Effects of Cigarette Smoking on Lung Function in Adolescent Boys and Girls
Diane R. Gold, M.D., M.P.H., Xiaobin Wang, M.D., Sc.D., David Wypij, Ph.D., Frank E. Speizer, M.D., James H. Ware, Ph.D., and Douglas W. Dockery, Sc.D.
Background Little is known about the sex-specific effects ofcigarette smoking on the level and growth of lung function inadolescence, when 71 percent of people in the United Stateswho smoke tried their first cigarette.
Methods We studied the effects of cigarette smoking on the leveland rate of growth of pulmonary function in a cohort of 5158boys and 4902 girls 10 to 18 years of age, examined annuallybetween 1974 and 1989 in six cities in the United States.
Results We found a dose–response relation between smokingand lower levels of both the ratio of forced expiratory volumein one second to forced vital capacity (FEV1/FVC) and the forcedexpiratory flow between 25 and 75 percent of FVC (FEF25–75).Each pack per day of smoking was associated with a 3.2 percentreduction in FEF25–75 for girls (P = 0.01) and a 3.5 percentreduction in FEF25–75 for boys (P = 0.007). Whereas theFVC level was elevated in smokers, the rate of growth of FVCand FEV1 was reduced. Among adolescents of the same sex, smokingfive or more cigarettes a day, as compared with never smoking,was associated with 1.09 percent slower growth of FEV1 per yearin girls (95 percent confidence interval, 0.70 to 1.47 percent)and 0.20 percent slower growth in boys (95 percent confidenceinterval, -0.16 to 0.56 percent), and with 1.25 percent slowergrowth of FEF25–75 per year in girls (95 percent confidenceinterval, 0.38 to 2.13 percent) and 0.93 percent slower growthin boys (95 percent confidence interval, 0.21 to 1.65 percent).Whereas girls who did not smoke reached a plateau in lung functionat 17 to 18 years of age, girls of the same age who smoked hada decline of FEV1 and FEF25–75.
Conclusions Cigarette smoking is associated with evidence ofmild airway obstruction and slowed growth of lung function inadolescents. Adolescent girls may be more vulnerable than boysto the effects of smoking on the growth of lung function. .
Among people in the United States who smoked in 1991, 71 percentreported that they tried their first cigarette before the ageof 19 years.1 In the 1950s many more boys than girls smoked,but adolescent girls now take up smoking at least as frequentlyas boys.2 Girls and boys begin smoking at similar ages,1,3 butthey may not be at similar stages of physical maturation. Smokingmay affect female and male lungs differently, and these sexdifferences may relate to the caliber of airways or to hormonalstatus at different stages of life. A higher prevalence of airwayhyperresponsiveness in women who smoke than in men who smokewas partly explained by lower airway caliber in women, as measuredby the absolute level of forced expiratory volume in one second(FEV1).4 Exposure to cigarette smoke led to a greater increasein the number of mucus-producing tracheal goblet cells in femalerats than in male rats; differences between the sexes were relatedto the estrous cycle.5,6,7 We examined the sex-specific effectsof smoking on the level and growth of lung function in children10 to 18 years of age. We previously reported the associationsbetween smoking and chest illness, chronic cough, acute bronchitis,and wheezing in these children.8
Methods
A total of 12,253 white children in the first through fourthgrades were enrolled from schools in six areas of the UnitedStates (Watertown, Massachusetts; Kingston and Harriman, Tennessee;Steubenville and Mingo Junction, Ohio; St. Louis; Portage, Wisconsin;and Topeka, Kansas) between 1974 and 1979.9,10 At each annualexamination, up to grade nine, parents or guardians completeda questionnaire requesting information about the smoking habitsof parents, demographic data, and a history of respiratory illnessesand symptoms for each child and his or her parents. Each childin grades four through eight was asked privately about personalsmoking. Starting in grade nine, the questionnaire was completedby the participating children themselves and included questionsabout personal smoking.
Annually, each child's standing height in stocking feet wasmeasured. Forced expiratory volumes were measured with a water-filledrecording spirometer (Survey Spirometer, Warren E. Collins,Braintree, Mass.) while the subjects were sitting without noseclips.Each child performed at least five forced expirations but notmore than eight. Forced vital capacity (FVC) and FEV1 were measuredfor each expiration judged acceptable by the examiner. The meanof the best three efforts was calculated after corrections forbody temperature, ambient pressure, and water saturation. Theflow between 25 percent and 75 percent of FVC (FEF25–75)was measured from the expiration with the highest value forthe sum of the FVC and FEV1.
Definitions
The children's smoking behavior was divided into five categories:never having smoked, having smoked formerly, or currently smoking1/2 to 4, 5 to 14, or 15 or more cigarettes per day. Maternalsmoking status, found previously to predict the level of lungfunction in this cohort,11 was modeled with the use of an indicatorfor former smoking and current smoking measured as the numberof cigarettes per day. When relations between smoking and lungfunction were linear, regression models were considered thatincluded the number of cigarettes smoked per day as a continuousvariable and former smoking as a categorical variable. The meaneducation of the parents was categorized as less than, equalto, or greater than 12 years.
