help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Data Supplement
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Apostol, G. G.
Right arrow Articles by Beckett, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Apostol, G. G.
Right arrow Articles by Beckett, W. S.
American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 166-172, (2002)
© 2002 American Thoracic Society

Original Article

Early Life Factors Contribute to the Decrease in Lung Function between Ages 18 and 40

The Coronary Artery Risk Development in Young Adults Study

George G. Apostol, David R. Jacobs, Jr., Albert W. Tsai, Richard S. Crow, O. Dale Williams, Mary C. Townsend and William S. Beckett

Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota; Institute for Nutrition Research, University of Oslo, Oslo, Norway; Ingenix Pharmaceutical Services, Eden Prairie, Minnesota; Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama; M.C. Townsend Associates, Pittsburgh, Pennsylvania; and Department of Environmental Medicine/Occupational Medicine Division, University of Rochester School of Medicine, Rochester, New York

Correspondence and requests for reprints should be addressed to David R. Jacobs Jr., Ph.D., Division of Epidemiology, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454. E-mail: jacobs{at}epi.umn.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Early life factors may influence pulmonary function. We measured forced expiratory volume in 1 second (FEV1) in 1985–1986 and 2, 5, and 10 years later in approximately 4,000 black and white men and women initially aged 18–30 years. We estimated the age pattern of FEV1 according to family smoking status, early diagnosis of asthma, early smoking initiation, adult asthma, and cigarette smoking. FEV1 followed a quadratic pattern from age of peak through age 40. The pattern varied by race and sex. Early smoking initiation was associated with a faster decrease in FEV1. Smoking by family members was related to early life asthma and may have contributed to faster FEV1 decrease by encouraging behaviors such as heavier smoking or earlier smoking initiation. Prevalence of smoking was 28% when no family member smoked, compared with 59% when four or more members smoked. The FEV1 decline was 8.5% in never-smokers without asthma; 10.1% in nonsmoking individuals diagnosed with asthma; and 11.1% in baseline smokers who smoked 15 or more cigarettes per day. The combination of asthma and heavier smoking was synergistic (17.8% decline). This study delineates an increased rate of decline in those with asthma or in those who smoke cigarettes and implicates early life exposures as contributing to the faster rate of FEV1 decline.

Key Words: lung development • family smoking • smoking • asthma


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Forced expiratory volume in 1 second (FEV1) is a powerful predictor of general, pulmonary, and cardiovascular mortality and morbidity (1–4). Therefore, it is of interest to quantify the influence of various risk factors on the growth of FEV1, including those that affect the lungs in early life and early life behaviors that affect the lungs in adulthood. One such factor is smoking by family members during the participant's childhood, which may predispose to early asthma and cigarette smoking initiation. These early life occurrences might prevent the lung from attaining complete development and therefore make it more prone to illnesses. Furthermore, they may lead to persistent asthma and smoking, which are known to affect FEV1 adversely.

Asthma is an important disease affecting increasing numbers of people in the U.S. and worldwide. In the last 20 years, its prevalence has almost tripled in the U.S., from 6.7 million cases in 1980 to 17.3 million cases in 1998, 4.8 million being children (5). Childhood asthma may lead to diminished lung function in adulthood.

Cigarette smoking is a second major factor that often begins in childhood and can affect lung function adversely in later life (6–9). Because the effect of cigarette smoking on lung function is dose dependent, damage would be expected to be worse the earlier smoking starts or the greater the number of cigarettes smoked. An early start of smoking increases the duration of lifelong smoking. Considering that even minor injuries to developing tissues can have major, long-term adverse effects, passive smoking may also have an adverse effect on lung function.

The analyses presented here are from the Coronary Artery Risk Development In Young Adults (CARDIA) study. Spirometry was conducted at the baseline exam in 1985–1986 in a cohort of black and white men and women initially aged 18–30 years. It was repeated 2, 5, and 10 years later. We first characterize the pattern of growth and deterioration of FEV1 from ages 18 to 40 among participants who never smoked and had no asthma, specific to the four race–sex groups. Using the resulting quadratic curves, we then assess differences in the pattern of FEV1 according to family smoking status, early diagnosis of asthma, early smoking initiation, diagnosed or undiagnosed asthma in young adulthood, and cigarette smoking in young adulthood. Our central hypothesis is that early life factors may injure lungs in childhood or may support behaviors and pathology that lead to lung injury in adulthood.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Participants and Measurements
CARDIA studied heart disease risk factors in 5,115 black and white men and women aged 18–30 years at baseline in 1985–1986 (n = 4,624, 4,352, and 3,950 reexamined 2, 5, and 10 years later, respectively). The cohorts were randomly sampled in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Questionnaires asked about demographic characteristics, respiratory health, cigarette smoking, physical activity, and medical history. Anthropometric measurements included height and weight (10, 11).

