a Effects of Marijuana Smoking on Pulmonary Function and Respiratory Complications A Systematic Review Jeanette M. Tetrault, MD; Kristina Crothers, MD; Brent A, Moore, PhD; ‘Reena Mehra, MD, MS; John Concato, MD, MS, MPH; David A. Fiellin, MD Background: The relationship between marijuana smok- ing and pulmonary function of respiratory complica- tions is poorly understood; therefore, we conducted a sys- tematic review of the impact of marijuana smoking on pulmonary function and respiratory complications. Methods: Studies that evaluated the effect of mari- juana smoking on pulmonary function and respiratory complications were selected from the MEDLINE, PsychINFO, and EMBASE databases according to pre- defined criteria [rom Januaty 1, 1966, 19 October 28,2005, Two independent reviewers extracted data and eval ated study quality based on established criteria. Study re- sults were critically appraised for clinical applicability and research methods. Results: Thirty-four publications met sel nia. Reports were classified as challenge studies if they examined the association between short-term mari- juana use and airway response; other reports were clas- sified as studies of long-term marijuana smoking and pul monaty function or respiratory complications. Eleven of 12 challenge studies fotind an association hetween short- term marijuana administration and bronchodilation (eg, increases of 0.15-0,25 L in forced expiratory volume in 1 second). No consi tween long-term marijuana smoking and airflow obstruc- tion meastres All 14 studies that assessed long-term mari- juana smoking and respiratory complications noted an ‘association with increased respiratory symptoms, includ- ing cough, phlegm, and wheeze (eg, odds ratio, 2.00; 05% confidence interval, 1.32-3.01, for the association be- ‘oven marijuana smoking and cough). Studies were vari- able in their overall quality (eg, controlling for confound- crs, including tobacco smoking). fent association was found be- Conelusions: Short-term exposure to marijuana is as- sociated with bronchodilation. Physiologic data were in- conclusive regarding an association between long. marijuana smoking and airflow obstruction measures. Long-term marijuana smoking is associated with in- creased respiratory symptoms suggestive of obstructive lung disease “Arch Intern Med. 2007;167:221-228 Author Afiistions: Clinical Epidemiology Research Center, Department of Veterans Allis ‘Connecticut Healthcare system, ‘West Haven Veterans Allaire ‘Medical Center, West Have, (Conn (Drs Teault and ‘Concato); Departments of Medicine (Drs Terault, CCrothers, Coneato and Fiellin) and Psychiatry (Dr Moore), Yale University School of Medicine, ‘New Haven, Conn; and Department of Medicine, Case ‘Western University School af Medicine, Cleveland, Ohio (Dr Mehra). ARIJUANA REMAINS THE. most commonly used illicit drug in the United States, with 14.0 million people 12 yearsand older reporting current use.’ The prevalence of marijuana abuse and depen- dence continues to increase and occurs in 18% of past-year marijuana users.” Given the persistently high prevalence of mari- juana use, abuse, and dependence in the community, it is important to under~ stand the potential adverse health out- ‘comes that result from both short-term and long-term marijuana smoking, Marijuana and tobacco smoke share many of the same compounds. Tobacco smoking isassociated with numerous sd- verse pulmonary clinical outcomes, af- Fecting both pulmonary function and re piratory complications. Some of the known tobacco smoking-related adverse effects inelude cough, chronic bronchitis, tm- pairment of gas exchange, and airway ob- sttuction that leads to chronic obstruc- tive pulmonary diseas: impact of marijuana smoking on pulmo- nary function and respiratory complica- tons