Statistical Analysis
The analyses were restricted to the 10,060 children (5158 boysand 4902 girls) 10 to 18 years of age with at least one measurementof FVC (Table 1). The logarithm of the level of lung functionwas modeled as a function of log height and age in sex-specificregressions. Because the relation between pulmonary functionand height varies according to age during adolescence, regressionmodels for lung-function level and rate of growth for each one-yearinterval were estimated. Age-specific intercepts and slopeswere linked to produce continuous expected values as a functionof age and height.12,13,14 Regression coefficients were estimatedwith independence-estimating equations, with estimated variancesadjusted for the correlation among repeated measurements.15
Table 1. Characteristics of 10,060 Children 10 to 18 Years of Age with at Least One Measurement of Forced Vital Capacity, According to Sex and Smoking Status.
Descriptive analyses showed that the effects of smoking on pulmonaryfunction were additive on the logarithmic scale — thatis, that smoking produced a proportional deficit in pulmonaryfunction. Estimates and confidence intervals for smoking effectswere calculated on the logarithmic scale and then expressedas percentage effects by taking the exponential of the estimates(or confidence intervals), subtracting 1, and multiplying theresult by 100. All final regression analyses were sex-specificand adjusted for age, log height at each age, residence, parentaleducation, and the smoking status of the mother. To test forthe modification of effects between age group (10 to 14 yearsor 15 to 18 years) or wheezing status and smoking, we incorporatedinteraction terms in these models, separately according to sex.We assessed P values for differences between the sexes in theeffects of smoking by comparing the difference between the estimatedsmoking effects in boys and girls, divided by the sum of thestandard errors of these estimates, with the standard normaldistribution. This is equivalent to assessing sex and smokinginteractions in a joint analysis of boys and girls, providedthat all other covariates also have sex interactions. All Pvalues are two-tailed.
Examining growth requires pairs of pulmonary-function valuesto express the changes in the level of function between consecutiveyears. Hence, there were approximately 10 percent fewer observationsfor analyses of the growth of lung function than for analysesof lung-function level. The categories of medium smoking andheavy smoking were combined because the number of observationsof heavy smoking was small, the observed effects of medium andheavy smoking were similar, and no statistically significantdifferences were found in the magnitude of the associationswith the growth of lung function. The effects of smoking onthe growth of lung function were examined on both a relativescale (comparing percentage differences) and an absolute scale(measuring in milliliters).
To assess whether differences in stage of maturity contributedto differences between the sexes in smoking effects, we repeatedthe analyses after each child's age was centered relative tohis or her age at peak growth in height (a measure of the timingof the adolescent growth spurt) — that is, it was expressedas the number of years since the year of peak height growth.16Peak growth in height was determined only for boys who had threemeasures of one-year changes in height between the ages of 11.75and 15.25 years, or four measures between the ages of 10.75and 16.25 years. Girls were required to have three measuresof one-year changes between the ages of 9.75 and 13.25 or fourbetween the ages of 8.75 and 14.25.
Peak height-growth velocity was determined for 70 percent ofthe girls and 62 percent of the boys. Since the peak height-growthvelocity occurred earlier for girls (average, 11.4 years) thanfor boys (average, 13.5 years), smoking data were sparse forthe period before peak growth. Sufficient data were availableon both boys and girls to permit comparison of smoking effectsbetween the age of peak height growth and six years later.
Results
Children who took up smoking had higher rates of having hadasthma (14 percent vs. 10 percent) and of having had wheezingbut not asthma (65 percent vs. 50 percent), and they were morelikely to have mothers who smoked than were children who neversmoked (Table 1). For both boys and girls, the proportion whosmoked increased with increasing age (Table 2).8 In observationsmade when the children were 15 to 18 years of age, the prevalenceof current smoking was 17 percent in the boys and 19 percentin the girls. The overall mean number of cigarettes smoked was8.9 (median, 5.7) for the boys and 7.5 (median, 4.3) for thegirls. Girls whose level of smoking was medium (5 to 14 cigarettesper day) or heavy (>15 cigarettes per day) smoked fewer cigaretteson average than boys (0.5 and 1.3 fewer cigarettes per day inthe medium and heavy categories, respectively). Rates of wheezingincreased according to the amount smoked and were higher forgirls than for boys at each level of smoking. In an equal proportionof observations of nonsmoking boys and girls, there was currentwheezing (25 percent). The proportion of observations of girlsas compared with boys that involved wheezing was 45 versus 39percent for light smoking, 56 versus 47 percent for medium smoking,and 69 versus 57 percent for heavy smoking (P<0.001 for thedifferences between the sexes).
Table 2. Prevalence of Smoking in 58,460 Observations of 10,060 Children 10 to 18 Years of Age, According to Sex and Age Group.
Smoking and Level of Pulmonary Function
A dose–response relation was found between smoking andlower levels of FEV1/FVC and FEF25–75 (Figure 1). Smoking15 cigarettes or more per day, as compared with never smoking,was associated with a reduction in FEF25–75 of 4.0 percentamong the boys (95 percent confidence interval, 0.7 to 7.1 percent)and of 3.2 percent among the girls (95 percent confidence interval,0.4 to 5.8 percent). No differences between the sexes or consistentage interactions were observed in the relation between smokingand the level of pulmonary function. Each pack per day of smokingwas associated with a reduction in FEF25–75 of 3.5 percentamong the boys (95 percent confidence interval, 1.0 to 5.9 percent)and of 3.2 percent among the girls (95 percent confidence interval,0.8 to 5.5 percent). Although there was no dose–responserelation between the number of cigarettes smoked and the FVC,the FVC was larger in smokers than nonsmokers, suggesting largerlungs in those who took up smoking.
Figure 1. Sex-Specific Effects of Direct Exposure to Smoke on the Level of Pulmonary Function in Children 10 to 18 Years of Age, Estimated by Regression Analysis.
