Impact of surgical and of bronchoscopic lung volume reductions in patients with emphysema and hyperinflation on lung structure, function and inflammation

Background – A robust biomarker for predicting and evaluating the response to lung volume reduction (LVR) interventions remains elusive. We investigated the hypothesis that LVR will be accompanied by measurable changes in novel indices of lung structure, function, and inflammation that can be correlated with changes to the conventional clinical parameters and that reliable identifiers of baseline predictors of therapeutic response (minimal clinically important difference, MCID, of at least 10% reduction of residual volume) will be identified. Methods – 72 consecutive subjects with severe emphysema and hyperinflation scheduled for lung volume reductions were recruited: lung volume reduction surgery (LVRS) – 15; Endobronchial valve (EBV) – 29, Endobronchial coil (EBC) – 28. All underwent detailed clinical phenotyping comprising demographics, symptom scores, computed tomography imaging, exercise capacity and lung function measurements during exacerbation-free periods at baseline and at three months after intervention. Novel techniques including quantitative computed tomography (qCT), impulse oscillometry (IOS) and multiple breath nitrogen washout (MBNW), and microvesicle quantification were employed to assess changes in lung structure, function and inflammation, respectively. Results – Surgery achieved the greatest lung volume reductions, △residual volume (RV) of -1.26 ± 0.58 litres (p<0.01), and more than 90% of recipients met the MCID of ≥10% RV reduction. It was the only intervention to be accompanied by improvements in functional gas trapping on CT, IOS expiratory airways resistance at 5Hz, expiratory and within-breath reactance at 5Hz, and peripheral resonant frequency, attributable to recovery of small airways function. Valve implantations reduced residual volume by -0.91 ± 0.66 litres (p<0.01) and 62% of recipients attained the MCID of ≥10% RV reduction. This was in addition to a smaller reduction in IOS expiratory and within-breath reactance at 5Hz without an accompanying signal in resistance, resonant frequency, or functional gas trapping on CT. Modest improvements to alveolar gas mixing (AME) and small airways function (Sacin) were measured using MBNW in a subset of patients. These data suggest the impact of valves on the peripheral airway compartment was less pronounced than with surgery and was achieved predominantly by deflation of emphysematous lung tissue and restoration of the mechanical pump. Coil implantations resulted in modest volume reductions, △residual volume of -0.31 ± 0.60L (p=0.01): Only 35% of subjects achieved the MCID of ≥10% RV reduction. Three-month physiological outcomes were similarly disappointing with improvements limited to CT-intraparenchymal blood vessel volume (perhaps due to greater radial traction exerted by the coils on the surrounding parenchyma) and the area under reactance during expiration (AXex) on IOS. The comparatively minor degree of volume reduction achieved (and the fall in gas transfer) using this technique may explain the relatively small impact on peripheral airways function. An inflammatory sub-study identified a variety of microvesicle (MV) populations in bronchoalveolar lavage fluid (BALF) and in the plasma of patients with mild to very severe COPD. Of these, polymorphouclear (neutrophil)-derived MVs were found to be substantially increased in BALF and their numbers correlated with airflow limitation, reduced exercise capacity, impaired of quality of life, and the BODE index. BALF neutrophil-derived MVs correlated with BALF neutrophil cell numbers but not with circulating neutrophil MV numbers, implying local alveolar release rather than translocation from the circulation. BALF neutrophil-derived MVs were also shown to be a more robust biomarker of disease severity than BALF neutrophil cell and cytokine levels. In a subset of valve and coil recipients, BALF-neutrophil derived MV levels were evaluated before and after intervention. Mean volume reduction in the coil recipients was exceeded threefold by that of the valve beneficiaries. Unexpectedly there was no statistically significant change in MV numbers at three months in the valve arm. Possible explanations include contamination from more proximal airway sampling / spill over from the ipsilateral lobe(s) or induction of a localised inflammatory response to biofilm formation overlying the nitinol-silicone implants. In contrast, a statistically significant fall in MV numbers was observed in the coil cohort in the absence of clinically meaningful volume reduction. It must however be borne in mind that despite the thin profile of the nitinol endobronchial coil, the surface area of the airway epithelium exposed to sampling is reduced. There were no identifiable predictors of therapeutic response among the novel indices of lung structure, function, and inflammation analysed. Conclusions – The degree of lung volume reduction achieved is critical in determining favourable clinical outcomes for patients with severe emphysema and hyperinflation. Similarly, the structural and functional impacts of lung volume reduction on the small airways compartment, the principal site of airflow obstruction, are proportional to the degree of volume reduction achieved (surgery > valves > coils). The impact of these therapies on airways inflammation requires further scrutiny. qCT and IOS qualify as structural and functional biomarkers, respectively, for evaluating volume reduction – however, their predictive value for therapeutic response is not established from this small dataset. BALF neutrophil-derived MV observations are potentially useful contributors to disease phenotyping alongside lung function tests and qCT imaging – their role as biomarkers for predicting and assessing therapeutic response remains to be seen. Larger randomised controlled trial designs are recommended to further investigate these preliminary findings.Open Acces

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at √ s = 5.02 and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of √s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within 0.8pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|2GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at √s=13TeV.

