Hypercapnia: An Aggravating Factor in Asthma

Shigemura, Masahiko; Homma, Tetsuya; Sznajder, Jacob I.

doi:10.3390/jcm9103207

Cited by 9 publications

(7 citation statements)

References 133 publications

(244 reference statements)

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“…One study of total hip replacements found that chronic obstructive pulmonary disease (COPD) increased 90- day mortality, mortality at one year, infections within the first year post-operatively, and 30-day readmissions [ 13 ]. Asthma is another common chronic respiratory comorbidity that may lead to alveolar hypoventilation and hypercapnia, potentially resulting in poor lung, skeletal muscle, and innate immune system function [ 14 ]. Furthermore, chronic steroid use, which is often used to treat severe asthma, has been shown to impair wound healing and could potentially increase wound complications [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Hypercarbia on Lower Extremity Primary Total Joint Replacement Infections

Goodeill¹,

Than²,

Pipitone³

et al. 2022

Cureus

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Introduction: Prosthetic joint infection (PJI) is a serious complication after total joint replacement (TJR). Adequate wound oxygenation is critical for wound healing and infection prevention. As carbon dioxide (CO 2 ) is exchanged for oxygen (O 2 ) in the lungs, serum bicarbonate (HCO 3 - ) may be used as a marker for predicting relative serum O 2 levels, and therefore, healing potential. No currently published literature explores the relationship between serum bicarbonate levels and PJI in TJR patients. Methods: We performed this retrospective review of lower extremity TJR patients to determine whether the risk of PJI and wound complications within one year was correlated with hypercarbia, which was defined as a preoperative serum bicarbonate level >30 mEq/L. Results: Out of 1,690 TJR procedures, 1.6% (N=27) had a PJI or superficial wound infection within one year postoperatively. The average preoperative serum bicarbonate was 26.9 (SD 2.6) among patients without PJI and 27.2 (SD 2.1) among patients with PJI (p=0.46). Hypercarbia was present in 9.2% of non-PJI patients and in 7.4% of PJI patients. The relative risk of PJI and wound complications did not differ for patients with vs without hypercarbia (RR = 0.79, 95% CI = 0.19-3.31, p=0.75). Conclusion: The results of this study provide preliminary evidence that preoperative hypercarbia may not be correlated with an increase in the risk of PJI or wound complications. However, due to the rarity of both PJI and hypercarbia, a larger patient population is needed to ensure adequate power to detect clinically meaningful effect sizes.

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Section: Discussionmentioning

confidence: 99%

Effects of Hypercarbia on Lower Extremity Primary Total Joint Replacement Infections

Goodeill¹,

Than²,

Pipitone³

et al. 2022

Cureus

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“…Hypercapnia [HP:0012416], i.e. an elevated level of CO 2 in the blood could be related to the effects of asthma on respiration 30 ; and Increased hematocrit [HP:0001899] could be related to chronic hypoxia, although our analysis does not allow any conclusions about the pathomechanisms of observed laboratory abnormalities. .…”

Section: Screen For Biomarkers Correlated With Progression Into Sever...mentioning

confidence: 99%

Building Population Phenotypic Journeys from Laboratory Tests in Electronic Health Records for Translational Research

Zhang

Lee

Liu

et al. 2022

Preprint

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Abundant volumes of clinical laboratory test results available within Electronic health records (EHRs) are essential for differential diagnosis, treatment monitoring, and outcome evaluation. LOINC2HPO is a recently developed deep phenotyping approach to transform laboratory test results into the Human Phenotype Ontology (HPO) terms. Here, we deployed the approach on a large EHR dataset from the Sema4 Data Warehouse to build patient phenotypic journeys at scale. Among 1.07 billion laboratory test results, we successfully transformed 774 million (72.5%) into HPO-coded phenotypes and built a patient phenotypic journey for over 2.2 million patients. First, a global analysis of patient phenotypic journeys revealed a longitudinal increase in patients with genitourinary system abnormality. The analysis also revealed abnormal phenotypes with strong racial patterns. Second, using severe asthma as an example case, we identified abnormal phenotypes in the past three years that were correlated with asthma progression to severe state. Lastly, we demonstrated that converting laboratory test results into HPO terms resulted in limited information loss. Our study demonstrated that the phenotypic journey framework opens the way to characterize phenotypic trajectories in population level and screen biomarkers for translational research.

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“…It is increasingly evident, that various non-excitable cells, such as alveolar epithelial cells, fibroblasts and immune cells are sensitive to the changes in CO 2 concentrations independently of intra-and extracellular pH, reactive oxygen species (ROS) and involvement of the carbonic anhydrases (Putnam et al, 2004;Shigemura et al, 2017;Cummins et al, 2019). In contrast to earlier reports, which suggested that hypercapnia might be tolerated or even beneficial in the setting of critically ill patients (Fuller et al, 2017;Roberts et al, 2018); more recent studies have shown that elevated CO 2 levels are associated with higher complication rates, increased risk of exacerbations, more severe disease states, worse outcomes and an increased risk of mortality both for acute and chronic lung diseases (Yang et al, 2015;Nin et al, 2017;Husain-Syed et al, 2020;Shigemura et al, 2020). In addition, translational studies established that high CO 2 levels impair alveolar fluid clearance, innate immunity and cellular host defense, decrease cytokine production, downregulate phagocytosis and macrophage activity.…”

Section: Introductionmentioning

confidence: 99%

“…Of note, ER stress plays a pivotal role in the pathomechanism of various respiratory diseases, including but not limited to COPD (and in particular cigarette smoke exposure), viral and bacterial pneumonia, asthma, interstitial lung diseases and cystic fibrosis (Korfei et al, 2008;Lawson et al, 2011;Kenche et al, 2013;Kim et al, 2013;van 't Wout et al, 2015;Lee et al, 2016;Marciniak, 2017;Tang et al, 2017;Schmoldt et al, 2019), many of which are accompanied by hypercapnia (Vadasz et al, 2012b;Shigemura et al, 2020). Notably, these disease states also often lead to hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction

Kryvenko

Vadász

2021

Front. Physiol.

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Protein transcription, translation, and folding occur continuously in every living cell and are essential for physiological functions. About one-third of all proteins of the cellular proteome interacts with the endoplasmic reticulum (ER). The ER is a large, dynamic cellular organelle that orchestrates synthesis, folding, and structural maturation of proteins, regulation of lipid metabolism and additionally functions as a calcium store. Recent evidence suggests that both acute and chronic hypercapnia (elevated levels of CO2) impair ER function by different mechanisms, leading to adaptive and maladaptive regulation of protein folding and maturation. In order to cope with ER stress, cells activate unfolded protein response (UPR) pathways. Initially, during the adaptive phase of ER stress, the UPR mainly functions to restore ER protein-folding homeostasis by decreasing protein synthesis and translation and by activation of ER-associated degradation (ERAD) and autophagy. However, if the initial UPR attempts for alleviating ER stress fail, a maladaptive response is triggered. In this review, we discuss the distinct mechanisms by which elevated CO2 levels affect these molecular pathways in the setting of acute and chronic pulmonary diseases associated with hypercapnia.

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Hypercapnia: An Aggravating Factor in Asthma

Cited by 9 publications

References 133 publications

Effects of Hypercarbia on Lower Extremity Primary Total Joint Replacement Infections

Effects of Hypercarbia on Lower Extremity Primary Total Joint Replacement Infections

Building Population Phenotypic Journeys from Laboratory Tests in Electronic Health Records for Translational Research

Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction

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