Amparo Solé

Diagnóstico y tratamiento de las bronquiectasias

Bronchiectasis is the end result of several different diseases that share principles of management. The clinical course usually involves chronic bronchial infection and inflammation, which are associated with progression. The cause of bronchiectasis should always be investigated, particularly when it can be treated. We recommend evaluating etiology, symptoms, bronchial colonization and infection, respiratory function, inflammation, structural damage, nutritional status, and quality of life in order to assess severity and to monitor clinical course. Care should be supervised by specialized units, at least in cases of chronic bronchial infection, recurrent exacerbations, or when there is a cause that is likely to respond to treatment. Improving symptoms and halting progression are the goals of management, which is based on treatment of the underlying cause and of acute or chronic infections and on the drainage of secretions. Complications that arise must also be treated. Antibiotic prescription is guided by how well infection is being controlled, and this is indicated by the color of sputum and a reduction in the number of exacerbations. We recommend inhaled antibiotics in cases of chronic bronchial infection that does not respond to oral antibiotics, when these cause side effects, or when the cause is Pseudomonas species or other bacteria resistant to oral antibiotics. Inhaled administration is also advisable to treat initial colonization by Pseudomonas species.

Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries

Background Individuals with chronic diseases and parent caregivers are at increased risk for symptoms of depression and anxiety. Prevalence of psychological symptoms was evaluated in adolescents and adults with cystic fibrosis (CF) and parent caregivers across nine countries. Methods Patients with CF, ages 12 years and older, and caregivers of children with CF, birth to18 years of age, completed measures of depression and anxiety across 154 CF centres in Europe and the USA. Psychological symptoms were compared across countries using χ2. Logistic regression examined extent of comorbid symptoms, predictors of depression and anxiety, and concordance between parent and adolescent symptomatology. Results Psychological symptoms were reported by 6088 patients with CF and 4102 parents. Elevated symptoms of depression were found in 10% of adolescents, 19% of adults, 37% of mothers and 31% of fathers. Elevations in anxiety were found in 22% of adolescents, 32% of adults, 48% of mothers and 36% of fathers. Overall, elevations were 2–3 times those of community samples. Participants reporting elevated anxiety were more likely to report depression (ORs: adolescents=14.97, adults=13.64, mothers=15.52, fathers=9.20). Significant differences in reports of depression and anxiety were found by patient age and parent respondent. Concordance between 1122 parent–teen dyads indicated that adolescents whose parents reported depression were more likely to be elevated on depression (OR=2.32). Similarly, adolescents whose parents reported anxiety were more likely to score in the elevated range on the anxiety measure (OR=2.22). Conclusions Symptoms of depression and anxiety were elevated in both patients with CF and parents across several European countries and the USA. Annual screening of psychological symptoms is recommended for both patients and parents.

Everolimus versus azathioprine in maintenance lung transplant recipients: An international, randomized, double-blind clinical trial

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double‐blind clinical trial, 213 BOS‐free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1–3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[ΔFEV1 >15%], graft loss, death or loss to follow‐up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of ΔFEV1 >15%, ΔFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Fungal infections after lung transplantation

Lung transplantation (LT) is now considered to be the standard therapeutic intervention in some patients with end-stage pulmonary disease. Infectious complications after LT are relatively common due to the aggressive immunosuppression used in these receptors and local host factors derived from this type of transplant. The incidence of fungal infections after LT ranges up to 30%. However, the incidence of invasive mycoses has declined over the past decade. These mycoses are associated with high overall mortality rates despite increase of the antifungal armamentarium in the last years. Candida and Aspergillus spp produce most of these infections, but unusual moulds such as Scedosporium spp are increasingly recognized as opportunistic pathogens in LT. This review highlights the changing spectrum of invasive fungal infections, risk factors, antifungal prophylaxis, diagnosis, and treatment after LT.

