Albrechtsenmaldonado7588

Tertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection with

but their roles remain elusive. The present study sought to examine the effects of B and/or T cell depletion on

infection and TLS development (lymphoid neogenesis) in mice.

C57Bl/6 mice were pretreated with (1) an anti-CD20 mAb (B cell depletion) or (2) an anti-CD4 and/or an anti-CD8 mAbs (T cell depletion) or (3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B and T cell depletion) or (4) with isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containing

(10

CFU/mouse). Fourteen days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.

Fourteen days after

-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pretreated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20

B lymphocytes had no effect on CD3

T lymphocyte infiltration, whereas CD4

/CD8

T-cell depletion markedly reduced CD20

B cell infiltration. Depletion of CD4

or CD8

T cells separately had limited effect on B cell infiltration but lead to the absence of germinal center.

TLS disorganisation is not associated with loss of infection control in mice persistently infected with

.

TLS disorganisation is not associated with loss of infection control in mice persistently infected with S. aureus.Whenever Pseudomonas aeruginosa (PA) is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by at least 6 months of negative bacterial airway cultures. However, we suspect that PA persists in airways without clinical detection for long periods.Of 298 PA-infected Copenhagen CF patients, we identified 80 with complete PA monitoring records and measured their maximum PA-free eradication periods (MEP). Isolates from 72 patients were whole genome sequenced (n=567) and clone typed. Select isolate relatedness was examined through phylogenetic analysis and phenotypic multivariate modelling.Sixty-nine patients (86%) exhibited eradication in the monitoring period (2002-2018). Sequenced isolates bridged the MEP of 42 patients, and the same clone type persisted over the MEP in 18 (43%). Patients with failed eradication were on average treated more intensively with antibiotics, but this may be linked to their more severe pre-MEP infection trajectories. Of the 42 patients, 26 also had sinus surgery; the majority (15) show MEPs adjacent to surgery, and only 5 had persisting clone types. Importantly, combined phylogenetic-phenomic evaluation suggests that persisting clone types are a result of re-emergence of the same strain rather than re-infection from the environment, and similar relatedness is exhibited by paired lower and upper airway samples and in transmission cases.In conclusion, nearly half of CF patients with supposed eradication may not truly be cleared of their original bacteria according to omics-based monitoring. This distinct cohort that is persistently infected would likely benefit from tailored antibiotic therapy.Inhaled corticosteroids (ICS) have been recommended as a maintenance treatment, either alone or together with long-acting inhaled β2-agonists, for all asthma patients. Short acting β2-agonists (SABA) are rapid onset bronchodilators, which provide symptom relief, but have no anti-inflammatory properties, yet are the most widely used as-needed reliever treatment for asthma, and often the only treatment prescribed. Asthma patients can find adhering to daily preventative medication with ICS difficult and will often revert to using as-needed SABA as their only treatment, increasing their risk of exacerbations. The purpose of this review was to evaluate the efficacy of reliever medications that contain an ICS when compared to SABA as a reliever, or to maintenance ICS and SABA as reliever, in mild asthma patients.Nine studies were identified which have evaluated the use of ICS as a component of an as-needed reliever in patients with mild asthma. Four of the most recent studies compared the combination of ICS/formoterol to SABA as reliever.An ICS containing reliever medication was superior to SABA as reliever alone, and was equivalent to maintenance ICS and SABA as reliever, particularly in reducing risks of severe asthma exacerbations, in studies which compared these reliever options.SABAs should not be used as a reliever without ICS. The concern about patients with mild asthma not being adherent to maintenance ICS, supports a recommendation that ICS/formoterol should be considered as a treatment option instead of maintenance ICS, to avoid the risk of patients reverting to SABA alone.Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000-2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 11 matching to TORCH participants, as follows. Control group 1 people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2 people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL versus SAL (0.85, 95% CI 0.74-0.97 versus 0.88, 0.81-0.95) but not for FP-SAL versus no FP-SAL (1.30, 1.19-1.42 versus 0.75, 0.69-0.81). ADH-1 ic50 In addition, active comparator results were consistent with TORCH for mortality (hazard ratio 0.93, 0.65-1.32 versus 0.93, 0.77-1.13) and pneumonia (risk ratio 1.39, 1.04-1.87 versus 1.47, 1.25-1.73).We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from randomised controlled trials provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.