Systemic inflammation impairs respiratory chemoreflexes and plasticity

Abstract

Many lung and central nervous system disorders require robust and appropriate physiological responses to assure adequate breathing. Factors undermining the efficacy of ventilatory control will diminish the ability to compensate for pathology, threatening life itself. Although most of these same disorders are associated with systemic and/or neuroinflammation, and inflammation affects neural function, we are only beginning to understand interactions between inflammation and any aspect of ventilatory control (e.g. sensory receptors, rhythm generation, chemoreflexes, plasticity). Here we review available evidence, and present limited new data suggesting that systemic (or neural) inflammation impairs two key elements of ventilatory control: chemoreflexes and respiratory motor (vs. sensory) plasticity. Achieving an understanding of mechanisms whereby inflammation undermines ventilatory control is fundamental since inflammation may diminish the capacity for natural, compensatory responses during pathological states, and the ability to harness respiratory plasticity as a therapeutic strategy in the treatment of devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.

Association Between Asthma and Risk of Developing Obstructive Sleep Apnea

“…19 Although the underlying mechanistic links between asthma per se and OSA remain to be tested, several pathways seem plausible: 1) augmented inspiratory negative intraluminal pressure in the deformable pharyngeal airway could occur during asthma attacks, along with active contraction of the respiratory muscles during forced expiration, yielding increased pressure in the surrounding pharyngeal airway tissues, 20 with both phenomena promoting upper airway collapse; 2) alterations in pharyngeal airway stiffness during sleep resulting from reduction in its tracheal tug 21 due to the more abrupt decline in lung volumes observed in sleeping patients with asthma; 22 3) sleep loss and fragmentation—caused by asthma—could affect upper airway collapsibility; 23 and 4) finally, the “spill-over” systemic inflammation resulting from the asthmatic process 24 may weaken the respiratory muscles, 25 and furthermore, trigger central nervous system inflammatory responses that could impair protective mechanisms of pharyngeal upper airway patency and destabilize the central breathing controller, as has been shown in response to other inflammatory insults. 26 An additional pathway from asthma to OSA may be the effect of systemic 8 and inhaled corticosteroid therapy on the pharyngeal airway, as suggested by a recent study. 27 Corticosteroids, which are prescribed for the treatment of asthma, may affect the deformable pharyngeal airway by raising the surrounding tissue pressure from centripetal fat accumulation/redistribution, and by diminishing the contractile properties of its protective, dilator muscles (myopathy), 27 similar to the postulated mechanism underlying dysphonia.…”

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

“…Since our limited analysis does not allow differentiation between microglial phenotypes (Colton, 2009; David and Kroner, 2011; Hanisch and Kettenmann, 2007; Nikodemova et al, 2013), we do not know if CTB–SAP microglial activation is beneficial or detrimental. Since systemic and neuro-inflammation both increase breathing frequency at rest and impair breathing capacity during chemoreflex activation (Huxtable et al, 2011, 2013; Vinit et al, 2011), activated microglia may impair breathing capacity in CTB–SAP rats. This possibility awaits further investigation.…”

Neuropathology in respiratory-related motoneurons in young Pompe (Gaa) mice

“…This has important implications since neuroinflammation is associated with neuronal loss (Kawashita et al, 2011; Vitner et al, 2012), motoneuron degeneration (Chiu et al, 2013), and also a blunted capacity for neuroplasticity in respiratory pathways (Huxtable et al, 2013, 2011). In other lysosomal storage disorders, apoptosis and microglial activation occur in parallel during disease progression.…”