TABLE 3.--Continued Cornstock et al. ( I Y70) Net change: 4.0 Ner ch;qc: IS.0 Net ch;qc: 0.0 Sharp et al. (1073) IS.4 X6.2 6.4 IO.2 77.0 I1.X x.0 x5.0 7.0 pJLq'"Llnea > rru Woolf and Zamel ( IYXO) `Ta\hkm et nl (IYX3r' C`om\tock t't 01. (IY70) Sharp et al. t lY73) Fwdm:cn et al. ( lY7.3) White male >I ppd Whate female >I ppd Wh,a/. Woollantl %amrl (IYXO)' Ta\hhin et al c IYX4)' 17.0 4.h II 0 IX.0 I I.2 x9.9 Ner change: 2.0 72.x Net ct1arrp!: -X.Y Net change: -I I .X 7 I .o 77.x 13.0 5.5 16.2 I I.0 I I .o IX.0 75.0 x.0 7.0 Yl .I) 3.2 x0.x 0.0 Net chance: I I .O Net chance: 1.0 14.4 72.x 12.x IO.1 70.x 0.0 %.I) s.0 5.0 YI .o 13.7 x2.1 4.2 7.0 - to.0 4.0 E TABLE 3.-Continued Continuing smokers Former smokers Never smokers Symptoms Age Reference (mean) Lost No change" Gained Lost No change' Gained Lost No change" Gamed Comstock et al. (1970)`" Net change: 5.0 Net change: -5.0 Net change: -2.0 Sharp et al. 13.4 77.0 9.6 II.1 7x.7 10.2 7.3 xx.4 4.3 (1973jrn "No change mdlcate\ that rqxratory symptom\ were ather conristently absent or conslstentty present. hOnly females. cough and/or phlegm. S-yr wdy period. `Llght=<70c1g./wk; moderate=?I-14Ocl~wk: hravy=more than 14Ocig/wk. `Former rmokers defined ab those who atoppd between haselms and followup. x4ales only. S-Cyr f~lltowup. `Males only. former htudws defined as thox who stoppd between baseline and followup. 7.yr t~llowup "Former studa defined as those who stopped between baaehne and followup. I.5yr followup. hppd=packs/day. `Grade 2 or 3 dyspnca. `Dyspnea not defined. `Dyspnea at ordinary pax. `Wheeze not defined. mEver wheeze. age: former smohers had a shorter duration of smoking in years than current arnoher5 of I /? to I pack per day. but similar cumulative pack-years ( 1 1.5 vs. 15.0). More former and never smokers reported consistent absence of cough or sputum. dyspnea. or u heerr compared with current smokers. Thirteen percent of former smokers developed cough or phlegm during the study period compared with 9 percent of never smoker\ and I6 percent of smokers. At enrollment. smokers had more respiratory symptoms and were more likely to develop symptoms over the 5 years of the study. Similarly, in a large population study in the Los Angeles area. respiratory symptom\ diminishedamongformersmokersafteronlySyearsofabstinence(Tashkinetal. 19X-l). In this study, the following 4 smoking groups were defined: 27X persistent \moher\: 3 I4 never smokers; IO6 quitters. subjects who smoked regularly at baseline but were nonsmokers at the conclusion of the study: and 294 former smokers. individual\ who were regular smokers but had quit at least 2 years prior to baseline. The mean age for female quitters (45.6 years) was comparable among the smoking categories: the mean age for male quitters (43.4 years) was similar to the mean ages for current and never smokers: however. it was 6.2 years less than that for former smokers. Quitters and former smokers had smoked similar numbers of cigarettes per day (26.3 vs. 23.6 for males: 19. I vs. 19.0 for females). but quitters had higher pack-years (3X.6 vs. 76.X for males; 27.4 vs. 16.2 for females). In addition. quitters had pack-years comparable with current smokers (38.6 vs. 40.5 for males: 27.4 vs. 30.9 for females). Over the 5 years of the study. quitters recovered from the symptoms of cough. sputum. and wheeze more frequently than continuing smokers. No difference in shortness of breath was found between the two groups in the 5-year study period. Quitters and former smokers were not compared to determine the relative importance of cumulative exposure versus time since exposure on the observed reduction of symptoms among ex-smokers. Comstock and coworkers (1970) reported comparable findings in a study of respiratory symptoms in 670 male telephone company employees studied for 5 to 6 years. Symptoms of chronic cough, phlegm production, and wheeze decreased sig- nificantly in quitters whose baseline prevalence for these symptoms was similar to persistent smokers but whose followup values were comparable to never smokers. Baseline and followup prevalence rates for breathlessness in quitters were equivalent to those of persistent smokers. Sharp and colleagues ( 1973) found similar trends in respiratory symptoms in 1,263 middle-aged males from an industrial population surveyed in 1961 and again in 196X. Former smokers were defined as individuals who stopped smoking after entry into the study; previous smoking histories were not provided. Over the 7 years of the study. 