has not been systematically as- sessed, The purpose of the eurrent review is to determine the association between short-term marijuana smoking and air way response and the association be- tween long-term marijuana smoking and pulmonary function or respiratory ‘complications. The adverse (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018[Hisaae erate Samo area] Sis i Sa re {5 owt hea Sues Stith oc 17 Daa epaulets ‘raenay fac seb an re tT 1008 [Sse erate ao] aia at Pe Say satan ites [>| se diter te egy Compe ‘Pony finan «Viee Ge Se at Fever Tan 15 ‘apd De aed amu ae aie i We ped Ro Pay Facoonane Sgn Spins Figur, Liste search ests. — ino VALIDITY ASSESSMENT Study quality was evaluated by 2 review ers (J.MT. and K.C.) using an estab- SEARCH STRATEGIES lished generic instrument? that as- sessed reporting, bias of confounding, English-language studies in persons and power, score of 12 or higher wae 18 years or older were identified from considered good study quality.” Wealso the MEDLINE, PsychINFO, and appliedexposureand disease-specific cri- EMBASE databases from January a teria to augment quality assessment us 1966, o October 28,2005, using met ing the generic instrument, For cross- calsubject headings and textwords (see sectional studies, these criteria were Appendix at hupAvww.tresearch.org _whetherdata were inchuded on prior to “ad-heaivi reviews hun)-Onlystde acco exposure and on dose and dura {es that involved marijuana smoking tana exposure and whether ‘were considered for review. ‘dmethod to assess the pul onary outcome of interest was used, For observational cohort studies, an ad ditional eriterion was ta screen pa- tients at baseline and exclude those with the outcome of interest. Challenge stud ies needed to meet the eriteria listed herein and also mask patents and study personnel to marijuana use. Difler- fences between reviewers were resolved by consensis with input from a thitd r= viewer (J.C. or DALE). interrater reli ability was high (F=0.79 for the ge- nevi evaluation criteria: r=0.89, Kendall ‘7-085; P=.001 for the exposure and disease-specific criteria). SELECTION Retrieval ofstudles was performed by Dreviewers (BAM. and RM), Who cvaluated tiles and abstract from the {nial electron search of potentially relevant articles. studies" were ex- duded if they did not report primary data, did not include human subject, Aid not report results of respiratory complications or pulmonary function teste or reported on a case eres with fewer than subjects, Forstudies hat resented data on similar or duplicate shorts we used data that represented the lat follow-up forthe cohort or DATA SYNTHESIS findings rom investigations that repre- The heterogeneous nature ofthe stud- sented assessments of unique domains jeg and their outcomes precluded quan- for variables. Articles that could not be itative synthesis (ie, meta-analysis). «categorized based on review of the ab- Therefore, this review focuses ona quali- Stract were evaluated im manuscript gue synthesis of the data, {orm Studies with discordant catego zalions by the 2 reviewers were re DATA ABSTRACTION solved in collaboration with a third reviewer (DAF, KC. or ].MT.) to Theinitl literature search identified 965 reach consensts citations. Inconsistencies regarding as- sessment of ligt criteria were dis- ssed by the whole team, OF the 965 shtrctstnially reviewed, 931 were not televan 436d not report primary da 252 didnotinclade human subjects 173 tacked evaluation of respiratory com plication or pulmonary function te Sowere cassie of ewer than 10 pa. tents, and reported data obained from thessime patients, Ukimately 34 unique ticles were included inthe review (Figure) “Thc outcomes of he 4 included stud tes werecasfed nt non-muttaly x= lhsve categories airway response ex