High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial.

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study.

BACKGROUND: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19. METHODS: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation. RESULTS: A total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%. CONCLUSIONS: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Greater exercise tolerance in COPD during acute interval, compared to equivalent constant-load, cycle exercise: physiological mechanisms.

KEY POINTS: Exercise intolerance is common in chronic obstructive pulmonary disease (COPD) patients. In patients with COPD, we compared an interval exercise (IE) protocol (alternating 30 s at 100% peak work rate (WRpeak ) with 30 s at 50% WRpeak ) with moderate-intensity constant-load exercise (CLE) at 75% WRpeak , which yielded the same work rate. Exercise endurance time and total work output were almost twice as high for IE than CLE. At exercise isotime (when work completed was the same between IE and CLE), IE was associated with less dynamic hyperinflation, lower blood lactate concentration, and greater respiratory and locomotor muscle oxygenation, but there were no differences in ventilation or cardiac output. However, at the limit of tolerance for each modality, dynamic hyperinflation was not different between IE and CLE, while blood lactate remained lower and muscle oxygenation higher with IE. Taken together, these findings suggest that dynamic hyperinflation and not muscle-based factors dictate the limits of tolerance in these COPD patients. ABSTRACT: The relative importance of ventilatory, circulatory and peripheral muscle factors in determining tolerance to exercise in patients with chronic obstructive pulmonary disease (COPD) is not known. In 12 COPD patients (forced expiratory volume in one second: 58 ± 17%pred.) we measured ventilation, cardiac output, dynamic hyperinflation, local muscle oxygenation, blood lactate and time to exhaustion during (a) interval exercise (IE) consisting of 30 s at 100% peak work rate alternating with 30 s at 50%, and (b) constant-load exercise (CLE) at 75% peak work rate, designed to produce the same average work rate. Exercise time was substantially longer during IE than CLE (19.5 ± 4.8 versus 11.4 ± 2.1 min, p = 0.0001). Total work output was therefore greater during IE than CLE (81.3 ± 27.7 versus 48.9 ± 23.8 kJ, p = 0.0001). Dynamic hyperinflation (assessed by changes from baseline in inspiratory capacity, ΔIC) was less during IE than CLE at CLE exhaustion time (isotime, p = 0.009), but was similar at exhaustion (ΔICCLE : -0.38 ± 0.10 versus ΔICIE : -0.33 ± 0.12 l, p = 0.102). In contrast, at isotime, minute ventilation, cardiac output and systemic oxygen delivery did not differ between protocols (P > 0.05). At exhaustion in both protocols, the vastus lateralis and intercostal muscle oxygen saturation were higher in IE than CLE (p = 0.014 and p = 0.0002, respectively) and blood lactate concentrations were lower (4.9 ± 2.4 mmol l-1 versus 6.4 ± 2.2 mmol l-1 , p = 0.039). These results suggest that (1) exercise tolerance with COPD is limited by dynamic hyperinflation; and (2) cyclically lower (50%) effort intervals in IE help to preserve muscle oxygenation and reduce metabolic acidosis compared with CLE at the same average work rate; but these factors do not appear to determine time to exhaustion.

De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

BACKGROUND: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. OBJECTIVES: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. METHODS: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. RESULTS: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). CONCLUSIONS: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

Cigarette Smoke-Induced Emphysema Exhausts Early Cytotoxic CD8+ T Cell Responses against Nascent Lung Cancer Cells.

