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142 O <br />AMERICAN JOURNAL OF RESPIRATORY AND CWTICAL CARE MEDICINE VOL to 1997 <br />marUuaoa use (15) to undergo repeat lung function testing on <br />up to six additional occasions at Intervals of at least I The <br />we also fitted A second random<ffccts model in which tobacco and <br />me"j'" <br />yr. <br />Present report presents the results of the analysis of this longitu- <br />nes status were constant ewvariabla, rather than t6nc-depesedent, <br />For this analysis, each subject was classified as a never or continuing <br />dinal study of lung function. <br />smoker oreaa substance uparstely, based on whether the subject was <br />either A nonsmoker or a smoker or that substance at each and every <br />Lino, respectively. Otherwise, subjects were classified as inlerrrjuent <br />METHODS <br />smokers for that substance <br />The initial sample consisted of healthy volunteers 25 to 49 yr of age, <br />including 144 heavy, habitual smokers of marijuana alone (MS), 133 <br />regular smokers or both marijuana and tobacco (MTS), 70 smokers or <br />tobacco only (TS), and 97 nonsmokers (NS) of any substance (11). Sub- <br />jects were Initially recruited from the general Los Angeles area through <br />newspaper and radio announcemenis from 19831hrough 1985. Criteria <br />for study entry have been pnwiou* reported (I5). Specifically excluded <br />were persons who reported current or previous intravenous drug use or <br />smoking of other illicit substances (eg.. crack cocaine, phencyclidine, <br />methamphetamine, heroin, and opium) more than 12 times In thdr Ilves <br />or within the previous 6 mo. Persons with significant occupational ex- <br />posures to substances potentially hazardous to rapbatory health, or with <br />a history of Chronic respiratory Illness, were also excluded. <br />Eligible subjects completed a detailed respiratory and drug use ques- <br />tionnaire adapted from the American Thoracic Society/National Han, <br />Lung and Blood Institute (ATS/NHLBI) questionnaire (20) and the Na. <br />bona) Institute on Drug Abuse (NIDA) nationwide survey on drug abuse <br />(21). An extensive battery of pulmonary function testa was also per. <br />formed. Details of the testing procedures, methods of Calculation, And <br />comparison with expected reference values used in the study haw been <br />described previously (15). A subsd of these participants (36 MS, 42 MTS, <br />267%and 40 NS) also underwent f4booptic broncbascopy, bronchoal- <br />veolar lavage (RAL), and bronchial mucosal biopsies at variable times <br />following pulmonary function testing. Results of the broachoscopic <br />studies have been reported previously (17, 18, 22. 23). <br />Since 1985, extensive efforts haw been made to reeootad at least <br />annually, by mall and telephone, all 446 participants who had under- <br />gone Initial testing in 1923 through 1985. Mail was scot under a US. <br />Postal Service arrangement that pronleled the tender with Identification <br />of the address to which the mail was delivered. Participants who were <br />lost to follow-up (cit-, unddivered mail with no forwarding address) were <br />traced through work telephone numbers, contacts with Individuals Iden - <br />ti fled by the subject as Likely to know his or be whereabouts, Stale depart- <br />ment of motor vehicle rosters, voter registration fila, the U.S. Social <br />Security forwarding syuem, and commercial credit seambes. A field visit <br />to the last known residence of a participant was utilind it necessary. <br />The National Death Index (NDI) was used to identify deaths In the study <br />group NDI searches were run eaeb year for individuals not known to <br />be alive at the end of that year. For deaths of study subjects identified <br />by the NDI, death eoreineatu and hospital and pathology records were <br />requested to determine the mum of death. <br />Recontacted particiPeats were Invited to undergo subsequent rounds <br />or examinations at periods of 3 I yr, Including an interval respiratory <br />and drug use interview and at least forced expiratory spirometry. Tro <br />experienced technicians who were sou -trained In the study procedures <br />Performed the Initial And follow-up pulmonary function tats. The same <br />pulmonary function equipment and testing procedures were used through- <br />out the study (I5). Questionnaires were administered by trained later - <br />viewers. <br />Data Analysis <br />For FEV„ random-erfects modeling