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Background: Multiple studies have shown that patients with severe emphysema can significantly benefit from bronchoscopic lung volume reduction endobronchial valve (EBV) treatment up to 1 year after treatment. However, hardly any data exist on longer term follow-up, especially on quality of life. Our aim was to investigate long-term follow-up after EBV treatment up to 3 years including quality of life in a real-life routine clinical setting., Methods: We retrospectively included patients who underwent EBV treatment in our hospital in the Netherlands at least 3 years prior. Patients were invited for annual visits to our hospital, and spirometry, body plethysmography, 6-min walk distance (6MWD) test and St George's Respiratory Questionnaire (SGRQ) were performed during these visits., Results: At 1-, 2- and 3-year follow-up, data were available from 189, 146 and 112 patients, respectively. Forced expiratory volume in 1 s, residual volume and SGRQ total score significantly improved up to 3 years after treatment compared with baseline, and 6MWD up to 2 years after treatment. In general, the magnitude of improvements gradually decreased over time., Conclusions: Our results show that patients can benefit at least up to 3 years after EBV treatment. For the first time we found that patients can also benefit in terms of quality of life in the long term, which is an important outcome for this group of patients with end-stage COPD., Competing Interests: Conflict of interest: K. Klooster reports payment or honoraria for lectures from PulmonX and Boehringer. D-J. Slebos reports grants or contracts from PulmonX, PneumRx/BTG/Boston Scientific, FreeFlowMedical and Nuvaira (principal investigator and advisor, to institution); consulting fees, payment or honoraria for lectures, support for attending meetings and/or travel, and receipt of study material and medical devices to institution from PulmonX, PneumRx and Nuvaira. All other authors have nothing to disclose., (Copyright ©The authors 2022.)

The COPD susceptibility SNP rs2070600 affects the levels of the COPD biomarker sRAGE in sputum as well as splicing of AGER . Moreover, @PouwelsScience et al. demonstrate large differences in sRAGE levels between serum and sputum. https://bit.ly/3t0pJtK., Competing Interests: Conflict of interest: A. Faiz has nothing to disclose. Conflict of interest: S.N.H. Rathnayake has nothing to disclose. Conflict of interest: N.H.T. ten Hacken has nothing to disclose. Conflict of interest: V. Guryev has nothing to disclose. Conflict of interest: M. van den Berge has nothing to disclose. Conflict of interest: S.D. Pouwels has nothing to disclose., (Copyright ©The authors 2021.)

Background: The forced expiratory flows (FEFs) towards the end of the expiration may be more sensitive in detecting peripheral airways obstruction compared to the forced expiratory volume in 1 s and forced vital capacity (FVC). However, they are highly variable. A partial solution is to adjust the FEFs for FVC (FEF/FVC). Here we provide reference equations for these adjusted FEFs at 25%, 50%, 75% and 25-75% of FVC, which are currently lacking., Methods: We included pulmonary healthy, never-smoker adults; 14 472 subjects from Lifelines, a biobank for health research, and 338 subjects from the department's control cohorts (NORM and Fiddle). Reference equations were obtained by linear regression on 80% of the Lifelines dataset and validated on the remaining data. The best model was defined as the one with the highest adjusted R 2 -value. The difference in variability between adjusted and unadjusted FEFs was evaluated using the coefficient of variation., Results: For all adjusted FEFs, the best model contained age, height and weight. The adjustment improved the coefficient of variation of the FEF 75 from 39% to 36% and from 43% to 40%, respectively, in males and females. The highest percentage of explained variance by the reference equation was obtained for FEF 75 /FVC, 32%-38% for males, and 41%-46% for females, depending on the validation set., Conclusion: We developed reference equations for FVC-adjusted FEF values. We demonstrated minimally yet significantly improved variability. Future studies in obstructive airway diseases should demonstrate whether it is worthwhile to use these (predicted) adjusted FEF values., Competing Interests: Conflict of interest: C.A. Cox has nothing to disclose. Conflict of interest: J.M. Vonk has nothing to disclose. Conflict of interest: H.A.M. Kerstjens reports research grants from GSK, Novartis and Boehringer, and fees for consultancy on advisory boards from GSK, Novartis and Boehringer, all paid to his institution. Conflict of interest: M. van den Berge reports grants paid to his university from AstraZeneca, TEVA, GSK and Chiesi outside the submitted work. Conflict of interest: N.H.T. ten Hacken has nothing to disclose., (Copyright ©ERS 2020.)