Chronic obstructive pulmonary disease is a chronic inflammatory disorder with an increased incidence of lung cancer. The emphysema component of chronic obstructive pulmonary disease confers the greatest proportion to lung cancer risk. Although tumors create inflammatory conditions to escape immunity, the immunological responses that control growth of nascent cancer cells in pre-established inflammatory microenvironments are unknown. In this study, we addressed this issue by implanting OVA-expressing cancer cells in the lungs of mice with cigarette smoke-induced emphysema. Emphysema augmented the growth of cancer cells, an effect that was dependent on T cytotoxic cells. OVA-specific OTI T cells showed early signs of exhaustion upon transfer in emphysema tumor hosts that was largely irreversible because sorting, expansion, and adoptive transfer failed to restore their antitumor activity. Increased numbers of PD-L1- and IDO-positive CD11c+ myeloid dendritic cells (DCs) infiltrated emphysema tumors, whereas sorted emphysema tumor DCs poorly stimulated OTI T cells. Upon adoptive transfer in immunocompetent hosts, T cells primed by emphysema tumor DCs were unable to halt tumor growth. DCs exposed to the emphysema tumor microenvironment downregulated MHC class II and costimulatory molecules, whereas they upregulated PD-L1/IDO via oxidative stress-dependent mechanisms. T cell activation increased upon PD-L1 blockade in emphysema DC-T cell cocultures and in emphysema tumor hosts in vivo. Analysis of the transcriptome of primary human lung tumors showed a strong association between computed tomography-based emphysema scoring and downregulation of immunogenic processes. Thus, suppression of adaptive immunity against lung cancer cells links a chronic inflammatory disorder, emphysema, to cancer, with clinical implications for emphysema patients to be considered optimal candidates for cancer immunotherapies.

Nasal High Flow Use in COPD Patients with Hypercapnic Respiratory Failure: Treatment Algorithm & Review of the Literature.

Nasal high flow (NHF) therapy has recently gained attention as a new respiratory support system and is increasingly being utilized in every day clinical practice. Recent studies suggest that it may also be effective in patients with hypercapnia and suggest NHF as a possible alternative for patients who cannot tolerate standard noninvasive ventilation. The present review discusses the mechanisms of action that make NHF potentially suitable for chronic obstructive pulmonary disease (COPD) patients and evaluates the current evidence of NHF use for treatment of stable hypercapnic COPD patients as well as acute hypercapnic exacerbation of COPD. An algorithm is also proposed for the clinical application of NHF in patients with acute hypercapnic exacerbation of COPD, based on current literature.

Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice.

Electronic cigarettes (e-cigs) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cig vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 wk to ambient air, CS, or e-cig vapor containing 1) propylene glycol/vegetable glycerol (PG:VG-Sol; 1:1), 2) PG:VG with nicotine (G:VG-N), or 3) PG:VG with nicotine and flavor (PG:VG-N+F) and determined oxidative stress, inflammation, and pulmonary mechanics. E-cig vapors, especially PG:VG-N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG-N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance, and airway resistance, whereas after 4 wk CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PG:VG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.

Changes in dynamic lung mechanics after lung volume reduction coil treatment of severe emphysema.

We assessed the relationships between changes in lung compliance, lung volumes and dynamic hyperinflation in patients with emphysema who underwent bronchoscopic treatment with nitinol coils (coil treatment) (n=11) or received usual care (UC) (n=11). Compared with UC, coil treatment resulted in decreased dynamic lung compliance (CLdyn) (p=0.03) and increased endurance time (p=0.010). The change in CLdyn was associated with significant improvement in FEV1 and FVC, with reduction in residual volume and intrinsic positive end-expiratory pressure, and with increased inspiratory capacity at rest/and at exercise. The increase in end-expiratory lung volume (EELV) during exercise (EELVdyn-ch=EELVisotime EELVrest) demonstrated significant attenuation after coil treatment (p=0.02).

Publisher Correction: Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone.

The original version of this article unfortunately contained a mistake. In Table 2, the frequency of Septic Shock reported just below the frequency of "At least 1 Episode of VAP" actually corresponds to the First (and not the Second) Episode of VAP during the postresuscitation period.

Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone.

PURPOSE: Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock. METHODS: We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an "as-treated" principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88). RESULTS: Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as "hypotension and/or myocardial ischemia" did not appreciably affect the aforementioned CSHRs. CONCLUSIONS: In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Celiac Artery Avulsion Secondary to Blunt Trauma: A Case Report.

Celiac artery (CA) injuries are very rare and are often associated with high mortality. These injuries are associated more often with penetrating trauma rather than blunt trauma injury. Our case highlights a blunt trauma injury of CA in a hemodynamically stable patient without any symptoms that was treated conservatively.

Exposure to cigarette smoke abrogates the beneficial effect of ischemic postconditioning.

