Investigating the spill-over hypothesis: Analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma

Teichert, Tom; Vossoughi, Mohammad; Vierkötter, Andrea; Sugiri, Dorothea; Schikowski, Tamara; Hoffmann, Barbara; Staudinger, Thomas; Roden, Michael; Raulf‐Heimsoth, Monika; Luckhaus, Christian; Krämer, Ursula; Herder, Christian

doi:10.1016/j.envres.2014.06.021

Cited by 11 publications

(4 citation statements)

References 60 publications

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“…The relationship between local (target organ) and systemic inflammation has been demonstrated previously in other respiratory conditions, such as chronic obstructive pulmonary disease [27]. Such findings prompted the "spill-over" hypothesis, which suggested the overflow of inflammatory cytokines reaching the blood stream from a local source [28]. Systemic inflammation may also contribute to weakening the respiratory muscles [29] and destabilising loop gain and respiratory control, thus impairing the protective airway patency mechanisms [30].…”

Section: Discussionmentioning

confidence: 80%

Upper airway and systemic inflammation in obstructive sleep apnoea

et al. 2016

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Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment.We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay.In PHAL, CD4 T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p<0.05). The AHI correlated with CD4, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery.In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found.

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Section: Discussionmentioning

confidence: 80%

Upper airway and systemic inflammation in obstructive sleep apnoea

et al. 2016

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“…At the same time, there is an increasing awareness of immune regulatory effects across compartments to remote sites, which to date are most appreciated for the gut microbiome [ 13 , 15 , 16 ]. Nevertheless, there is also evidence for inflammatory processes in the respiratory tract to influence systemic immunity [ 13 , 17 , 18 , 19 ]. While we are only beginning to understand these multi-faceted interactions, the underlying mechanisms to date remain mostly elusive.…”

Section: Introductionmentioning

confidence: 99%

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Jeron

Boehme

Volckmar

et al. 2018

IJMS

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The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica as the underlying model to comprehensively address effects on subsequent immune responses. Carriage was associated with the stimulation of Bordetella-specific CD4+, CD8+, and CD4+CD25+Foxp3+ T cell responses, and broad transcriptional activation was observed in CD4+CD25+ T cells. Importantly, transfer of leukocytes from carriers to acutely B. bronchiseptica infected mice, resulted in a significantly increased bacterial burden in the recipient’s upper respiratory tract. In contrast, we found that respiratory B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. Adaptive responses to vaccination and influenza A virus infection, were unaffected by B. bronchiseptica carriage. These data showed that there were significant immune modulatory processes triggered by B. bronchiseptica carriage, that differentially affect subsequent immune responses. Therefore, our results demonstrated the complexity of immune regulation induced by respiratory bacterial carriage, which can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.

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“…In earlier investigations of the SALIA cohort, these NO derivatives correlated well with the exposure to environmental air pollution. 27 , 29 Nitrogen oxides (nitrate and nitrite) in sputum have earlier been described to be relevant inflammatory parameters in COPD patients, which correlate with disease markers including tissue-destructing metalloproteinases. 30 , 31 It is assumed that due to the oxidative stress, nitrogen monoxide is converted into nitrogen metabolites.…”

Section: Discussionmentioning

confidence: 99%

Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals

Unfried¹,

Krämer²,

Sydlik³

et al. 2016

COPD

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BackgroundCompatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial.ObjectiveThe objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution.MethodsA double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined.ResultsWhile the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45–0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase.ConclusionThe current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum parameters, the study proves the feasibility of the therapeutic approach in an aged study group.

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Investigating the spill-over hypothesis: Analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma

Cited by 11 publications

References 60 publications

Upper airway and systemic inflammation in obstructive sleep apnoea

Upper airway and systemic inflammation in obstructive sleep apnoea

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals

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