.1 6.0 (274) to each secondborn twin, since hypermorbidity Females ... 13.6/7.6 1.8 3.0/ 2.3 1.33 (264) Group B analysis—using each for smoking persists DZ Males .... 12.8/5.5 2.25 4.5/ 1.8 2.54 (733) twin set as matched pair. in smoking-discordant Females ... 14.5/5.7 2.57 5.5/ 1.8 3.0 (653) All comparisons in Groups A MZ population, a and B are between smoking- easual relationship of discordant pairs. smoking and broncho- pulmonary symptoms is supported. Cederlof 4,379 twin Prevalence of respiratory symptoms No ex-smokers included et al., pairs (all Group A: in Group B analysis. 1969, U.S. veterans) NS » AD 4.3 1.6 Group A-—as above. The authors conclude U\S.A. in U.S. 1-10 peeeeee OF 6.4 2.7 Group B—as above. that the data indicate (45). National 11-380 pee ee ee LSB 15.3 8.0 a strong probability Academy of 31 ee bene eee ebad 27.7 16.8 of a causal connection Sciences Twin Pipe, cigar ............. 7.1 TA 2.7 with smoking. Even Registry (of Group B: NS SM NS SM these symptoms, 9,000 avial- MZ oo ce eee ee 2.4 5.4 18 4.8 however, seem to be able). DZ 9.8 1.6 9.1 influenced by genetic ' Data collected by either direct interview, questionnaire, review of medical records and/or medical examination. factors. 90% TABLE A3.—Smoking and ventilatory function (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV ve Miscellaneous Comments reference population Chivers, 463 male Height-in-inches ¢Mean EFR 1959, employees Cigarettes/day: 64"" 66" 68"" 70"" in liters England of alkaline 0-5 peeeee $97 (28) 91 (35) 108 (81) 101 (21) per minute. (52). industry 6~20 - 89(50) 8&8 (75) 101 (112) 109 (75) Regression plant. >20 . 63 (6) 88.5 (9) 92.5 (9) 113(12) analysis of data revealed & significant re- lationship between smoking and de- creasing function. Higgins 773 males 25-34 55-64 FEV 9.45 expressed et al., in various NS 145 (56) 10% (29) as mean indirect 1959, occupations BX 148 (81) 89 (62) MBC. England (25-34 and 1-14 grams (116). 55-64 years -140(193) 87(157) of age). >>15 grams -133 (89) 80(136) Wilson 28 male RV/TLC etal., residents of NS..... 5.59 (14) NS 211 1960 Dallas, SM ..... 34.44 (14)SM ....... 227.01 U.S.A. Texas, (232). former rural dwellers; matched for body surface, age, and height. 202% TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV ve Miscellaneous Comments reference population Ashford 4,014 male FEV, 9 Data represent etal., coal workers Age: NS 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(555) sitting height. (11). 31-40 .3.44(188) 3.88(777) SM includes pipe 41-50 .3.04(110) 2.96 (755) smoker. 51-60 .2.71(102) 2.56(610) Data on ex-smoker >60 ...2.38 (42) 2.21(287) not included. FEV, found significant; lower for SM than NS. Fletcher 363 male Mean peak EFR and London NS ......-. 570 (30) Tinker, transport I-14 grams 537 (156) 1961, employees, >15 grams 628 (116) England EX ........ 555 (61) (85). Franklin 213 male FEV, 9 FEVo 9, FEVo.s9 Heavy smoker and factory He . 0.75 0.75 | represents an Lowell, workers favy 2,670 3,011 2,710 Light .. 3,703 (59) amount equal 1961, 40-60 years Light 12,489 72,656 72,284 Heavy 13,578 (104) to or more U,S.A. of age. than 30 pack (87). years. 802 TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group ) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV vc Miscellaneous Comments reference population Balchum 1,451 male MMEFR Data for: MMEFR etal., employees NS ....... 15.6 (88) 7.8(19) given as pereent 1962, in Pack/year: of individuals U.S.A. California <1 ..... 15.0 (257) 8.0 with a value of (24). light indus- 1-9 .... 10.0 (263) 6.0 <500 L/M; try. 10-19 ... 10,0 (303) 12.0 FEV, 5 20-29 ... 19.0 (236) 24.0 given as percent 30-39 ... 33.0 (144) 26.0 of individuals 40-49 ... 38.0 (92) 40.0 with value of 50-59 ... 55.0 (29) 45.0 <70 percent >60 ..... 71.0 (24) 62.0 of expected. Goldsmith 3,311 active MEFR FEV, 4 Authors concluded etal., or retired NS ........ 313.63 (250) 2.99 that cigarette 1962, longshore- Pipe, cigar 299.26(125) 2.80 smoke was found U.S.A. men. EX ....... 295.23(102) 2.84 to have a slight (95). Cigarettes/day: effect on =20..... 309.73 (144) 2.89 pulmonary 20-40 ... 303.44(346) 2.91 function. 240 ..... 307.63 (57) 2.90 Martt, 73 healthy D,co Smokers defined 1962, medical per- u as those smoking U.S.A. sonnel with- NS 2 33.10(30) >20 cigarettes/ (161) out signifi- SM <6 years 728.40 (8) oy for varyi . B-l0 years ...°28.20(10) CY *OP Varying cant age 10 years ...524.90(25) Petiods. difference between smokers and nonsmokers. 60% TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV vc Miscellaneous Comments reference population Revotskie 1,130 male FEV 0 Data presented et al., and 1,818 Males Females in terms of 1962, female NS .....0.98 (55) 0.98(255) ratio of U.S.A. residents in Cigarettes/day: observed to (192). Framing- 1-10 .0.97 (90) 0.99 (92) predicted ham par- 10-29 .0.91(163) 0.93 (157) values. ticipating >30 ..0.90 (81) 0.91 (22) in the pro- spective study. Krumholz 18 physicians MEFR Mean D, etal., 24-87 years NS ...eeae 580 (9) NS SM 1964, of age. SM ........ 1590 (9) Rest .......ee 36 231 U.S.A. Exercise: (149). 2minutes . .50 S41 4minutes . .50 143 3 minutes post exercise 39 135 Zwi 20 medical MMEFR Authors found etal, studentsor NS . 187 (10) 4.34 5.77 a significant difference 1964, graduate SM ...1193 (10) 15.09 15.58 between SM and UOS.A. physicians. NS for RV/TLC, (241). compliance, and non- elastic resistance. Coates 1,342 male FEV, 14 Timed VC! FEV, ,/VC et al., and 242 Age: NS 25 cig/day NS >285/day NS >25/day 1965, female post 40-44 12,99(186) 2.85 (69) 3.89 3.85 30.77 0.74 U.S.A. office 45-49 52.95(170) 2.64 (42) 3.92 3.83 30.74 0.70 (53). employees 50-54 12.75(116) 2.62 (22) 3.71 3.74 20.74 0.70 >40 years 55-59 12.64 (64) 2.44 (18) 3.54 3.61 50.74 0.68 of age. 60-64 12.85 (53) 2.80 (8) 3.30 3.83 10,72 0.70 "aBB Jo “HOO Foz SIB94 89-07 PezIeITOD uaaq aswasip aaBy san[ea Tq 4x04 “1Bak youd 96°F 5 -eiidsa1 Jo “(egr) ] uBy} Ja}8a18 3e9 oe 410381] ‘wsn 30 sayous-xe pus OUn}Oa SZ eA Lee Ag qsud ‘9961 srayours teZ1o pus 4710747P TTS" *"* SN g90T gH (49) LIITr** WS a 4noqyTH “Te 42 adidsepnpurgn /7q 1g lags (89) T@IT ** SN saree gaz EWE *ALOISIY IBBA YIV g UBY} tayBIIs 10 0} [ends WAM Sr0'0s ‘WS asoy} ele stayoug 2-01 | ay “sUuBIDISAUd ‘Gr) “quatayip AyUwa Dag /aounmyduey ayenpylzs v sa “Yrusis ousem (OT)LLT0e OWS 20 syuepnys . 2961 Bdnoi8 ZAof waIe (OT) THZOT SN [sotpaut “Ts 7 aoBjans Apoq usa aounydumos Alpuouwjng aeurg2 = zoyuniy “qUBOYUsIS A[[@o14819848 7OU St puaty ft “sdnoiz ; 2 288 79-09 ‘6h-Sb . 92°F . 80's | (98) BIg bend teen eens 92 sop yueoyyUBys a he id {ee (1) 86F LU etery ugg eee Pe-9r“pusyurg St ABP /S3< eae OnTr PLS Lvs (LL) Ter (BOE) BTQ ttt py Uy UuOoLser PUB GN Uaamyeq + ABD /893}91BFIC) [Bani & Jo sUatayid $ 6r's I9'F S8°S 688 (08) sor (TFT) Tgg otc “ss Xa squepisar *“(98T) “papnyaur 8T’s or avs 9P's (604) OIF (BBE) G9G ttt eee SN ayeuay Pas[urd jou slayours saypway «sappy sao eaj0W sappma gy aa]0 2g pus 9961 TeS1D pus adig FOA p90s09 Yaga +addd areur gag nyny uwonjurndod aouedayor S}USUIIOD, SNOOUB_LIOSI AL OA AGI qd oaN pu P camoy *“Axyunoo ‘1oqyny “sdayqows-xq = YY (dnoiz Zuryows zenozaud Ul S[ENPLAIpUL Jo JaquINU [8207 JUasaIdaI SasaqjUusrEd Ul slaquin yy) (7409) uorvjounf Asozopjzuaa pun Suryomsg—ey Aavy ‘saayomg = WS “SI@HOUSUON = SN . 210 LLe TABLE A3.—Smoking and ventilatory funetion (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV ve Miscellaneous Comments reference population Edelman 410 male FEV, 4 Vital capacity Ex-smokers of etal., community NS ........ 164 (152) 7.89 2.83 4.93 cigarettes only. 1966, dwellers Current Difference signifi- U.S.A. 20-103 cigarette cant between NS (78). years of smokers. .5161(118) 7.86 52.64 34.74 and current age. EX seveees 157 (98) 8.09 2.80 4.17 cigarette smokers Pipe, cigar .. 167 (47) 8.20 2.91 5.08 at p<0.01. Peters 124 male MEFR FEV, 4 FEV, /VCe Heavy smoker refers and college age NS ........ 210.28 (41) 4.68 287.5 to greater than Ferris, students, Moderate 10.06 (54) 4.59 85.3 or equal to + 1967, Heavy 9.64 (29) 4.43 83.9 pack years. U.S.A. EX ....... 9.48 (10) 4.74 83.2 Moderate smoker (182). includes pipe and cigar smokers, Difference between NS and heavy smoker is significant. Higgins 926 white FEV, 5 et al., male NS ........ 3.64(160) 1968, residents EX ........, 3.25(148) U.S.A. of Marion Cigarette SM 3.48(611) (118). County, 1-14 .. 3.67 (88) West 15-24 ....... 8.57(278) Virginia, D>25 we... eee. 8.30(150) 20-69 years of age. Le TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, Number and country, type of MBC EFR FEV vc Miscellaneous Comments reference population Sluis- 5383 white 35-44 45-54 >55 FEV 5.4 1 cigarette = Cremer male NS ........ 553 (106) 527 (101) 444 (27) B5-44 45-54 >bS 1 gram. and factory Grams/day: 3.70 3.22 2.76 1 ounce tobacco = Sichel, workers 1-14, 557 (26) 519 (17) 410 (7) 3.64 3.31 2.24 26 grams. 1968, over 35 15-24 532 (94) 446 (35) 401(13) 3.66 2.94 2.28 leigar=2to5 South years of 25 1528 (66) 494 (31) 1380(10) 3.54 3.05 12.12 grams. Africa age. t Derived slopes (208). found signifi- eantly different from 0. Stanescu 87 male bus FEV, 4 Nitrogen gradient et al, drivers; Younger Older Younger Older Younger Older 1968, 27 aged NS ..... 