Percent differences and 95 percent confidence intervals are plotted for groups of children with differing levels of smoking as compared with children of identical age and log height who had never smoked, with adjustment for age, log height at each age, residence, parental education, and maternal smoking status. Never denotes never having smoked; Former, formerly having smoked; Light, 1/2 to 4 cigarettes per day; Medium, 5 to 14 cigarettes per day; and Heavy, 15 or more cigarettes per day. FVC denotes the forced vital capacity, FEV1 the forced expiratory volume in one second, and FEF25–75 the forced expiratory flow between 25 and 75 percent of FVC.
The girls reached the maximal level of lung function betweenthe ages of 16 and 18 years, a period when the level of lungfunction was still increasing in the boys. For the girls whonever smoked, the mean FEF25–75 was 3.82 liters per second,3.80 liters per second, and 3.80 liters per second at the agesof 16, 17, and 18 years, respectively. Lower mean levels ofFEF25–75 were observed in the girls who smoked five ormore cigarettes per day: 3.62, 3.69, and 3.65 liters per secondat the ages of 16, 17, and 18 years, respectively.
Smoking and Growth of Pulmonary Function
Over the age range of 10 to 18 years, girls who smoked fiveor more cigarettes per day had a rate of growth of FVC thatwas 0.76 percent slower per year and a rate of growth of FEV1that was 1.09 percent slower per year than those of girls whonever smoked (Table 3). For boys, smoking five or more cigarettesper day was not significantly associated with the growth ofFVC (estimated effect, 0.03 percent slower growth per year;95 percent confidence interval, -0.24 to 0.30 percent; P<0.001for the difference between the sexes) or FEV1 (estimated effect,0.20 percent slower growth per year; 95 percent confidence interval,-0.16 to 0.56 percent; P = 0.001 for the difference betweenthe sexes). Smoking five or more cigarettes per day was associatedwith a significantly slower percentage growth in FEF25–75for both boys and girls. No significant interactions were foundbetween age and smoking in their relations to lung-functiongrowth.
Table 3. Sex-Specific Effects of Direct Exposure to Smoke on the Annual Growth Rate of Pulmonary Function in Children 10 to 18 Years of Age, Estimated by Regression Analysis.
Girls, but not boys, were observed at ages when growth in heightand pulmonary function was completed. After the ages of 16 to17, girls smoking five or more cigarettes per day appeared tohave a decline in FEF25–75 and FEV1; in girls who didnot smoke, pulmonary function stopped growing (i.e., reacheda plateau) but did not decline (Figure 2).
Figure 2. Mean Rates of Pulmonary-Function Growth According to Age, Sex, and Category of Smoking.
The circles represent the children who had never smoked, and the triangles those who smoked five or more cigarettes per day. There were fewer than 15 observations for smokers before the age of 13. The numbers of observations of FEV1 in boys who smoked five or more cigarettes per day were 41 at age 13, 120 at age 14, 213 at age 15, 311 at age 16, 361 at age 17, and 151 at age 18. In girls who smoked five or more cigarettes per day, the numbers of observations of FEV1 were 39 at age 13, 109 at age 14, 197 at age 15, 254 at age 16, 290 at age 17, and 90 at age 18. FEV1 denotes the forced expiratory volume in one second, and FEF25–75 the forced expiratory flow between 25 and 75 percent of the forced vital capacity.
Expressing each child's age relative to the age at peak growthin height had little effect on the estimated differences betweengirls and boys in the effect of smoking on the rate of growth.The estimates of the effects of smoking five or more cigarettesper day on FVC and FEV1 growth were still significantly largerfor girls than for boys (P = 0.02 and P = 0.04 for differencesbetween the sexes, respectively). Boys at or beyond their peakheight growth who smoked five or more cigarettes per day had0.23 percent slower growth per year in FVC (95 percent confidenceinterval, -0.07 to 0.52 percent) and 0.42 percent slower growthper year in FEV1 (95 percent confidence interval, 0.03 to 0.81percent) than boys who never smoked. Girls at or beyond theirpeak height growth who smoked five or more cigarettes per dayhad 0.85 percent slower growth per year in FVC (95 percent confidenceinterval, 0.42 to 1.26 percent) and 1.12 percent slower growthper year in FEV1 (95 percent confidence interval, 0.60 to 1.63percent) than girls who never smoked.
In analyses expressing each child's age relative to the ageat peak growth in height, smoking was also associated with agreater absolute deficit in the growth of FVC and FEV1 for girlsthan for boys, despite the fact that boys in adolescence hadsignificantly higher values for FVC (suggesting larger lungvolumes) and FEV1 (suggesting larger airways) than girls.17For FVC, smoking five or more cigarettes per day, as comparedwith never smoking, was associated with growth that was 25 mlper year slower in girls (95 percent confidence interval, 10to 39); the estimated effect in boys was not significant (growthwas 1 ml per year slower; 95 percent confidence interval, -13to 15; P = 0.03 for the difference between the sexes). For FEV1,smoking five or more cigarettes per day was associated withgrowth of lung function that was 31 ml per year slower in girls(95 percent confidence interval, 16 to 46) and 9 ml per yearslower in boys (95 percent confidence interval, -6 to 24) (P= 0.05 for the difference between the sexes). As with percentagegrowth, the effect of smoking in slowing the absolute growthof FEF25–75 in boys and girls was similar (for boys, 48ml per second per year; 95 percent confidence interval, 14 to81; for girls, 38 ml per second per year; 95 percent confidenceinterval, 3 to 80). For all the measures of lung function considered,estimates of the effects of cigarette smoking on absolute growthin lung function were similar in analyses with and without adjustmentfor peak growth in height.
