Abstract
BackgroundHyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses.Methods and FindingsIn order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs.ConclusionsIn this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between DBRI and HP-like conditions.
Highlights
Certain occupations and surroundings increase the risk of exposure to inhaled non-infectious microbial particles, referred to as NIMPs in this article
In this study, the proteomic changes in bronchoalveolar lavage of damp building-related illness (DBRI) patients were distinct from other NIMP exposure associated lung diseases, while changes in agricultural type of microbial exposure (AME) overlapped those observed for Hypersensitivity pneumonitis (HP) patient samples
Screening of potential biomarkers was performed for a total of 24 bronchoalveolar lavage (BAL) samples from the healthy control (CTR n = 6) and four disease groups (AME n = 5, DBRI n = 5, HP n = 4, and SARC n = 4)
Summary
Certain occupations and surroundings increase the risk of exposure to inhaled non-infectious microbial particles, referred to as NIMPs in this article. Working in an agricultural environment, especially handling of moldy hay or grain, exposes farm workers to NIMPs. The exposure to the indoor air in damp buildings, will cause exposure for NIMPs. Hypersensitivity pneumonitis (HP), is a well-known yet complex syndrome associated with the exposure to NIMPs. HP is an inflammatory disease of the lung alveoli caused by exposure to a wide range of airborne substances: bacteria, fungi, even inorganic materials like certain chemicals. Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses
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