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Pages 294-337

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From page 294...
... In this appendix, we assume that a weighted average of 1.3 is causally related to differences in environmental tobacco smoke (ETS) exposure between ~exposed" and "unexposed" individuals and not to bias (e.g., misclassification of smokers as nonsmokers-see Chapter 12~.
From page 295...
... on ferrets of urinary cotinine in "exposed" and "unexposed" individuab to estimate this true relative risk by two different methods. In Section D-2, we combine the existing epidemiologic data on active smokers with data on nonsmokers exposed to ETS to estimate the ETS exposure of an average nonsmoker in cigaretteequivalents per day.
From page 296...
... The estimated lifetime risk of lung cancer attributable to ETS in a nonsmoker with moderate ETS exposure lies between 390 and 990 in 100,000. The estimated lifetime risk of lung cancer attributable to other people's cigarette smoke for an exsmoker who
From page 297...
... relative risk In "exposers Individuals is 3 tunes that of "unexposed individuals. Hence, in the absence of bias, the summary rate ratio of t.3 equals the ratio of the true relative risk in "exposers individuals to that in "unexposed" individuals.
From page 298...
... . It is possible to estimate the true relative risk in "exposed" and "unexposed" study subjects, given two additional pieces of information (see Remark 8 in the Technical Discussion)
From page 299...
... Smaller differences postulated between the lifetime ETS exposures of "exposed" and ~unexposed" individuals will be associated with larger estimates of the true relative risk. (Having an observed rate ratio as large as I.3 when there is truly only a small difference in dose between the "exposed" and "unexposed~ subjects would imply that ETS is a potent carcinogen.)
From page 300...
... 300 o ~¢ :: .o et :> s: · ·O o u' · 5~5 o x .o e~ o p~ ·= E~ o~ ~ ;^ ~4 uO o ~o <: :^ o o ~o ~: ~: o ~ ~ , ~ o - ~ O o ~ o 1 o 1 o 1 o o o o o o .
From page 301...
... studies. In this case the overall range in the estimates of the true relative risk was 1.19 to 1.35 in the Exposed and 1.04 to 1.18 ~ the Unexposed.
From page 302...
... Each of our three methods of deriving an estimate for p4/~i from data on active smokers also produces an estimate of,Bl. In particular, estimates of ,61 of 2.93, 0.803, and 0.14 are associated with p4/~i of 0.0124, 0.225, and 1.8, respectively.
From page 303...
... dose of active carcinogen In nonsmokers without smoking spouses to the pulmonary dose in active smokers is equal to the ratio of the pulmonary dose of BaP, NDMA, or RSP in the same populations. The estimates in Table D-4 are based on (1)
From page 304...
... , . the range of values for RSP and BaP do not reflect differences between the particulate phase of ETS and that of mainstream smoke with regard to deposition sites, clearance rates, and particle size, the range of values given for BaP in Table D-4 could be orders of magnitude too high if, as discussed above, the BaP entries in Table 2-10 represent the total environmental BaP inhaled by a nonsmoker, and .
From page 305...
... Third, we completely ignore the epidemiologic data on passive smoking and estimate the true relative risk by combining estimates offs and p4/~i extrapolated from data on "five smokers, and estimates of do based on dos~metry (Method 3~. In a sensitivity analysis, we allow do to equal 0.01, 0.2, and 2 to crudely represent (approximate)
From page 306...
... studies is used in place of the overall summary rate ratio of 1.3.) If the true value of do were 0.01 cigarettes per day, then 259 lung cancer deaths in nonsmoking women would be attributable to ETS.
From page 307...
... Given that the assumptions of Method 2 hold, we can obtain an estimate of AF(M) for each value of p4/~t "6 each of the 30 exposure histories for the "exposed" and ~unexposed" study subjects, provided we have data on the age-specific lung cancer rates in nonsmoking women, Io (t)
From page 309...
... 309 - - - oo ~ ~n oo - ' =1 ~ ~ o ~ ~ - ~ - ~ - ~ - ~ ~ o o - ~ =1 s ~ - ~ ~ - ~ c~ - - d" ~ ~ ~ - l o l <5 ~ - ~ - ~ - oo ~ - o 4 ~ - ~ 1 _ 1 _ ~ ~ - ~ _ r~ _ - ~ - o l - ~ - tc, I i I I - - ~ J ~ ~ O ~ _ _ _ r~ _ ~ _ ~ ~ O I/)
From page 310...
... is the difference between the lung cancer mortality rate at age t, given her total smoke exposure, and her lung cancer mortality rate at age i, had she had the same active smoking history without exposure to other people's cigarette smoke. We require the same assumptions and information to estimate AF(M)
From page 311...
... For continuing smokers, it lies between 580 and 3,310 per 100,000. A similar calculation, using the summary rate ratio of 1.14 from the U.S.
From page 312...
... , we believe that the estimate of the lifetime risk of lung cancer among lifelong nonsmokers attributable to moderate ETS exposure [AF(M)
From page 313...
... We also did not make risk estimates under the assumption that the causal summary rate ratio was greater than I.3, largely because the estunated lifetime risk of lung cancer at this rate ratio of 1.3 was sufficiently large that it did not seem important to quantify how large the lifetime risk might be if the true causal rate ratio were 1.48 (the 95%0 upper confidence bound for the summary rate ratio of 1.3~. Finally, it would have been helpful to be able to compare estimates of risk derived from the 13 epidemiologic studies of nonsmokers exposed to ETS with independent estimates based on dos~rnetric measurements made ~ active and passive smokers.