Excluding children with a history of asthma from the analysisdid not significantly alter the sex-specific relations betweencigarette smoking and the level or growth of pulmonary function.For girls, but not for boys, there was an interaction betweencurrent wheezing and cigarette smoking. Girls who wheezed whenthey smoked five or more cigarettes per day had a 2.84 percentlower FEV1/FVC ratio (95 percent confidence interval, 2.12 to3.55) and a 6.69 percent lower FEF25–75 level (95 percentconfidence interval, 4.15 to 9.16) than nonsmoking girls withoutwheezing symptoms, after adjustment for age and height.
Discussion
For adolescent girls and boys, we found that relatively smallamounts of cigarette smoke cause similar deficits in levelsof both FEV1/FVC and FEF25–75, measures described in manystudies as the earliest spirometric indicators of airway obstructionand small-airway disease in adult smokers.18,19,20 Our findingsalso suggest that although smoking may slow the growth of lungfunction in both girls and boys, the deficits may be greaterin girls. The effects of smoking on the growth of lung functionwere greater in girls in absolute as well as percentage terms,despite the fact that boys had larger forced expiratory volumesand reported that they smoked more cigarettes. Tager and colleagues21demonstrated associations between smoking and both a lower leveland slower growth of lung function in both female and male adolescentsfrom East Boston, Massachusetts; the size of the sample limitedthe study's capacity to examine sex-specific differences. Previousstudies of adults from the same six areas of the United Statesas the children in our study suggested that cigarette smokehad a larger effect on lung function in men; the effect on lungfunction of smoking one pack of cigarettes per day for a year(one pack-year) was a 0.36 percent annual loss of FEV1 for menand a 0.29 percent annual loss for women.22,23 This sex-specificdifference may relate not to heightened sensitivity of men'slungs to cigarette smoke but to a cohort effect, since womenhad fewer cumulative pack-years of smoke exposure and begansmoking at later ages. In a cross-sectional study from Canada,women had greater deficits in lung function per pack-year ofcigarettes smoked.24
In our cohort of teenagers, rates of wheezing were higher amonggirls than boys at each level of smoking. This may relate, inpart, to the smaller absolute caliber of the girls' airways,as reflected in their lower absolute levels of FEV1.4,17 Wheezingin response to smoking may not result from the same physiologicmechanisms as wheezing in people with atopic asthma. In analysesadjusted for smoking, premenopausal women were at greater riskfor asthma than postmenopausal women, and postmenopausal womenreceiving hormone therapy were at greater risk than women whowere not receiving such therapy.25 Further studies would beneeded to assess whether the effect of cigarette smoke on eitherwheezing symptoms or lung function is modulated by hormonalfactors reflected in the stage of the subject's menstrual cycle,the onset of menarche during adolescence, the onset of menopause,or the administration of hormone therapy at other times.
It was not possible to evaluate differences between the sexesin the maximal level of lung function attained or in the effectsof smoking on the decline of lung function. Since boys attaintheir maximal pulmonary function in their early 20s, we werenot able to observe the effects of smoking once the growth ofpulmonary function ceased. Although our findings suggest thatgirls who smoke attain a lower maximal level of pulmonary functionthan nonsmokers and have an earlier decline in pulmonary function,this apparent trend could not be analyzed in girls beyond theage of 18 because of the lack of follow-up data.
There are limitations on the interpretation of analyses comparingthe sex-specific effects of cigarette smoking on the growthof lung function in boys and girls in which each child's ageis expressed relative to his or her age at peak growth in height.Although we believe that this approach brought us closer toa fair comparison between boys and girls, children at the samestage of peak growth in height are not necessarily at the samestage in other aspects of the onset of puberty. No data wereobtained on development of pubertal hair, breast development,or other markers of maturation. Peak growth in height is directlyrelated to peak growth of lung function, and its use as an indicatorof the stage of maturation enabled us to exclude fewer observationsthan if we had centered the children's ages on peak growth oflung function. Nevertheless, a significant proportion of thedata could not be used in the comparisons between the sexesthat used age at peak growth in height, because of the sparsityof data on smoking for girls before peak height growth and thesparsity of any data for boys more than six years after peakheight growth. A decrease in the number of observations by asmuch as 55 percent in boys and 40 percent in girls may explainthe decrease in the magnitude of the significance of sex-specificdifferences in the analyses centering on peak growth in heightas compared with the analyses that included all available data.
The sex-specific differences we observed in the growth of lungfunction may relate to unmeasured confounders such as sex-specificreporting bias, differences between the sexes in the amountof inhaled smoke per cigarette, or differences in unmeasuredexposure to environmental tobacco smoke outside the home. Wedid not measure cotinine levels to verify the reporting of cigarettesmoking. Before taking up smoking, future smokers did not differfrom those who had never smoked in their history of illnessbefore the age of two, bronchitis, or chest illness. The ageat peak growth in height was similar in these two groups.
Although the growth of FVC was slower among female smokers thannonsmokers, smoking was associated with a higher level of FVC.In the year before they started to smoke, many already had elevatedFVC values (data not shown). Other investigators have foundthat whereas older symptomatic adult smokers with historiesof large numbers of pack-years may have lower FVC levels thannonsmokers, young adult smokers have FVC levels equivalent toor higher than age-equivalent nonsmokers.26,27,28,29 It is possiblethat at the time they started smoking, children who had recentlydeveloped somewhat larger lungs experienced less discomfortwhen they experimented with cigarettes and were therefore moreinclined to smoke on a regular basis.
