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

Hironori Masuko¹, Tohru Sakamoto¹, Yoshiko Kaneko¹, Hiroaki Iijima², Takashi Naito², Emiko Noguchi³, Tomomitsu Hirota⁴, Mayumi Tamari⁴, Nobuyuki Hizawa^1
1Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan; ²Tsukuba Medical Center, Ibaraki, Japan; ³Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan; ⁴Laboratory for Respiratory Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan

Abstract: Few studies have investigated the significance of decreased FEV₁ in non-COPD, nonasthmatic healthy subjects. We hypothesized that a lower FEV₁ 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 FEV₁/FVC ratio was ≥70% (n = 1369) into 2 groups according to their prebronchodilator FEV₁ (% 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 FEV¹ – 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 FEV₁ had never smoked, smoking was the main risk factor for the decreased FEV₁ in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV₁ had a significantly higher annual decline in FEV₁ 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 FEV₁% predicted, corrected P = 0.015–0.033 for FEV₁/FVC). This study highlights the importance of early recognition of a decreased FEV₁ in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV₁ 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