Perimentally administered marijuana (challenges) changes in pmo nary function seconday to long-term Imafjana smoking." and respratory Complications secondary to long-term tmanjuana smoking "===" The Sues reviewed had diverse study de- Signs 12 studies hada laboratory al Tenge study design" 15 were crose- secllonal® 3 were observational coho Studies-™- 3 were cae series” and Tae a ease contol study EEE REVIEW OF STUDIES ‘CATEGORIZED BY STUDY OUTCOME Short-term Marijuana Use and Airway Response Twelve studies able 1) assessed the impact of short-term marijuana use on airway response. The studies used various measures to evaluate airway response: specific airway conductance (sGaw) (ameasure that is inversely related to airway resis- tance),*7#"4*" forced expiratory vol- ume in 1 second (FEV,),°#* peak flow. airway resistance," and change in methacholine- and exercist induced bronchospasin." ‘Among the 7 studies that used sGaw to assess the airway response to marijuana challenge, 6 stud- ies812518 showed an increase in sGaw after marijuana challenge that ranged [rom 8% to 48%. Two of these studies showed that the in- crease in sGaw lasts tp to 60 min- utes after marijuana administra- tion, and 1 study!" demonstrated that peak sGaw occurred 15 minutes al- ler smoking. References 18, 19, 2-25, 25,27, 28,30, 31, 3438 (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018Table 4. Challenge Studies That Reported Elects of Short-term Marijuana Inhalation on Alrway Respons ean Expose We. ot conte or Mean denere source subjects esas confounding ova Vechon ataP 107410. Marjuanasmolng associated wi narsealn aw 1h None star smoking (P001) Tashkinctal7 1974 10——Atar smoking marjuara, average sGow increased Tobacco ns a immediatly (P05 compare with contol and pla) inpatients wih asthma Bemstoinstal! 1076 2812 1Ssubjerts showed increases in pak xpatory None 7 2 fw mmedataly ster smoing mariana igre Lavoe and 11 Matjuan smoking produced increase in sGaw (P01) Tobacco 10 25 Bulanar? 1966 and FEV (P08) Furaud and Cormac” 12 FEN; increased immediatly ater mariana smoking None 2 a 16 (ee ‘Stadad and 20° ‘Nodifrence in FEV ater smakingmaruana compared None 5 2 Sigh 1975 ‘ith hasalieo placebo ‘shh etal 1973 32—Atar smoking marjuara, thre was animmedata Tobacco 165 a intease in sGav, ic pakad at 15min ate smoking and remained elevated 269 min “bln et 1075, 8 Aterboth methacholine indued and wercsesnduced Tobacco a ‘ronchoepasm in aethte patents, marta ‘caused craton of bronchospasm ard assodaad say hpi Tastkinctal¥ 1076 28 —_—Atar 4710 59 dof hoy arvana smoking, mean FEV; Tobacco ° a creased (Pe) and mea sSaw decane (001). Modest but signieant decrease simasing capacity also noted. Catlin betwaon rage quanty of daly marijuana smoked daring the Stuy and reduction of a. Tash ctal" 1077 11——~FEV, and sGaw increased ater smokod mariana Tobacco us a (P05) schon atl!° 1972 17-_—_Ineens in aw ater maaan inslston Tobacco w a Wu etal” 1902 2 Atarsmokng marjuana, away esistnce decreased Tobatco 118 a lgfanty al vel of maruana compared th plato (P05) ‘Abbreviations: FEV, fred expiratory volume in 1 second; sa speci aay conductance, Among the 5 studies that used cm H.O/L per second for high-dose Long-term Marijuana Smoking FEV, to assess airway response to marijuana challenge, 3 studies’ showed an increase in FEV, alter smoking matijuana compared with baseline, ranging from 0.15 10 0.25, L. One Study" showed no differ- cence in FEV, after marijuana chal- lenge compared with baseline or placebo. ‘One study" used peak flow to as- sess marijuana ellect on airway re- sponseand showed that 12 0f 15 pa tients had an increase in peak flow immediately alter marijuana inha- lation, with a meanSD prechal- lenge vs posichallenge peak flow of 509.2476.1 vs 549.2460.4 Lmin X 100, respectively (P<.05), Another study" showed a mean sSD decrease in airway resistance after marijuana smoking compared with placebo (2.0840.36 em H,O/L per second for low-dose marijuana smoking vs 1490.26 em H.O/L per second for placebo and 1.9740.35, alter marijuana challenge One study last to the short smoked and decrease in sGaw. ‘marijuana smoking vs 1180.14 em H,O/L persecond for placebo; P= for both comparisons). Finall third study"* showed immediate re- versal of both methacholin induced and exercise-induced bron- chospasm in patients with asthma examined the im- pact of a more prolonged exposure to marijuana on airway response, in which subjects smoked marijuana ad libitum for 47 to 59 days in a se- questered environment. In con- jerm exposure studies, this study demonstrated a decreace in sGaw compared with baseline (change of 16% 42%: 001) after the more prolonged exposure to marijuana, as well as a decrease in FEV, compared with baseline. This study also demon- and Changes in 05 Pulmonary Function Fourteen studies (Table 2) ad- dressed the impact of long-term mat Juana smoking (described as nonto- bacco cigarette smoking in 2 studies") on abnormalities in pul monary function, including 10 eross- sectional studies +3 observational co- hort studies." and 1 case series. Of thes a0 ported data on the effect of mari- jana smoking on FEV), forced vital ‘apacity (FVC), and FEV /EVC. One observational eohort study ported no change in FEV, among Tarijuana smokers for a meanaSD follow-up of 4.92.0 years. Another ‘observational cohort study" showed ‘4142: decrease in FEV, among pa tients who had previously smoked ‘9 studies! strated a correlation between aver- age daily quantity of marijuana ‘FReferences 18,19, 21-23, 25,27, 28,30, 31 (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018Table 2. Studies That Reported Etfects of Long-term Marijuana Inhalation on Pulmonary Funetion, ean Expose a ta ot Conreltor ean Genore Disease spect source sty Design subjects esas Confounding Quay Score Guay Boom atal™ —_Cross-secional 90. For sprometie dat: no sigan act ot Tobacco © 2 ‘er nonlbaceaclgarate smoking a FEV, ot FYE. Cet roles of ontoarco gates showed gear dns in FRYE tea P09 compare th tonsrkers and toltzo sas Cickshank® Cross-section! 60.—_-Nolvenees pulmonary funcion stun None 65 15 ‘976 tananasmolars and conto Hendrson_Casesaies —200-—-Among patents presenting wth complaints None 45 1 eal? 1972 onus wil chonc oi wi capacity reducd 15-20% HemanderCoss-seconal_—28—_Spamsty ress normal inmarjvana users None 95 3 tal 1984 Meoreetal —Cross-seconal 6728 Compared wth nonusers, maruana and Tobacco 175 3 3008 "aba wssts had higher proportion of sajete wth an FEV rato < 70% prdiced (OR, 256; 95% CL. 1 5-435: and ‘OR 6:25; 05% C, 476-83, respective) Contoling or ez, maiuana ue was rot associated tha deceased FEVJEVC Shormanetal® Cross-secional 63 No sgrifeantditerenc in FEVYFVC and Da Tobacco 10 3 ‘aot “in anjanaemakers compared wth sonsmokes ‘Shai etale* Observation! 856 Indore of pulmonary function ware Tobacco 135 a “01 cotot ‘onc redid in subet reporting ontbaceasigarte smoking longitudinal Tashin etal Cross-sectional 180 Matjuana smolars hai lower saw compared Tobacco a5 25 “eo with conta (P= 001) ‘asin etal Obsevationd 384 —_‘Noffect of gam maruara smoking on Tobacco 2 a “07 cohet BV dcine Tashin etal” Crose-tetonal 542 Association between marijuana smoking and Tobacco 105 a 003 deca of FEV sponse ow doses of rtachata, ating arvay Inpertesponshenass Tyloretal!! Cross-sectional 862 Greater proportion of maruana-dependet Tobacco 125 a 200 Indvduals showed a reduced FEV/EVC rato compared wh noramotrs (P= 007) Tyloretal® —Obsavationd’ —980_—_Linarlatonship eteen numb of ines Tobacco 135 a 202 cotot ‘anrabis used and decreasing FEV/FVC (05). However