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Background: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. Objectives: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. Methods: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. Results: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV1] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV1, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. Conclusions: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Pulmonary rehabilitation (PR) has positive effects on exercise capacity in Chronic Obstructive Pulmonary Disease (COPD). However, not all COPD patients benefit from PR to the same extent. We investigated whether there is a patient profile, which is associated with the improvement in endurance exercise capacity. Methods: In this observational study, we included 102 COPD patients who followed PR (age 60 ± 10 (mean ± SD) years, FEV1%predicted 44 ± 16%, 54 men). Lung function, maximal incremental cycle testing (Wpeak, VO2peak, Δlactate), quadriceps force and incremental and endurance shuttle walk test (ISWT/ESWT) were performed at the start of PR. The ESWT was repeated after 7 weeks of PR. Results: Mean change in ESWT (ΔESWT) was 100 ± 154%. Four variables showed a statistically significant negative correlation with ΔESWT: FEV1%pred. (ρ = −0.20), Wpeak (ρ = −0.24), Δlactate (ρ = −0.33) and incremental shuttle walk test (ISWT) (ρ = −0.31). A cluster analysis identified two patient profiles: A profile with high ΔESWT, TLC and RV and low FEV1, VO2peak, quadriceps force, Δlactate, HRpeak%pred. and ISWT distance and a profile with low ΔESWT, TLC and RV and high FEV1, VO2peak, quadriceps force, Δlactate, HRpeak%pred. and ISWT distance. Conclusions: Single variables from lung function or exercise testing at baseline have limited predictive value for response to exercise training. However, patients with worse disease status (i.e. a combination of lower FEV1, more hyperinflation, lower exercise capacity and worse quadriceps force) improve more in endurance exercise capacity. [Copyright &y& Elsevier]

Abstract The study of low abundant proteins contributes to increasing our knowledge about (patho)physiological processes and may lead to the identification and clinical application of disease markers. However, studying these proteins is challenging as high-abundant proteins complicate their analysis. Antibodies are often used to enrich proteins from biological matrices prior to their analysis, though antibody-free approaches have been described for some proteins as well. Here we report an antibody-free workflow on the basis of strong cation exchange (SCX) enrichment and liquid chromatography-mass spectrometry (LC-MS) for quantification of the soluble Receptor of Advanced Glycation End-products (sRAGE), a promising biomarker in chronic obstructive pulmonary disease (COPD). sRAGE was quantified in serum at clinically relevant low to sub ng mL−1 levels. The method was validated according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and was compared to an antibody-based LC-MS sRAGE method. The SCX-based method builds upon the bipolar charge distribution of sRAGE, which has a highly basic N-terminal part and an acidic C-terminal part resulting in an overall neutral isoelectric point (pI). The highly basic N-terminal part (pI calculated = 10.3) allowed for sRAGE to be enriched by SCX at pH 10, a pH at which most serum proteins do not bind. This study shows that ion exchange-based enrichment is a viable approach for the LC-MS analysis of several low abundant proteins following a thorough analysis of their physical-chemical properties. Graphical abstract Image 1 Highlights • Serum sRAGE was quantified in the low to sub ng mL−1 range without using antibodies. • sRAGE was enriched by SCX at pH 10, despite having a calculated protein pI of 8. • Look beyond a calculated pI when considering ion exchange for protein enrichment. • Correlation between the SCX-based method and an antibody-based method was moderate. • Measured protein levels must be seen in the context of the measuring principle. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation. Methods: Twenty-one chronic obstructive pulmonary disease (COPD) patients were randomized to an experimental group that followed a regular rehabilitation program plus the counseling intervention or to a control group that only followed rehabilitation. The primary outcome was daily physical activity assessed by pedometers. Secondary outcomes were physical fitness, health-related quality of life, activities of daily living, depression and self-efficacy. Results: The experimental group showed an increase of 1430steps/day (+69% from baseline), whereas the control group showed an increase of 455steps/day (+19%) (p =0.11 for group×time interaction). The secondary outcomes showed no differences. Conclusion and practice implications: This study showed that the use of the pedometer, in combination with exercise counseling and the stimulation of lifestyle physical activity, is a feasible addition to pulmonary rehabilitation which may improve outcome and maintenance of rehabilitation results. [Copyright &y& Elsevier]