was used to estimate the rate of <br />decline In lung function with age in relation to snacking status fm mariju. <br />ana or tobacco at any point In time, with smoking staters as a time - <br />dependent covariable (24, 23). Other potential covar(ables were height <br />(constant) and intensity of use of marijuana (joints/day) and tobacco <br />(cigarettes/day), the tobaao-marijwna interaction, and former smok- <br />ing of each substance, which were all assessed at each survey (time. <br />dependent). The model Also included data from subjects with only one <br />measurement These single observations contribute to the estimate of <br />the Intercept but do not affect the slope csdmatt The advantage of this <br />model is that it allows for one or more changes in smoking status ower <br />flue. Analyses were performed rot men and women scpamtdy. <br />RESULTS <br />Of the 446 eligible subjects Initially enrolled in the study, 394 <br />underwent measurements of lung function. Demographic char- <br />acteristics, smoking status, and FEV, of the 394 study participants <br />with evaluable lung function are shown in Table I by smoking <br />category at the lime of study entry (Visit 1). The tobacco -only <br />smokers were slightly older than subjects in the other smoking <br />categories (P <0.05). The marijuana smokers were heavy daily <br />smokers (mean of more than 3.5 joints/d), w ^ as the tobacco <br />smokers smoked an average of nearly I to 1.5 packs of cigarettes <br />Per day. The combined smokers of marijuana plus tobacco <br />smoked less tobacco than did the tobacco -only smokers (p < <br />0.03), whereas the current intensity and lifetime amount of <br />marijuana smoking was not significantly different between the <br />dual and maiijuaaa-only smokers. The mean age and tobacco <br />consumption of the female subjects in each smoking category <br />were similar to those of the male subjects in the same category. <br />Baseline % predicted FEV, did not differ across smoking cate- <br />gonm <br />Table 2 shows the number of longitudinal assessments by gen- <br />der. The mean interval between consecutive visits was 1.7 d: 1.1 <br />(SD) yr, with minimum and maximum intervals of approximately <br />I and 8 yr, respectively. The mean interval between the first and <br />last visit for each subject was 4.9 t 2.0 yr. Nearly two-thirds <br />of the cohort (255/394) were festal on two or more occasions. <br />Nearly all of those not retested bad moved out of the area or <br />were otherwise lost to follow -u0. The proportion of male and <br />female subjects who underwent morethan one set of lung func- <br />tion tests was similar, and the proportion of subjects who were <br />tested more than once (MS 66.7%; MTS 56.391s; TS 64.65o; NS <br />73.3%) did not differ significantly from those who did not un. <br />dergo follow-up testing by baseline smoking category (p> 0.09; <br />chi-square analysis). Moreover, within each smoking category, <br />no significant differences were found in the age, baseline smok- <br />ing characteristics, or baseline FEV, of the subjects who were <br />studied only once and those with multiple tests, except that MTS <br />in the follow-up group were slightly lighter tobacco smokers (16.0 <br />cigarettes/d) than MTS who were studied only once (21.7 ciga. <br />rettes/d) (p < 0.05). <br />Fourteen participants were known to have died during the <br />follow-up period, including 8 MTS, 2 MS, 3T& and 1 NS. Known <br />causes of death included acquired immune deficiency syndrome <br />(AIDS) (1 MS, 1 MTS, and 2 TS); violence (3 MTS); suicide (1 <br />MTS); drug overdose (1 MTS); breast cancer (1 MTS and I NS); <br />and asphyxiation from aspirated food (1 TS). <br />The number of subjects in each smoking category who re. <br />mained "continuing smokers" of each substance or temporarlly <br />quit (or started) smoking a particular substance during the follow- <br />up period Cintermittent smokers") is shown in Table 3. More <br />than 80% of smokers of marijuana with or without tobacco con- <br />tinued to smoke marijuana throughout the follow-up period, and <br />RPPmsxjmately 90% of (obacco-ordy smokers continued to smoke, <br />Whereas; 75% of dual smokers of tobacco and mar))uana Con. <br />tinued to smoke tobacco. Relatively few subjects in any smoking <br />category began smoking either tobacco or marijuana during <br />follow-up. Although most smokers of marijuana (nitially (587e <br />of MS and 67% of MTS), including those who quit smoking <br />