Early Respiratory Infections and the Development of Asthma in the First 27 Years of Life

Aino K. Rantala; Maritta S. Jaakkola; Elina M. S. Mäkikyrö; Timo T. Hugg; Jouni J. K. Jaakkola

Disclosures

Am J Epidemiol. 2015;182(7):615-623. 

In This Article

Results

Characteristics of the Study Population

There were no substantial differences between the baseline population (part 2) and the study population of 2,228 subjects (part 1) followed for up to 20 years (Table 2). In addition, the assumption of proportionality held for all variables.

Part 1: Respiratory Infections During the 12 Months Preceding Baseline Data Collection and Risk of Asthma

The estimated incidence rates of respiratory infections occurring during the 12 months preceding baseline data collection are shown in Table 3 . A total of 954 persons (42.8%) were categorized as exposed to URTIs and 368 (16.5%) to LRTIs (see Methods). The risk of asthma was consistently increased throughout the 20-year follow-up period in relation to both LRTIs and URTIs. The risk of developing asthma increased significantly in relation to LRTIs throughout the follow-up period, with a slightly decreasing trend in hazard ratios with increasing age periods (adjusted hazard ratio (HR) from baseline age to age 6 years (HRbaseline-6) = 3.20 (95% confidence interval (CI): 1.54, 6.65); from baseline age to age 12 years, HRbaseline-12 = 2.80 (95% CI: 1.84, 4.28); from baseline age to age 18 years, HRbaseline-18 = 2.24 (95% CI: 1.55, 3.24); and from baseline age to age 27 years, HRbaseline-27 = 2.11 (95% CI: 1.48, 3.00)) ( Table 3 ; see Web Table 1 http://aje.oxfordjournals.org/content/182/7/615/suppl/DC1, available at http://aje.oxfordjournals.org/, for crude hazard ratios). The relationship between the experience of early LRTIs and the risk of developing asthma decreased monotonically with chronological age, as indicated by a test for a linear trend in the age-specific hazard ratio (Wald χ2: P < 0.001). Similarly, the risk of developing asthma was related to early URTIs throughout all age periods (adjusted HRbaseline-6 = 2.49 (95% CI: 1.29, 4.80), HRbaseline-12 = 2.08 (95% CI: 1.45, 2.98), HRbaseline-18 = 1.75 (95% CI: 1.29, 2.38), and HRbaseline-27 = 1.64 (95% CI: 1.22, 2.19)) ( Table 3 and Web Table 1 http://aje.oxfordjournals.org/content/182/7/615/suppl/DC1), and the decreasing trend was statistically significant (Wald χ2: P < 0.01). Figure 2 illustrates that subjects with LRTIs during the past 12 months at baseline developed asthma at an earlier age than those with no LRTIs, and this difference remained throughout the 20-year follow-up period. In Figure 3, a similar pattern is seen in relation to the occurrence of URTIs.

Figure 2.

Development of asthma throughout the 20-year follow-up period among children who had had lower respiratory tract infections (LRTIs) during the past 12 months at baseline (broken line) and those with no past-year LRTIs at baseline (solid line), The Espoo Cohort Study, 1991–2011. Follow-up time started at the baseline age of each study subject.

Figure 3.

Development of asthma throughout the 20-year follow-up period among children with upper respiratory tract infections (URTIs) during the past 12 months at baseline (broken line) and those with no past-year URTIs at baseline (solid line), The Espoo Cohort Study, 1991–2011. Follow-up time started at the baseline age of each study subject.

The risk of developing asthma was also increased in relation to specific infections, such as acute bronchitis, pneumonia, common cold, and sinusitis ( Table 3 ). There were 753 persons (35.8%) who had experienced recurrent otitis media as defined in Methods. The risk of developing asthma was related to early recurrent otitis throughout the follow-up period, with a slightly decreasing trend in hazard ratios by age period (adjusted HRbaseline-6 = 1.94 (95% CI: 0.99, 3.78), HRbaseline-12 = 1.73 (95% CI: 1.16, 2.57), HRbaseline-18 = 1.46 (95% CI: 1.03, 2.05), and HRbaseline-27 = 1.38 (95% CI: 0.99, 1.91)) (Wald χ2: P = 0.06) ( Table 3 ).

The risk of developing asthma was more strongly associated with LRTIs and URTIs experienced at 1–2 years of age than with infections experienced later in childhood ( Table 4 ).

Part 2: LRTIs Leading to Hospitalization From Birth to Age 6 Years and Risk of Asthma

Table 1 shows numbers of participants according to a diagnosis of LRTI leading to hospitalization by the age of 6 years and the corresponding incidence rate. A total of 85 persons (3.3%) were categorized as exposed to LRTIs that required hospitalization (see Methods). The risk of developing asthma was related to early hospitalized LRTI throughout the study period (from birth to age 6 years, adjusted HR = 2.05 (95% CI: 0.70, 6.05); from birth to age 12 years, HR = 1.72 (95% CI: 0.82, 3.63); from birth to age 18 years, HR = 2.09 (95% CI: 1.19, 3.67); and from birth to age 27 years, HR = 1.93 (95% CI: 1.10, 3.38)) ( Table 5 ; see Web Table 2 http://aje.oxfordjournals.org/content/182/7/615/suppl/DC1 for crude hazard ratios).

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