Abstract
Rationale: There is an association between childhood chest illness and impairment of adult ventilatory function. It has not yet been established whether respiratory illness in childhood predisposes to chronic obstructive pulmonary disease by accelerating the decline in adult lung function.
Objectives: To determine the effects of childhood chest illness and smoking on the rate of decline of adult ventilatory function from the age of 35 to 45 yr in a large, nationally representative sample of British adults.
Methods: Spirometry measurements were compared at 35 and 45 yr of age in 1,158 adults participating in the British 1958 Birth Cohort. Multiple regression analysis was used to measure the association between childhood chest illness and within-person change in spirometric volumes between age 35 and 45 yr, adjusting for potential confounding factors.
Measurements and Main Results: The mean reduction in FEV1 between ages 35 and 45 yr was 35 ml/yr. Compared with subjects without the relevant respiratory history, the rate of decline was not significantly associated with pneumonia (mean difference, −0.2; 95% confidence interval, −6.1 to +5.8 ml/yr), whooping cough (0.7, −5.1 to +6.5 ml/yr), wheeze by age 7 yr (0.4, −5 to +5.9 ml/yr), or wheeze onset by age 8 to 16 yr (−3.4, −10.5 to +3.6 ml/yr). A similar pattern emerged for forced vital capacity.
Conclusions: Childhood chest illness does not adversely affect the rate of decline of lung function in mid-adult life.
There is an association between childhood chest illness and impairment of adult ventilatory function. It has not been established whether such illness predisposes to chronic obstructive pulmonary disease by accelerating the decline in adult lung function.
Childhood chest illness does not adversely affect the rate of decline of lung function in mid-adult life.
The link between childhood chest illness and chronic adult respiratory disease has been of interest to researchers for some time (1–6). There is evidence that asthma in childhood reduces the maximal lung function achieved by an individual (7, 8). Because lung function decline starts after the age of 35 yr in asymptomatic nonsmokers (9), subjects from key longitudinal studies of asthma that started in the 1960s are of an age when the rate of decline of lung function can be evaluated with respect to childhood chest illness and smoking habit.
Two such studies found conflicting results on this issue (7, 10); only one of these recruited a population-based sample, and both studied small numbers (< 300) of subjects.
A previous study of ventilatory function in a British nationally representative sample of adults monitored from birth concluded that the association between childhood wheezing illnesses and chronic respiratory disease in adult life might be caused by progressive pulmonary changes in those with persistent asthma (11). Here, data are presented on the effects of prior wheezing illness, pneumonia, and whooping cough on the rate of decline of adult respiratory function in the same cohort between the ages of 35 and 45 yr.
The British 1958 Birth Cohort (National Child Development Study) is a longitudinal study of all people in England, Scotland, and Wales born in 1 wk in March 1958 (11–13).
In 1992–1993, when the cohort members were 35 yr old, examinations involving measurements of ventilatory function were performed in 1,156 cohort members with a history of asthma, wheezy bronchitis, or pneumonia at any postnatal follow-ups (“cases”) and 293 control subjects (cohort members with no history of these conditions) (5, 11).
This same group of cohort members were again questioned about asthma, wheezing, and cigarette smoking at age 42 yr and measurements of ventilatory function were repeated at age 45 yr (2002–2003).
Spirometry measures performed at age 35 yr have been described previously (11). At age 45 yr, subjects were examined in their home by a trained research nurse. Forced expiratory maneuvers were performed according to the criteria of the American Thoracic Society (14), in the standing position, without noseclips. After a period of instruction and practice attempts, at least three (and up to five) spirograms were recorded by pneumotachograph (Micro; Vitalograph, Buckingham, UK) until three technically satisfactory blows were obtained. The highest technically satisfactory values of FEV1 and FVC from each set of spirograms were used in the analysis. All subjects gave written consent to examination. Ethical approval was given by the South East Multicentre Research Ethics Committee.
Analyses were restricted to 1,158 subjects who had satisfactory spirometry readings at both age 35 and 45 yr. The difference between FEV1 measurements at age 45 and 35 yr was used as the outcome.
Subjects examined at age 35 yr were asked to take any bronchodilator medication only on an “as required” basis for 6 h before the nurse's visit. This instruction was not applied at the 45-yr examination. Therefore, for the 29 subjects who, at age 45 yr, had used an inhaler within 6 h of spirometry, the postsalbutamol FEV1 and FVC at age 35 yr were used to calculate the change in lung function.