Cigarette smoking is one of the risk factors for coronary artery disease. Although conditioning decreases infarct size in hearts from healthy animals, comorbidities may render it ineffective. We investigated the effects of cigarette smoke (CS) exposure on intracellular myocardial signaling, infarct size after ischemia-reperfusion, and the potential interference with ischemic conditioning. Exposure of mice to CS increased blood pressure, caused cardiac hypertrophy, and upregulated the nitric oxide synthatse (NOS)/soluble guanylate cyclase (sGC)/cGMP pathway. To test the effect of CS exposure on the endogenous cardioprotective mechanisms, mice were subjected to regional myocardial ischemia and reperfusion with no further intervention or application of preconditioning (PreC) or postconditioning (PostC). Exposure to CS did not increase the infarction compared with the room air (RA)-exposed group. PreC was beneficial for both CS and RA vs. nonconditioned animals. PostC was effective only in RA animals, while the infarct size-limiting effect was not preserved in the CS group. Differences in oxidative stress markers, Akt, and endothelial NOS phosphorylation and cGMP levels were observed between RA and CS groups subjected to PostC. In conclusion, exposure to CS does not per se increase infarct size. The beneficial effect of ischemic PreC is preserved in mice exposed to CS, as it does not affect the cardioprotective signaling; in contrast, PostC fails to protect CS-exposed mice due to impaired activation of the Akt/eNOS/cGMP axis that occurs in parallel to enhanced oxidative stress.

Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation.

BACKGROUND: Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury. METHODS: Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey's post hoc tests. RESULTS: Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were induced by HVt but were significantly attenuated by simvastatin. Microvascular protein permeability increase 20-fold by injurious ventilation but only 4-fold with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor-α, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to control. Lung tissue vascular endothelial cadherin expression was significantly reduced by injurious ventilation but remained preserved by simvastatin. CONCLUSION: High-dose simvastatin prevents experimental hyperinflation lung injury by angioprotective and anti-inflammatory effects.

Nasal steroids in snorers can decrease snoring frequency: a randomized placebo-controlled crossover trial.

Although it is anecdotally known that nasal obstruction is associated with snoring, it remains unknown whether the application of nasal steroids could decrease oral/oro-nasal breathing and increase nasal breathing, and subsequently decrease snoring indices. This study evaluated the effect of nasal budesonide on breathing route pattern and snoring. Twenty-four snorers were enrolled in a randomized, double-blind, crossover trial of 1-week treatment with nasal budesonide compared with 1-week intervention with nasal placebo. At the start and end of each treatment period, patients underwent nasal resistance measurement and overnight polysomnography with concomitant measurement of breathing route pattern and snoring. Twelve patients were randomly assigned to a 1-week treatment with nasal budesonide, followed by 2-week washout period and a 1-week intervention with the nasal placebo; and 12 patients were randomly assigned to a 1-week intervention with nasal placebo, followed by 2-week washout period and a 1-week treatment with nasal budesonide. Nasal budesonide was associated with a decrease in oral/oro-nasal breathing epochs and concomitant increase in nasal breathing epochs, decrease of snoring frequency by [median (interquartile range)] 15.8% (11.2-18.8%), and an increase of rapid eye movement sleep; snoring intensity decreased only in patients with increased baseline nasal resistance by 10.6% (6.8-14.3%). The change in nasal breathing epochs was inversely related to the change in snoring frequency (Rs = 0.503; P < 0.001). Nasal budesonide in snorers can increase nasal breathing epochs, modestly decrease snoring frequency and increase rapid eye movement sleep.

Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand.