Quantification of intact proteins in complex biological matrices by liquid chromatography-mass spectrometry (LC-MS) is a promising analytical strategy but is technically challenging, notably for concentrations at or below the ng/mL level. Therefore, MS-based protein quantification is mostly based on measuring protein-specific peptides, so-called 'surrogate peptides', that are released through proteolysis. While quantitative protein bioanalysis based on peptide LC-MS is much more sensitive, not every peptide is suitable in this respect. For example, some peptides are too small to be unique for a protein while others are too large to be measured with sufficient sensitivity, so careful selection of appropriate peptides is essential. Here we present a validated LC-MS method for quantification of surfactant protein D (SPD) at clinically relevant levels between 5 and 500 ng/mL using 50 μL of serum. This method targets two SPD-specific peptides in the C-type lectin, ligand binding domain of the SPD protein. One of these peptides contains a methionine residue which would typically be avoided because of its unstable nature. Some quantitative methods do target methionine-containing peptides, and corresponding workflows feature an oxidation step at the peptide level using hydrogen peroxide (H 2 O 2) to convert all methionine residues to more stable methionine sulfoxides. For our method, such a procedure was associated with peptide loss, hence we developed an oxidation procedure at the protein level using H 2 O 2 to oxidize methionine residues and the enzyme catalase to quench excess H 2 O 2. This procedure may be applicable to other quantitative methods based on a surrogate peptide-based approach and may potentially also be useful for MS-based workflows targeting intact proteins. Image 1 • We present an LC-MS method for quantification of Surfactant Protein D in serum. • The method meets requirements as stipulated in EMA and FDA guidelines. • The method includes an H 2 O 2 -based methionine oxidation step at the protein level. • Excess H 2 O 2 was quenched with the enzyme catalase prior to trypsin digestion. • Good correlation (R2 = 0.9) between the LC-MS method and a commonly-used SPD ELISA. [ABSTRACT FROM AUTHOR]

The study of proteins is central to unraveling (patho)physiological processes and has contributed greatly to our understanding of biological systems. Corresponding studies often employ procedures to enrich proteins from their biological matrix using antibodies or other affinity binders coupled to beads with a large surface area and a correspondingly high binding capacity. Striving for maximal binding capacity may, however, not always be required or desirable, for example for proteins of low abundance. Here we describe a simplified immunoprecipitation in 96-well ELISA format (IPE) approach for fast and easy enrichment of proteins. The applicability of this approach for enriching low-abundant proteins was demonstrated by an IPE-based quantitative workflow using liquid chromatography-mass spectrometry (LC-MS) for the soluble Receptor of Advanced Glycation End-products (sRAGE), a promising biomarker in chronic obstructive pulmonary disease (COPD). The method was validated according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and enabled accurate quantitation of sRAGE between 0.1 and 10 ng/mL in 50 µL serum. The assay showed substantial correlation with the two most commonly-used sRAGE immunoassays (ELISAs) (R 2 -values between 0.7 and 0.8). However, the LC-MS method reported 2–4 times higher sRAGE levels compared to the ELISAs, which is largely due to a suboptimal amount of capturing antibody and/or calibration strategy used by the immunoassays. In conclusion, our simplified IPE approach proved to be an efficient strategy for enriching the low-abundant protein sRAGE from serum and may provide an easy to use platform for enriching other (low-abundant) proteins from complex, biological matrices. [ABSTRACT FROM AUTHOR]

Highlights: [•] Synthesis of deuterated- and 18O-labeled DES and IDS standards. [•] Method development for free and total DES and IDS analysis in human urine. [•] Full method validation according to FDA and EMA regulations. [•] Comparison of surrogate matrix and surrogate analyte approaches. [•] Validated method application to the analysis of clinical samples. [Copyright &y& Elsevier]