Multiple regression models were adjusted for sex, socioeconomic position at birth and at age 42 yr, smoking history and number of cigarettes currently smoked at age 35 and 42 yr, month of test (at age 35 and 45 yr), observer, and spirometer at each follow-up. A similar approach was adopted for FVC. All analyses were performed using Stata version 8.0 (StataCorp, College Station, TX).
Table 1 shows the characteristics of the subjects examined at ages 35 and 45 yr and of those with satisfactory spirometry at both ages who were included in the analysis.
Characteristic | Spirometry at Age 35 yr, n (%) | Examined at Age 45 yr, n (%) | Satisfactory Spirometry at Age 35 and 45 yr, n (%) |
|---|---|---|---|
| Total | 1,392 | 1,266 | 1,158 |
| Male | 695 (50) | 617 (49) | 565 (49) |
| Never smoked by 35 yr | 425 (31) | 403 (32) | 369 (32) |
| Ex-smoker by 35 yr | 530 (38) | 490 (39) | 446 (39) |
| Current smoker at 35 yr | 437 (31) | 373 (29) | 343 (30) |
| Pneumonia by 7 yr | 193 (14) | 177 (14) | 165 (14) |
| Whooping cough by 7 yr | 215 (15) | 193 (15) | 178 (15) |
| Asthma/wheeze by 7 yr | 539 (39) | 488 (39) | 439 (38) |
| Asthma/wheeze age 8–16 yr | 198 (14) | 177 (14) | 164 (14) |
| Asthma/wheeze by age 17–23 yr | 102 (7) | 93 (7) | 83 (7) |
| Asthma/wheeze by age 24–35 yr | 221 (16) | 202 (16) | 185 (16) |
| No asthma/wheeze/pneumonia | 275 (20) | 234 (18) | 218 (19) |
| Pneumonia with no asthma/wheeze | 57 (4) | 50 (4) | 47 (4) |
Approximately 91% of the 1,392 cohort members who undertook spirometry at age 35 yr were re-examined at age 45 yr and 83% are included in the analysis. Proportions of subjects with onset of wheeze at less than 7 yr of age or with a history of pneumonia or whooping cough were similar in the groups studied at age 35 and at 45 yr. There was a slightly higher proportion of ex-smokers at age 45 yr.
Among the 1,158 participants measured in both surveys, there were 139 men (mean height, 177 cm) and 127 women (mean height, 164 cm) with no history of wheezing illness. At age 35, the mean FEV1 and FVC were, respectively, 4.26 and 5.25 L for male nonwheezers and 3.25 and 3.94 L for female nonwheezers. Among 426 men (mean height, 176 cm) and 466 women (mean height, 163 cm) with a history of wheezing at any age, the equivalent values were 4.12 and 5.22 L for males and 3.10 and 3.85 L for females.
The within-subject change in FEV1 ranged from a reduction of 195 ml/yr to an increase of 170 ml/yr, with a mean (95% confidence interval [CI]) reduction of 35 ml/yr (32–36 ml/yr). The change in FVC ranged from a reduction of 249 ml/yr to an increase of 186 ml/yr, with a mean (95% CI) reduction of 31 ml/yr (28 to 34 ml/yr).
Table 2 shows that smokers at age 42 yr suffer a higher rate of decline in FEV1 and FVC between the ages of 35 and 45 yr than former or never-smokers (p = 0.008) in both cases. A similar pattern is seen with smoking at age 33 yr, although this is only of borderline statistical significance for FEV1 (p = 0.05).
