Failure of HFNC might cause delayed intubation and worse clinical outcomes in patients with respiratory failure. Large prospective and randomized controlled studies on HFNC failure are needed to draw a definitive conclusion.

Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.

Rationale: Idiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation. Objectives: To use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis. Methods: Bronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and highthroughput cDNA sequencing. Measurements and Main Results: Four of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n ¼ 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P ¼ 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses. Conclusions: Viral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.Keywords: acute lung injury; virus; infection; pulmonary fibrosis; etiology Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with no known cause or cure (1, 2). Although some patients experience a steady progression of disease over time, many have periods of relative stability punctuated by episodes of acute respiratory worsening that can be fatal (3, 4). When no identifiable cause for this acute worsening is found, it is termed an "acute exacerbation" of IPF (5).Acute exacerbation of IPF is defined as an idiopathic acute worsening of dyspnea characterized radiologically by the presence of bilateral ground glass abnormality on high-resolution computed tomography scan of the chest (5). It is estimated that between 5% and 10% of patients with IPF experience an acute exacerbation annually, with more physiologically advanced disease at higher risk (4-6). It remains unclear whether acute exacerbation of IPF represents a primary acceleration of the underlying fibroproliferative process in IPF or is a clinically occult secondary complication (e.g., infection) (5, 7).Acute exacerbation of IPF is often accompanied by fever, increased cough, and myalgia, suggesting an infectious etiology. Respiratory viruses have been considered a particularly likely cause, based on the similarities in clinical and radiologic presentation between acute exacerbation of IPF and viral pneumonitis and the poor sensitivity of standard methods of viral detection (5). Also, there may be ...

The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

Our findings indicate lactate and lactate clearance are both useful targets in patients with septic shock defined by Sepsis-3. Serum lactate level at 6-hour can be an easier and more effective tool for prognosis of septic shock patients who were treated with protocol-driven resuscitation bundle therapy.

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The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production. Administration of FL-WRS into Salmonella typhimurium-infected mice reduced the levels of bacteria and improved mouse survival, whereas its titration with the specific antibody aggravated the infection. The N-terminal 154-amino-acid eukaryote-specific peptide of WRS was sufficient to recapitulate FL-WRS activity and its interaction mode with TLR4-MD2 is now suggested. Based on these results, secretion of FL-WRS appears to work as a primary defence system against infection, acting before full activation of innate immunity.

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