Lung function was measured using a Collins Survey 8-L water sealed spirometer and an Eagle II Microprocessor (Warren E. Collins, Inc., Braintree, MA). Standard procedures of the American Thoracic Society (12, 13) were followed. Daily checks for leaks and volume calibration with a 3-L syringe and weekly calibration in the 4- to 7-L range were undertaken to minimize methodological artifacts between exams. We analyzed FEV1 (maximum of five satisfactory maneuvers) adjusted for height squared (FEV1/ht2) (14–17). To ease interpretation, we multiplied by the mean ht2 and presented FEV1.

Asthma diagnosis (18) was made if the subject was receiving asthma medication (medicine containers examined) or self-reported doctor or nurse diagnosis of asthma (not asked at Year 5). The age of onset of asthma was self-reported. Undiagnosed asthma was self-reported wheeze and shortness of breath at baseline, Year 2, or Year 10 (symptoms were not otherwise queried), not necessarily at the same examination (date of onset not ascertainable). Self-report of only one of these symptoms was not undiagnosed asthma.

Smoking initiation at or before age 15 was considered as early smoking initiation. Because it appeared that quitting smoking was often the result of worsening or newly acquired asthma (18), we did not analyze smoking change during CARDIA. The total number of smokers in the family (0, 1, 2, 3, or >= 4) was derived from questions at baseline: "Has your (given relative) ever ... smoked cigarettes?"

Statistical Methods
Repeated measures regression analysis (SAS PROC MIXED) separates estimates of age-related differences and time-related changes (19), reflecting cross-sectional and longitudinal aspects of the data (see the online data supplement). The analysis accounts for within-person correlation between exams while estimating the serial cross-sectional age slope, an average of the cross-sectional estimates at Years 0, 2, 5, and 10. We assumed constant correlation between examinations (the within person correlation of FEV1/ht2 was about 0.8, attenuated slightly with time between examinations). A small age-matched time trend likely reflected differences in the spirometry between examinations. Longitudinal estimates (the sum of the annual age slope and the annual age-matched time trend) are therefore similar to cross-sectional estimates of FEV1/ht2. We formed quadratic models to describe the duration of plateau FEV1/ht2 and the rate of deterioration from peak FEV1/ht2 in never-smokers without asthma in each race–sex group. To compare variables representing childhood influences on young adult FEV1/ht2, we added variables that gave (1) an estimate of the mean difference in FEV1/ht2 at age 18, and (2) an estimate of the mean annual linear divergence between ages 18 and 40 of the FEV1/ht2 groups from each other. The parameter for quadratic divergence was generally small and was omitted.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Response Bias
Among those whose last examination was at Year 0 (n = 224) or at Year 2 (n = 259), about 40% smoked cigarettes at baseline, compared with 36% among those who last attended at Year 5 (n = 234), 32% among those who last attended at Year 7 (n = 439), and 28% among those who attended at Year 10 (n = 3,901). White women were most likely to attend the Year 10 examination (82%), followed by white men (81%), black women (76%), and black men (69%). There was a tendency for those with lower educational attainment to have shorter follow-up. Mean FEV1 at baseline was significantly lower for participants who attended only at Year 0 compared with those who attended at Year 10 (3.42 L versus 3.52 L). For those whose last examination was after baseline, the mean FEV1 measured at baseline and at later visits was similar to that measured among those who attended at Year 10. Asthma prevalence and incidence did not differ with the duration of follow-up.

Description of Study Population
The mean ± standard deviation for age for the study sample at baseline in 1985–1986 was 24.8 ± 3.6 years. Participants were nearly equally distributed among race–sex groups. About 40% had no education beyond high school. The asthma analysis included 5,057 participants who contributed 17,106 observations at the four examinations. Prevalence of asthma diagnosis at baseline in 9.9% of the participants, of whom 48% were diagnosed before age 6. An additional 2.2% had undiagnosed asthma. Asthma diagnosis first occurred after baseline in 6.4% of participants.

Among 5,023 participants reporting smoking status, 43.7% had ever-smoked (9.3% exsmokers of < 15 cigarettes per day, 4.1% exsmokers of 15 or more cigarettes per day, 20.4% current smokers of < 15 cigarettes per day, 9.9% current smokers of 15 or more cigarettes per day). Among smokers, 21.0% started smoking before age 15. Among 5,016 participants reporting family smoking status, about half reported that their mother smoked, and some two-thirds reported that their father smoked. More than 20% had one sibling who smoked, and 29% had more than one sibling who smoked. Combining these rates of parental and sibling smoking, only 15.1% came from families with no smokers, and 25.1, 25, 15.5, and 19.3% of participants came from families with 1, 2, 3, or 4 or more smokers, respectively.

Normal Aging Patterns of FEV1
Among those who never smoked and never had asthma, the quadratic model in age provided a generally good fit (Figure 1); however, the fit was poorer in the youngest ages, before peak FEV1 was achieved. Observed mean FEV1 increased from age 18 in each race–sex group; age at peak is shown in Table 1. We defined a plateau in FEV1 as the age interval in which the FEV1 remains within 50 ml. Plateaus appeared starting at about age 19; based on the quadratic model, the plateau lasted in white men until age 24, in white women until age 28, in black men until age 24, and in black women until age 27. FEV1 is generally higher among men than among women and among whites than among blacks. The decline, as a percentage of the peak level, was about 10% but greater in men than in women and in blacks than in whites.