4,470(14) 3,310 (40) 5,125 4,290 1,53 2.49 Rumania 20-25, 60 SM... .. -4,500(13) 13,200 (20) 15,285 14,290 1Y.47 53.77 (212). aged 40-60, all without respiratory symptoms. Densen 5,287 male FEV 14 FEV expressed as et al., postal and Postal standardized for 1969, 7,213 male White Non-white specified postal U.S.A transit NS ....... 3.29 (685) 3.05 (204) and transit (69) workers in All cigarette cece cece eter eae ee vanes 8.11 (2,340) 2.94 (768) workers at age New York <25 grams/day ..... 0. cee cee cee ce eee 3.14 (1,292) 2.95 (599) 45 and at sitting City. 2225 grams/day 3.06 (1,038) 2.93 (161) height of 35 Transit inches. White Non-white Includes mixed NS occ cece eee e tee teen ene eee 3.39 (620) 3.08 (298) smokers. All cigarette 3.11 (2,941) 2,99(1,041) <25 grams/day 3.15 (1,929) 3.00 (891) 2225 grams/day ............0..000ee-eeee+ 8.02(1,011) 2.95 (149) £k@ TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) EX = Ex-smokers. NS = Nonsmokers. SM = Smokers, Author, year, Number and country, type of MBC EFR FEV vc Miscellaneous Comments reference population Rankin 60 male FEV, FEV expressed as et al., and 10 NS wee es 497.5 (12) percent of 1969, female SM . 78.4 (58) predicted value Australia patients for age, sex, (190). with chronic and height. alcoholism 26-66 years of age. Wilhelmsen 313 male PEFR FEV, ve 1963 values only. etal., residents NS Lecce cee ee ee ee eens 525 (88) 3.77 4.83 1969, of Géteburg DD, Ca 539 (67) 3.69 4.77 Sweden 50-54 years 1-14 grams/day ..........-.0065 521(94) 3,62 4.83 (231). of age. S15 grams/day ............0065 492 (64) 3.39 4.56 Lefcoe 310 male MMFR FEV 1.9 MMFR has been and physicians NS ....... 4.09 (88) 3.39 standardized for Wonna- of London, Cigarette age and height. cott, Ontario. smokers. 3.64(101) 3.11 1970, EX ....... 3.99 (61) 3.38 Canada Pipe, cigar 4.17 (33) 3.17 (151). Pyle TABLE A3.—Smoking and ventilatory function (cont.) (Numbers in parentheses represent total number of individuals in particular smoking group) NS = Nonsmokers. SM = Smokers, EX = Ex-smokers. Author, year, country, FEV Miscellaneous Comments reference Lundman, 37 MZ and FEV 9 N, washout gradient MZ = monozygotic. 1966, 62 DZ twin os 7 ss : DZ = dizygotic. Sweden pairs selected Significant differences Significant differences The author concludes that the degree of ventilation as measured by N : between smoking discordant between smoking dis- . : : 2 (159). from Swedish : . . . washout was correlated with cigarette consumption, The FEV : : twin pairs found for: cordant twin pairs se 2-0 Twin-Pair . was significantly lower for smokers and there was a correlation Registry. 1. Group A MZ males found for: with cigarette consumption. . and females. Group B DZ males. 2. Group B DZ males. 3. Group A DZ males. Explanation of analyses for respiratory symptom prevalence: Group A analysis—using each firstborn twin as one group in an unmatched relationship to each secondborn twin. Group B analysis—using each twin set as matched pair. All comparisons in Group A and B are between smoking-discor- dant pairs. 1 Not significant (difference or trend). 2 p<0.05 3 p<0.01 4 p<0.005 5 p<0.001 a 4 TaBLE A4.—Glossary of terms used in tables and text on smoking and ventilatory function Symbo} Term Volume or rate Definition MBC......... Maximal breathing LiterS. 0. cc eee eee eee The maximal volume of gas that can be breathed in one minute. capacity. MVV......... Maximal voluntary ventilation. EFR......... Expiratory flow rate............ Liters/minute.... 2.0... 00sec eee Rate of flow for a specified portion of a forced expiration (MMEFR—rate PEFR .. Peak expiratory flow rate. of flow measured for middle half of FVC). MEFR........ Maximal expiratory flow rate. MMEFR...... Maximal] midexpiratory flow rate, FEV ......... Forced expiratory Liters... ee eee eee Volume expired within a specified time interval. (FEV, ,—volume expired volume. in first second of expiration.) VG... eee Vital capacity........ 0. eee Liters. ... 00. cee ee ee eee Maximal volume of a gas that can be expelled from the lungs by forceful FVG......... Forced vital capacity. effort following a maximal expiration. FEV /VC. ... Foreed expiratory Percent... .... cece eee e eens Volume of forced expiration (in time specified) related to vital capacity, volume/vital capacity. dD, wee nutes Pulmonary diffusing ml/min/mmHg The ability of a chosen gas to pass from the alveolus to within the pulmonary ; capacity. eapillary. N, washout... Nitrogen washout Exponential The stepwise pulmonary alveolar clearance of a gas. (Slope of curve depends gradient. curve. upon the uniformity and adequacy of ventilation of all parts of the lung.) It may be done as a single--or multiple—breath procedure. Compliance....... - Liters/CMH,0. paveteueuees Volume change of the lung produced by a unit pressure change. RV.. . Residual volume..........