Diagnosis and Treatment of Bronchiectasis

Bronchiectasis is the end result of several different diseases that share principles of management. The clinical course usually involves chronic bronchial infection and inflammation, which are associated with progression. The cause of bronchiectasis should always be investigated, particularly when it can be treated. We recommend evaluating etiology, symptoms, bronchial colonization and infection, respiratory function, inflammation, structural damage, nutritional status, and quality of life in order to assess severity and to monitor clinical course. Care should be supervised by specialized units, at least when there is a history of chronic bronchial infection, recurrent exacerbations, or a cause that is likely to respond to treatment. Improving symptoms and halting progression are the goals of management, which is based on treatment of the underlying cause and of acute or chronic infections and on the drainage of secretions. Complications that arise must also be treated. Antibiotic prescription is guided by monitoring how well infection is being controlled, and this is indicated by the color of sputum and a reduction in the number of exacerbations. We recommend inhaled antibiotics when bronchial infection is chronic and does not respond to oral antibiotics or when these cause side effects, or when the cause is Pseudomonas species or other bacteria resistant to oral antibiotics. Inhaled administration is also advisable to treat initial colonization by Pseudomonas species.

Efficiency and Safety of Inhaled Amphotericin B Lipid Complex (Abelcet) in the Prophylaxis of Invasive Fungal Infections Following Lung Transplantation

BACKGROUND Invasive fungal infections (IFIs) in patients undergoing lung transplantation (LT) are associated with significant mortality. Previous studies have shown the efficacy of aerosolized amphotericin B deoxycholate and oral fluconazole for antifungal prophylaxis. Evolving data show a potential advantage of prophylaxis with lipid-based formulations of amphotericin B in the prevention of IFIs. We reviewed the incidence of IFIs among patients receiving aerosolized amphotericin B lipid complex (ABLC) in LT. METHODS We undertook a retrospective review of the results of our antifungal protocol in a cohort of 60 LT patients. We analyzed the efficiency, safety, and tolerability of 50 mg of aerosolized ABLC administered postoperatively for IFI prophylaxis once every 2 days for 2 weeks and then once per week for at least 13 weeks. In addition, these transplanted patients received fluconazole (200 mg/d) during the first 21 days posttransplant. The prophylaxis-related efficiency and safety were quantified for IFIs and adverse events (AEs) for 6 months after study drug initiation. RESULTS Prophylaxis was efficient in 59 (98.3%) patients. Only one patient developed a possible IFI, due to Aspergillus fumigatus. Four patients presented nausea and vomiting as an AE, although aerosolized amphotericin B was ongoing. CONCLUSIONS Nebulized ABLC was effective, safe, and well tolerated for the prophylaxis of aspergillosis in lung transplant patients during the early posttransplant period.

Visceral leishmaniasis in lung transplantation

Infection by intracellular microorganisms with a special geographic distribution, such as Leishmania spp, has been reported in a limited number of patients undergoing solid-organ transplant (SOT). No cases of Leishmania spp infection in lung transplant patients were found in a review of the literature. In our series of 222 lung or heart and lung transplantations performed from February 1990 to October 2002, two cases of visceral leishmaniasis (VL) were diagnosed and treated with liposomal amphotericin B. All cases reported to date in transplant patients, including the ones discussed here, occurred in people living in or traveling to countries in the Mediterranean area. We therefore consider it advisable to include serological testing for latent infection due to Leishmania spp in pretransplantation screening for our geographical setting, despite the limited return of this strategy.

A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients.

Seventy‐six cytomegalovirus (CMV)‐seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post‐transplantation and follow‐up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue‐invasive disease (5.2% vs. 4.6%, p = ns), longer time‐to‐onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis.

Guidelines for the prevention of invasive mould diseases caused by filamentous fungi by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)

Invasive fungal infections (IFIs) caused by filamentous fungi still have high rates of mortality, associated with difficulties in early detection of the infection and therapeutic limitations. Consequently, a useful approach is to prevent patients at risk of fungal infection from coming into contact with conidia of Aspergillus and other mould species. This document describes the recommendations for preventing IFI caused by filamentous fungi worked out by Spanish experts from different medical and professional fields. The article reviews the incidence of IFI in different risk populations, and questions related to environmental measures for prevention, control of hospital infections, additional procedures for prevention, prevention of IFI outside of hospital facilities and antifungal prophylaxis are also analysed.

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.