In conclusion, the effect of relatively small amounts of cigarettesmoke on the level and growth of lung function of children andadolescents is yet another reason to prevent young people fromstarting to smoke.
Supported in part by a grant (ES-01108) from the National Instituteof Environmental Health Sciences, a contract (RP-1001) withthe Electric Power Research Institute, and a cooperative agreement(CR11650) with the Health Effects Research Laboratory of theU.S. Environmental Protection Agency. Dr. Gold is an Amalieand Edward Kass Faculty Scholar at the Harvard Medical School.
This paper is dedicated to Professor (Emeritus) Benjamin G.Ferris, Jr., the original principal investigator of the HarvardSix Cities Study, who died August 1, 1996.
Source Information
From the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (D.R.G., F.E.S., J.H.W., D.W.D.); and the Environmental Epidemiology Program, Department of Environmental Health (X.W., D.W.D.), and the Department of Biostatistics (D.W., J.H.W.), Harvard School of Public Health — all in Boston.
Address reprint requests to Dr. Gold at the Channing Laboratory, Brigham and Women's Hospital, 180 Longwood Ave., Boston, MA 02115.
References
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994.
Department of Health and Human Services. The health consequences of smoking for women: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1980.
Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1989. (DHHS publication no. (CDC) 89-8411.)
Kanner RE, Connett JE, Altose MD, et al. Gender differences in airway hyperresponsiveness in smokers with mild COPD: the Lung Health Study. Am J Respir Crit Care Med 1994;150:956-961. [Abstract]
Hayashi M, Huber GL. Quantitative differences in goblet cells in the tracheal epithelium of male and female rats. Am Rev Respir Dis 1977;115:595-599. [Medline]
Hayashi M, Sornberger GC, Huber GL. Differential response in the male and female tracheal epithelium following exposure to tobacco smoke. Chest 1978;73:515-518. [Free Full Text]
Chalon J, Loew DA, Orkin LR. Tracheobronchial cytologic changes during the menstrual cycle. JAMA 1971;218:1928-1931. [CrossRef][Medline]
Gold DR, Rotnitzky A, Damokosh AI, et al. Race and gender differences in respiratory illness prevalence and their relationship to environmental exposures in children 7 to 14 years of age. Am Rev Respir Dis 1993;148:10-18. [Medline]
Ferris BG Jr, Speizer FE, Spengler JD, et al. Effects of sulfur oxides and respirable particles on human health: methodology and demography of populations in study. Am Rev Respir Dis 1979;120:767-779. [Medline]
Ware JH, Dockery DW, Spiro A III, Speizer FE, Ferris BG Jr. Passive smoking, gas cooking, and respiratory health of children living in six cities. Am Rev Respir Dis 1984;129:366-374. [Medline]
Wang X, Wypij D, Gold DR, et al. A longitudinal study of the effects of parental smoking on pulmonary function in children 6-18 years. Am J Respir Crit Care Med 1994;149:1420-1425. [Abstract]
Smith PL. Splines as a useful and convenient statistical tool. Am Stat 1979;33:57-62.
Wegman EJ, Wright IW. Splines in statistics. J Am Stat Assoc 1983;78:351-65.
Wypij D, Pugh M, Ware JH. Modeling pulmonary function growth with regression splines. Stat Sinica 1993;3:329-50.
Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13-22. [Free Full Text]
Wang X, Dockery D, Wypij D, et al. Pulmonary function growth velocity in children 6 to 18 years of age. Am Rev Respir Dis 1993;148:1502-1508. [Medline]
Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol 1993;15:75-88. [Medline]
Macklem PT. Workshop on screening programs for early diagnosis of airway obstruction. Am Rev Respir Dis 1974;109:567-571. [Medline]
Wright JL, Cagle P, Churg A, Colby TV, Myers J. Diseases of the small airways. Am Rev Respir Dis 1992;146:240-262. [Medline]
Zamel N, Altose MD, Speir WA Jr. Statement on spirometry: a report of the section of respiratory pathophysiology of the American College of Chest Physicians. J Asthma 1983;20:307-311. [Medline]
Tager IB, Munoz A, Rosner B, Weiss ST, Carey V, Speizer FE. Effect of cigarette smoking on the pulmonary function of children and adolescents. Am Rev Respir Dis 1985;131:752-759. [Medline]
Xu X, Dockery DW, Ware JH, Speizer FE, Ferris BG Jr. Effects of cigarette smoking on rate of loss of pulmonary function in adults: a longitudinal assessment. Am Rev Respir Dis 1992;146:1345-1348. [Medline]
Dockery DW, Speizer FE, Ferris BG Jr, Ware JH, Louis TA, Spiro A III. Cumulative and reversible effects of lifetime smoking on simple tests of lung function in adults. Am Rev Respir Dis 1988;137:286-292. [Medline]
Chen Y, Horne SL, Dosman JA. Increased susceptibility to lung dysfunction in female smokers. Am Rev Respir Dis 1991;143:1224-1230. [Medline]
Troisi RJ, Speizer FE, Willett WC, Trichopoulos D, Rosner B. Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma: a prospective cohort study. Am J Respir Crit Care Med 1995;152:1183-1188. [Abstract]
Ferris BG Jr. Epidemiological studies on air pollution and health. Arch Environ Health 1968;16:541-555. [Medline]
Walter S, Nancy NR, Collier CR. Changes in the forced expiratory spirogram in young male smokers. Am Rev Respir Dis 1979;119:717-724. [Medline]
Peters JM, Ferris BG Jr. Smoking, pulmonary function, and respiratory symptoms in a college-age group. Am Rev Respir Dis 1967;95:774-782. [Medline]
Anderson DO, Ferris BG Jr, Zickmantel R. The Chilliwack Respiratory Survey, 1963. IV. The effect of tobacco smoking on the prevalence of respiratory disease. Can Med Assoc J 1965;92:1066-1076.