Adjusted† | Adjusted† | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | n | Mean Change in FEV1, ml/yr (SD) | Difference in Change in FEV1, ml/yr (95% CI) | p Value (heterogeneity) | Mean Change in FVC, ml/yr (SD) | Difference in Change in FVC, ml/yr (95% CI) | p Value (heterogeneity) | ||
| Sex | |||||||||
| Male | 565 | −35.6 (38.3) | −2.1 (−6.1 to 1.9) | 0.27 | −33.5 (45.9) | −3.9 (−9.1 to 1.3) | 0.12 | ||
| Female | 593 | −33.4 (31.2) | 0 (ref) | −28.6 (43.4) | 0 (ref) | ||||
| Socioeconomic position at birth | |||||||||
| Manual-labor class | 796 | −35.6 (33.9) | −2.5 (−6.9 to 1.9) | 0.48 | −33.8 (44.1) | −7.0 (−12.7 to −1.3) | 0.03 | ||
| Nonmanual-labor class | 360 | −32.0 (36.9) | 0 (ref) | −24.7 (45.5) | 0 (ref) | ||||
| Socioeconomic position at age 42 yr | |||||||||
| Manual-labor class | 382 | −37.3 (34.6) | −3.1 (−7.5 to 1.2) | 0.24 | −36.5 (42.8) | −7.4 (−13.0 to −1.8) | 0.01 | ||
| Nonmanual-labor class | 759 | −32.9 (35.1) | 0 (ref) | −28.0 (45.5) | 0 (ref) | ||||
| Smoking status at age 35 yr | |||||||||
| Current | 343 | −38.4 (35.2) | −5.6 (−10.8 to −0.4) | 0.05 | −33.8 (44.3) | −7.8 (−14.5 to −1.1) | 0.04 | ||
| Former | 446 | −33.2 (36.0) | −0.7 (−5.6 to 4.1) | −32.1 (45.5) | −5.6 (−11.9 to 0.7) | ||||
| Never | 369 | −32.3 (32.9) | 0 (ref) | −27.2 (43.8) | 0 (ref) | ||||
| Smoking status at age 42 yr* | |||||||||
| Current | 260 | −41.5 (34.7) | −7.9 (−13.5 to −2.3) | 0.008 | −34.9 (41.7) | −7.7 (−14.9 to −0.4) | 0.008 | ||
| Former | 515 | −32.2 (35.0) | −0.4 (−5.1 to 4.3) | −30.7 (45.6) | −4.8 (−10.8 to 1.3) | ||||
| Never | 364 | −32.3 (32.8) | 0 (ref) | −27.6 (43.7) | 0 (ref) | ||||
FVC declined more rapidly over the study period in subjects from a manual-labor social class at birth (p = 0.03) or at age 42 yr (p = 0.01) compared with those from nonmanual social classes.
There were 165 subjects with a history of pneumonia, 178 subjects with a history of whooping cough, and 439 subjects with a history of asthma/wheezy bronchitis before the age of 7 yr. There was no significant difference in the rate of change of FEV1 or FVC over the study period between those subjects who had suffered pneumonia, whooping cough, or asthma/wheezy bronchitis, any of these conditions and those who had not (Table 3). The effects of childhood chest illness on lung function decline in smokers and nonsmokers were very similar: the 95% CIs for the smokers almost fit within the corresponding CIs for nonsmokers.
Condition Present | Condition Absent | Adjusted* | Mean Change in FVC, ml/yr (SD) | Adjusted* | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Condition | n | Mean Change in FEV1, ml/yr (SD) | n | Mean Change in FEV1, ml/yr (SD) | Difference in Change in FEV1,† ml/yr (95% CI) | p Value (1 df) | Condition Present | Condition Absent | Difference in Change in FVC,† ml/yr (95% CI) | p Value (1 df) | |||||
| Pneumonia | 165 | −33.6 (35.5) | 989 | −34.7 (34.7) | −0.2 (−6.1 to 5.8) | 0.95 | −23.8 (50.7) | −32.1 (43.5) | 5.9 (−1.8 to 13.6) | 0.10 | |||||
| Whooping cough | 178 | −33.5 (32.0) | 936 | −34.4 (35.1) | 0.7 (−5.1 to 6.5) | 0.79 | −27.6 (45.7) | −30.9 (44.1) | 1.9 (−5.6 to 9.3) | 0.59 | |||||
| Asthma/wheezy bronchitis | 439 | −33.5 (33.5) | 717 | −35.2 (35.5) | 0.9 (−3.4 to 5.1) | 0.67 | −30.6 (46.4) | −31.2 (43.6) | −0.4 (−5.9 to 5.2) | 0.88 | |||||
| Any childhood chest illness (smokers) | 408 | −34.6 (35.4) | 386 | −36.4 (36.1) | 1.7 (−3.6 to 7.0) | 0.49 | −31.4 (47.9) | −33.9 (41.8) | 0.7 (−6.0 to 7.4) | 0.83 | |||||
| Any childhood chest illness (nonsmokers) | 204 | −31.4 (32.2) | 160 | −33.3 (33.7) | 4.5 (−3.2 to 12.2) | 0.15 | −26.1 (45.4) | −29.5 (41.5) | 1.5 (−9.0 to 12.0) | 0.73 | |||||
Wheezers with any age of onset might be expected to have a faster rate of decline in lung function than never-wheezers. Similarly, one would anticipate that wheeze starting during the study period would be associated with a greater rate of fall in lung function than in nonwheezers. However, Table 4 shows that there was no significant difference in the rate of decline of FEV1 between wheezers at any age of onset and never-wheezers. A greater decline in FVC was seen in subjects who developed wheeze up to the age of 35 yr compared with never-wheezers. The differences in rates of decline among the groups with wheeze of different ages of onset did not reach statistical significance. Recent-onset wheezers demonstrated less decline in both FEV1 and FVC than never-wheezers.