once confounders fae, {obact, and waht wera adjusted fo, felatonchip wae na longer signicant (P= 09) es tal” Cross-sectional 68 _—-Matiuana smoking, wh or without tabacco Tobacco 105 25 086 ‘smolng was ssecatd wih 2 reduction ‘ingle breath Dy compara wth onsmoting cats (P= 08) Tashin etal —Cross-seonal 446 Male marjuana smokers had reduced sGaw Tobacco 2 a ‘67 ‘compar th mle abaeco smokers a Gforce De among marjuana srokers Sn nonsmokers ‘Abreiatons: Cl, contdence intra DL. sing capac of the ung or carbon monoxide FEV, fred oxpatory volume in 1 econ FV, fred vital capaci OR ods a, say, speci ray conductance. nontobacco cigarettes P<01).One and tobacco smokers (90% pre-_ PEV/PVC was reduced 1 year or case series! noted that long-term dicted vs 05.2% predicted: P<.05). more alter nontobacco cigarette hashish smokerswho presentedwith Two other cross-sectional stud- smoking compared with nonsmol- respiratory complaints hada 15% to es"™“reportedadecreaseinthe FEV/ ing (decreased 1.9%10.7%: P<01), 40% decreased EVC compared with FVC ratio among marijuana smok- but dose-response relationship was controls. One large cross-sectional erswhencompared with nonsmokers, noted, Another large observational co- study" showed that male nonto- but after adjusting for tobacco use, hort study.” which followed up a bacco cigarette smokers had ade- ofthese studies" demonstrated no birth cohort into adoleseence, found crease ip FEV,/PVC ratio compared —_dillerence between masijuanasmok- that individuals sing cannabis more with both nonsmokers (90% pre-_ersand nonsmokers. One observa-_ than 900 times had mean FEV\/ dicted vs 98.4% predic 3) ional cohort study reported that FVC values that were decreased 7.2% (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018atthe age of 18 years, 2.5% at the age (of 21 years, and 5.0% at the age of 26, years compared with nonsmokers (P<.05 for all comparisons), but when adjusted forage, tobacco stok- ing, and weight, the association was no longer statistically significant. Two cross-sectional studies" reported no differences with respect to FEV\/ PVC ratio, Three studies*?°*" examined changes in the diffusing capacity of the lung for carbon monoxide (Dlg) with long-term marijuana use. The DL. was reduced in long- term marijuana smokers (74%20% predicted) compared with nonsmok- ing controls (02% 119% predicte P<.05) in 1 cross-sectional study,” although 2 studies” reported no difference in Dz» between long- lerm marijuana smokers and nonsmokers, Four studies"2"°! examined the impact of long-term marijuana smoking on airway resistance and. airway hyperresponsiveness. Long- term marijuana smoking was ass0- ciated with a decrease in sGaw in 2 cerose-sectional studies; one” showed ‘decrease compared with control subjects (0.170.00 L/s per centi- meter H,O for marijuana smokers and 0.2440.01 Lis per centimeter H.0 for controls; P=.001), and the other” showed that, among men only, sGaw was decreased in mari- juana smokers compared with to- bacco smokers (0.19 L/s per centi- meter H,O for marijuana smokers ‘and 0.21 L/s per centimeter H,O for tobacco smokers; P<.03). Another cross-sectional study" reported no cchange in airway resistance in re- sponse to inhaled histamine in mari- jiana users compared with non- smoking controls. Finally, another cross-sectional study" reported an. association between long-term mari- juana smoking and a decrease in FEY, to lower doses of methacho- line compared with nonsmoking controls, suggesting nonspecific a way hyperresponsiveness, Long-term Marijuana Smoking. and Respiratory Complications We reviewed 14 studies (Table 3) that assessed the impact of long- term marijuana smoking on respi- ratory complications; 9 were cross- sectional,'*22%-9%% 3 were case series," 1 was a case-control