Abstract
Rationale & AimPulmonary surfactants are essential components of lung homeostasis. In chronic obstructive pulmonary disease (COPD), surfactant expression decreases in lungs whereas, there is a paradoxical increase in protein expression in plasma. The latter has been associated with poor health outcomes in COPD. The purpose of this study was to determine the relationship of surfactants and other pneumoproteins in bronchoalveolar lavage (BAL) fluid and plasma to airflow limitation and the effects of budesonide/formoterol on this relationship.MethodsWe recruited (clinical trials.gov identifier: NCT00569712) 7 smokers without COPD and 30 ex and current smokers with COPD who were free of exacerbations for at least 4 weeks. All subjects were treated with budesonide/formoterol 400/12 µg twice a day for 4 weeks. BAL fluid and plasma samples were obtained at baseline and the end of the 4 weeks. We measured lung-predominant pneumoproteins: pro-Surfactant Protein-B (pro-SFTPB), Surfactant Protein-D (SP-D), Club Cell Secretory Protein-16 (CCSP-16) and Pulmonary and Activation-Regulated Chemokine (PARC/CCL-18) in BAL fluid and plasma.ResultsBAL Pro-SFTPB concentrations had the strongest relationship with airflow limitation as measured by FEV1/FVC (Spearman rho = 0.509; p = 0.001) and FEV1% of predicted (Spearman rho = 0.362; p = 0.028). Plasma CCSP-16 concentrations were also significantly related to airflow limitation (Spearman rho = 0.362; p = 0.028 for FEV1% of predicted). The other biomarkers in BAL fluid or plasma were not significantly associated with airflow limitation. In COPD subjects, budesonide/formoterol significantly increased the BAL concentrations of pro-SFTPB by a median of 62.46 ng/ml (p = 0.022) or 48.7% from baseline median value.ConclusionIncreased severity of COPD is associated with reduced Pro-SFTPB levels in BAL fluid. Short-term treatment with budesonide/formoterol increases these levels in BAL fluid. Long term studies will be needed to determine the clinical relevance of this observation.
Highlights
The human and economic burden of Chronic obstructive pulmonary disease (COPD) are rapidly growing worldwide [1]
bronchoalveolar lavage (BAL) Pro-surfactant protein B (SFTPB) concentrations had the strongest relationship with airflow limitation as measured by FEV1/forced vital capacity (FVC) (Spearman rho = 0.509; p = 0.001) and FEV1% of predicted (Spearman rho = 0.362; p = 0.028)
Increased severity of COPD is associated with reduced Pro-SFTPB levels in BAL fluid
Summary
The human and economic burden of Chronic obstructive pulmonary disease (COPD) are rapidly growing worldwide [1]. The advent of novel therapies has been impeded to a certain extent by the paucity of surrogate markers that can be used in early clinical studies and trials to evaluate the therapeutic potential of promising compounds. To overcome this limitation, there has been a great deal of interest in the identification and validation of biomarkers for use in COPD [4,5]. Very few studies have interrogated bronchoscopic specimens It is not certain which of the pneumoproteins, if any, may have biomarker potential in bronchoalveolar fluid, which can be obtained through bronchoscopy.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