Age at Onset of Wheeze (yr) | Adjusted* | Adjusted* | |||||||
|---|---|---|---|---|---|---|---|---|---|
| n | Mean Change in FEV1, ml/yr (SD) | Difference in Change in FEV1,† ml/yr (95% CI) | p Value (5 df) | Mean Change in FVC, ml/yr (SD) | Difference in Change in FVC,† ml/yr (95% CI) | p Value (5 df) | |||
| 0 to 7 | 439 | −33.5 (33.5) | 0.4 (−5.0 to 5.9) | −30.6 (46.4) | −5.9 (−12.9 to 1.1) | ||||
| 8 to 16 | 164 | −37.4 (34.8) | −3.4 (−10.5 to 3.6) | −34.9 (37.4) | −11.9 (−21.0 to −2.8) | ||||
| 17 to 23 | 83 | −35.4 (43.1) | 0.0 (−9.0 to 9.0) | −36.3 (46.7) | −12.1 (−23.7 to −0.4) | ||||
| 24 to 35 | 185 | −35.8 (35.2) | 0.6 (−6.4 to 7.6) | −33.5 (48.2) | −7.2 (−16.3 to 1.8) | ||||
| 36 to 45 | 21 | −28.1 (31.7) | 9.1 (−6.7 to 24.9) | −21.9 (40.7) | 1.9 (−19.0 to 22.8) | ||||
| Never | 266 | −33.5 (34.3) | 0 (ref) | 0.62 | −26.7 (42.7) | 0 (ref) | 0.05 | ||
Subjects who suffered wheeze before the age of 7 yr only showed the steepest rate of decline of FEV1 (−36.3 ml/yr) compared with other transient, persistent, and never-wheezers (−33.5 ml/yr) (Table 5). FVC declined more rapidly in the transient and persistent wheeze groups compared with the never-wheezers, with a statistically significant difference across the groups (p = 0.04). The persistent wheezers showed the greatest rate of decline in FVC, −34.9 ml/yr as compared with −26.7 ml/yr in the never-wheezed group.
Asthma/Wheeze at Age | Adjusted* | Adjusted* | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0–7 yr | 7 yr | 34–35 yr | n | Mean Change in FEV1, ml/yr (SD) | Difference in Change in FEV1,† ml/yr (95% CI) | p Value (3 df) | Mean change in FVC, ml/yr (SD) | Difference in Change in FVC,† ml/yr (95% CI) | p Value (3 df) | ||||
| Yes | No | No | 161 | −36.3 (30.4) | −5.0 (−12.0 to 2.0) | −30.6 (47.1) | −8.8 (−17.9 to 0.4) | ||||||
| Yes | Yes | No | 102 | −32.0 (29.5) | 4.3 (−3.9 to 12.6) | −27.9 (43.3) | −0.5 (−11.2 to 10.1) | ||||||
| Yes | No | Yes | 83 | −29.8 (28.7) | 6.0 (−2.8 to 14.8) | −29.0 (41.6) | −2.8 (−14.2 to 8.5) | ||||||
| Yes | Yes | Yes | 93 | −33.5 (44.9) | 0.1 (−8.3 to 8.4) | −34.9 (52.8) | −9.8 (−20.6 to 1.0) | ||||||
| Never wheezed | 266 | −33.5 (34.3) | 0 (ref) | 0.14 | −26.7 (42.7) | 0 (ref) | 0.04 | ||||||
Table 6 shows the effect of wheeze at age 11 yr on change in adult ventilatory function to allow a comparison with the findings of the Aberdeen WHEASE Study Group (10). No significant difference was found in the rate of decline of FEV1 or of FVC between subjects who suffered from asthma or from wheezy bronchitis only at age 11 yr and subjects who had never wheezed. Those with asthma at age 11 yr tended to have a greater fall in FEV1 (−41.6 ml/yr) compared with never-wheezers (−33.5 ml/yr) and in FVC (−45.4 vs. −26.7 ml/yr).