study.."and 1 was an observational cohort" All 14 studies showed an association between marijuana smoking (or nontobacco cigarette smoking) and an increased risk of various respiratory complications. Increased cough, sputum produc- tion, and wheeze were reported in 4 of these studies." One cross- sectional study” reported increased prevalence of chronic cough (18%- 2496), sputum production (20%- 26%), and wheeze (25%-379%) among, ‘marijuana and/or tobacco smokers compared with nonsmokers (P<.05 for all comparisons) but not b ‘ween manijianaand tobacco smok- ers. A large cross-sectional study" suggested a dose response between intensity and duration of nonto- bacco cigarette smoking and cough. Another large crose-sectional study showed that alter controlling for sex, age, current asthma, and number of tobacco cigarettes smoked per day marijuana smoking was associated with increased odds of cough (odds ratlo [OR], 2.00; 95% confidence in- terval [CI], 132-3.01), phlegm (OR, 1.80; 95% C1, 1.35-2.66),and wheeze (OR, 2.98; 05% Cl, 2.05-4.34) com- pared with controls (P<01 for all comparisons). A large observational cohort study showed an increased odds of cough (OR, 1.73; 95% Cl, 121-247), phlegm (OR, 1.53; 05% G1, 1.08-2.18), and wheeze (OR, 2.01; 95% Cl, 1.50-2.70) in current non- tobseco smokers compared with non- smokers alter adjusting for age, to- bacco smoking, and occurrence of symptoms reported previously The remainder of the studies showed an association between ‘marijuana smoking and various res- -atory complications: bronchi- Ganesh dpspnen 2 phar ‘worsening asthma symptoms," ab- normal chest sounds, worsening cystic fibrosis symptoms, "acute e acerbations of bronchial asthma and chest tightness." STUDY QUALITY (On the basis of study design, the studies reported were of variable quality using the standardized scale” The mean quality score was 12.6 (range, 6-18) for the 12 challenge studies, 5.2 (range, 4-7) for the 3 cease series, 10.5 (range, 3-19) for the 15 cross-sectional studies, 12 for the 1 case-control study, and 13 (range 10-14) for the 3 observational co- hort studies, ‘Study quality was also evaluated based on study outcome. The mean quality score for the airway re- sponse in studies ofshort-term mati- jana use was 12.6 (range, 6-18). For studies that evaluated changes in pulmonary function secondary to long-term marijuana smoking, the mean quality score was 11.1 (range 4-10), Forthe studies categorized as, respiratory complications second- ary to long-term marijuana smok- ing, the mean quality score was 10.3 (range, 4-18). ‘When also scoring publications based on disease-specific criteria, the studies that met the highest level of study quality using both scales wer the 3 observational cohort stud- ies. Therefore, a discussion of these 3 studies in greater detail is warranted. The most recent obser vational cohort study® followed up birth cohort of 930 participants in New Zealand to the age of 26 years. AL18, 21, and 26 years of age, mari jana and tobacco smoking were as- sessed with a standardized question- naire, and pulmonary function was measured by spirometry. Confound- ing factors (age, tobacco smoking measured as cigarettes per day, and weight) were accounted for using a lixed-effects regression model. The authors report that during 8 years of follow-up, the dose-dependent re- lationship seen between cumula- live marijuana smoking and decreas- ing PEV\/PVC was reduced to nonsignificant once the confound: ing factors were controlled for. The authors suggest that longer fol- low-up time is necessary for the dose-dependent relationship to per- sist in the context of confounding factors. ‘Another observational cohort study® followed up a convenience sample of 304 white adults for 8 years. Among the study partic pants, 