-6.. 045 Liters... 0... ccc ee ce ce eee Volume of gas remaining in the lungs at the end of a maximal expiration. TLC......... Total lung capacity..........0.. Liters... 0.0. cee eee ee ee Volume of gas contained in the lungs at the end of a maximal inspiration. FRC .Functional residual Liters... cee ccc eae Volume of gas remaining in the lungs at the resting expiratory level. capacity. Aleveolar volume. ............. Liters. 0... eee eee eee ene eee Volume of gas contained in pulmonary alveoli. SOURCE: Comroe, J. et al. (56) TABLE A6,—Epidemiological studies concerning the relationship of air pollution, social class, and sinoking to chronic obstructive bronchopulmonary disease (COPD) Author, year, Number and type country, of population Results reference Higgins, 301 males and Male data only (170): oo 1957, 280 females (a) The frequency of recurrent chest illnesses was high England living in 2 er in the more polluted region but the prevalence of (112). separate other respiratory symptoms and mean valueg were districts. similar. (45-64 years (b) Significant difference observed in COPD mortality of age.) rate. College of 787 males and (a) Male urban inhabitants manifested almost twice the General 782 females prevalence of chronic bronchitis as rural males: this Practi- 45-64 years of difference could not be explained on the basis of tioners, age from smoking habits. 1961, medical doctors’ (b) No significant urban/rural differences noted for England case lists. PEFR! (55). (c) No significant urban/rural differences noted for COPD symptoms among females. Ferris and Anderson, 1962, U.S.A. (81). 1,219 males and females living in 3 different areas of a New Hampshire town, Following adjustment for differences in smoking habits, no significant differences in chronic bronchitis were observed among the 3 pollution areas. Mork, 1962, U.S.A. (171). 339 male trapsport employees from London and Norway. The excess prevalence of serious respiratory symptoms (dy. spnea, wheezing) and PEFR dysfunction among London Transport employees was only partly eliminated after standardization for smoking, and the author suggests that this is due to differences in air pollution levels, Schoettlin, 1962, US.A. (204). 2,622 males 45-75 years of age. (a) No positive correlation found between chronic respira. tory illness and city size. (b) A positive correlation was found between chronic res. piratory illness and cigarette smoking (particularly du- ration}. Anderson et al., 1965, Canada (8). Holland and Reid, 1965, England (124). Bates 778 residents of Berlin, N.H., and 918 residents of Chilliwack, Canada. 676 male transport employees in Londen and rural England. 216 hospitalized veterans from various areas of Canada (all standardized for age, tobacco consumption, and eecupation) . Berlin, New Hampshire, has higher SO, and particulate air pollution levels and the higher respiratory disease preva- lence rates among its residents were not accounted for by age differences, but were aceounted for after stan- dardization for smoking habits (except that PEFR and FEV, 4 dysfunction was more prevalent in New Hamp- shire, and the authors suggest that this difference re flects air pollution differences). (a) London employees manifested a greater prevalence of COPD symptoms and PEFR dysfunction than did the rural employees. {b) Smoking habit differences alone were not sufficient to explain this difference in COPD manifestations. {c) Both groups manifested pulmonary dysfunction cor- related with tobacco consumption. Winnipeg (cleanest of all areas in 50, and industrial dustfall}) residents manifested decreased prevalence of chest ilnesses, less severe grades of dyspnea, and less sputum volume produced when compared to residents of all uther areas. 216 Tas_e A6.—Epidemiological studies concerning the relationship of air pollution, social class, and smoking to chronic obstructive bronchopulmonary disease (COPD) (cont.) Author, year, Number and country, type of Results reference population Ashley, Standardized Positive correlations: 1969, mortality (a) Smoke concentration and bronchitis mortality. England ratios for (by) SO, and smoke concentration and bronchitis mor- (12). males (1958-63) tality and social class. for 53 boroughs (c) Pollution and social class. with air pollution indexes. Holland 10,971 children Factors affecting prevalence of respiratory symptoms: etal, over 11 years of (a) Smoking—highly significant association. 