72.3 percent of former smokers with persistent cough and 64.4 percent with persistent phlegm recovered from the symptoms. These rates of recovery were higher than for the other smoking groups with similar symptoms. Additionally, former smokers who originally complained of dyspnea and wheeze tended to lose these symptoms over the study period, but less dramatically (49-percent and 45.5percent recovery, respective- ly). New reports of cough and phlegm were made by less than IO percent of never and former smokers and I6 percent of continuing smokers, whereas new wheeze was found in 13.5 percent of former and 14. I percent of continuing smokers. In contrast. dyspnea developed in 18. I percent of former smokers and 22.4 percent of continuing smokers. In a study of shorter duration. Friedman and Siegelaub ( 1980) confirmed the findings of Tashkin and coworkers (1983). Cornstock and associates ( 1970). and Sharp and colleagues ( 1973). Over approximately I.5 years of observation, 3.815 recent quitters more often reported decreased chronic cough but noexertional dyspnea when compared with 9.391 persistent smokers. Findings from two Finnish studies and one British study support the results of these North American investigations (Huhti and Ikkala 1980; Poukkula. Huhti. MPknrBinen I982 Leeder et al. 1977). In the I O-year study of Huhti and lkkala ( 1980). respiratory symptoms increased in all groups of smoherr except male quitters. who had lower prevalence of phlegm production and wheezing (Table 4). Similarly. in a IO-year followupof male pulp mill workers. Poukkula. Huhti. and Makarainen ( 19X2) observed a decrease in respiratory symptoms only for quitters and only for cough and phlegm production. No explanation for the increase in symptoms over time for never smokers was provided in either study. During a 6-year period. Leeder and colleagues ( 1977) evaluated chronic cough and phlegm annually in 3.9 I6 young married adults. Men who pave up smoking had a progressive decline in the reporting of cough and phlegm. Only, a small number of female ex-smokers were included. In summary. the findings from these longitudinal studies agree with those from the cross-sectional surveys and suggest that cough. phlegm production. and vvheering reverse after cessation. regardless of duration or quantity prev#iously smoked. Dyspnea. however. may he less likely to resolve in subjects with longer smoking histories. possibly indicating irreversible damage induced by smoking up to time of cessation. Clinical Studies of Possible Mechanisms Few studies have investigated the mechanisms by vv hich respiratory symptoms improve after smohing cessation. Reversal of mucous gland hyperplasia and reduction in airway inflammation have been considered likely mechanisms but have not been documented. Recovery of epithelial integrity has been shown in two small clinical studies of epithelial permeability (Minty. Jordan. Jones 1981: Mason et al. 19X.3). Improvement in tracheal mucous v,elocity. another possible mechanism by, which respiratory symptoms may' decrease after smokin, cr cessation. has also been examined. Goodman and coworkers ( 197X) reported that five of nine y'oung former smohers had tracheal mucous velocities that were comparable uith age-matched never smohers. One subject had a minimally~ depressed velocity,. and three had markedly depressed values. Only one subject was restudied 2 months after baseline and 9 months after cessation. and at that time. tracheal mucous velocity was found still to be reduced. Because subjects were not studied while smohin,. 