View larger version (25K):
[in this window]
[in a new window]
  		Figure 1. Observed mean and quadratic fit for FEV1 for each year of age, 18–40, according to race and sex, The CARDIA Study, 1985–1996. Observed means are represented by symbols and the quadratic fit by continuous lines.

 

View this table:
[in this window]
[in a new window]
  		TABLE 1. Fev1* and its changes from peak through age 40 according to race and sex, the cardia study, 1985–1996

 
The Influence of Asthma and Asthma Symptoms on FEV1
The pattern of FEV1 across categories of asthma symptoms is given in Figure 2. Table E1 (see the online data supplement) presents FEV1 differences and their 95% confidence intervals for all pairwise comparisons at age 18 and for divergence of FEV1 per year of age. FEV1 was higher and deteriorated more slowly (9.3% by age 40) in participants with no diagnosed asthma who never reported wheeze or shortness of breath than in the other groups in Figure 2, although the difference from the group that reported only one of the two symptoms only once (10.5% decline by age 40) was not statistically significant (Table E1 in the online data supplement). Percent decrease was 10.9% by age 40 in those who reported one symptom repeatedly and 13.7% in those with incident asthma. The prevalent (at baseline) and undiagnosed asthma groups had lowest FEV1 at age 18 and decreased by 13.2 and 14.3%, respectively, by age 40. The pattern of FEV1 was similar for prevalent asthma diagnosed before or after age 6 (data not shown).



View larger version (30K):
[in this window]
[in a new window]
  		Figure 2. Race–sex adjusted quadratic fit for FEV1 for each year of age, 18–40, according to asthma and respiratory symptom status, The CARDIA Study, 1985–1996.

 
The Influence of the Age of Starting Smoking on FEV1
Figure 3 shows more rapidly declining FEV1 in those who started smoking before age 15 than in those who started later (p = 0.01 for divergence in FEV1 per year of age). FEV1 in both groups declined more rapidly than in never-smokers (p = 0.0001 and 0.03, respectively). The FEV1 difference between smokers who started smoking earlier versus later in life disappeared after adjustment for the current smoking status.



View larger version (21K):
[in this window]
[in a new window]
  		Figure 3. Race–sex adjusted quadratic fit for FEV1 for each year of age, 18–40, according to age at smoking initiation, The CARDIA Study, 1985–1996.

 
The Influence of Smoking Quantity on FEV1
As shown in Figure 4, never-smokers experienced a decline of 9.3% in FEV1 by age 40. Exsmokers had the highest predicted FEV1 at the age of 18. The exsmokers of less than 15 cigarettes per day had a similar FEV1 evolution as the never-smokers. Their divergence was not statistically significant (see Table E2 in the online data supplement). The FEV1 in exsmokers of 15 or more cigarettes per day decreased more rapidly, by 11.9% (p = 0.01 for divergence from never-smokers). Current smokers of less than 15 cigarettes per day had the same FEV1 as never-smokers at age 18, but it decreased rapidly by 10.6% by age 40 (p = 0.06). Current smokers of 15 or more cigarettes per day had the lowest FEV1 at age 18 and had the largest relative drop, 13.1% by age 40 (p < 0.001).



View larger version (29K):
[in this window]
[in a new window]
  		Figure 4. Race–sex adjusted quadratic fit for FEV1 for each year of age, 18–40, according to smoking status, The CARDIA Study, 1985–1996.

 
Interaction of Cigarette Smoking and Asthma
The decrease in FEV1 was 8.5% among never-smokers with no asthma or related symptoms (Table 2). There was a 10–11% decline among individuals without asthma who currently smoked 15 or more cigarettes per day and never-smokers who had asthma or related symptoms. However, there was an 18% decline in FEV1 among those with both asthma and current smoking of 15 or more cigarettes per day (p for interaction = 0.04).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Predicted fev1 levels at age 18 and 40 according to smoking and asthma status, the cardia study, 1985–1996

 
The Influence of Smoking by Family Members on Participant FEV1
Family smoking was associated with an increased likelihood of having an asthma diagnosis before age 6 (Table 3). The prevalence of asthma diagnosis before age 6 among those whose family members did not smoke was 2.8%, in contrast to 4.6–5.6% among those who had one or more family members smoking. The prevalence of smoking initiation before age 15 increased with the number of family members who smoked. The prevalence of smoking increased proportionally with the number of family members smoking: 29% for no family member smoking, increasing stepwise to 58% for four or more family smokers. Family smoking status was not directly related to the FEV1 evolution (data not shown).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Prevalence (%) of participant asthma-related and smoking characteristics according to number of participant's family members who smoked, the cardia study, 1985–1996

