PAGINA TIPO

SUMMARY. Aim. The aim of this work is to determine the incidence of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) and to define the define the most important respiratory pathogens in patients with inhalation injury. Introduction. Infectious complications in severely burned patients present serious problems. Patients with inhalation injuries are exposed to greater risk owing to the possible development of infectious complications in the lower respiratory tract. VAP is the predominant cause of death in these patients. This is due to the increasing resistance of strains of Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Design. Retrospective, monocentric. Setting. A five-bed burn intensive care unit. Material and methods. Between 2004 and 2009, 348 adult patients were hospitalized in the intensive care unit of the Department of Burns and Reconstructive Surgery, Brno University Hospital, Czech Republic. Of these, 127 (36.49%) were diagnosed by bronchoscopy as having inhalation injury. The prerequisite for inclusion in the cohort was an inhalation injury requiring artificial ventilation for at least 48 h. The lower airway microbiological condition was monitored regularly by sampling biological material for cultures (sputum, tracheobronchial aspirates, etc.). For the diagnosis of VAP and VAT we used the Centers for Disease Control and Prevention criteria and the Clinical Pulmonary Infection Score. Results. The average age of the 127 patients (31 women/96 men) included in the study was 38.4 yr (range, 21-69 yr) and the average total body surface area (TBSA) burned was 29.3% (range, 2-75%). The average length of hospital stay was 49.4 days (range, 4-150 days) and the duration of mechanical ventilation 8.7 days; 18 patients (14.2%) died. In patients with inhalation injury, 309 strains of bacteria were cultivated from the lower respiratory tract, of which 234 were Gram-negative. All of these bacterial strains were isolated in significant quantities for lower respiratory tract infection. The most common bacteria isolated from the lower respiratory tract was Klebsiella pneumoniae (78 times), followed by Pseudomonas aeruginosa (49x), and Acinetobacter baumannii (28x). VAT was diagnosed in 109 patients (85.8%) in the cohort. The incidence of VAT was calculated to be 98.8 per 1000 days of mechanical ventilation. VAP was diagnosed in 34 patients in the cohort (26.8%). The incidence of VAP was calculated as being 30.8 cases per 1,000 days of mechanical ventilation. In eight patients (23.5%), VAP was diagnosed within 5 days of initiation of mechanical ventilation (early onset) and in 26 patients (76.5%) after a longer period (late onset). The most common aetiological agent of VAT and VAP was Klebsiella pneumoniae (respectively 41.3% and 35.3%). Conclusion. In this study we were able to determine the incidence of VAP and VAT in patients with inhalation injury. In spite of the advances in diagnostics and therapy, inhalation injury is still burdened with disappointingly high morbidity and mortality rates. For this reason, the treatment of VAP remains a major challenge for all physicians caring for patients with inhalation injury

Inflammasomes: a novel therapeutic target in pulmonary hypertension?

Pulmonary hypertension (PH) is a rare, progressive pulmonary vasculopathy characterized by increased mean pulmonary arterial pressure, pulmonary vascular remodelling and right ventricular failure. Current treatments are not curative, and new therapeutic strategies are urgently required. Clinical and preclinical evidence has established that inflammation plays a key role in PH pathogenesis, and recently, inflammasomes have been suggested to be central to this process. Inflammasomes are important regulators of inflammation, releasing the pro-inflammatory cytokines IL-1β and IL-18 in response to exogenous pathogen- and endogenous damage-associated molecular patterns. These cytokines are elevated in PH patients, but whether this is a consequence of inflammasome activation remains to be determined. This review will briefly summarize current PH therapies and their pitfalls, introduce inflammasomes and the mechanisms by which they promote inflammation and, finally, highlight the preclinical and clinical evidence for the potential involvement of inflammasomes in PH pathobiology and how they may be targeted therapeutically

Role of Kv7 channels in responses of the pulmonary circulation to hypoxia

Hypoxic pulmonary vasoconstriction (HPV) is a beneficial mechanism that diverts blood from hypoxic alveoli to better ventilated areas of the lung, but breathing hypoxic air causes the pulmonary circulation to become hypertensive. Responses to airway hypoxia are associated with depolarization of smooth muscle cells in the pulmonary arteries and reduced activity of K(+) channels. As Kv7 channels have been proposed to play a key role in regulating the smooth muscle membrane potential, we investigated their involvement in the development of HPV and hypoxia-induced pulmonary hypertension. Vascular effects of the selective Kv7 blocker, linopirdine, and Kv7 activator, flupirtine, were investigated in isolated, saline-perfused lungs from rats maintained for 3–5 days in an isobaric hypoxic chamber (Fi(O(2)) = 0.1) or room air. Linopirdine increased vascular resistance in lungs from normoxic, but not hypoxic rats. This effect was associated with reduced mRNA expression of the Kv7.4 channel α-subunit in hypoxic arteries, whereas Kv7.1 and Kv7.5 were unaffected. Flupirtine had no effect in normoxic lungs but reduced vascular resistance in hypoxic lungs. Moreover, oral dosing with flupirtine (30 mg/kg/day) prevented short-term in vivo hypoxia from increasing pulmonary vascular resistance and sensitizing the arteries to acute hypoxia. These findings suggest a protective role for Kv7.4 channels in the pulmonary circulation, limiting its reactivity to pressor agents and preventing hypoxia-induced pulmonary hypertension. They also provide further support for the therapeutic potential of Kv7 activators in pulmonary vascular disease