1963, age in 4 areas. (b) Area of residence (pollution)—-significant association England except for periods of cough and phlegm lasting more (122). than 3 weeks. Winkelstein and Kantor, 1969, U.S.A. (288), 842 females over 25 years of age in various regions of Buffalo. {c) Social class, age, sex—-no association noted. (a) The increased prevalence of respiratory symptoms could not be explained by social class differences. (b) No overail association noted between productive cough and air pollution. Cooley and Reid, 1970, England (58). 10,887 children 6-10 years of age from con- trasting urban and rural areas. Ilinesses 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 ITV and V showed a clear excess in fre- quency of chest illnesses among urban residents over rural residents. Lambert and Reid, 1970, England (146). 9,975 males and females responding to questionnaire survey. fa) The trend of increasing prevalence of bronchitic symp- toms from rural to urban respondents was not negated by adjustment for smoking differences. (b) After adjustment for age and smoking habits, male respondents manifested a clear correlation of persistent cough and phlegm prevalence with increasing air pollu- tion. Correlation was not as 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- ereased with increased cigarette consumption, suggesting 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. 1 See Glossary of Terms: Bronchopulmonary table A4. 217 TaBLeE A7.—Epidemiological studies concerning the relationship of occupational exposure and smoking to chronic obstructive bronchopulmonary disease Author, year, Number and country, type of Results reference population Higgins 185 males Miners showed increased symptom prevalence (breathless- et al. (84 nonminers, ness, cough, sputum). 1956, 101 miners) Miners showed increased prevalence of chronic bronchitis, - England without pneumo- Miners showed decreased MBC. (119). coniosis. Differences in smoking between the two groups did not ac- count for above differences. Phillips 1,274 males None of the industrial environments were associated with etal. factory employees 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. (185). process}. Higgins 325 males 25-34 Miners as compared to workers in non-dusty occupations: etal, 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 55-64 years of age—less significantly increased prevalence (116). various occupa- of chronic bronchitis and MBC abnormalities than in tions. 25-34 years of age group, No smoking information available. Chivers, 463 males in No significant differences in PEFR?! between dusty and 1959, non-dusty and non-dusty groups. England dusty occupations Cigarette smoking (especially in those >40 years of age) (52). (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, years of age. Total dust exposure was not directly correlated with these England findings. (115). Wives of miners showed similar symptom and test changes as compared with wives of nonminers. Brinkman 1,317 males 40-65 Increased silica exposure was associated with an increased and years of age prevalence of chronic bronchitis. Coates, with various Highest prevalence of chronie bronchitis was noted in the 1962, silica exposure non-exposed group; and this group was noted to have U.S.A. histories. the highest number of smokers and highest consumption. (42). Hyatt 267 male miners Increased history of underground work was associated with etal., and ex-miners an increased bronchopulmonary symptom prevalence and 1964, 45-55 years decreased pulmonary function values. U.S.A, of age. The impairment of pulmonary function associated with (128). underground work was separate from effect of smoking; but smoking and underground work did show additive effects. Elwood 2,528 male and Preparing room workers who manifested byssinosis symp- etal., female flax toms also showed an increased prevalence of chronic 1965, workers over 35 bronchitis independent of age or smoking when compared Ireland years of age. with non-preparing room workers. (77). Female workers manifested a signiticant association be- tween byssinosis symptoms and smoking while male work- ers did not. Sluis-Cremer et al., 1967, South Africa (209). 