0 the change after cessation could not be determined. Camner. Philipson. and Arvidsson ( 1973) studied tracheal v,elocity in subjects before and after smohinp cessation. They found that in I I of I7 male former smokers. tracheal mucous v,elocity improved 3 months after cessation and that in the remaining 6 former smohers. velocity was slower or similar when compared with baseline values. Improved tracheal mucous velocity may lead to less mucus in the airways and thereby reduce symptoms of cough and u heere among fomrer smohers. 303 TABLE A.-Percentage of subjects with respiratory symptoms b> smoking status, 1961 and 1971, in a cohort of middle-aged, rural Finns 1 \e\er \moher\ IY61 se\er \nlohrn 197 I Mule\ S! mptom\ (X0) Phleem all da\-* inter I')61 -I I')71 6 b'heetms! most daw 1961 1071 2 Weather affect\ chru 1961 6 1071 1') Breaihle\we\\ grade< 34 IY6l 1 lY7l IO Chrome bronchitk IY61 Y IY7l II Mean ape (y) so in IYhl Femab 1573) II Evwwhw lY6l I Y7 I Female\ 1261 1 III IV Smohrr\ IYhl Smr)her\ I Y6 I Ex-vnoher\ I Y7 I Smohw I Y7 I Female\ Mdf\ , I41 I?111 Female\ 117, I I IX 27 -I Ii 3 -l I IO 3 IO I? IS I6 II Y I7 I7 I6 `I 21 6 I4 I5 so I5 23 IS I? 10 13 24 2') Y so 4 Y I I I3 I6 39 I6 36 5 11 47 4Y 2 II 6 IY 71 71 46 Respiratory Infections Numerous clinical studies have shown alterations in immune and inflammatory function among cigarette smokers compared with never smokers. Studies of peripheral blood have shown that current smokers have as much as 30 percent higher leukocyte counts than never smokers (Corre. Lellouch. Schwaart/ 1971: Friedman et al. 1973). Increases have been reported in polymorphonuclear leukocytes (Bridges. Wy,att. Rehm 1985). which appear to have nonnal chemotactic. microbicidal. and secretory functions (Nobel and Penny 1975: Abhoud et al. IY83). and monocytes (Nielsen IYXS). which may partially lack the ability to kill intracellular C`rr~rtlitltr (Nielsen IYXS). Total 305 numbers of T lymphocytes are increased among \mohers (Kas7uhowki. Wysocki. Machatski IYXI: Robertson et al. 1983: Burton et al. IYX?: Smart et al. 15%). Light and moderate smokers have increa\ei in OKT3+ (total T cell\) and OKT3+ (T-helper cells) (Hughes et at. 1985: Ginns et al. 1982). and heavy smoker\ have decreases in OKT4+ and increases in OKTX+ (T-suppressor cells) (Ginns et al. IY81: Miller et at. 1982). Additionally. functional changes in T lymphocyte\ from smokers have been observed (Whitehead et ai. 1974: Suciu-Foca et at. 1974: Onxi et al. I YXO). but these findings remain controversial. Changes in serum components have also been reported. Smokers have higher levels of CS. CY. Cl inhibitor (Wyatt. Bridges. Halatek I%1 ). C-reactive protein. and autoantibodies (antinuclear and rheumatoid factors) (Heiskett et al. 1962). but lower levels of specific immunogtobutins (IgG. IgM. and IgA) (Ferson et al. 1979: Vos-Brat and Rumke 1969: Kosmider. Fetus, Wycocki tY73: Dale\ et al. 107-l: Wingerd and Sponzitti 1977: Guts\,ik and Fugerhot tY7Y: Gerrard. Heineret al. 1980: Leitch, Lumb. Kay IYXI: Andersen et al. 19X1: Bartetik. Zioto. Bartetik 19X-l: McSharry. Banham. Boyd 1985). As previously dewribed. IsE is elevated in smoker{ (Burrows et al. 198 I: Zetterstriim et at. 19X1: Hittgren et al. 1982: Warren et al. 1987: Bonini IYX?: Stein et at. 19X3). and this increase may result from suppression of regulatory T-lymphocyte function (Hott 19X7). Bronchoatveotar lavage has provided evidence on the noncellular and cellular com- ponents of the peripheral airways and alveoli amon, 0 smokers and nonsmokers. Data have indicated that smokers appear to have normal or \lightt!, elevated level? of IgA and IgG (Reynotd\ and New ball 1973: Warr and Martin I Y77: Bell et al. I YX 1: Vetluti et at. 19X3: Pre. Btudier. Batte\ti 19X0: Gotoh et at. 19X3). Similarly. value\ for lysoqme (Harris et al. 1975). complement component\ (Rohertwn et al. 1976). and fibronectin (Villiger et al. IYXI ) are elevated in tavage fluid from \mohers. The total number of cells retrieved from tavage of smoher\ i\ increawd with marked elevation in the percentage\ of activated mucrophages and neutrophils (Hunninghahe et al. IY79: Harris. Swenson. Johnwn 1970). Ahwlute typhncyte number\ remain unchanged. although T-cell function ma!' be altered (Danielc et at. IY77: DeShaLo et al. 19x3). Recovered mucrophage\ have increaed chemotactic funcrwn (Warr and Martin 197-t: Labed/ki et at. I%.?: Rwhartts et HI. 19X4) and increaed release of damaging product\ huch a\ wperoside anion\ (Hoidat ct at. 1970: Hoidat et at. 19X0: Jowph et al. 19X0: Hoidat and NieHoehncr 19X2: Grecnin, cr and Loarie 19X3: Rwma et at. IYXI). hut diminished microbicidal acti\ it? (iLlartin and Wxr tY77: Fisher et al. 14X2: Ando et al. 19X1). Smoker\ hake twn \houn to have reduced \peciiic immune reywnws to inhaled antigen\ 111 4ever;lt occupation;lt \tudieh. Fxmer\ u ho Mere newr w-ioher\ had higher levels ofwrum precipitin\ to .