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Because lower lung function is linked to risk for respiratory illness, coronary heart disease, and all-cause mortality, even in asymptomatic healthy populations (1–4), an understanding of factors determining the growth, development, and loss of lung function is important for formulation of strategies to prevent respiratory disease. According to Weiss and Ware, lung function evolves in three stages: growth, peak or plateau, and decline (20). We observed increases in FEV1 between age 18 and the early 20s, followed by a plateau, then decline. The plateau and decline through age 40 were well fitted by quadratic models. These age-patterns were modified by race, sex, smoking, and asthma. In turn, smoking and asthma were correlated with some childhood exposures. Prevalence of cigarette smoking was more likely if more family members smoked. Furthermore, the earlier cigarette smoking was initiated, the more likely it was to be heavy, and the greater the number of family members who smoked, the more likely it was to persist (current smoker at baseline). The risk of early asthma onset was nearly double if any family member smoked. Presumably much of this family smoking occurred during the participant's childhood. Therefore, early life factors, namely, smoking by family members, early onset asthma, and early smoking initiation contributed indirectly through adult asthma and cigarette smoking to a less favorable pattern of FEV1.

Peak, Plateau, Decline, Race, and Sex
Some authors (21, 22) have found that the peak for FEV1 was achieved between 15 and 20 years of age, whereas others have found that the FEV1 continued to increase up to 25 years (23–25) or beyond (26, 27). Some authors have suggested that it would be more informative to define a plateau over a range of ages instead of focusing on a peak at a particular age (25, 26, 28). Hankinson and coworkers (29) found that the change from adolescent growth to a gradual decline with age occurred between ages 19 and 23 for males and between ages 17 and 21 for females. They picked age 20 for males and age 18 for females for dividing their prediction equations. In this study, information about age at which peak FEV1 was achieved was limited because only a subset of the sample of nonsmoking people without asthma were observed at ages between 18 and 22 and then only at baseline and some at the second examination. Therefore, rather than relying on the smoothed quadratic model that fit our data well for most ages, we estimated the age of peak FEV1 as the age of highest observed FEV1, even if the observed means were not monotonically increasing before that age. The estimate of the duration of a plateau in FEV1 was more robust, being based on a broader range of observations in more subjects than was the peak and using the smoothed quadratic model. FEV1 was estimated to remain within 50 ml of peak value through age 24 in men and 27–28 in women. Once the plateau ended, the rate of decline until age 40 was steeper in men than in women and in blacks than in whites. Blacks and women also had lower FEV1 at age 18, a difference that was accentuated by age 40. This study corroborates the findings of other published reports that have described lower lung function in blacks than in whites and in women than in men of the same race (17, 27–34). Harik-Khan and coworkers found this difference to be partially explained by a shorter upper body segment in blacks (35). In the CARDIA data, blacks also have a shorter sitting height and an increased leg length when compared with the trunk; sitting height was nonsignificantly more strongly related to FEV1 among blacks than among whites (17). This study also extends the evidence from earlier CARDIA examinations (17, 34); here we show that the race and sex differences persist over multiple examinations and through age 40.

Asthma, Smoking, and Their Interaction
In agreement with other studies (6–9), smoking appeared to have an adverse effect on the evolution of FEV1. This study adds some detail to the extent of this adverse effect. Current smokers had a lower lung function at age 18 and had a faster rate of deterioration than nonsmokers. The rate of decrease was highest in people who smoked more than 15 cigarettes per day, even if they had quit smoking before baseline. The ex-smokers who had smoked less than 15 cigarettes per day had a higher FEV1 at baseline and a rate of decline similar to that of never-smokers. Earlier age of smoking initiation was also associated with poorer FEV1, a finding that appeared to be secondary to the fact that those who started smoking earlier were more likely to continue smoking and to be heavier smokers.

Findings in this study agree with those in previous studies, which showed that diagnosed asthma (36, 37) or asthma symptoms can lead to a decrease in lung function (33, 37–41). As expected, people who never had asthma or asthma symptoms (wheeze and shortness of breath) had the highest FEV1 and the smallest relative decrease in lung function over the observed time interval. Although wheezing has been considered to be an indicator of bronchial hyper-reactivity according to the Epidemiology Standardization Project (42), participants who reported only wheezing or only shortness of breath showed little difference in FEV1 pattern from those with neither symptom. However, the participants who reported having both wheeze and shortness of breath (in some cases years apart) had an FEV1 pattern that closely resembled that of the participants who had asthma. We therefore assumed that these participants actually have undiagnosed and untreated asthma. Their lung function was not much different from those who were diagnosed (and treated) for asthma. Recently, Louis and coworkers (43) have shown that airway inflammation at the cellular level in patients with asthma continues despite treatment with topical corticosteroids. Moreover, Boulet and coworkers (44) have shown that corticoid treatment, even in high doses, did not reduce subepithelial fibrosis over an 8-week period, once asthma has become symptomatic. Although the existing CARDIA data did not allow the precise quantification of the treatment methods and of the treatment duration and may suffer from indication bias, our findings are concordant with the current concept (45) that asthma treatments as available and employed before 1995 are not as efficient in forestalling gradual loss of lung function as in improving acute symptoms.