218 827 miners and nonminers over 35 years of age, Those smokers exposed to gold mine dust manifested more symptoms of COPD! than did non-dust exposed smokers, while prevalence of symptoms, among nonsmokers, was similar for the two groups, TaBLE A7.—Epidemiological studies concerning the relationship of occupational exposure and smoking to chronic obstructive bronchopulmonary disease (cont.) Author, year, Number and country, type of reference population Results 827 miners and nonminers over 35 years of age. Sluis-Cremer etal., 1967, South Africa (209). (cont.) The dose relationship of cigarettes and COPD?! symptoms was much more noticeable among those exposed to dust. The authors stressed the synergistic actions of cigarette smoking and dust exposure. Those exposed to dust manifested a significantly greater prevalence of byssinosis symptoms than nonexposed, Smokers manifested a significantly greater prevalence of byssinosis symptoms than nonsmokers. No significant differences in Monday morning FEV? values were observed between smokers and nonsmokers. Prevalence of byssinosis symptoms did not show any re- lationship to length of employment. Hemp workers (especially the older ones) were noted to have different smoking habits from control group—fewer heavy smokers, more light smokers, more ex-smokers due to doctor’s orders. Aged 20-49 — a. No difference in FEV, values . between controls and hemp workers in any smok- ing category. b. No difference in FEV, values between men in different smoking categories. Aged 50-69-41. Hemp workers manifested decreased FEV 1.) values in all smoking groups except for heaviest smokers. Ex-smok- ers had lowest FEV 1. values. b. Those smoking most had lower FEV, 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, although the selection process whereby those with symptoms have a greater tendency to stop smoking may obscure such a relationship. Chlorine-exposed group manifested no difference in symp- toms and a decreased MBC value when compared with non-exposed group, Smokers in chlorine-exposed group had significantly de- ereased MBC and FEV values as compared with non- smokers in non-exposed group. Sensitized group manifested lower FEV, ,/FVC1 values as compared with nonsensitized group even after smok- ing habits were controlled for. Bouhuys 455 male cotton et al., textile workers 1969, (214 exposed to U.S.A. dust in carding (39). and spinning rooms, 241 not exposed). Bouhuys 216 male hemp etal, workers and 247 1969, workers in other U.S.A. industries in (88). same region, 20-69 years of age. Chester 189 male chlorine etal., plant workers 1969, (55 with history U.S.A. of severe ex- (49). posure). Greenberg 121 workers in et al., washing powder 1970, factory (48 found England to be sensitized (97). to product, 73 not). Tokuhata 801 male miners et al., 1970, ULS.A. (218). Increased mine exposure was associated with residual vol- ume and FEV abnormalities even after adjustments for age and smoking. A systematic exposure-impairment relationship was noted only among smokers while relatively few nonsmokers shuwed COPD impairment, Smoking miners manifested more X-ray alterations and COPD symptoms than nonsmokers, regardless of num- ber of years of underground exposure. 1 See Glossary of Terms in Bronchopulmonary table Aé4. 219 TaBLE A10.—Experiments concerning the effect of the chronic inhalation of NO, upon the tracheobronchial tree and pulmonary parenchyma of animals Author, year, country, Animal Results reference Freeman Sprague-Dawley 25 p.p.m.: and rats. (a) after 37-41 days-—-moderate hypertrophy and hyper. Haydon, plasia uf bronchial and bronchiolar epithelium. 1964 (b) after 146-157 days—(1} Advanced hypertrophy and U.S.A. hyperplasia of bronchial and (90). bronchiolar epithelium, (2) Increased lung volume. (3) Proliferation of connective tissue. Haydon Sprague-Dawley 12.5 p.p.m. to death: et al., rats. (a) Hypertrophy and occasional metaplasia of bronchial 1965 and bronchiolar epithelium. U.S.A. (b) Increase in number of actively secreting goblet cells. (107). Haydon Albino rabbits. 8-12 p.p.m. for 4 months: et al., (a) Abnormal dilatation of peripheral air spaces. 1967 (b) Decreased density of alveolar walls, U\S.A. (¢) Hypertrophy and hyperplasia of bronchial epithelium (106). (especially terminal bronchiolar). (d) Increase in size of alveolar ducts. (e) Increased elastic tissue staining. (f) Increased alveolar size. Freeman Sprague-Dawley 0.8 p.p.m.-2 p.p.m, for entire lifespan: et al., rats. (a) Alveolar distention. 1968, (b) Reduction in number of cilia. U.S.A. (ce) Epithelial inactivity (‘‘dormancy”). (91). Freeman Sprague-Dawley 18 p.p.m. et al., rats. (a) 5 days—terminal bronchiolar epithelial hypertrophy. 