Seasonal variation of serum KL-6 and SP-D levels in bird-related hypersensitivity pneumonitis.

Bird-related hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by inhalation of bird dropping extracts and antigens in feathers (1). Environmental assessment and removal of the avian antigen are crucial in the management of bird-related HP. Measurement of serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) is widely accepted in Japan, as a diagnostic test for interstitial lung diseases (ILDs) and as a marker of disease activity (2, 3). In our experience of patients with summer-type HP, serum KL-6 and SP-D levels increase together with disease activity in hot and humid times of year, when Trichosporon Asahii and other causative molds grow best (4). Conversely, patients with bird-related HP seem to present with higher serum levels of KL-6 and SP-D in winter.To our knowledge, no earlier reports have described seasonal differences of serum KL-6 and SP-D levels in patients with ILDs. We therefore decided to investigate the seasonal variations of serum KL-6 and SP-D levels in patients with bird-related HP. We collected data about serum KL-6 and SP-D levels retrospectively in patients with bird-related HP and idiopathic pulmonary fibrosis (IPF) diagnosed between 2002 and 2012 in our institution. The bird-related HP was diagnosed by inhalation provocation test using avian antigen (5) and IPF was diagnosed based on a multidisciplinary review according to established criteria (6). Twenty-five patients with bird-related HP and 28 patients with IPF were enrolled. No treatments were administered during the period between the first patient visit and enrollment in the study more than 1 year later, and serum KL-6 and SP-D were measured at least once every season in every patient. The serum cut-off levels were 500 U/ml (KL-6) and 110 ng/ml (SP-D). All statistical analyses were performed using Prism 6 (GraphPad Software, Inc., San Diego, CA, USA). The significance of differences among frequency data was evaluated using the chi-square test. Intergroup comparisons were assessed using the MannWhitney U test. The Wilcoxon matched-pairs test was used to compare serum KL-6 and SP-D levels from season to season. Significance was defined as p < 0.05. This study conformed to the Declaration of Helsinki and was approved by the institutional review board (approval number: 1677). Patient’s characteristics are shown in Table 1. Of the patients with bird-related HP, 14 had histories of bird breeding and 23 had used duvets, jackets, or other products insulated with bird feathers mainly in winter. All cases of HP were chronic forms. Histologically, all 8 of the patients who underwent Seasonal variation of serum KL-6 and SP-D levels in birdrelated hypersensitivity pneumonitis