There was a synergy between asthma and smoking. In individuals without asthma, smoking 15 or more cigarettes per day was associated with an FEV1 decline of 0.19 L (2.6%) more than the decline in those who never smoked or never had asthma; similarly, among never-smokers, having asthma was associated with an additional 1.6% decrease in FEV1. The additional decrease in those who both smoked 15 or more cigarettes per day and also had asthma was of 9.3%, compared with the decrease of 4.2% that would be expected if there were no synergy. This leads to the conclusion that the combined effect of heavy smoking and asthma is much more harmful for the long-term lung function than is either of these two factors taken separately. Jaakkola and coworkers (46) also found an interaction between smoking and wheezing, but they did not find that smoking alone was associated with reduced FEV1.

Early Life Factors
Of the childhood exposures, the most important appeared to be family smoking, presumably during the participant's childhood. Previous studies have shown that mother's smoking was associated with reduced peak expiratory flow and FEV1 in children (47, 48). We observed no direct link between family smoking and FEV1 decrease, which suggests that family smoking did no direct damage to participants' lungs. However, family smoking did appear to influence the child's future behaviors that related to poorer FEV1. Participants in families that included one or more smokers were more likely to start smoking earlier in their life and to be current and heavy smokers. They were also more likely to have an early asthma diagnosis (18). The CARDIA questions about family smoking were weak for the purpose used here, in that they did not indicate when the family members smoked, how much they smoked, or whether they smoked with the child in the room. Therefore, we likely understate the potential direct influence of family smoking on adult FEV1 in the CARDIA participants. This observation, indirectly linking family smoking and FEV1 to the future adult behavior of the participants, emphasizes the importance of nonsmoking, especially in families with children. The direct link of early smoking initiation with faster decline in FEV1 emphasizes the importance of preventing smoking initiation at young ages for the future development of lung function.

This study has many strengths, including the large amount of data on blacks and women, two understudied groups. In addition, it captures an age range during which peak lung function usually occurs. Also, as is necessary in longitudinal studies, the quality control across exams was very high, maintaining the replication of measurements over time to make valid comparisons.

However, as in every epidemiologic study, there are some limitations. First, we acknowledge that a learning effect might push up FEV1 estimates in later examinations, such that the actual decline might be underestimated; however, this learning is unlikely to be very important, considering that the measurements took place years apart. Second, longitudinal studies are subject to bias due to loss–to–follow-up; this phenomenon has been noted in other studies (6, 49). However, this was not observed in CARDIA, as the cohort was young, retention was excellent, and the regression methods included all available information, even in dropouts. In fact, because the age-matched time trend was small, we found little difference between cross-sectional and longitudinal estimates of age pattern of FEV1. Smoking, asthma, and childhood exposures had similar relations to FEV1 in those who missed examinations and in those who did not, and mortality was low; about 1.5% of participants by Year 10. Third, the important questions about childhood exposure to family smoking were nonspecific in this study.

In summary, family smoking, presumably during the participant's childhood, probably contributed to a less favorable FEV1 aging pattern by leading to an increased risk of early asthma and an increased likelihood of behaviors unfavorable for FEV1. However, family smoking and early asthma diagnosis were not directly related to the pattern of FEV1. Decline in FEV1 began earlier and was more rapid in smokers and in those who had asthma (either treated or untreated). The combined effect of smoking and asthma led to an even larger decrease in FEV1 than did either factor alone. The FEV1 aging pattern varied between race and sex groups. These differences were not explained by differences in asthma, smoking, or early life exposures.

Principles for Estimating Age and Period Effects in FEV1
Following Jacobs and coworkers (19), we define age effects as FEV1 changes with age, common to all birth cohorts and calendar times. Similarly, period effects are FEV1 changes with calendar time, common to all birth cohorts and ages. In this model, birth cohort effects are then deviations from the sum of age and period effects; that is, the interaction of age and period effects. It is not possible to estimate historical birth cohort effects (that occur before baseline of a longitudinal study); however, the evolving birth cohort effects (that occur after baseline) are estimable as the interaction between age and period effects. In the present data, such interaction terms were not statistically significant. Given the narrow age range and the apparent absence of evolving birth cohort effects, we assumed that birth cohort effects were zero. Assuming that FEV1 at birth was similar across all participants and that period effects in the years before birth of the youngest participants are small (period effects between 1985 and 1995 were small in these data), the expected value of FEV1 at age j and calendar year k can be represented as the sum of a series of annual age- and period-related increments:

where {partial}Am is the age-related change in FEV1 from ages m - 1 to m and {partial}Tn is the period-change from years n - 1 to n.

Consequently, the longitudinal change for 1 year compares age j + 1 with age j; as age increases, calendar time increases from k to k + 1. Longitudinal change is represented as follows:

The cross-sectional age slope for 1 year has an expected value:

Each cross-sectional age slope compares people of different ages at the same calendar time. Thus, an average of the cross-sectional age slopes across the serial examinations estimates the age effect.