~~rc,/,o/lr~/\.\/~r~/.c~,f;/[,/r/ than furmer~ u ho ~rnohed (.\lorgan et at. tY71: Morgan et at. I Y75: Gruchw ct al. 19X I: Cormier and B2tunser I YXY: Kuuh et 111. I YXY). M herca\ pigeon breeder\ \j ho had ne\ er wohed had higher precipitating antibodic\ to pigeon 7 globulin compared u ith their mohin? counterpurts (McShurr> ct at. IYXI: Andcrsen and Chri\tcnwl IYX3: Bo>d et 4. 1977). Similar result\ h3i.e been t'ound in pouttr) N orhcrs ( Anderwn and Schonheyder I YXI) and proceaing uorher\ (McSharr! XICI Withinwn 19X6, in relation to I@.2 rr\ponses to hen serum antigen and prawn antigen, respectively. Whether smokers have a lower in- cidence of hypersensitivity pneumonitis has not been adequately studied. Finally. smokers manifest a blunted immune response to influenza vaccination. Although smokers and nonsmokers have similar postvaccination titers at 3 months (Knowles. Taylor. Turner-Warwick I98 1). current smokers have reduced titers at 1 year when compared with nonsmokers (Finklea et al. 197 1; Mackenzie. Mackenzie. Holt 1976). In a large clinical trial comparing responses to killed and live attenuated vaccine. smokers had a decreased primary immune response to the killed vaccine (Mackenzie. Mackenzie. Halt 1976). Although effects of smoking on the immune system have been demonstrated. feM studies have investigated the association between smoking and acute respirator) illnesses of presumed infectious etiology. Aronson and coworkers ( 1982) found that smoking was associated with an increased risk of acute respiratory tract illness. In addition. these investigators found that smoking increased the likelihood of having a lower respiratory tract illness and increased the duration of the symptom of cough. These findingscorroborated the resultsofother investigations (Haynes. Krstulovic. Bell 1966: Peters and Ferris 1967: Parnell. Anderson. Kinnis 1966) that showed the came trend for increased respiratory infections among smokers compared with nonsmokers. In contrast, Pollard and associates (197.5) found no difference in the incidence of respiratory illness observed among smokers compared with nonsmokers. Short fol- low-up of 9 weeks and selection of Naval recruits who had a high prevalence of acute respiratory disease as patients may explain the discrepancy in results. Kark. Lebiush. and Rannon (1982) studied an outbreak of influenza among 3.76 men serving in a military unit in Israel. They found that 68.5 percent of 168 current and occasional smokers had clinically apparent influenza as compared with 47.2 percent of never and former smokers. Smokers and nonsmokers with influenza had comparable serologic response rates. Among smokers, the attributable risk percentage for severe influenza, defined as illness resulting in bedrest or loss of workdays. was 40.6 percent (95-percent confidence interval (CI), 2 1.6-54.8 percent). Similar results have also been reported by several other researchers (Finklea, Sandifer. Smith 1969: MacKenzie. Mackenzie, Halt 1976; Kark and Lebiush 198 I ). Smoking Cessation and Respiratory Infection The relationship between altered immune and inflammatory functions and the occur- rence of respiratory infections among ex-smokers has not been extensively investigated. This Section reviews available relevant studies. Studies of animals have shown a return to normal immune and inflammatory function after cessation of cigarette smoke exposure (Holt and Keast 1977). Investigations of humans have yielded similar findings. Specifically. among former smokers, serum concentrations of IgG, IgA, and IgM (Hersey, Prendergast. Edwards 1983) and bronchoalveolar lavage cell numbers and percentages return to those of