Hertsgaard, L. A., Hanson, K., Hecht, S. S., Lindgren, B. R., Luo, X., Carmella, S. G., Riley, W. T., Zylla, E. B., Murphy, S. E., Hatsukami, D. K.
(2008). Exposure to a Tobacco-Specific Lung Carcinogen in Adolescent versus Adult Smokers. Cancer Epidemiol. Biomarkers Prev.
17: 3337-3343
[Abstract][Full Text]
Rennard, S. I.
(2008). Lessons from Multidisciplinary Cross-Fertilization: Chronic Obstructive Pulmonary Disease, Lung Cancer, and Heart Disease. Proc Am Thorac Soc
5: 865-868
[Abstract][Full Text]
Flouris, A. D., Faught, B. E., Klentrou, P.
(2008). Cardiovascular disease risk in adolescent smokers: evidence of a `smoker lifestyle'. J Child Health Care
12: 221-231
[Abstract]
Subbarao, P., Sears, M. R
(2008). The chicken or the egg? Perhaps the egg. Arch. Dis. Child.
93: 552-553
[Full Text]
Minai, O. A., Benditt, J., Martinez, F. J.
(2008). Natural History of Emphysema. Proc Am Thorac Soc
5: 468-474
[Abstract][Full Text]
Voigt, R. G., Johnson, S. K., Hashikawa, A. H., Mellon, M. W., Campeau, L. J., Williams, A. R., Yawn, B. P., Juhn, Y. J.
(2008). Why Parents Seek Medical Evaluations for Their Children With Mild Acute Illnesses. CLIN PEDIATR
47: 244-251
[Abstract]
Suglia, S. F., Wright, R. O., Schwartz, J., Wright, R. J.
(2008). Association Between Lung Function and Cognition Among Children in a Prospective Birth Cohort Study. Psychosom. Med.
70: 356-362
[Abstract][Full Text]
Tyc, V. L.
(2008). Introduction to the Special Issue: Tobacco Control Strategies for Medically At-Risk Youth. J Pediatr Psychol
33: 113-118
[Full Text]
Suglia, S. F., Ryan, L., Laden, F., Dockery, D. W., Wright, R. J.
(2008). Violence Exposure, A Chronic Psychosocial Stressor, and Childhood Lung Function. Psychosom. Med.
70: 160-169
[Abstract][Full Text]
Sin, D. D., Cohen, S. B.-Z., Day, A., Coxson, H., Pare, P. D.
(2007). Understanding the Biological Differences in Susceptibility to Chronic Obstructive Pulmonary Disease between Men and Women. Proc Am Thorac Soc
4: 671-674
[Abstract][Full Text]
Colby, S. M., Gwaltney, C. J.
(2007). Pharmacotherapy for adolescent smoking cessation.. JAMA
298: 2182-2184
[Full Text]
Ben-Zaken Cohen, S., Pare, P. D., Man, S. F. P., Sin, D. D.
(2007). The Growing Burden of Chronic Obstructive Pulmonary Disease and Lung Cancer in Women: Examining Sex Differences in Cigarette Smoke Metabolism. Am. J. Respir. Crit. Care Med.
176: 113-120
[Abstract][Full Text]
Tonnesen, P., Carrozzi, L., Fagerstrom, K. O., Gratziou, C., Jimenez-Ruiz, C., Nardini, S., Viegi, G., Lazzaro, C., Campell, I. A., Dagli, E., West, R.
(2007). Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy. Eur Respir J
29: 390-417
[Abstract][Full Text]
de Marco, R., Accordini, S., Cerveri, I., Corsico, A., Anto, J. M., Kunzli, N., Janson, C., Sunyer, J., Jarvis, D., Chinn, S., Vermeire, P., Svanes, C., Ackermann-Liebrich, U., Gislason, T., Heinrich, J., Leynaert, B., Neukirch, F., Schouten, J. P., Wjst, M., Burney, P.
(2007). Incidence of Chronic Obstructive Pulmonary Disease in a Cohort of Young Adults According to the Presence of Chronic Cough and Phlegm. Am. J. Respir. Crit. Care Med.
175: 32-39
[Abstract][Full Text]
Tyc, V. L., Throckmorton-Belzer, L.
(2006). Smoking Rates and the State of Smoking Interventions for Children and Adolescents With Chronic Illness. Pediatrics
118: e471-e487
[Abstract][Full Text]
Zielinski, J., Bednarek, M., Gorecka, D., Viegi, G., Hurd, S. S., Fukuchi, Y., Lai, C. K. W., Ran, P. X., Ko, F. W. S., Liu, S. M., Zheng, J. P., Zhong, N. S., Ip, M. S. M., Vermeire, P. A.
(2006). Increasing COPD awareness.. Eur Respir J
27: 833-852
[Full Text]
Mannino, D. M., Watt, G., Hole, D., Gillis, C., Hart, C., McConnachie, A., Davey Smith, G., Upton, M., Hawthorne, V., Sin, D. D., Man, S. F. P., Van Eeden, S., Mapel, D. W., Vestbo, J.
