Intraalveolar Catecholamines and the Human Lung Microbiome

Abstract

biomarkers are encouraging and show that we have indeed targeted BMPR2 in patients with reduced levels of BMPR2. It will be of interest to determine whether the same effect can be achieved in patients with documented mutations and whether a subset of patients is particularly sensitive to the beneficial effects of this strategy and could therefore be identified up front as potential "responders" on the basis of BMPR2 levels. n

The microbiome and critical illness

“…Bacterial pneumonia, a true lung infection, exemplifies these features: it is characterised by increased bacterial burden and low community diversity (generally one dominant pathogen). 62,83,130 These features correlate tightly with multiple indices of host inflammation, including alveolar neutrophilia 93 and high alveolar concentrations of catecholamines 50 and TNF-α. 131 …”

“…The normally nutrient-poor environment of the alveolus is flooded with nutrient-rich oedema, 55 pockets of oxygen and heterogeneous temperature gradients are established, 48,49 and the signalling molecules of the host stress response selectively promote the growth of potential pathogens. 23,50,51 The ubiquitous use of systemic antibiotics further alters the relative reproduction rates of community members. The predicted effect of these ecological forces in the lungs, therefore, is a state of increased immigration, decreased elimination, and favourable growth conditions for potential pathogens.…”

“…51 In human bronchoalveolar lavage samples, increased alveolar catecholamine concentrations correlate strongly with collapse of the lung microbiome around one dominant species (most frequently P aeruginosa , figure 4). 50 Thus any source of alveolar injury and inflammation, whether direct (eg, aspiration or ventilator-induced lung injury 60 ) or indirect (eg, sepsis or shock) can trigger a cascade of inflammation leading to increased concentrations of intra-alveolar catechol amines, 120 which in turn promote the growth and virulence of select bacterial community members and a disordered bacterial community that perpetuates alveolar inflammation (figure 4). Bacterial growth promotion by host stress molecules is not unique to P aeruginosa , and is also seen with Streptococcus pneumoniae , 121 S aureus , 122 and Klebsiella pneumoniae .…”

“…51 (B) In the human lung microbiome, increased catecholamine concentrations are strongly associated with community collapse and the emergence of one dominant species. 50 (C) In states of critical illness, direct and indirect lung injury provoke alveolar inflammation, which promotes catecholamine production and creates a positive-feedback loop of dysbiosis and inflammation. 50 CFU=colony forming unit.…”

“…50 (C) In states of critical illness, direct and indirect lung injury provoke alveolar inflammation, which promotes catecholamine production and creates a positive-feedback loop of dysbiosis and inflammation. 50 CFU=colony forming unit. VILI=ventilator-induced lung injury.…”