Lung volume reduction (LVR) treatment in patients with severe emphysema has been shown to have a positive effect on hyperinflation, expiratory flow, exercise capacity and quality of life. However, the effects on diffusing capacity of the lungs and gas exchange are less clear. In this review, the possible mechanisms by which LVR treatment can affect diffusing capacity of the lung for carbon monoxide ( D LCO ) and arterial gas parameters are discussed, the use of D LCO in LVR treatment is evaluated and other diagnostic techniques reflecting diffusing capacity and regional ventilation ( V ')/perfusion ( Q ') mismatch are considered.A systematic review of the literature was performed for studies reporting on D LCO and arterial blood gas parameters before and after LVR surgery or endoscopic LVR with endobronchial valves (EBV). D LCO after these LVR treatments improved (40 studies, n=1855) and the mean absolute change from baseline in % predicted D LCO was +5.7% (range -4.6% to +29%), with no real change in blood gas parameters. Improvement in V ' inhomogeneity and V '/ Q ' mismatch are plausible explanations for the improvement in D LCO after LVR treatment., Competing Interests: Provenance: Submitted article peer reviewed Conflict of interest: M. van Dijk has nothing to disclose. Conflict of interest: K. Klooster reports other funding from PulmonX Inc., outside the submitted work. Conflict of interest: N.H.T. Ten Hacken has nothing to disclose. Conflict of interest: F. Sciurba has nothing to disclose. Conflict of interest: H.A.M. Kerstjens reports research grants from GSK, Novartis and Boehringer, and fees for consultancies on advisory boards from GSK, Novartis and Boehringer, all paid to his institution, outside the submitted work. Conflict of interest: D-J. Slebos reports grants, personal fees, non-financial support and other funding from PulmonX Inc, during the conduct of the study., (Copyright ©ERS 2020.)

Approximately 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls.We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function.Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated i n cis with gene expression at ACKR2 and DGKQ Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium.CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls., Competing Interests: Conflict of interest: C.J. Vermeulen reports grants from GSK, during the conduct of the study. Conflict of interest: C-J. Xu has nothing to disclose. Conflict of interest: J.M. Vonk has nothing to disclose. Conflict of interest: N.H.T. ten Hacken has nothing to disclose. Conflict of interest: W. Timens reports personal fees from Pfizer, GSK, Chiesi, Roche Diagnostics/Ventana, Biotest, Merck Sharp Dohme, Novartis, Lilly Oncology, Boehringer Ingelheim, AstraZeneca, Bristol-Myers-Squibb and AbbVie, and grants from the Dutch Asthma Fund, outside the submitted work. Conflict of interest: I.H. Heijink has nothing to disclose. Conflict of interest: M.C. Nawijn reports grants from GSK and the Lung Foundation of the Netherlands, outside the submitted work. Conflict of interest: J. Boekhoudt has nothing to disclose. Conflict of interest: A.J. van Oosterhout reports and holds GSK shares. Conflict of interest: K. Affleck is an employee of GSK and a member of the company share schemes. Conflict of interest: M. Weckmann has nothing to disclose. Conflict of interest: G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, TEVA, GSK, Vertex and Ubbo Emmius Foundation, outside the submitted work; and has served on an international advisory board for GSK (money to institution). Conflict of interest: M. van den Berge reports grants paid to his university from AstraZeneca, TEVA, GSK and Chiesi, outside the submitted work., (Copyright ©ERS 2020.)

Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroid-resistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1β, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1β-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus production in vitro IL-1β-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air-liquid interface (ALI)-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed.The IL-1β-induced CCL20 expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls . IL-1β induced lower MIR146A expression in asthma-derived ASMCs compared with controls. Decreased MIR146A expression was validated in vivo in bronchial biopsies from 16 asthmatic patients versus 39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients.Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the anti-inflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma., Competing Interests: Conflict of interest: M. Van den Berge reports research grants (paid to university) from Teva, Chiesi and GlaxoSmithKline, outside the submitted work. J.L. Black reports grants from the National Health and Medical Research Council, during the conduct of the study. J.K. Burgess reports grants from the National Health and Medical Research Council, during the conduct of the study., (Copyright ©ERS 2018.)

Biomass and functional small airway disease http://ow.ly/gXu730abpKu., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com