CAL02 Liposomes and Other Antitoxins: A New Generation of Anti-Infectives

While new generations of existing classes of antibiotics have predominated pipelines, novel nonantibiotic approaches such as antitoxins are gradually taking a more prominent position to address today’s most challenging issues in the field, notably the threatening rise of resistant strains and the unacceptably high rates of treatment failure and mortality despite the best of care. This review presents the clinical stage broad-spectrum antitoxin agent CAL02, which is active against both gram-positive and gram-negative bacteria including ESKAPE pathogens. CAL02 neutralizes bacterial pore-forming toxins, enzymes, and toxin-effector virulent appendages that play a vital and upstream role in pathogenic processes responsible for the progress and severity of infections such as severe pneumonia, bacteremia, and sepsis. The present overview underlines how combination therapies with antimicrobial agents operating in synergy with antibiotics, via unprecedented mechanisms of action, hold promise to dramatically improve standard of care and overturn the morbidity and mortality associated with resistant pathogens. The concerted efforts of academia, industry, clinicians, and regulatory agencies are contributing to a more accurate understanding of the various nontraditional approaches in development. Novel antitoxin treatments help reshape the antibiotic-driven set of mind. …

Monoclonal Antibody Therapy for Asthma

Asthma is characterized by airway inflammation and reversible airflow limitation. Severe asthma accounts for 5% to 10% of asthmatic patients but more than half of the cost of asthma care in the United States. There is increasing interest in characterizing and managing this difficult population. The mainstay of asthma treatment is the use of inhaled corticosteroids and bronchodilators, although in patients with severe asthma, many rely on systemic glucocorticoids for asthma control. Newer monoclonal antibodies are providing an alternative to systemic glucocorticoids for asthma control and exacerbation prevention. The first monoclonal antibody therapy approved for treatment of asthma was omalizumab, targeting IgE, a component of the allergic cascade. More recently, 2 monoclonal antibodies have been approved as add-on therapy for poorly controlled eosinophilic asthma. These target interleukin-5, a key cytokine in promoting eosinophil differentiation, survival, and recruitment. Another antibody targeting the interleukin-5 receptor on eosinophils is anticipating approval. Other monoclonal antibodies targeting a wide variety of intermediaries in the inflammatory cascade are under development. Evaluation of previously approved monoclonal antibodies that may have benefit in asthma is ongoing. An understanding of the pathophysiology of asthma and airway hyperreactivity, as well as use of biomarkers, will help clinicians appropriately target monoclonal antibody therapy to patients who are most likely to respond to these newer therapies. …

High-Flow Nasal Cannula Therapy in Adults

Oxygen is the first-line therapy for hypoxemic respiratory failure and is usually delivered through nasal cannulae or a face mask. More recently, there has been increased interest in the use of high-flow nasal cannula (HFNC) oxygen therapy, in which optimally heated and humidified oxygen is delivered at high flow rates of up to 60 L/min. HFNC therapy has a number of advantages over traditional, low-flow oxygen therapy: provision of low-level positive-end expiratory pressure, flushing of anatomical dead space, provision of higher and more predictable fraction of inspired oxygen and enhanced patient tolerance and compliance. Much of the available evidence for its clinical utility comes from its use in neonatal and pediatric settings, but HFNC therapy has been studied in adults with acute hypoxemic respiratory failure, patients with chronic obstructive pulmonary disease and heart failure, and for preoxygenation before intubation, as well as postextubation to avoid or treat respiratory failure in high-risk groups. Currently, there are only a few high-quality studies evaluating outcomes of HFNC therapy in these patient groups, and a number of key questions remain to be answered, meaning that it is not possible to make strong recommendations regarding its use. Nevertheless, this is an exciting and innovative addition to the field of respiratory support for adult patients with a variety of respiratory pathologies. …

Tranexamic Acid for Hemoptysis: A Review

Tranexamic acid (TXA) is an antifibrinolytic agent used to promote hemostasis. TXA is widely used to arrest bleeding in trauma, perioperatively after cardiac surgery, for menorrhagia, and in hemophilia. Less attention has been given to using TXA to lessen hemoptysis, which is the subject of this systematic review. Three small, underpowered randomized controlled trials have examined the efficacy of TXA in hemoptysis. Two of these assessed intravenous TXA, one of which showed significant reduction in the severity and duration of hemoptysis. The third trial examined oral TXA for controlling hemoptysis and failed to show a significant reduction in the amount or duration of hemoptysis. Although inhaled TXA has been described in several case reports and small series, no trial has examined the efficacy of inhaled TXA. The weight of evidence suggests that systemic administration of TXA is safe and does not increase the risk for thrombosis; no adverse effects have been described in the few available reports of inhaled TXA. Overall, TXA is an underrecognized treatment that may have temporizing value in managing patients with nonmassive hemoptysis. In the context that the available literature is sparse, large, well-designed clinical trials are needed to advance understanding of the role of TXA in hemoptysis. …