Similarly, age-matched time trend is represented by

The age-matched time trend compares people of the same age at different calendar times and therefore estimates the period effect.

We used SAS PROC MIXED to estimate age and period effects. The PROC MIXED code shown below is used for computing Figure 1. The dependent variable is FEV1/ht2 (represented below as "fevht") at Years 0, 2, 5, and 10. Independent variables are current age (age at each of the repeated observations, represented below as "curage") and time. The coefficient of current age is the estimate of cross-sectional age slope, adjusted for period effects. The coefficient of time is age-matched time trend. Other variations are possible, such as quadratic age and categoric time. For Figure 1, the regression was restricted to those who did not smoke at baseline and never had asthma. The first regression estimates the quadratic curves, whereas the second estimates the mean FEV1/ht2 for each year of age.

proc mixed noclprint info;

class id time race sex;

model fevht = time curage|curage|race|sex/solution;

repeated/type = CS sub = id;

run;

proc mixed noclprint info;

class id time race sex curage;

model fevht = time curage|race|sex/solution;

repeated/type = CS sub = id;

lsmeans curage*race*sex/om;

run;

Models for analyses of other variables, such as age of smoking initiation (represented below as "smokage") were formed by adding additional age interactions, e.g.,

proc mixed noclprint info;

class id time race sex;

model fevht = time curage|curage|race|sex curage|smokage/solution;

repeated/type = CS sub = id;

run;


   FOOTNOTES
 
This article has an online data supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Received in original form July 11, 2000; accepted in final form March 20, 2002