Λc+\Lambda^+_c production in pppp and in pp-Pb collisions at sNN\sqrt {s_{NN}}=5.02 TeV

International audienceThe production cross section of prompt $\mathrm{\Lambda_{c}^{+}}$ charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}} = 5.02$ TeV. The $\mathrm{\Lambda_{c}^{+}}$ and $\rm {\overline{\Lambda}{}_c^-}$ baryons were reconstructed in the hadronic decay channels $\rm \Lambda_{c}^{+} \rightarrow p K^{-}\pi^{+}$ and $\rm \Lambda_{c}^{+}\to p K^{0}_{S}$ and respective charge conjugates. The measured differential cross sections as a function of transverse momentum ($p_{\rm T}$) and the $p_{\rm T}$-integrated $\mathrm{\Lambda_{c}^{+}}$ production cross section in pp and in p-Pb collisions are presented. The $\mathrm{\Lambda_{c}^{+}}$ nuclear modification factor ($R_\mathrm{pPb}$), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the $R_\mathrm{pPb}$ of D mesons. The $\mathrm {\Lambda_{c}^{+}}/\mathrm {D^0}$ ratio is also presented and compared with the light-flavour baryon-to-meson ratios p$/\pi$ and $\Lambda /\mathrm {K^0_S}$, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators

Global polarization of Λ and Λ hyperons in Pb-Pb collisions at √ s N N = 2.76 and 5.02 TeV

The global polarization of Λ and Λ hyperons is measured for Pb-Pb collisions at √sNN = 2.76 and 5.02 TeV recorded with the ALICE at the Large Hadron Collider (LHC). The results are reported differentially as a function of collision centrality and hyperon’s transverse momentum (pT ) for the range of centrality 5–50%, 0.5 < pT < 5 GeV/c, and rapidity |y| < 0.5. The hyperon global polarization averaged for Pb-Pb collisions at √sNN = 2.76 and 5.02 TeV is found to be consistent with zero, ⟨PH⟩(%)≈0.01±0.06(stat.)±0.03(syst.) in the collision centrality range 15–50%, where the largest signal is expected. The results are compatible with expectations based on an extrapolation from measurements at lower collision energies at the Relativistic Heavy Ion Collider, hydrodynamical model calculations, and empirical estimates based on collision energy dependence of directed flow, all of which predict the global polarization values at LHC energies of the order of 0.01%

Charged-particle multiplicity fluctuations in Pb–Pb collisions at √ sNN = 2.76 TeV

Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisionsat √sNN = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η| < 0.8 and transverse momentum 0.2 < pT < 2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions

First measurements of N-subjettiness in central Pb–Pb collisions at √ sNN = 2.76 TeV

The ALICE Collaboration reports the first fully-corrected measurements of the N-subjettiness observable for track-based jets in heavy-ion collisions. This study is performed using data recorded in pp and Pb–Pb collisions at centre-of-mass energies of √s = 7 TeV and √ sNN = 2.76 TeV, respectively. In particular the ratio of 2-subjettiness to 1-subjettiness, τ2/τ1, which is sensitive to the rate of two-pronged jet substructure, is presented. Energy loss of jets traversing the strongly interacting medium in heavy-ion collisions is expected to change the rate of two-pronged substructure relative to vacuum. The results are presented for jets with a resolution parameter of R = 0.4 and charged jet transverse momentum of 40 ≤ pT,jet ≤ 60 GeV/c, which constitute a larger jet resolution and lower jet transverse momentum interval than previous measurements in heavy-ion collisions. This has been achieved by utilising a semi-inclusive hadron-jet coincidence technique to suppress the larger jet combinatorial background in this kinematic region. No significant modification of the τ2/τ1 observable for track-based jets in Pb–Pb collisions is observed relative to vacuum PYTHIA6 and PYTHIA8 references at the same collision energy. The measurements of τ2/τ1, together with the splitting aperture angle ∆R, are also performed in pp collisions at √s = 7 TeV for inclusive jets. These results are compared with PYTHIA calculations at √s = 7 TeV, in order to validate the model as a vacuum reference for the Pb–Pb centre-of-mass energy. The PYTHIA references for τ2/τ1 are shifted to larger values compared to the measurement in pp collisions. This hints at a reduction in the rate of two-pronged jets in Pb–Pb collisions compared to pp collisions

KS0\mathrm {K_S}^{0}- and (anti-)Λ\Lambda -hadron correlations in pp collisions at s=13{\sqrt{s}} = 13 TeV

International audienceTwo-particle Azimuthal correlations are measured with the ALICE apparatus in pp collisions at $\sqrt{s} = 13$ TeV to explore strangeness- and multiplicity-related effects in the fragmentation of jets and the transition regime between bulk and hard production, probed with the condition that a strange meson ($\mathrm {K_S}^{0}$) or baryon ($\Lambda$) with transverse momentum $p_{\mathrm T} >3$ GeV/$c$ is produced. Azimuthal correlations between kaons or $\Lambda$ hyperons with other hadrons are presented at midrapidity for a broad range of the trigger ($3< p_\mathrm {T}^\mathrm {trigg} < 20$ GeV/$c$) and associated particle $p_{\mathrm T}$ (1 GeV/$c< p_\mathrm {T}^\mathrm {assoc} < p_\mathrm {T}^\mathrm {trigg}$), for minimum-bias events and as a function of the event multiplicity. The near- and away-side peak yields are compared for the case of either $\mathrm {K_S}^{0}$ or $\Lambda$(${\overline{\Lambda }}$) being the trigger particle with that of inclusive hadrons (a sample dominated by pions). In addition, the measurements are compared with predictions from PYTHIA 8 and EPOS LHC event generators