From page 314...
... If, in Equation D-l, ,B(t) = ~ independent of t, we say that we have a linear excess relative risk model.
From page 315...
... Since the true relative risk associated with passive smoking exceeds I.3, Crump et al.'s argument may not be relevant. In Remark 18, we empirically assess the validity of Assumption la under the further assumption that cigarette smoke affects two stages of a five-stage multistage cancer process.
From page 316...
... 316 where city is a known constant independent of u. Note crusty is a ratio of the average exposure at age u of "exposed subjects at risk at age t to that of "unexposed subjects at risk at t.
From page 317...
... Remark ~ Note that the investigators of the 13 epidemiologic studies analyze their results as if their observed rate ratios were not dependent on age, as evidenced by the fact that none of the authors reported age-specific rate ratios. But if the rate ratio varies with age, then the observed rate ratio reported In each study will be a weighted average of varying age-specific rate ratios.
From page 318...
... in England, since women In those countries are likely to spend less time in contact with cigarette smokers outside the home. It follows that one might expect the observed rate ratio in the Hirayama (1984)
From page 319...
... = 3 holds for the United States, we would estimate the true relative risk in "exposed" and "unexposed" study subjects in the United States to be 1.225 and 1.075. Nonetheless, since 1.225 is less than the observed rate ratios of 1.45 and 2.01 in the Hirayama and ~ichopoulos et al.
From page 320...
... For example, in the 1930s and 1940s, nonsmoking women study subjects (who were then 20 to 30 years old) were presumably less often in contact with smokers outside the home.
From page 321...
... We then fit the data in three different ways. First, we used the reported actual mean age of onset of cigarette smoking (19.2 years)
From page 322...
... We actually are not so skeptical. If the sensitivity analysis shows that such large differences in estunates of p4/~ have little influence on our estimate of the true relative risk in "exposed" and ~unexposed" study subjects, this win indicate a high degree of robustness (insensitivity)
From page 323...
... 3. We next consider ETS exposures between the ages of O and 20.
From page 324...
... It follows that, as a rough approximation, the exposure to ETS of a child with nonsmoking parents is approximately 0.3do since Wald and Ritchie (1984) found the urinary cotinine levels of currently-"unexposed" individuals were approximately 1/200 that of an average active smoker and 0.44 x 200/300 _ 0.3.
From page 325...
... Remark 8: Estimating the True Relative Risk UnderAssumptions for Mode! 2 Above Consider a group of individuals (i.e., the Exposed individuals or the 'unexposed individuals in Garfinke!
From page 326...
... Since I.3 is assumed to be the ratio of the true relative risk in "exposed" subjects to that in "unexposed" subjects at age 70, we have 1 ~ (,C, do)
From page 327...
... and FJ2E(70) into Equation D-9 to give an exposure-history-,B4/,0~specific estimate of the true relative risk at age seventy in "exposed" individuals.
From page 328...
... We have not done so here. We expect that the effect on our estimates of the true relative risk in "exposed" and "unexposed subjects using Method 2 would not be great (because of the insensitivity of these estimates to uncertainty In ,81/,B4~.
From page 329...
... This reflects the fact that BaP is in the particulate phase and, as discussed in Chapter 7, a rough estimate of the deposition rates for particulates in ETS and in mainstream smoke is logo and 705,0, respectively. iThis calculation ignores important differences between the ETS and mainstream particulate phases in terms of deposition site, clearance rates, and particle size.
From page 330...
... dOm for RSP was calculated as follows. In Chapter 7 it was calculated that the amount of tar deposited in the lungs after ~ hours of ETS exposure would be about 0.005~o-0.26% of that deposited in the lungs of an active smoker of 20 cigarettes containing 14 mg tar each.
From page 331...
... IN contrast, nicotine in mainstream and sidestream smoke and in fresh ETS is largely in the particulate phase. Therefore, most of the nicotme directly inhaled in mainstream smoke by a smoker reaches the lower respiratory tract (and from there the bloodstream)
From page 332...
... the true carcinogen is in the particulate phase in both ETS and mainstream smoke, or (3) the true carcinogen is in the particulate phase in mainstream smoke, the vapor phase in ETS, and is, in addition, water soluble (so that the total dose of the carcinogen from ETS greatly exceeds the pulmonary dose)
From page 333...
... is the incidence of lung cancer death at t in the absence of all exposure, and RREXcEss~t) is the excess relative risk for lung cancer due to exposure history M
From page 334...
... We will show in Remark 19 that when one takes into account the inevitable misclassification of childhood ETS exposure occurring some 60 years previously, the observed relative risk expected from a case-control study of childhood ETS exposure could be as low as 1.01 and would be no greater than I.3. Thus, it is not surprising Garfinke!
From page 335...
... Remark 19 We now estimate the maximum and minimum relative risk (at age 70) we would expect to observe in a case-control study of ETS exposure in childhood (controlling for ETS exposure in adult life)
From page 336...
... Patterns of lung cancer risk among filter and nonfilter cigarette smokers.
From page 337...
... Effects of environmental tobacco smoke on urinary cotinine excretion in nonsmokers.


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