BACKGROUND: Increased mortality rates in patients with chronic obstructive pulmonary disease (COPD) are largely due to severe infectious exacerbations. Impaired respiratory immunity is linked to the enhanced susceptibility to infections. Dendritic cells (DCs) direct host immune responses toward immunity or tolerance. Pulmonary CD1c(+) DCs elicit robust antiviral immune responses in healthy subjects. Nevertheless, their functional specialization in patients with COPD remains unexplored. OBJECTIVE: We sought to better understand the mechanisms that suppress respiratory immunity in patients with COPD by examining the immunostimulatory and tolerogenic properties of pulmonary CD1c(+) DCs. METHODS: We analyzed the expression of costimulatory and tolerogenic molecules by pulmonary CD1c(+) DCs from patients with COPD (CD1c(+)DCCOPD) and former smokers without COPD. We isolated lung CD1c(+) DCs and determined their ability to stimulate allogeneic T-cell responses. The suppressive effects of lung CD1c(+) DCs and CD1c(+) DC-primed T cells on mixed leukocyte reactions were examined. An experimental human model of COPD exacerbation was used to investigate the levels of critical immunosuppressive molecules in vivo. RESULTS: CD1c(+) DCs from patients with COPD hinder T-cell effector functions and favor the generation of suppressive IL-10-secreting CD4(+) T cells that function through IL-10 and TGF-ß. IL-27, IL-10, and inducible T-cell costimulator ligand signaling are essential for CD1c(+)DCCOPD-mediated differentiation of IL-10-producing suppressive T cells. Exposure of lung CD1c(+) DCs from nonobstructed subjects to lungs of patients with COPD confers tolerogenic properties. IL-27 and IL-10 levels are increased in the lung microenvironment on rhinovirus-induced COPD exacerbation in vivo. CONCLUSION: We identify a novel tolerogenic circuit encompassing suppressive CD1c(+) DCs and regulatory T cells in patients with COPD that might be implicated in impaired respiratory immunity and further highlight IL-10 and IL-27 as potent therapeutic targets.

CXCL13 production in B cells via Toll-like receptor/lymphotoxin receptor signaling is involved in lymphoid neogenesis in chronic obstructive pulmonary disease.

RATIONALE: Little is known about what drives the appearance of lymphoid follicles (LFs), which may function as lymphoid organs in chronic obstructive pulmonary disease (COPD). In animal infection models, pulmonary LF formation requires expression of homeostatic chemokines by stromal cells and dendritic cells, partly via lymphotoxin. OBJECTIVES: To study the role of homeostatic chemokines in LF formation in COPD and to identify mechanism(s) responsible for their production. METHODS: Peripheral lung homeostatic chemokine and lymphotoxin expression were visualized by immunostainings and quantified by ELISA/quantitative reverse transcriptase-polymerase chain reaction in patients with COPD with and without LFs. Expression of lymphotoxin and homeostatic chemokine receptors was investigated by flow cytometry. Primary lung cell cultures, followed by ELISA/quantitative reverse transcriptase-polymerase chain reaction/flow cytometry, were performed to identify mechanisms of chemokine expression. Polycarbonate membrane filters were used to assess primary lung cell migration toward lung homogenates. MEASUREMENTS AND MAIN RESULTS: LFs expressed the homeostatic chemokine CXCL13. Total CXCL13 levels correlated with LF density. Lung B cells of patients with COPD were important sources of CXCL13 and lymphotoxin and also expressed their receptors. Cigarette smoke extract, H2O2, and LPS exposure up-regulated B cell-derived CXCL13. The LPS-induced increase in CXCL13 was partly mediated via lymphotoxin. Notably, CXCL13 was required for efficient lung B-cell migration toward COPD lung homogenates and induced lung B cells to up-regulate lymphotoxin, which further promoted CXCL13 production, establishing a positive feedback loop. CONCLUSIONS: LF formation in COPD may be driven by lung B cells via a CXCL13-dependent mechanism that involves toll-like receptor and lymphotoxin receptor signaling.

Apnea or normal breathing during repeated high-intensity swimming enhance sprint efficiency and which metabolic disorder?

BACKGROUND: The aim of this study was to investigate the effect of normal breath and apnea swimming on acid-base balance, physiological responses and performance during high-intensity interval training in swimming. METHODS: Sixteen swimmers completed 6×50 m intervals of freestyle swimming with normal breath and apnea at maximum intensity, with 1 minute rest. Capillary blood gases (pH, PCO2, PO2, HCO3, Hct, Hb) were collected at four (4) measurement time points: 1) at rest once; 2) at rest just after the 3rd repetition; 3) at finish; and 4) at 10 min of recovery. Heart rate (HR) during swimming, lactate acid (La) concentration and swimming time (t50) were measured. RESULTS: Our study showed uncompensated metabolic acidosis due to increased lactic acidosis in both breathing conditions, more pronounced in apnea, and faster swimming times in apnea without different heart rate responses. CONCLUSIONS: Apnea during repetitive high intensity long distance interval 50 m freestyle swimming causes uncompensated metabolic acidosis but improves sprint performance.