Breakdown of pulmonary host defense in the immunocompromised host: cancer chemotherapy.
ABSTRACT The number of immunocompromised patients is steadily increasing due to HIV infection, solid organ and stem cell transplantation, intensified chemotherapy, immunosuppression for autoimmune diseases, and a marked increase in the use of monoclonal antibodies. Prevention strategies for pulmonary infections and diagnostic methods have evolved and patient outcome has improved. However, therapies affecting the immune system are also given to older patients and patients with comorbidities. While the rate of pulmonary complications in HIV patients has dramatically decreased under antiretroviral therapy, we are seeing more patients with pulmonary problems after chemotherapy. Neutropenia is still the most important risk factor for bacterial and fungal infection. Flexible bronchoscopy with BAL remains an important diagnostic method with a low morbidity and high diagnostic yield in patients with pulmonary infiltrates following cancer chemotherapy.
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ABSTRACT: Community-acquired pneumonia (CAP) is a curable disease. Both the European and American clinical practice guidelines provide algorithms how to manage patients with CAP.However, as populations worldwide are aging and bacteria are becoming multidrug resistant, it is necessary to address the major factors that put patients at risk of poor outcome. These may include age, comorbidities, the settings where pneumonia was acquired or treated, the need for hospitalisation or ICU admission, likely causative pathogen (bacteria or virus) in a certain region and their local susceptibility pattern. One complicating fact is the lack of definite causative pathogen in approximately 50% of patients making it difficult to choose the most appropriate antibiotic treatment. When risk factors are present simultaneously in patients, fewer treatment options could be rather challenging for physicians. For example, the presence of comorbidities (renal, cardiac, hepatic) may exclude certain antibiotics due to potential adverse events.Assessing the severity of the disease and monitoring biomarkers, however, could help physicians to estimate patient prognosis once diagnosis is confirmed and treatment has been initiated. This review article addresses the most important risk factors of poor outcome in CAP patients.Respiratory Medicine 11/2014; 109(2). DOI:10.1016/j.rmed.2014.10.018 · 2.92 Impact Factor
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ABSTRACT: Neutrophils play critical roles in innate immunity and host defense. However, excessive neutrophil accumulation or hyper-responsiveness of neutrophils can be detrimental to the host system. Thus, the response of neutrophils to inflammatory stimuli needs to be tightly controlled. Many cellular processes in neutrophils are mediated by localized formation of an inositol phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), at the plasma membrane. The PtdIns(3,4,5)P3 signaling pathway is negatively regulated by lipid phosphatases and inositol phosphates, which consequently play a critical role in controlling neutrophil function and would be expected to act as ideal therapeutic targets for enhancing or suppressing innate immune responses. Here, we comprehensively review current understanding about the action of lipid phosphatases and inositol phosphates in the control of neutrophil function in infection and inflammation.EMBO Reports 01/2015; 16(2). DOI:10.15252/embr.201439466 · 7.86 Impact Factor
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ABSTRACT: The Th17 cytokines IL-17A, IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens including Klebsiella pneumoniae (KP). Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with KP. We hypothesized that pre-existing allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute KP infection and thereby increases lung KP burden. As hypothesized, we found that allergic airway inflammation decreased KP-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in post-infection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased lung KP burden and post-infection mortality. We showed that decreased lung KP burden was independent of IL-4, IL-5, and IL-17A, and partially-dependent on IL-13 and STAT6. Additionally, we demonstrated that decreased lung KP burden associated with allergic airway inflammation was both neutrophil and CCL8-dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against KP and suggest new methods of orchestrating lung antibacterial immunity.Infection and immunity 06/2014; 82(9). DOI:10.1128/IAI.00035-14 · 4.16 Impact Factor