(2006). The natural history of chronic obstructive pulmonary disease.. Eur Respir J
27: 627-643
[Full Text]
Kim, D. S., Kim, Y. S., Jung, K.-S., Chang, J. H., Lim, C.-M., Lee, J. H., Uh, S.-T., Shim, J. J., Lew, W. J., on behalf of the Korean Academy of Tuberculosis an,
(2005). Prevalence of Chronic Obstructive Pulmonary Disease in Korea: A Population-based Spirometry Survey. Am. J. Respir. Crit. Care Med.
172: 842-847
[Abstract][Full Text]
Winickoff, J. P., Berkowitz, A. B., Brooks, K., Tanski, S. E., Geller, A., Thomson, C., Lando, H. A., Curry, S., Muramoto, M., Prokhorov, A. V., Best, D., Weitzman, M., Pbert, L., for the Tobacco Consortium, Center for Child Healt,
(2005). State-of-the-Art Interventions for Office-Based Parental Tobacco Control. Pediatrics
115: 750-760
[Abstract][Full Text]
Harik-Khan, R. I., Muller, D. C., Wise, R. A.
(2004). Racial Difference in Lung Function in African-American and White Children: Effect of Anthropometric, Socioeconomic, Nutritional, and Environmental Factors. Am J Epidemiol
160: 893-900
[Abstract][Full Text]
Patel, B D, Luben, R N, Welch, A A, Bingham, S A, Khaw, K-T, Day, N E, Lomas, D A, Wareham, N J
(2004). Childhood smoking is an independent risk factor for obstructive airways disease in women. Thorax
59: 682-686
[Abstract][Full Text]
Gold, D. R.
(2004). Less Childhood Obesity--Less Persistence of Wheeze in Teenage Girls and Boys?. Am. J. Respir. Crit. Care Med.
170: 8-9
[Full Text]
Celli, B.R., MacNee, W., Agusti, A., Anzueto, A., Berg, B., Buist, A.S., Calverley, P.M.A., Chavannes, N., Dillard, T., Fahy, B., Fein, A., Heffner, J., Lareau, S., Meek, P., Martinez, F., McNicholas, W., Muris, J., Austegard, E., Pauwels, R., Rennard, S., Rossi, A., Siafakas, N., Tiep, B., Vestbo, J., Wouters, E., ZuWallack, R.
(2004). Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J
23: 932-946
[Full Text]
Rizzi, M., Sergi, M., Andreoli, A., Pecis, M., Bruschi, C., Fanfulla, F.
(2004). Environmental Tobacco Smoke May Induce Early Lung Damage in Healthy Male Adolescents. Chest
125: 1387-1393
[Abstract][Full Text]
Svanes, C, Omenaas, E, Jarvis, D, Chinn, S, Gulsvik, A, Burney, P
(2004). Parental smoking in childhood and adult obstructive lung disease: results from the European Community Respiratory Health Survey. Thorax
59: 295-302
[Abstract][Full Text]
Hemila, H., Virtamo, J., Albanes, D., Kaprio, J.
(2004). Vitamin E and Beta-Carotene Supplementation and Hospital-Treated Pneumonia Incidence in Male Smokers. Chest
125: 557-565
[Abstract][Full Text]
Chatila, W. M., Wynkoop, W. A., Vance, G., Criner, G. J.
(2004). Smoking Patterns in African Americans and Whites With Advanced COPD. Chest
125: 15-21
[Abstract][Full Text]
Winickoff, J. P., Buckley, V. J., Palfrey, J. S., Perrin, J. M., Rigotti, N. A.
(2003). Intervention With Parental Smokers in an Outpatient Pediatric Clinic Using Counseling and Nicotine Replacement. Pediatrics
112: 1127-1133
[Abstract][Full Text]
Winickoff, J. P., McMillen, R. C., Carroll, B. C., Klein, J. D., Rigotti, N. A., Tanski, S. E., Weitzman, M.
(2003). Addressing Parental Smoking in Pediatrics and Family Practice: A National Survey of Parents. Pediatrics
112: 1146-1151
[Abstract][Full Text]
Doyle, L. W., Olinsky, A., Faber, B., Callanan, C.
(2003). Adverse Effects of Smoking on Respiratory Function in Young Adults Born Weighing Less Than 1000 Grams. Pediatrics
112: 565-569
[Abstract][Full Text]
Langhammer, A., Johnsen, R., Gulsvik, A., Holmen, T.L., Bjermer, L.
(2003). Sex differences in lung vulnerability to tobacco smoking. Eur Respir J
21: 1017-1023
[Abstract][Full Text]
Pbert, L., Moolchan, E. T., Muramoto, M., Winickoff, J. P., Curry, S., Lando, H., Ossip-Klein, D., Prokhorov, A. V., DiFranza, J., Klein, J. D.
(2003). The State of Office-Based Interventions for Youth Tobacco Use. Pediatrics
111: e650-660
[Abstract][Full Text]
Zhang, L-X., Enarson, D.A., He, G-X., Li, B., Chan-Yeung, M.
(2002). Occupational and environmental risk factors for respiratory symptoms in rural Beijing, China. Eur Respir J
20: 1525-1531
[Abstract][Full Text]
Forastiere, F., Goldsmith, D. F., Sperati, A., Rapiti, E., Miceli, M., Cavariani, F., Perucci, C. A.
