ABSTRACT
Chronic alcohol abuse increases the risk of mortality and poor outcomes in patients with acute respiratory distress syndrome. However, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the effects of chronic alcohol consumption on lung injury and clarify the signaling pathways involved in the inhibition of alveolar fluid clearance (AFC). In order to produce rodent models with chronic alcohol consumption, wildtype C57BL/6 mice were treated with alcohol. A2a adenosine receptor (AR) small interfering (si)RNA or A2bAR siRNA were transfected into the lung tissue of mice and primary rat alveolar type II (ATII) cells. The rate of AFC in lung tissue was measured during exposure to lipopolysaccharide (LPS). Epithelial sodium channel (ENaC) expression was determined to investigate the mechanisms underlying alcoholinduced regulation of AFC. In the present study, exposure to alcohol reduced AFC, exacerbated pulmonary edema and worsened LPSinduced lung injury. Alcohol caused a decrease in cyclic adenosine monophosphate (cAMP) levels and inhibited αENaC, ßENaC and γENaC expression levels in the lung tissue of mice and ATII cells. Furthermore, alcohol decreased αENaC, ßENaC and γENaC expression levels via the A2aAR or A2bARcAMP signaling pathways in vitro. In conclusion, the results of the present study demonstrated that chronic alcohol consumption worsened lung injury by aggravating pulmonary edema and impairing AFC. An alcoholinduced decrease of αENaC, ßENaC and γENaC expression levels by the A2ARmediated cAMP pathway may be responsible for the exacerbated effects of chronic alcohol consumption in lung injury.
Subject(s)
Acute Lung Injury/metabolism , Alveolar Epithelial Cells/metabolism , Epithelial Sodium Channels/drug effects , Epithelial Sodium Channels/metabolism , Ethanol/pharmacology , Receptors, Adenosine A2/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Alveolar Epithelial Cells/pathology , Animals , Cyclic AMP/metabolism , Cytokines , Lipopolysaccharides/adverse effects , Lung/metabolism , Lung Injury/chemically induced , Lung Injury/metabolism , Lung Injury/pathology , Mice , Mice, Inbred C57BL , Pulmonary Alveoli/metabolism , Pulmonary Edema/chemically induced , Pulmonary Edema/metabolism , Pulmonary Edema/pathology , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , Rats , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2A/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND: The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS: A detailed search of the scientific and popular literature was performed. RESULTS: There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION: Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.