1968, (b) 4 weeks—(1) Widespread bronchiolar epithelial hy- U.S.A. pertrophy. {89), (2) Non-necrotizing emphysema. Blair Female Swiss 0.5 p.p.m.: etal, Albino mice. (a) 6 hours/day for 3 months—pneumonitis. 1969, (b) 24 hours/day for 3 months—(1) Respiratory bronchi- ULS.A. olar obstruction. (32). (2) Alveolar expansion and bronchiolar inflammation con- sistent with early focal emphysema. Kleinerman, Male Syrian Golden 100 p.p.m. for 513 hours: 1970, hamsters. (a) thymidine autoradiography—intense burst of prolif. U.S.A. eration of epithelium returning to normal in 4 days (186). (more persistent distally). 220 (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. TABLE A18.—Experiments concerning the effect of cigarette smoke or tts constituents upon ciliary function Author, year, country, System Method ! Results reference Mendenhall /7 vitro: Cigarette smoke Controls—ciliary activity depressed approxi- and Calf trachea. by direct appli- mately 4 percent. Shreeve, eation or in Experimental—ciliary activity depressed ap- 1937, solution. proximately 40 percent. U.S.A. (164). Rakieten In vitro: I, Nicotine in J. Ciliary activity depressed only upon ex- etal. {a) rabbit Locke-Ringers posure to 100 mg. percent solution. 1942, and rat solution. Il. Ciliary activity depressed after 15-20 min- USA. trachael Il. Cigarette smoke utes exposure depending on concentration (188). rings. in solution. of smoke in solution. (b) human nasal mucous membrane Kordik In vitro: Nicotine in Locke’s Nicotine at 10—° g./ce had no effect on ciliary etal. Rabbit solution. activity. 1952, trachea England (187), Hilding, In vitro: Cigarette smoke All tracheas showed depressed or absent ciliary 1956, Cow trachea (direct activity. U.S.A. exposure}. (120). Krueger In vivo: Cigarette smoke. Cigarette smoke decreased ciliary activity by and Rabbit approximately 200 beats/minute. Smith, trachea 1958, ULS.A. (139). Dalhamn, Tn vivo: Cigarette smoke. I. 7/10 showed cessation of ciliary activity 1959, I. Rat after one exposure. Sweden trachea II. 6/10 showed cessation of ciliary activity (59). In vitro: after one exposure. Il. Rabbit TIl. 6/7 showed cessation of ciliary activity trachea after one cigarette exposure. Ili. Human ciliated mucosa Falk In vitro: Cigarette smoke. Decreased ciliary activity noted on exposure to et al, Rat and rabbit cigarette smoke: 1959 tracheal (a) Repetitive exposure was associated with U.S.A, epithelium. persistence of response over longer periods (80). of time. (b) ‘‘Tar’-rich cigarette was more inhibitory than ‘‘tar’’-poor. {c)} Filtered smoke was less inhibitory than unfiltered. Ballenger, Jn vitro: Cigarette smoke Ciliary activity was fully inhibited within 5-28 1960, Human in solution. minutes of exposure depending upon concen- U.S.A, bronchial tration of smoke in solution. (25). and tracheal epithelium obtained during anesthesia. 221 TABLE A13.—Eaperiments concerning the effect of cigarette smoke or its constituents upon ciliary function (cont.) Author, year, country, System Method 2 Results reference Wynder In vivo: Cigarette smoke; Unfiltered cigarette smoke—ciliastasis by 2nd. et al., Fresh water and its fractions 5th puff, 1963, mussel in solution. Acid (phenolic) fraction solution—immediate U.S.A. ciliated ciliastasis. (286). epithelium. Whole extract fraction solution—no ciliastasis, Neutral fraction solution—no ciliastasis. 1 percent phenol solution—immediate ciliasta- sis. Dalhamn In vivo: Cigarette smoke. Unfiltered cigarettes—ciliastasis in 3/5 cats and Cat trachea. after 5 cigarettes. Rylander, Filtered cigarettes—no ciliastasis after 8 ciga- 1964, rettes (5 cats). Sweden Controls—no ciliastasis (5 cats). (61), Ballenger Invitro: Nicotine in solution. Initial stimulation of activity followed by de et al., Human celine and complete ciliastasis after 12-24 1965, ciliated hours of exposure. U.S.A. tracheal (26). epithelium obtained during. anesthesia. Dalhamn in vive: Cigarette smoke. The longer the time interval between expo- and Cat trachea. sures, the more puffs were required to cause Rylander, ciliastasis, 1965, Sweden (62). Wynder In vivo: Various compounds Formic, acetic, propionic, benzoic acids all etal, Fresh water in solution. more ciliatoxic than phenol. 1965, mussel Oxalie acid less ciliatoxie than phenol. U.S.A. ciliated Formaldehyde, acrolein more ciliatoxic than (285). epithelium phenol. Carson In vivo: Cigarette smoke. Percent decrease in ciliary activity etal., Cat trachea. Control . 