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Sobol B, Herbert W, Emirgil C. The high incidence of pulmonary functional abnormalities in patients with coronary artery disease. Chest 1974;65:148–151.[Abstract/Free Full Text]
  2. Vestbo J, Lange P. Forced expiratory volume in 1 second (FEV1)—a respiratory physiological measurement of considerable prognostic value. Ugeskrr Laeger 1991;153:2292–2295.
  3. Keys A, Aravanis C, Blackburn H, Djordjevic BS, Dontas AS, Fidanza F, Karvonen MJ, Menotti A, Taylor HL. Lung function as a risk factor for coronary heart disease. Am J Public Health 1972;62:1506–1511.[Free Full Text]
  4. Knuiman MW, James AL, Divitini ML, Ryan G, Bartholomew HC, Musk AW. Lung function, respiratory symptoms, and mortality: results from the Busselton Health Study. Ann Epidemiol 1999;9:297–306.[CrossRef][Medline]
  5. Asthma At-A-Glance 1999 – Asthma Prevention Program of the National Center for Environmental Health, CDC, Atlanta, GA; 1999. p. 2.
  6. 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]
  7. Samet JM, Lange P. Longitudinal studies of active and passive smoking. Am J Respir Crit Care Med 1996;154:S257–S265.
  8. Gold DR, Wang X, Wypij D, Speizer FE, Ware JH, Dockery DW. Effects of cigarette smoking on lung function in adolescent boys and girls. N Engl J Med 1996;335:931–937.[Abstract/Free Full Text]
  9. Tager IB, Munoz A, Rosner B, Weiss S, Carey V. Effect of cigarette smoking on the pulmonary function of children and adolescents. Am Rev Respir Dis 1985;131:752–759.[Medline]
  10. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105–1116.[CrossRef][Medline]
  11. Keller J, Higgins M, Wagenknecht L, Townsend M, Sparrow D, Jacobs D. Pulmonary function, smoking and respiratory symptoms in young black and white men and women: the CARDIA study [abstract]. Am Rev Respir Dis 1989;139:A24.
  12. Renzetti AD Jr. Standardization of spirometry. Am Rev Respir Dis 1979; 119:693–694.[Medline]
  13. American Thoracic Society. Standardization of spirometry — 1987 update. Am Rev Respir Dis 1987;136:1285–1298.[Medline]
  14. Honig E. Pulmonary function in patients with cardiac disease. Schlant R, Rackley C, Sonnenblick E, Wenger N, editors. The heart. New York: McGraw-Hill Information Services Company; 1989. p. 2078–2081.
  15. Humerfelt S, Eide GE, Kvale G, Gulsvik A. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) variability in asymptomatic never-smoking men. Clin Physiol 1998;18:387–393.[CrossRef][Medline]
  16. Rodriguez B, Masaki K, Burchfiel C, Curb JD, Fong KO, Chyou PH, Marcus EB. Pulmonary function decline and 17-year total mortality: the Honolulu Heart Program. Am J Epidemiol 1994;140:398–408.[Abstract/Free Full Text]
  17. Jacobs DR, Nelson ET, Dontas AS, Keller J, Slattery ML, Higgins M. Are race and sex differences in lung function explained by frame size? The CARDIA Study. Am Rev Respir Dis 1992;146:644–649.
  18. Beckett WS, Jacobs DR, Yu X, Iribarren C, Williams OD. Asthma is associated with weight gain in females but not males, independent of physical activity. Am J Respir Crit Care Med 2001;164:2045–2050.[Abstract/Free Full Text]
  19. Jacobs DR, Hannan PJ, Wallace D, Liu K, Williams OD, Lewis CE. Interpreting age, period and cohort effects in plasma lipids and serum insulin using repeated measures regression analysis: the CARDIA Study. Stat Med 1999;18:655–679.[CrossRef][Medline]
  20. Weiss S, Ware J. Overview of issues in the longitudinal analysis of respiratory data. Am J Respir Crit Care Med 1996;154:S208–S211.
  21. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;123:659–664.[Medline]
  22. Morris JF, Koski A, Johnson LC. Spirometric standards for healthy nonsmoking adults. Am Rev Respir Dis 1971;103:57–67.[Medline]
  23. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983;127:725–734.[Medline]
  24. Brandli O, Schindler C, Kunzli N, Keller R, Perruchoud AP. Lung function in healthy never smoking adults: reference values and lower limits of normal of a Swiss population. Thorax 1996; 51:277–283.[Abstract]
  25. van Pelt W, Borsboom GJJM, Rijcken B, Schouten JP, van Zomeren BC, Quanjer PH. Discrepancies between longitudinal and cross-sectional change in ventilatory function in 12 years of follow-up. Am J Respir Crit Care Med 1994;149:1218–1226.[Abstract]
  26. Burrows B, Lebowitz MD, Camilli AE, Knudson RJ. Longitudinal changes in forced expiratory volume in one second in adults: methodologic considerations and findings in healthy nonsmokers. Am Rev Respir Dis 1986;133:974–980.[Medline]
  27. Sherrill DL, Lebowitz MD, Knudson RJ, Burrows B. Smoking and symptom effects on the curves of lung function growth and decline. Am Rev Respir Dis 1991;144:17–22.[Medline]
  28. Tager IB, Segal MR, Speizer FE, Weiss ST. The natural history of forced expiratory volumes: effect of cigarette smoking and respiratory symptoms. Am Rev Respir Dis 1988;138:837–849.[Medline]
  29. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general US population. Am J Respir Crit Care Med 1999;159:179–187.[Abstract/Free Full Text]
  30. Schoenberg J, Beck G, Bouhuys A. Growth and decay of pulmonary function in healthy blacks and whites. Respir Physiol 1978;33:367–393.[Medline]
  31. Binder R, Mitchell C, Schoenberg J, Bouhuys A. Lung function among black and white children. Am Rev Respir Dis 1976;114:955–959.[Medline]
  32. Gold D, Rotnitzky A, Damokosh A, Ware JH, Speizer FE, Ferris BG Jr, Dockery DW. 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]
  33. Gold D, Wypij D, Wang X, Speizer FE, Pugh M, Ware JH, Ferris BG Jr, Dockery DW. Gender- and race-specific effects of asthma and wheeze on level and growth of lung function in children in six US cities. Am J Respir Crit Care Med 1994;149:1198–1208.[Abstract]
  34. Higgins M, Keller J, Wagenknecht L, Townsend MC, Sparrow D, Jacobs DR Jr, Hughes G. Pulmonary function and cardiovascular risk factor relationships in black and in white young men and women: The CARDIA Study. Chest 1991;99:315–322.[Abstract/Free Full Text]
  35. Harik-Khan RI, Fleg JL, Muller DC, Wise RA. The effect of anthropometric and socioeconomic factors on the racial difference in lung function. Am J Respir Crit Care Med 2001;164:1647–1654.[Abstract/Free Full Text]
  36. Jaakkola MS, Jaakkola JJK, Ernst P, Becklake MR. Respiratory symptoms in young adults should not be overlooked. Am Rev Respir Dis 1993;147:359–366.[Medline]
  37. Weiss ST, Tosteson TD, Segal MR, Tager IB, Redline S, Speizer FE. Effects of asthma on pulmonary function in children: a longitudinal population-based study. Am Rev Respir Dis 1992;145:58–64.[Medline]
  38. Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS, Tashkin DP. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease: the Lung Health Study. Am J Respir Crit Care Med 2000;161:381–390.[Abstract/Free Full Text]
  39. Sherman CB, Xu X, Speizer FE, Ferris BG Jr, Weiss ST, Dockery DW. Longitudinal lung function decline in subjects with respiratory symptoms. Am Rev Respir Dis 1992;146:855–859.[Medline]
  40. Krzyzanowski M, Camilli AE, Lebowitz MD. Relationship between pulmonary function and changes in chronic respiratory symptoms. Chest 1990;98:62–70.[Abstract/Free Full Text]
  41. Jedrychowski W, Maugeri U, Falk E, Bianchi I. Reversibility of asthma-like symptoms and lung function growth over two-year follow-up in preadolescent children. Med Sci Monit 2001;7:293–298.[Medline]
  42. Ferris BG Jr. Epidemiology Standardization Project. Am Rev Respir Dis 1978;118:1–120.[Medline]
  43. Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanovic R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med 2000;161:9–16.[Abstract/Free Full Text]
  44. Boulet LP, Turcotte H, Laviolette M, Naud F, Bernier MC, Martel S, Chakir J. Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma: influence of inhaled corticosteroids. Am J Respir Crit Care Med 2000;162:1308–1313.[Abstract/Free Full Text]
  45. Vestbo J, Sorensen T, Lange P, Brix A, Torre P, Viskum K. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999;353: 1819–1823.[CrossRef][Medline]
  46. Jaakkola MS, Jaakkola JJ, Ernst P, Becklake MR. Ventilatory lung function in young cigarette smokers: a study of susceptibility. Eur Respir J 1991;4:643–650.[Abstract]
  47. Gilliland FD, Berhane K, McConnell R, Gauderman WJ, Vora H, Rappaport EB, Avol E, Peters JM. Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Thorax 2000;55:271–276.[Abstract/Free Full Text]
  48. Li YF, Gilliland FD, Berhane K, McConnell R, Gauderman WJ, Rappaport EB, Peters JM. Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma. Am J Respir Crit Care Med 2000;162:2097–2104.[Abstract/Free Full Text]
  49. Vollmer W. Reconciling cross-sectional with longitudinal observations on annual decline. Occup Med 1993;8:339–351.