never smokers (Holt 1987). Additionally, Miller and coworkers (1982) found that within 6 weeks of smoking cessation. the number and function of T lymphocytes reverted to normal. Finally, Raman. Swinburne. and Fedulla (19X3) found that 3 year\ after smoking 307 ce\hation. former \mokra had pneumococcal orophar> ngeal adherence value\ com- parable uith those of nwer smoker\. The \ignific;mcc of thehe change< in specific component\ of ho\t defense\ to the ri4. of \uhsequent respiratory infection\ amon? f'ormer smokers ha\ not been chxrcterixed. Mortality from int1uenc.a and pneumonia M ith wpect to ciyxette \mokin_c ha\ been as\e\sed in several cohort \tudie\ (Table 5). Mortality from influenza and pneumonia was increaed in ever smoher\ reluti\ e to never smohera in the American Cancer So&t) Cancer Prevention Study I (ACS CPS-I) t'ollouup from I959 through I963 (Hammond 1965). In the British Phyhicilrns Study. current and former smokers had small excesses of mortality from pneumonia. but annual mortalit) rate\ from pneumonia increaed with the amount smoked (571 IOO.000 for I - I4 g tobacco/day. 61/iOO.O00 for 15-21 g tobacco/day. 9l/lOO.tMK~ for 29.5 p/day) (Doll and Peto 1976). A similar exposure- response relationship v. 3s found in the U.S. Veterans Stud! (Roget and Murray 1980). Finding\ from ACS CPS-II WI afe-ad.justed mortality from influenza and pneumonia have been examined for the effect\ of active smoking and smoking cessation (Table 5). Male former smokers of t'eber than 21 cigarette\ per day have mortlrlit~ ratio\ after IO years of abstinence that are approachin, ~7 unit\ Male former smohers of' more than 1 I _ cigarettes per day have mortalit! ratio\ approaching unity after I5 years of abstinence. hut much higher for shorter period\ ot` abstinence. Female former smohers of an) amount have mortalit> ratios that approach those of never smokers within 3 to 5 years ofab\tincnce. The a\\ociation het\+een cigarette \mohing status and mortality from intlurwa and pneumonict ma)' partlall!, retlect the rft`ects of smohing on respirator> defense mechanism\ including immune rwponws. The ~ulnerahilit\ of perxon~ M ith clgarztte- related cardiopulmonar! di\c:r\e\ to resprratorl infection\ ma\ alo cwntribute to the association. For ewiiple. Glexn. Decher. 2nd Perrotta ( 1987) studied underl!,ing diagnow\ in patient\ hwpitalixd u lth xutr reyrator> disease during intluewu epidemics in Houwn. TX. Chronic pulmonar! condition\ were the mwt co1~m~o11 underI> in? condition. and cardiac condition\ \\ere the ne\t most frequent. PART II: PI~L1IONARY FI'NCTIOV AI\IO\v(; FORILlER S1ZOKERS Cross-Sectional Population Studies of FEYI `OX TABLE K-Age-standardized mortality ratios for influenza and pneumonia for current and former smokers compared with never smokers Doll and Pete 34.440 male (1876) Briri\h doctor\ 20 vr TABLE K-Continued ..J I.4 2.1 I .x t.x I.1 I.1 7 0 .3 2.4 2.2 2 I 7.1 0.`) I 2 .2 h - - 2.7 .I) -- I.4 0.6 0.3 I.2 3-t `I'AHLE 6.-Association between cigarette smoking status and C'KVI levels in selected cross-sectional studies of'adult populations `TABLE k--Continued I `)0X Finding\ AliJU\td "XX, kVeh FEVl FEV I/FVC ratlo Nwrr \moher\ 2.7 X6.7 Former \moher\ 1.6 xs.0 Current \moher\ 1.5 X4.6 Mean value ol the FEVl/FVC ratio Never \mohcr\ 76.0 Former \moher\ 74.3 Current \moher\ 73.6 Adfuwf FEV, (L) Never vnoher\ 3.3 Former \moher\ 3.2 Current maker\ 3.0 Mean normnlwxl FEV 1 wow MtX Women Never \moher\ 10.2 IO. f Former wwher\ Y.0 IO.0 Current smoker\ 9.6 Y.X `TABLE 6.--Continued Krtrrrlce Anderwn ( I Y7Y) Year of sludy Location Lufa. Papua New Gutnea Popui;~lion 733 men and women aged 25 and older H~penbottm et al. ( IYXO) Huhti and Ikkalu (IYXO) IY6l BO\\t! et ill. ( IYXO) I Y6.1 London. Englmd I X.403 male civil wrvant5. aged 40-W Bwton. MA 703 healthy male veteran\ lolloued for IO yr `I'AHLK h.--C'ontinued TABLE 6.--Continued Reference Year of study Location Carnilli et al. (10X7) Tucson. A% Dockcry et al. (19Xx) 1974-77 6 US communities h54 men nnd XY3 women agctl ?I) and older, who had FEV, at hnwline and fbllowup exams Initial FEVl a percentage of predicted Men Women Nonsmoher\ 0Y.X 97.x Former \moher\ Y3.7 9.5.6 Current vnohw" s1.x YI .h Deficit ot FEVl (L) compared with expected K. IO I men and women aged 15-74 Nonvnoherh Former \mohcr\ Current \moher\ Mf3l Women 0.03 -o.oL? -O.