0... ec ee cece eee eens 0 1966, Unfiltered smoke ...........-.: eee cece eee 5B U'S.A. Cellulose acetate filter .......... 45 (44). Carbon cellulose acetate filter 30 Dalhamn, In vivo: Cigarette smoke. Mean number of puffs required to produce 1966, Cat trachea. ciliastisis Sweden No filter 0... cc eee ee eee eee eee 91 (60). Charcoal filter ........ 0... cece cece eee eee 170 Commercial cellulose acetate filter ........ 194 Charcoal and acetate filter .............. 512 Cambridge filter 2.0.00... . cc ccc eee eee 600 Kensler In vivo: 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, eattrachea, solution. Other species—All found sensitive to ciliastatic U.S.A. dog trachea, components of cigarette smoke. Bulk of ac- (185). monkey tivity noted in gas phase (HCH, formalde- trachea, hyde, acrolein). rat trachea. TaBLe A13.—Experiments concerning the effect of cigarette smoke or its constituents upon ciliary function (cont.) Author, year, country, System Method 1 Results reference Dalhamn In vivo: Cellulose acetate- Increased amounts of tar were associated with and Cat trachea. filter cigarettes decreased number of puffs required to inhibit Rylander, with varying ciliary activity. 1967, amounts of Sweden “tar” but simi- (63). lar gas phases. Dalhamn In vivo: Unfiltered and Whole smoke found to be markedly more toxic and Cat trachea. Cambridge-filter to ciliary activity than volatile (gas) phase Rylander, cigarettes. at lower dosages (puff volume). This differ- 1968, ence diminishes with increasing puff volume. Sweden (64). Kaminski In vivo: 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 (188). chamber” made filters. to stimulate oral mucosa and saliva. Krahl In vivo: Cigarette smoke Significant ciliastasis, reversible. and Common dissolved in Bulmash, mollusk 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’s puffs to cause ciliastasis. 1970, epithelium. solution, (2) Activated charcoal filtered smoke was U.S.A. less ciliastatic than cellulose acetate filtered (28). 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 vivo: Cigarette smoke. The authors observed that: and Hen trachea. (1} Whole smoke acutely depressed ciliary Kensler, activity in 4-6 puffs. 1970, (2) Gas phase was only slightly less depres- U.S.A. sant than whole smoke. (29). (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 A1l3.—Experiments concerning the effect of cigarette smoke or its constituents upon cittary function (cont.) Author, year, country, System Method 1 Results reference Dalhamn In vivo: Unfiltered cigarette Average number of puffa required to arrest and Cat trachea. and cigar smoke. ciliary activity Rylander, Cigarette smoke ....... 13 1970, Cigar smoke ......... “rap (@<0.01) Sweden The authors note that cigar smoke is of a (65). different pH and that it contains more igo- prene, acetone, toluene, and acetonitrile, Kennedy In vivo: 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 struc- (194). ture, (3) Gas phase alone, while ciliatoxic, did cause mitochondrial swelling but no dis- ruption of membrane structure. +Unless otherwise stated, method entailed the direct observation of ciliary activity using markers. 224 St TABLE Al4.-Experiments concerning the effect of cigarette smoke on pulmonary surfactant and surface tension Author, year, country, System Method Results reference 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 tension 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 bronchoscopy: values of surfactant 1966, 14 normal 20 100 Stability index (reflects + Values significantly U.S.A. 7 nonsmokers with percent percent surfactant activity) different from (57) pulmonary disease area area values of normals 19 smokers with and Normal .....-+-5- 6.5 60.0 1.61 at p<0.02 level. without pulmonary Pulmonary disease. patients .....- 717.0 $50.0 1.00 Chronic smokers .. 15.7 51.0 1.04 Giammona In vitro: Exposed to In vitro: 1967, Surfactant material cigarette Exposure to cigarette smoke was associated with a significant decrease in maximal surface U.S.A. induced from dogs smoke for tension. (94) and rats. 3 hours/day In vivo: In vivo: for up to Dogs and cats (exposed for 1 week)—no significant change. Dogs, cats, and 3 weeks. Guinea pigs (exposed for 3 weeks)~-significant decrease in maximal] surface tension. guinea pigs. Webb, Bronchial Direct Surface tension valucs of surfactant et al. washing, exposure to 20 percent 100 percent 1967, from cigarette smoke. Number areca arca Stability index U.S.A. dog lungs. Control .......- 11 U1 : 60.7 1.60 (224) Smoke 10 is.74 (P<0.002 weet (p<0.002) 0.84