Lower FEV1 in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes

Abstract

Few studies have investigated the significance of decreased FEV(1) in non-COPD, nonasthmatic healthy subjects. We hypothesized that a lower FEV(1) in these subjects is a potential marker of an increased susceptibility to obstructive lung disease such as asthma and COPD. This was a cross-sectional analysis of 1505 Japanese adults. We divided the population of healthy adults with no respiratory diseases whose FEV(1)/FVC ratio was ≥ 70% (n = 1369) into 2 groups according to their prebronchodilator FEV(1) (% predicted) measurements: < 80% (n = 217) and ≥ 80% (n = 1152). We compared clinical data - including gender, age, smoking habits, total IgE levels, and annual decline of FEV(1) - between these 2 groups. In addition, as our group recently found that TSLP variants are associated with asthma and reduced lung function, we assessed whether TSLP single nucleotide polymorphisms (SNPs) were associated with baseline lung function in non-COPD, nonasthmatic healthy subjects (n = 1368). Although about half of the subjects with lower FEV(1) had never smoked, smoking was the main risk factor for the decreased FEV(1) in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV(1) had a significantly higher annual decline in FEV(1) independent of smoking status. Airflow obstruction was associated with increased levels of total serum IgE (P = 0.029) and with 2 functional TSLP SNPs (corrected P = 0.027-0.058 for FEV(1)% predicted, corrected P = 0.015-0.033 for FEV(1)/FVC). This study highlights the importance of early recognition of a decreased FEV(1) in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV(1) irrespective of smoking status. Our series of studies identified TSLP variants as a potential susceptibility locus to asthma and to lower lung function in non-COPD, nonasthmatic healthy subjects, which may support the contention that genetic determinants of lung function influence susceptibility to asthma.

Keywords: airflow obstruction; asthma; chronic obstructive pulmonary disease; pulmonary function test; thymic stromal lymphopoietin.

Figure 1

Recruitment and enrollment of study participants. Of the 1,505 participants, 113 subjects with a history of asthma, COPD, chronic bronchitis, or pulmonary tuberculosis were excluded, and 4 of those excluded were identified as having 2 or 3 pulmonary diseases. Of the 1,392 subjects without respiratory diseases, 23 subjects had FEV₁/FVC < 70%. To characterize the group of individuals with decreased FEV₁ (predicted FEV₁ < 80%) and normal ratio of FEV₁/FVC, we divided 1,369 healthy subjects whose FEV₁/FVC was ≥70% into 2 subgroups according to their prebronchodilator FEV₁ (% predicted): <80% (lower FEV₁, n = 217) and ≥80% (higher FEV₁, n = 1,152). We also examined the relationship between TSLP single nucleotide polymorphisms and baseline lung function using 1,368 healthy subjects, who agreed to provide a DNA sample for genotyping. Of the 1,392 healthy subjects, the median number of measurements was 9 (range 4–18 measurements) and the median number of years in retrospective follow-up was 11 (range 4–23 years) for the 866 subjects who had an annual checkup for 4 or more years of the retrospective follow-up and had at least 4 separate pulmonary function test measurements. Valid estimates of the annual decline of FEV₁ were obtained for 849 healthy subjects with FEV₁/FVC > 70% or for 827 healthy subjects with FEV₁/FVC > lower limit of normal.

Figure 2

Plot of individual values of FEV₁% predicted and FEV₁/FVC. Data from 1392 healthy adults with no respiratory diseases.