Hypercapnia and its relationship with respiratory infections

ABSTRACT

Introduction

Hypercapnia is developed in patients with acute and/or chronic respiratory conditions. Clinical data concerning hypercapnia and respiratory infections interaction is limited.

Areas covered

Currently, the relationship between hypercapnia and respiratory infections remains unclear. In this review, we summarize studies on the effects of hypercapnia on models of pulmonary infections to clarify the role of elevated CO2 in these pulmonary pathologies. Hypercapnia affects different cell types in the alveoli, leading to changes in the immune response. In vitro studies show that hypercapnia downregulates the NF-κβ pathway, reduces inflammation and impairs epithelial wound healing. While in vivo models show a dual role between short- and long-term effects of hypercapnia on lung infection. However, it is still controversial whether the effects observed under hypercapnia are pH dependent or not.

Expert opinion

The role of hypercapnia is still a controversial debate. Hypercapnia could play a beneficial role in mechanically ventilated models, by lowering the inflammation produced by the stretch condition. But it could be detrimental in infectious scenarios, causing phagocyte dysfunction and lack of infection control. Further data concerning hypercapnia on respiratory infections is needed to elucidate this interaction.

KEYWORDS:

• Hypercapnia
• pneumonia
• respiratory infections
• inflammation
• CO₂

Article highlights

• Hypercapnia act on NF-κβ pathway.

• Despite reduce inflammation, hypercapnia decreased macrophage phagocytosis.

• In sepsis model hypercapnic acidosis reduced the severity of early septic shock and lung damage.

• Detrimental effects of hypercapnia in lung infection were observed.

• A better understanding of the effects of hypercapnia is needed to implement measures to reduce or tolerate CO2 levels in cases where it may be harmful or beneficial.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript has received an honorarium from Expert Review of Respiratory Medicine for their review work. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

Financial support was provided by Institut d’Investigació i Innovació Parc Taulí, European Society of Intensive Care Medicine (ESICM) and Sociedad Española de Neumología y Cirugía Torácica (SEPAR). The funding sources had no role in the management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and in the decision to submit the manuscript for publication. E Campaña-Duel acknowledges receiving financial support from Ministerio de Ciencia, Innovación y Universidades (FPU22/00725). A Ceccato acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087).