(2002). Silicosis and Lung Function Decrements among Female Ceramic Workers in Italy. Am J Epidemiol
156: 851-856
[Abstract][Full Text]
Apostol, G. G., Jacobs, D. R. Jr., Tsai, A. W., Crow, R. S., Williams, O. D., Townsend, M. C., Beckett, W. S.
(2002). Early Life Factors Contribute to the Decrease in Lung Function between Ages 18 and 40: The Coronary Artery Risk Development in Young Adults Study. Am. J. Respir. Crit. Care Med.
166: 166-172
[Abstract][Full Text]
Rasmussen, F., Taylor, D. R., Flannery, E. M., Cowan, J. O., Greene, J. M., Herbison, G. P., Sears, M. R.
(2002). Risk Factors for Airway Remodeling in Asthma Manifested by a Low Postbronchodilator FEV1/Vital Capacity Ratio: A Longitudinal Population Study from Childhood to Adulthood. Am. J. Respir. Crit. Care Med.
165: 1480-1488
[Abstract][Full Text]
Van Winkle, L. S., Gunderson, A. D., Shimizu, J. A., Baker, G. L., Brown, C. D.
(2002). Gender differences in naphthalene metabolism and naphthalene-induced acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol.
282: L1122-L1134
[Abstract][Full Text]
Holmen, T.L., Barrett-Connor, E., Clausen, J., Holmen, J., Bjermer, L.
(2002). Physical exercise, sports, and lung function in smoking versus nonsmoking adolescents. Eur Respir J
19: 8-15
[Abstract][Full Text]
PHILLIPS, M. F., QUINLIVAN, R. C. M., EDWARDS, R. H. T., CALVERLEY, P. M. A.
(2001). Changes in Spirometry Over Time as a Prognostic Marker in Patients with Duchenne Muscular Dystrophy. Am. J. Respir. Crit. Care Med.
164: 2191-2194
[Abstract][Full Text]
Committee on Substance Abuse,
(2001). Tobacco's Toll: Implications for the Pediatrician. Pediatrics
107: 794-798
[Abstract][Full Text]
Langhammer, A., Johnsen, R., Holmen, J., Gulsvik, A, Bjermer, L
(2000). Cigarette smoking gives more respiratory symptoms among women than among men The Nord-Trondelag Health Study (HUNT). J. Epidemiol. Community Health
54: 917-922
[Abstract][Full Text]
Shriver, S. P., Bourdeau, H. A., Gubish, C. T., Tirpak, D. L., Davis, A. L. G., Luketich, J. D., Siegfried, J. M.
(2000). Sex-Specific Expression of Gastrin-Releasing Peptide Receptor: Relationship to Smoking History and Risk of Lung Cancer. JNCI J Natl Cancer Inst
92: 24-33
[Abstract][Full Text]
Becklake, M. R, Kauffmann, F.
(1999). Gender differences in airway behaviour over the human life span. Thorax
54: 1119-1138
[Full Text]
Chen, Y.
(1999). Genetics and pulmonary medicine bullet 10: Genetic epidemiology of pulmonary function. Thorax
54: 818-824
[Full Text]
Prescott, E., Vestbo, J.
(1999). Socioeconomic status and chronic obstructive pulmonary disease. Thorax
54: 737-741
[Full Text]
ULRIK, C. S., BACKER, V.
(1999). Markers of Impaired Growth of Pulmonary Function in Children and Adolescents. Am. J. Respir. Crit. Care Med.
160: 40-44
[Abstract][Full Text]
Oddoze, C., Dubus, J. C., Badier, M., Thirion, X., Pauli, A. M., Pastor, J., Bruguerolle, B.
(1999). Urinary Cotinine and Exposure to Parental Smoking in a Population of Children with Asthma. Clin. Chem.
45: 505-509
[Abstract][Full Text]
PETERS, J. M., AVOL, E., GAUDERMAN, W. J., LINN, W. S., NAVIDI, W., LONDON, S. J., MARGOLIS, H., RAPPAPORT, E., VORA, H., GONG, H. Jr., THOMAS, D. C.
(1999). A Study of Twelve Southern California Communities with Differing Levels and Types of Air Pollution . II. Effects on Pulmonary Function. Am. J. Respir. Crit. Care Med.
159: 768-775
[Abstract][Full Text]
Giarelli, E.
(1999). Prevention of Smoking Among Adolescent Girls: Health Promotion Strategies for Nurses. The Journal of School Nursing
15: 23-28
[Abstract]
SUNYER, J., ANTO, J. M., MCFARLANE, D., DOMINGO, A., TOBIAS, A., BARCELO, M.-A., MUNOZ, A.
(1998). Sex Differences in Mortality of People Who Visited Emergency Rooms for Asthma and Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med.
158: 851-856
[Abstract][Full Text]
TAGER, I. B.
(1998). Smoking and Childhood Asthma---Where Do We Stand?. Am. J. Respir. Crit. Care Med.
158: 349-351
[Full Text]
LEYNAERT, B., BOUSQUET, J., HENRY, C., LIARD, R., NEUKIRCH, F.
(1997). Is Bronchial Hyperresponsiveness More Frequent in Women than in Men? . A Population-based Study. Am. J. Respir. Crit. Care Med.
156: 1413-1420
[Abstract][Full Text]
(1996). Adolescent Smoking: Are Girls Worse Off Than Boys?. JWatch Psychiatry
1996: 19-19
[Full Text]
(1996). ADOLESCENT SMOKING: ARE GIRLS WORSE OFF THAN BOYS?. JWatch General
1996: 3-3
[Full Text]
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