This article has been cited by other articles:


Home page
 Eur Respir JHome page
M. R. Sears
Lung function decline in asthma
Eur. Respir. J., September 1, 2007; 30(3): 411 - 413.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
E. H. Walters, D. W. Reid, D. P. Johns, and C. Ward
Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling
Eur. Respir. J., September 1, 2007; 30(3): 574 - 588.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
T. R. Bai, J. M. Vonk, D. S. Postma, and H. M. Boezen
Severe exacerbations predict excess lung function decline in asthma
Eur. Respir. J., September 1, 2007; 30(3): 452 - 456.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. Chaudhuri, E. Livingston, A. D. McMahon, J. Lafferty, I. Fraser, M. Spears, C. P. McSharry, and N. C. Thomson
Effects of Smoking Cessation on Lung Function and Airway Inflammation in Smokers with Asthma
Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 127 - 133.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. Moshammer, G. Hoek, H. Luttmann-Gibson, M. A. Neuberger, T. Antova, U. Gehring, F. Hruba, S. Pattenden, P. Rudnai, H. Slachtova, et al.
Parental Smoking and Lung Function in Children: An International Study
Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1255 - 1263.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
M. S.-m. Ip, F. W.-s. Ko, A. C.-w. Lau, W.-c. Yu, K.-s. Tang, K. Choo, M. M.-w. Chan-Yeung, and on Behalf of the Hong Kong Thoracic Society and Am
Updated spirometric reference values for adult chinese in Hong Kong and implications on clinical utilization.
Chest, February 1, 2006; 129(2): 384 - 392.
[Abstract] [Full Text] [PDF]

Home page
 Occup. Environ. Med.Home page
M-L Wang, Z-E Wu, Q-G Du, E L Petsonk, K-L Peng, Y-D Li, S-K Li, G-H Han, and M D Atffield
A prospective cohort study among new Chinese coal miners: the early pattern of lung function change
Occup. Environ. Med., November 1, 2005; 62(11): 800 - 805.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
N.C. Thomson, R. Chaudhuri, and E. Livingston
Asthma and cigarette smoking
Eur. Respir. J., November 1, 2004; 24(5): 822 - 833.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. A. Covar, J. D. Spahn, J. R. Murphy, and S. J. Szefler
Progression of Asthma Measured by Lung Function in the Childhood Asthma Management Program
Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 234 - 241.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. N. Melgert, D. S. Postma, M. Geerlings, M. A. Luinge, P. A. Klok, B. W. A. van der Strate, H. A. M. Kerstjens, W. Timens, and M. N. Hylkema
Short-Term Smoke Exposure Attenuates Ovalbumin-Induced Airway Inflammation in Allergic Mice
Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 880 - 885.
[Abstract] [Full Text] [PDF]

Home page
 Int J EpidemiolHome page
B. Jackson, L. D Kubzansky, S. Cohen, S. Weiss, and R. J Wright
A matter of life and breath: childhood socioeconomic status is related to young adult pulmonary function in the CARDIA study
Int. J. Epidemiol., April 1, 2004; 33(2): 271 - 278.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
H. Hemila, J. Virtamo, D. Albanes, and J. Kaprio
Vitamin E and Beta-Carotene Supplementation and Hospital-Treated Pneumonia Incidence in Male Smokers
Chest, February 1, 2004; 125(2): 557 - 565.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
W. M. Chatila, W. A. Wynkoop, G. Vance, and G. J. Criner
Smoking Patterns in African Americans and Whites With Advanced COPD
Chest, January 1, 2004; 125(1): 15 - 21.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, and Pulmonary Function Testing in AJRCCM 2002
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 306 - 318.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Data Supplement
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Apostol, G. G.
Right arrow Articles by Beckett, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Apostol, G. G.
Right arrow Articles by Beckett, W. S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society