Adjusted* | Adjusted* | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Wheeze Status at Age 11 yr | n | Mean Change in FEV1, ml/yr (SD) | Difference in Change in FEV1,† ml/yr (95% CI) | p Value (2 df) | Mean Change in FVC, ml/yr (SD) | Difference in Change in FVC,† ml/yr (95% CI) | p Value (2 df) | ||
| Asthma/wheezy bronchitis | 44 | −41.6 (45.6) | −3.2 (−17.0 to 10.6) | −45.4 (51.9) | −15.2 (−31.4 to 1.1) | ||||
| Wheezy bronchitis only | 66 | −35.2 (32.7) | −3.0 (−14.7 to 8.7) | −29.0 (39.6) | −5.3 (−19.1 to 8.4) | ||||
| Never wheezed | 266 | −33.5 (34.3) | 0 (ref) | 0.73 | −26.7 (42.7) | 0 (ref) | 0.06 | ||
Three other studies have looked at the association between childhood wheeze and rate of decline of lung function in adult life (7, 10, 15). Ours is the only population-based study that has followed subjects from childhood to middle age and it is considerably larger than the others.
The key finding of this study was that there was no difference in the rate of change of adult lung function between subjects who suffered childhood wheeze and those who did not. This is consistent with the findings of the Melbourne Asthma Study (7) in which follow-up to age 42 yr revealed that, although subjects in the severe asthma group had lost lung function by the age of 14 yr in comparison with subjects from the other groups, the magnitude of the difference between the severe and mild asthma groups did not increase over time. Sears and colleagues (15) drew a similar conclusion, finding the slopes of change in FEV1:FVC ratio to be similar in each outcome group (persistent, relapse, remission, intermittent, transient, never-wheezed) monitored up to age 26 yr.
Our findings (Table 6) contradict those of the Aberdeen WHEASE Study Group (10) who examined a small sample of 46 subjects with asthma, 65 subjects with wheezy bronchitis, and 66 subjects with no respiratory symptoms (recruited between the ages of 10 and 15 yr) and found that the absolute decline in FEV1 over a 12-yr period to age 45 to 50 yr was significantly greater in both the childhood asthma and the childhood wheezy bronchitis groups. Their study showed higher rates of decline of lung function (mean FEV1 decline was 65 ml/yr in the wheezing groups, and 50 ml/yr in the control group) than reported elsewhere (9, 16, 17).
The mean values of change in FEV1 (−34.5 ml/yr) and in FVC (−31.0 ml/yr) seen in our study are consistent with those found elsewhere. For example, other studies have found a decline in FEV1 of approximately 35 ml/yr in smokers and nonsmokers (9), 32 ml/yr in women and 45 ml/yr in men without asthma (16), and 30 ml/yr in nonasthmatic individuals (17).
Cigarette smoking at both age 35 and 42 yr was associated with a more rapid deterioration in FEV1 and FVC. Although some changes in smoking may have occurred between 42 and 45 yr, this is fully consistent with the findings of other studies (15, 18, 19).
No association was found between early childhood pneumonia and rate of decline in adult lung function. Because it has been shown that childhood pneumonia is associated with reduced ventilatory function in the fourth decade of life (5), it is likely that the disease causes a reduction in the maximal attained lung function rather than an accelerated decline during adulthood or that premorbid lung function is a predisposing factor for childhood pneumonia.
A history of childhood whooping cough does not predispose subjects to a reduction in adult lung function (2, 5, 6). Our study is the first to show that the rate of decline of FEV1 and FVC is not affected by a history of whooping cough.
The Dutch hypothesis that asthma and chronic obstructive pulmonary disease share common origins would predict a greater rate of longitudinal decline in FEV1 in subjects with asthma compared with nonasthmatic subjects (20). Our findings after 10 yr of follow-up do not support this, although it is possible that a difference may emerge more clearly with a longer follow-up period.
Age at onset of wheeze was not seen to influence the rate of decline of ventilatory function. Also, there was no significant heterogeneity across groups with different patterns of wheeze (transient, persistent). In particular, children who outgrow their wheezing tendency in childhood can expect no adverse lung function sequelae in adulthood compared with nonwheezers with similar smoking habits.
The authors thank the cohort members who participated in the study and the two teams of research nurses. They also thank Professor Janet Peacock for statistical advice.
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