In this large retrospective cohort study of nationally representative U.S. adults, the highest risk of incident asthma was in participants who were weight gain (non-obesity to obesity) from early to middle adulthood; stable obesity across adulthood was also associated with increased risk of incident asthma. In addition, there was a dose-response effect of absolute weight gain on asthma incidence, independent of weight in early adulthood. The effects of weight gain on the annual odds of developing asthma were more pronounced in female than in male. The findings underscored the importance of prevention of weight gain in early adulthood, for reducing incident asthma risk in later life.
Prior epidemiological data on the relationship between adulthood weight change and asthma were sparse. The California Teachers Study (CTS) including 88 304 women observed that weight gain ≥ 5 kg since age 18 years was statistically significantly associated with increased prevalence of adult-onset asthma.[22] However, weight gain did not clearly precede the observed asthma, these results may have simply reflected antecedent asthma followed by activity limitation and weight gain. By assessing weight change from the ages of 25 years to the baseline, the current study attempted to capture the changes in BMI during adulthood before the asthma starts, and to minimize reverse causation. In our study, weight gain from a non-obesity to an obesity pattern since young adulthood had a 63% higher incident asthma risk. Extreme weight gain (≥ 20 kg) from early to middle adulthood was associated with a 53% higher incident asthma risk. Higher weight gain predicted subsequent incident asthma in some,[23–25] but not all,[26] participants in the relevant prospective studies. Using data from the Nurses’ Health Study (NHS) with 85 911 female nurses aged 26–46 years at entry, Camargo et al. found that women who gained weight > 10 kg after age 18 were at significantly increased risk of developing asthma during the 4-year follow-up period.[23] Similarly, during a 3-year follow-up period of 67 229 women aged 40–65 years in the E3N Cohort Study, Romieu et al. reported that women who gained approximately ≥ 10 kg between the age of 20 years and baseline had a 89% increased risk of incident asthma.[25] Our results were consistent with these studies and indicated that avoiding obesity at young age and preventing weight gain from young to middle adulthood could be an important strategy to reduce future asthma risk.
We also found evidence that weight gain was related to incident asthma in women but not men. A number of population-based studies have suggested that the relationship between obesity and asthma may be stronger in females.[27, 28] Several possible mechanisms have been postulated to explain the obesity-asthma relationship. A sexual dimorphism exists in relation to body composition, in that females carry more fat subcutaneously and males carry more fat viscerally.[27] This led to distinct differences in the inflammatory pattern exhibited. For example, leptin is secreted more highly from subcutaneous adipose tissue and is therefore higher in females than males.[27] Compared to males, females have a smaller airway size relative to lung size.[23] An additional reduction in airway size caused by weight gain may disproportionately increase the susceptibility of females to asthma.[7] The increased estrogen levels associated with obesity are also thought to be one mechanism to explain the strong association between female obesity and adult-onset asthma.[28, 29]
In our study, weight loss from young to middle adulthood was generally not significantly related to incident asthma compared with the stable normal group or stable obesity group. As weight loss from the obesity to the non-obesity among adulthood was rare, representing only 0.9% of the total population, and the results should be interpreted cautiously. More studies are needed to confirm the results in larger populations and explore the potential effect of weight loss among obesity people.
Adults gain weight more rapidly from young to middle adulthood, and excess adiposity mostly accrues in this period compared with the period from middle to late adulthood when weight begins to stabilize or even decrease.[14] In addition, preventing weight gain from young to middle adulthood might be more important than promoting weight loss, because achieving long term weight loss and maintaining it are difficult once a person becomes obese.[14, 30] Evaluating the long term effect of weight change, particularly weight gain from early to middle adulthood, on future health is thus important. Weight gain from early to middle adulthood is a well-established risk factor for diabetes, hypertension, cardiovascular disease, cancer, non-traumatic death, and many other diseases.[14–17] Our findings support adding asthma to this list and should provide yet one more piece of information to prevent weight gain and to support the aggressive implementation of public health measures to support the attainment of this goal.
We used population attributable fraction to explore the potential effect of prevention initiatives targeting weight gain. If all those who were non-obesity at age 25 prevent weight gain by midlife, 10.2% of observed incident cases of adult-onset asthma could be averted. In total, we found that 21.8% of asthma new cases during this time period could be reduced if the entire population maintained a weight in the normal range between early and middle adulthood in U.S. adults.
Our study had several strengths. Using a retrospective cohort design, we were able to take advantage of a large, nationally representative cohort of U.S. adults to estimate associations between weight change and incident asthma across the life course. As a nationally representative survey, results using NHANES are more broadly generalizable than those from other cohorts like the NHS, CTS and E3N Cohort Study. The advantage of focusing on weight gain throughout adult life is that it primarily reflects the accumulation of excess adiposity from early to middle adulthood, which is often ignored by individuals and their physicians because the consequences of modest weight accumulation may not yet be apparent. If the association between early adulthood weight gain and adult-onset asthma is proved to be causal, understanding and preventing early adulthood weight gain would be the next steps in research and translation, which is not only beneficial to future cardio-metabolic health, but also to mitigation of future asthma risk.
Our study also had several limitations. Firstly, we used recalled and self-reported weight data at age 25 years and 10 years before the NHANES survey and thus misclassification bias might have been introduced. However, a recent meta-analysis showed that recalled early life weight could be a valid measure to use in life course epidemiological analysis.[31] Secondly, we could not adjust for physical activity or diet because recall data on these variables were not collected. The results might thus partly reflect the effects of physical activity and dietary factors over the life course. Thirdly, members of the relevant cohorts who had died before the survey were not represented in the retrospective data set. Their experience might have differed from that of survivors in ways that affected the estimated relationship between obesity and asthma. Furthermore, our report relied on self-reported data on asthma status, which may have missed people who had not been diagnosed with the condition. Lastly, we did not evaluate the relations of changes in other adiposity related markers such as waist circumference and fat mass with incident asthma owing to lack of data at different time points. Further studies with repeated data on these markers may provide a more comprehensive picture of the changes in obesity status and asthma risk.