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

Abstract

Hironori Masuko1, Tohru Sakamoto1, Yoshiko Kaneko1, Hiroaki Iijima2, Takashi Naito2, Emiko Noguchi3, Tomomitsu Hirota4, Mayumi Tamari4, Nobuyuki Hizawa11Division 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, JapanAbstract: 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