Vitamin D and Lower Respiratory Tract Infection in Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background and objectives: Vitamin D has been found to have antimicrobial properties. Studies on vitamin D and lower respiratory tract infection (LRTI) in children have mixed findings. This systematic review aimed to evaluate the effect of vitamin D supplementation for prevention and treatment of LRTI in children. Methods: We searched PubMed, Embase, and Cochrane library for randomized controlled trials (RCTs) concerning vitamin D supplementation and LRTI in children. We extracted data using a structured form and did a meta-analysis using Review Manager version 5. Results: Four studies enrolling a total of 3946 subjects were reviewed, in which vitamin D was used in different doses and for variable duration. Vitamin D supplementation did not reduce the incidence of LRTI (odds ratio, 0.82; 95% confidence interval, 0.47-1.45). Vitamin D did not decrease the time to resolution of LRTI compared with placebo (mean difference, –0.01; 95% confidence interval, –0.56 to 0.54 d). No significant side effects of vitamin D supplementation were seen. Conclusions: The limited number of RCTs on the effect of vitamin D supplementation for prevention and treatment of LRTI in children did not show any beneficial effect. More RCTs are needed to determine the adequate dose, frequency, and duration of vitamin D supplementation and to identify specific groups of children who may benefit from supplementation. …

Bronchiectasis Phenotype in COPD Patients

Chronic obstructive pulmonary disease and bronchiectasis have as many features in common as they have differences. They are both chronic airway diseases with a similar inflammatory profile and they often present an interchangeable clinical and functional picture but nevertheless their diagnosis, treatment, and evolution set them apart. It has recently been discovered, however, that the resemblance between these 2 diseases could be more than a matter of chance, and that their relationship could have distinct therapeutic and prognostic implications, which would mean that patients with both chronic obstructive pulmonary disease and bronchiectasis would present a distinct clinical phenotypic profile. Further studies are required to investigate whether they also have a specific genotypic profile. …

Review of Endoscopic Lung Volume Reduction Interventions

Endoscopic lung volume reduction is a less invasive and potentially beneficial intervention for patients who may not be candidates for traditional lung volume reduction surgery. There are many different interventions, ranging from various stents and occluders to polymers, coils, and thermal vapor ablation. In this review article, we will discuss the various therapies available, analyze the available literature, provide insight into future direction, and offer guidance for the practicing pulmonologist in navigating this ever-expanding field. …

Evaluation of Imatinib Mesylate in the Treatment of Pulmonary Arterial Hypertension

Imatinib mesylate is a small molecule inhibitor that selectively inhibits the PDGF receptor kinase as well the cKIT and Abl kinases, among other targets. Various studies have implicated the PDGF pathway in the pathogenesis of pulmonary arterial hypertension (PAH). Inhibition with imatinib mesylate has shown efficacy in human case reports and experimental models of PAH. Results from a Phase II trial of imatinib mesylate in PAH did not meet the primary end point but showed improvement in several secondary end points and in a subgroup analysis. As suggested by this study as well as a few case reports, imatinib may be effective in a subset of patients with more severe disease. However, this remains to be further validated through a Phase III study, which is already underway. In conclusion, it appears that imatinib mesylate may hold promise as an adjunct drug in PAH therapy, especially since it is directed at a pathway not previously targeted. …

The Value of Computed Tomography Scanning for the Detection of Coronary Artery Disease in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND AND OBJECTIVE:
Patients with idiopathic pulmonary fibrosis (IPF) have a higher prevalence of coronary artery disease and this could have an impact on their outcomes. We investigated the predictive ability of coronary artery calcification, assessed by routine CT, which may predict the presence of coronary artery disease. METHODS:
The study cohort consisted of patients with IPF and with left heart catheterization data plus CT scans from July 2003 to July 2008. Grades of coronary calcification on CT were compared with left heart catheterization determination of coronary artery disease. RESULTS:
There were 57 patients in whom left heart catheterization review demonstrated significant coronary artery disease in 28.1% (16/57), mild disease in 40.3% (23/57) and none in 31.6% (18/57). The median time interval between the catheterization and the reviewed CT scan was 39 days. The sensitivity of moderate to severe calcification for significant coronary artery disease was 81%, while the specificity was 85%, with an associated odds ratio of 25.2 (4.64-166, P < 0.005). There was excellent agreement among three radiologists in the grading of coronary calcification. CONCLUSIONS: Coronary calcification, as assessed by routine CT of the chest, has very good performance characteristics in predicting underlying significant coronary artery disease in patients with IPF. The routine availability of this study enables the ready screening for coronary artery disease in IPF patients. ...