`h -0.05 A).51 -0.23 reported that the level of FEVl had a highly significant quantitative relationship with pack-years in a general population sample of 1.369 subjects in Tucson. AZ. and that smokers and former smokers had comparable levels accounting for pack-years. Higenbottam and coworkers ( 1980) assessed lung function in the I X.WO males in the Whitehall Civil Servants Study. Mean FEVl values among former smokers. adjusted for age and height. were lower than those for never smokers. but greater than those for current smokers. FEVl among former smokers decreased with increasing total con- sumption of cigarettes. but length of abstinence had little effect on FEV I among former smokers, although the minimum period considered was less than 6 years. The authors suggested that the depression of lung function associated with cigarette smoking has two components-an irreversible component related to total consumption and a com- ponent rapidly reversible on cessation. Beck. Doyle. and Schachter ( I98 I ) analyzed FEVI data from 4.690 subjects. aged 7 years and older. in 3 separate U.S. communities. These investigators also found that the deficit in FEVl compared with that expected for never smokers increased with cumulative smoking as measured by pack-years and duration of smoking. After adjusting for cumulative smoking. FEVl was I47 mL lower among male smokers and 78 mL lower among female smokers compared M ith former smokers. Dockery and coworkers ( 198X) studied X.191 randomly selected adults in 6 U.S. communities. These researchers found that the deficit of observed FEVl compared u ith expected age-. height-. and sex-specific values increased linearly Lvith cumulative pack-year\ among former smoher\ and current smoher\ (Figure 7) (Dockery et al. 198X). For the same pack-year\. FEV 1 M as I3 mL higher among male former makers and I07 mL higher among female former smoher\ compared with current smoker\. In a follow up study of 227 men. Tal lor. Joyx. and cob orher\ ( 1985) reported that percent-predicted FEVl for former \mohers ( 107.X percent predicted, uas between that of smokers ( 100.5) and neier smoker\ ( I 19. I ). Within each smoking catego?. men with increased bronchial reactiliry to inhaled histamine had lower level\ of percent- predicted FEVl than did nonreactor\. Thehe differences Mere srati\tically \ignificunt among smoher\ (K-l.6 ~`4. 10X.5 percent predIcted for reactors and nonreacrorz. respec- tivel! ) and former \moher\ (96.1 1'4. I I! I .S percent predicted for reactors and nonreac- tor4. re\pccti\cl! 1. Pulmonary Function Studies After Smoking Cessation .Studie\ in v. hich the lung function ofmoherc M;L\ measured hefore and after smoking ce\\ation are re\ ie\rctl in thi4 Src~iori: tt'4t\ ofpulnionar! function included \pirornetr) nitrogen u;r\hout. and other technique\ potentialI! wn\iti\e to the effect\ ofce\\a1ion. Inflammatory le\ionh of the small air\+ ;t! \ hai e been demonstrated to occur in 1 oung adult wwher\ before the :lppcarance ot` clinicall! significant Artlo% ob\truction MEN 8 -1000 300 200 b 5 100 8 0 300 200 c-r 5 100 8 0 PACK-YEARS 0 10 20 30 40 50 60 70 60 90 295 A m c5 10 20 30 PACK-YEARS fJ;;F?tT SMOKERS L- 40 50 60 70 60 90 295 FIGCRE 7.-Sex-specific mean height-adjusted FEV 1 residuals versus pack-years for current and ex-smokers, and distributions of number of subjects by pack-Jears NOTE: FE\`l=I -WC forced c\p~raror> \ ol~m~. SO1 RCE: Do&r~ c`t al. I IYXX, 317 WOMEN PACK-YEARS 0102030405060r65 I 2l t; 2 -250 I5 8 -500 s Ei $ -750 5 ii -1000 300 200 g 100 8 0 EX-SMOKERS CURRENT SMOKERS 8 <5 10 20 30 40 50 60 ~65 PACK-YEARS FIGURE 7. (Continued)--Sex-specific mean height-adjusted FEVl residuals versus pack-years for current and ex-smokers, and distributions of number of subjects by pack-years NOTE: FEV I =I -vx forced erpirxor~ 1 olume. SOURCE: Docker> et al. (I%#). (Niewoehner. Kleinerman. Rice lY73). Te5ts sensitive to abnormulitie\ of the small airways (e.g.. helium-oxygen flop volume curves. the single