New disease targets and medicinal chemistry approaches are urgently needed to develop novel therapeutic strategies for treating pulmonary diseases. Emerging evidence suggests that reduced activity of protein phosphatase 2A (PP2A), a complex heterotrimeric enzyme that regulates dephosphorylation of serine and threonine residues from many proteins, is observed in multiple pulmonary diseases, including lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Loss of PP2A responses is linked to many mechanisms associated with disease progressions, such as senescence, proliferation, inflammation, corticosteroid resistance, enhanced protease responses, and mRNA stability. Therefore, chemical restoration of PP2A may represent a novel treatment for these diseases. This review outlines the potential impact of reduced PP2A activity in pulmonary diseases, endogenous and exogenous inhibitors of PP2A, details the possible PP2A-dependent mechanisms observed in these conditions, and outlines potential therapeutic strategies for treatment. Substantial medicinal chemistry efforts are underway to develop therapeutics targeting PP2A activity. The development of specific activators of PP2A that selectively target PP2A holoenzymes could improve our understanding of the function of PP2A in pulmonary diseases. This may lead to the development of therapeutics for restoring normal PP2A responses within the lung.

Leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is highly expressed throughout the body in multiple tissues and cell types. LIF is primarily known to induce the differentiation of myeloid leukemia cells, but recent studies show that LIF has many other functions, including playing multiple roles in cancer and normal physiology. LIF expression is linked to cellular proliferation, metastasis, inflammation, and chemoresistance. LIF expression and secretion are triggered by many means and its downstream signaling can vary based on tissue types. Recent publications suggest that LIF may play a role in pulmonary diseases and its regulation is altered through external factors, such as cigarette smoke, inflammation stimuli, or infections. This review outlines the current knowledge of the function of LIF protein, mediators of LIF expression, receptors it interacts with, downstream LIF signaling, and possible pulmonary outcomes mediated by LIF.

A 63 -year -old man who presented to the hospital with altered mental status and decreased responsiveness was found to have severe symptomatic hyponatremia with a sodium level of 96 mmol/L and pneumonia. The patient was admitted to the medical intensive care unit for septic shock and acute severe hyponatremia. He was intubated for airway protection, and treated with 3% hypertonic saline bolus and antibiotics. After four days, sodium levels were corrected to 128 mmol/L, and the patient was extubated and downgraded to the medical floor. This case demonstrates one of the lowest recorded sodium lab values ever and the patient was successfully treated and discharged home with appropriate outpatient appointments.