131 were heavy and habitual smokers of marijuana, 112 smoked marijuana and tobacco, 05 smoked nly tobacco, and 86 were nonsmok- (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018Table 3. Studies That Reported Etats of Long-term Marijuana Inhalation on Respiratory Complications ean Expose a Noot Conte tr Mean Gener Disease spetie source ‘Sey Design subjects esuts Confounding ually Sora Guay Teamatal™ Cross-sectional 000 — Wlvarabl amas shows acocaion Tobacco © 2 ‘er baten tnt and duration of ontabacco tigaretes and cough lg, and when Hendezon etal Case saree 200 Canabisemolars complained ot pharyngitis None 45 0s 1972 (n= 150), ns (n= 26), chen bronchitis (220) andasthna =) Moorstal® Cross-sectional 6728 Marjuana use associated with espatory ‘Tobacco 175 a 20s ‘symptoms, chronic brnchts, bushing on ros ay, log, hosing, and chest, unde without Shonlletal Observational 1802 Marjuana smoking assorited wih cough, _Tobasco 135 a ‘aot “otot pho, and whee Tyloretal:! Cross-sectional 948 Marjuana use associated wih wheazing apa Tobacco 125 a 200 trom cold execenralate sornes ot beat nocturnal waking with chee tightness, and maring sputum production Tashinetal™ Cross-sectional 446 Marsuana soles hadimcteased aes of Tobacco 15 a ‘67 ‘hone cough sputum prositon, whose, and mae than 1 prolonged episode ot bronchitis during th previous 3 y compared ‘wth he nonsmokers Gatastal® Casecontol_ 20044 fasta group compared with 20% of None 2 1 “006 onto roup admit oo forrecent substance use (OR, Inatute bronchospasm group, 2% art to recenlyusing inal substances mgarod vith 55% of contol (08, 3.68 BE) No erence in proporons ot asthma and contel groups tat epred rmaiuara use Teonant"1080 Case series {36 —Marjuaa smokrscompland of increased None 1 2 ‘nouns of jsprea and excess sputum production Bougupours et Cross-sectional 2 _—Vetbalhoarsnoss was detected ind ol None 8 15 ‘1076 ahi users and of 38 con. Two of 1 vate and 38 contol ad eg of emphysema. Chopra*1973 Cross-sectional 124 Lani, pharyngitis, bronchitis, dyspnea, None 3 1 asthma, iain cough hoarse vie, nd yess ofthe oat were more common in those who smoked higher daly dose of maar Mebodrata and Cross-sectional 75 Camabisemoare complained of weghtars, None 8 15 Wig 1075 ough spa, and poor slap Polnatale"” Cross-sectional $02 Marjuaa smokers reported more day with Tobacco 15 a 1m03 al, or sare thet n past yea han ronemors Stematal® 1987 Cross-sectional 178 Ingatents with ys boss, 20% of None 18 1 ‘ariara users noted immediate and 5% ood ang-trsmproverart symptoms 2D of ut nated imate and &D"s noted anger wrseing of spor Teonantand Case ties 31 Bvatmanjuana smokers complanad ot None 4 0s Prendergast thinpharygil and 29% complaiod of i971 bronahtie ‘Abreaten OR, ade ra, cers; 255 participants had measure ment of FEV, at least 6 times dur- ing an 8-year period. random- celfects model, including height, intensity of marijuana use (mari- juana cigarettes per day), and inten- sity of tobacco use (cigarettes per day) was used and failed to show a significant relationship between, marijuana smoking and FEV, de- cline, Potential weaknesses of this study include lack of adjustment of duration of marijuana smoking and alow follow-up rate of 65%. ‘An additional observational co- hort study*" used data obtained from 3-year follow-up surveys con- ducted during a 6-year period in a random stratified cluster sample of households in Tueson, Ariz, be- ween 1981 and 1988, Using a 2-stage random-elfects model with height and sex as constant covari- ates and nontobacco cigarette smok= ing and tobacco cigarette smoking (and their interactions) as time- dependent covariates, the authors (©2007 American Medical Association, All rights reserved. Downloaded From: by a Mexico | Access Provided by JAMA. User on 06/07/2018