breath nitrogen test or other tests of closing volume, and frequency dependence of compliance) uould be expected to be particularly sensitive for detecting changes in function after cessation. In most of the studies reviewed in thi$ Section. participants were enrolled through smoking cessation clinics and subsequentI), monitored for pulmonary function and smoking status. The data from these studies can assess reversible effects of smoking throqh documentation of functional change coincident with ceh\ation; irreversible effects can be estimated by comparison of lung function le\,el M ith predicted value\ for normal function. Changes in Spirometric Parameters After Cessation Studies ofspirometric measurements of pulmonq function before and after smoking cessation are cummariLed in Table 7. Many of these studies suggested an improvement in pulmonary function following cessation. although the magnitude of the improvement was \mull in some of the studies. Dirksen. Janzon. and Lindell ( lY73) studied a randomly selected sample of men born in 19 14 in MalmB. Sweden. Fifty-eight heavy smoker\ were solicited to participate in a smoking cessation program. with 31 abstaining for 2 months. Vital capacity (VC) and FEV l/FVC improved 8 to 10 days after cessation. Bode and coworkers ( 1975) studied IO healthy subjects who participated in a smoking cessation program and remained abstinent for 6 to I4 weeks. Small and nonsignificant improvements were found for VC (0.3 percent change) and FEVt (0.9 percent change). Maximum expiratory flow rates with helium at SO and 25 percent of VC sifnificantlq increased. Martin and colleagues (1975) observed 1 2 successful subjects from a smoking . . cessation clinic for 1 to 3 months. Changes of V~XX) and Vrnak2c after smohins cessation were variable and not statistically significant. Residual volume and total pulmonary resistance w/ere also unchanged. McCarthy, Craig. and Chemiack (1976) studied a group of smokers who volunteered to participate in a smoking cessation program. At 25 to 4X weeks after cessation. only IS participants were still not smoking. Among these subjects, FVC increased from 3.92 L to 4.04 L (3.1 percent change). but FEVI (Go.3 percent change) and mid-maximum expiratory flow (MMEF) (-9.6 percent change) decreased. Fifty-nine subjects were evaluated between 6 and 23 weeks following cessation. Significant improvements were noted for FVC (2.3 percent of initial value) and the peak expiratory flow rate (6.7 percent of initial value). The FEVl. Vmax~. and \jmax25 did not change significant]}. Bake and colleagues ( 1977) observed I7 subjects who were abstinent from cigarette\ for at least 5 months. During this int$rval. VC a;d FEVt improved by 4.3 and 4.X percent predicted. respectively, while Vrnax~n and Vmax2 were reduced by 2.5 percent predicted and 7.3 percent predicted, respectively. At 3-vear followup. only nine , subjects were still smoking. No significant differences from baseline function were found in this group. 3 I 0 TABLE 7.-Spirometric studies of participants in smoking cessation programs l-1.(` WC or vc I IO mL 20 ml. 0.3'X 4.x I.h -40 ml. -70 ml. +30 ml. +hO IllL I.5 I.6 3.3 -V.h'/r -2.5 -7 3 0.7 -I I.1 ho rnL/wc t IO IllL/wc +10 IllL/W IMI lllL/W TABLE 7.--Continued Buikt and coworherh ( 1976) observed a group of \ix men and seven women who stopped \mohing for at Ieat I year after a smoking cessation program. Small changes were noted in \pirometric parameters. The author\ reported that MMEF distinguished between smokers and quitters in that over a 1 -year period MMEF declined significantly among smohers but not among quitters. Buist. Nagy. and Sexton (1979) supplemented this sample with participants from another smoking cessation program and extended followup to 30 months for both groups. Significant improvement> were observed in VC. FEVl. and MMEF among the quitters during the first 6 to 8 months (Figure 8). No further improvement was observed up to 30 months. FVC FE'/1 7 4 -2 * 0 .