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Background: Air pollution is a major cause of global morbidity and mortality. Air pollution and aeroallergens aggravate respiratory illness, but the variable effects of air pollutants and allergens in the lung are poorly understood., Objective: To determine the effects of diesel exhaust (DE) and bronchial allergen challenge as single and dual exposures on aspects of innate immunity in the airway as reflected by surfactant protein D (SPD), myeloperoxidase (MPO) and club (Clara) cell secretory protein 16 (CC16) in 18 atopic individuals., Methods: In this double-blind, randomized crossover study, atopic individuals were exposed to DE or filtered air, followed by endobronchial allergen or saline 1 hour after inhalational exposure. Bronchoalveolar lavage, bronchial washings, nasal lavage and blood samples were obtained 48 hours after exposures and assayed for CC16, MPO and SPD by ELISA., Results: In bronchial samples, the concentration of SPD increased from 53.3 to 91.8 ng/mL after endobronchial allergen, with no additional contribution from DE. MPO also increased significantly in response to allergen (6.8 to 14.7 ng/mL), and there was a small additional contribution from exposure to DE. The concentration of CC16 decreased from 340.7 to 151.0 ng/mL in response to DE, with minor contribution from allergen. These changes were not reflected in nasal lavage fluid or plasma samples., Conclusions and Clinical Relevance: These findings suggest that allergen and DE variably influence different aspects of the innate immune response of the lung. SPD and MPO, known markers of allergic inflammation in the lung, are strongly increased by allergen while DE has a minor effect therein. DE induces a loss of CC16, a protective protein, while allergen has a minor effect therein. Results support site- and exposure-specific responses in the human lung upon multiple exposures., (© 2016 John Wiley & Sons Ltd.)