Natural progression of childhood asthma symptoms and strong influence of sex and puberty

Abstract

Rationale: Asthma prevalence, onset, remission and relapse, and healthcare use have been intensively studied. However, asthma symptom progression through childhood and adolescence has not been well studied, in part due to the challenges in obtaining consistent and robust long-term follow-up data on a large series of subjects with asthma.

Objectives: To use the asthma diary symptom data of the Childhood Asthma Management Program placebo group (5 yr, 418 subjects, and total 564,518 records) to establish sex-specific high-resolution time courses of the natural progression of asthma symptoms through childhood and adolescence.

Methods: We used the asthma diary symptom code as a measure of daily disease severity. Annual records of Tanner stage were used to determine the influence of puberty on severity. A data alignment technique was used to derive 13-year time courses of mean symptoms and mean Tanner stage.

Measurements and main results: Data analyses showed three age- and sex-related phases of asthma symptom progression: Phase 1 (ages 5 and 6 yr)-greater severity in boys; Phase 2 (ages 7 to 9 yr)-no sex difference in severity; and Phase 3 (age 10-17 yr)-greater severity in girls. The continuous decline of symptoms in both sexes stops abruptly at the onset of puberty.

Conclusions: The severity of asthma symptoms varies through childhood and adolescence, and patterns differ by sex. Puberty has a strong influence on symptom progression in both sexes. Progression of symptoms is a distinct aspect of asthma epidemiology.

Keywords: epidemiology; sex difference; sex dominance.

Figure 1.

Modeling of the diary symptom code data, XSYMP (Childhood Asthma Management Program [CAMP] placebo group), by truncated Poisson distribution. The truncated Poisson distribution (blue) was fitted to the actual histogram (red) of XSYMP at each time point for girls (A) and boys (B). As an evaluation of the goodness of fit, the average χ² (over all time points) is 0.01 for girls and 0.004 for boys. The results demonstrated that the XSYMP data of all time points in both sex-specific time courses can be accurately modeled by the truncated Poisson distribution. The four bins (from left to right) in each histogram correspond to the four values of XSYMP: 0, 1, 2, and 3; the details about XSYMP are in Methods and the online supplement.

Figure 2.

Sex-specific time courses of mean XSYMP and mean Tanner stage (Childhood Asthma Management Program [CAMP] placebo group). (A) We used Aligning Samples by Age to generate the sex-specific time courses of mean Tanner stage. Note that the Tanner stage is discrete number (1–5), but the mean Tanner stage is continuous. The error bars are 95% confidence intervals (CIs) (some are too small to be visible). These curves are highly consistent with the documented puberty development data, demonstrating the effectiveness of this method. (B) Using Aligning Samples by Age, we generated the sex-specific time courses of mean XSYMP. The time courses have high time resolution (with time interval of 1 year) and long coverage (covering 13 years, ages 5 to 17 years). Note that age X in the time course denotes the range [X−0.5, X+0.5). The extremely small 95% CIs (error bars) indicate the high statistical power of CAMP diary symptom data. (C) The curve of mean XSYMP versus mean Tanner stage. This curve shows that the continuous decline of symptom severity in both sexes stops abruptly and the female sex dominance in severity starts precisely at the onset of puberty where the mean Tanner stage just departs from the value of 1. This indicates that puberty is a critical stage in symptom progression. With high temporal resolution and parallel Tanner stage data, we are able to clearly distinguish between the influences of two concurrent variables (i.e., age and puberty). The sudden interruptions of continuous symptom improvements at the onset of puberty in both sexes can only be attributed to puberty.