-mm"" --- * 10 20 30 MO AFTER CLINIC Quitters - - - - - - Smokers FIGURE &--Mean values for FVC and FEL'l, expressed as a percentage of predicted values, in 15 quitters and 42 smokers during 30 months after 2 smoking cessation clinics SOTE- .A\tt`rIAx t I know ;I \tfntttc.mt d~ltrrct~cc from thr IIIIILII \.IIw .II p41.05 F\`C=f~wrd t it,il cnpacit!: FE\`, = I -a. ttvccd c`\plral,rr> i OILIIW Zamel. Leroux. and Ramcharan ( 1979) studied X healthy hmoher\ for 2 month\ after cessation. They reported Ggnificant increase\ in VC and FEVl of 3.0 and 3.0 percent change. reqecti\,ely. In contra\t. Pride and coworkers ( 1980) in a -t-year study of eight male smokers "who thought they would find it easy to give up smoking." reported no improvement in apirometric tehts of MMEF. Taken together, these studies suggest that smoking cessation quickly results in small improvements in lung function. as assessed by spirometry. Although the changes were not uniformly statistically significant in the investigations reviewed in this Section. the number of subjects was small in most of the studies. Compared with baseline before cessation, FVC or VC and FEVt may improve by about 4 or 5 percent at 3 to X months after cessation. In absolute value, this improvement is COtnpmbk with the ap- proximately IOO-mL improvement reported by Beck, Doyle. and Schachter ( 19X I ) and Dockery and coworkers ( 198X) based on cross-sectional comparison of former smoherc to current smokers. Tests of Small Airways Function Several investigators have studied the effects of smoking cessation using measures of small airways function as determined by the single breath nitrogen test (Table X) and other tests. In the single breath nitrogen test, the subject breathe\ one breath of l(K) percent oxygen from residual volume to total lung capacity (TLC). A concentration gradient of nitrogen is thus established with the highest concentrations at the apex. Subsequently, the subject exhales, and the nitrogen concentration of the exhaled air is monitored. The indices of small airways function provided by this test include the closing volume (CV) expressed as a percentage of the vita1 capacity (CV/VC percent). the closing capacity (CC) expressed as a percentage of TLC (CC/rLC percent). and the slope of the nitrogen concentration during the alveolar plateau (slope of phase III). Both CV and CC are increased by abnormalities of the small airways, whereas the slope of the nitrogen concentration reflects the evenness of the ventilation distribution. Buist and colleagues (1976) studied a group of 25 cigarette smokers who attended a smoking cessation clinic. Cessation resulted in significant improvements in CV. CC. and the slope of alveolar plateau at 6 and I2 months after cessation. Participants in a second smoking cessation clinic were added, and the followup continued to 30 month\ (Buist. Nagy, Sexton 1979). At the 6- to g-month followup, CV had improved by 33 percent predicted among those who quit. CC by 20 percent predicted, and the slope of the alveolar plateau by 52 percent. No further improvements were evident at the 30-month fo1lowup (Figure 9). Similar improvements have been reported by several other investigators. Bode and coworkers (I 975) found that CV improved by 20 percent 6 to I4 weeks after cessation compared with initial values among 10 subjects. These investigators reported that the slope of phase III was unchanged by cessation. McCarthy. Craig, and Cherniack ( 1976) observed 131 smokers aged 17 to 66 years who volunteered to attend a smoking cessation clinic. For I5 persons abstinent from 2.5 to 48 weeks, cessation resulted in a significant 13-percent reduction in CC and a 27-percent reduction in the slope of phase 111. Bake and coworkers (1977) showed a 33-percent reduction in the percent-predicted slope of phase III among I7 subjects at 5 months after cessation. On the other hand. only small changes in CV and CC were observed. Zamel. Leroux. and Ramcharan ( 1979) investigated 26 smokers for an average of 62 days after cessation. Similarly. 323 TABLE: K-Studies of closing volume (CV/VC% ), closing capacity (CC/TLC% 1, and slope of alveolar plateau (SBNrlL) among participants in smoking cessation programs HAC Cl ;d. I 1977) Hui\t. Nag>. SL~\ll)ll I IO70) (I.O'A -o.X'k + I .h% -5.7% 2.6% t .x 0.3 -I .h - 19.5 --15.4 TABLE 8.--Continued