Biological therapies in the treatment of inflammatory disease and cancer: impact on pulmonary infection.

Biological therapies are increasingly used for the treatment of inflammatory conditions in the realms of rheumatology, dermatology, and gastroenterology due to their ability to target specific cytokines in the inflammatory cascade. The impact of these biologic therapies is immunosuppression leading to an increased risk of infection. This review focuses on commonly used biologic agents in the treatment of inflammatory conditions and cancer and their impact on pulmonary infections. We have summarized potential pathogens in this group of patients. The hope being that this will increase awareness and therefore prevention timely diagnosis and successful treatment of patients receiving biologic therapies. It is also important to note that it is not solely the choice of an agent that predisposes to particular infections. Concomitant factors that might increase an individuals' risk of contracting an infection include the underlying disease, comorbid diseases, increased age, and other medical treatment as well as exposure to opportunistic pathogens. In the treatment of cancers many immunotherapies are being developed. The most notable adverse effects from immunotherapy are due to stimulation of the immune response, and these may mimic infection by causing flu-like symptoms and breathlessness due to pneumonitis. The treatment of this is immunosuppression, further leading to an increased risk of infection. Biologic therapies have been a revolution in the treatment of inflammatory conditions and cancers. They have improved outcomes and quality of life for patients. However, the use of these drugs needs to be balanced against the risk of infection and every patient needs to be assessed on an individual basis

Current and emerging evidence for immunomodulatory therapy in community-acquired pneumonia

Community-acquired pneumonia (CAP) is the most common infectious disease related cause of death worldwide despite the use of effective antimicrobials. Much of the morbidity and mortality seen in CAP patients at high risk of death has been attributed to exaggerated host responses that result in bystander tissue damage and organ failure. Therefore there is great need to further understand the effect of hyperinflammatory phenotypes on CAP outcomes and develop adjuvant therapy that can attenuate excessive inflammatory responses without compromising host defense. Furthermore, there is growing concern regarding the development of antimicrobial resistance and recent research aims to modulate immune mechanisms that boost pathogen killing and clearance. In this review we summarize the growing body of evidence for the use of adjuvant immunomodulators in the treatment of CAP and highlight emerging immunomodulators that have been tested in pre-clinical studies, which need to be evaluated and developed for clinical trials. In summary, current evidence supports the use of macrolide combination antibiotic therapy and unless contraindicated continuation of pre-admission statin and antiplatelet therapy. Corticosteroids are beneficial in the context of septic shock and critical illness related adrenal insufficiency and may be of benefit to individuals with severe CAP and a hyperinflammatory phenotype given the potential for improving patient-centered and economic outcomes with negligible adverse effects. Despite much promise in pre-clinical work, many clinical trials of drugs targeting the coagulation pathways have unfortunately failed to demonstrate clinical benefits in humans. Results of trials evaluating aspirin, intravenous immunoglobulin (IVIg) and thrombomodulin are awaited and may yet influence practice, whilst further identification of inflammatory phenotypes will in the future allow personalized approaches and identify subgroups of patients that may respond to adjuvants that have previously not demonstrated favorable outcomes when used in heterogeneous cohorts

Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity

Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice

Review of the British Thoracic Society Winter Meeting 2016, 7-9 December, London, UK

This article reviews the British Thoracic Society Winter Meeting 2016 and highlights the new developments in scientific and clinical research across the breadth of respiratory medicine

Chyle leakage in port incision after video-assisted thoracoscopic surgery: case report

A 26-year-old Asian male was found to have chyle leakage from the port incision after video-assisted thoracoscopic surgery (VATS) for excision of pulmonary bullae. The diagnosis was confirmed by oral intake of Sudan black and by lymphoscintigraphy. The leakage resolved after 5 days of restricted oral intake and total parenteral nutrition. No leakage recurred after return of oral intake. Possible explanations for the port incision chyle leakage are obstruction of the thoracic duct, which induced retrograde drainage of the lymphoid fluid, or an aberrant collateral branch of the thoracic duct in the chest wall

Relevance of vein wall thickness in Behcet's disease: A systematic review and meta-analysis.

ObjectivesTo perform a meta-analysis on articles evaluating the common femoral vein wall thickness (VWT) in Behcet's disease and its possible clinical, laboratory and treatment correlates (BD).MethodsSystematic search of EMBASE and PubMed databases from inception to October 2023; we employed random effect meta-analyses for continuous outcomes.ResultsThe meta-analysis included 9 case-control and 1 cohort study: the VWT was greater in BD (n = 650) than in controls (n = 396) (p 2 = 94.4%); a sensitivity analysis that included mean age of BD participants, gender, disease duration and activity, C-reactive protein, smoking status, immune-suppressive and anti-inflammatory medication, revealed that the heterogeneity variance was partly explained by age (p ConclusionVWT is greater in BD than controls: age, male gender, disease duration and smoking relate to VWT that was greater in BD patients with a history of thrombotic/vascular disease. Prospective studies are required to assess whether VWT may be considered a vascular marker of disease activity