In Vitro Evaluation of Aerosols Delivered via the Nasal Route.

BACKGROUND: Infants and young children are obligate nose breathers; therefore, a transnasal route seems the logical delivery method of inhaled aerosols. The efficiency of aerosol delivery depends on several factors, such as interface, type of nebulizer, and patient age and breathing pattern. We hypothesized that the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head model and breathing pattern of an older child would result in a higher lung dose. We also hypothesized that the use of an anatomically correct model would more accurately reflect lung dose than models that do not include airways. METHODS: A model comprising a breathing simulator and an anatomically correct model of a 7-month-old infant and a 5-y-old child with an interposed collection filter (lung dose) were used. Breathing patterns of a newborn, infant, and child were used with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol mass was determined via spectrophotometer (276 nm). RESULTS: Lung dose varied between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh nebulizer. The front-loaded mask was the most efficient interface. We also found that higher tidal volumes were associated with higher lung doses and that the use of a larger airway model resulted in a lower lung dose. Finally, the model showed a good correlation with in vivo data and rendered lung doses severalfold lower than previous data obtained with oral models. CONCLUSIONS: Careful pairing of the aerosol generator and interface is very important during transnasal aerosol delivery.

Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections.

We developed an immunodeficiency scoring index for respiratory syncytial virus (ISI-RSV) infection, based on a cohort of 237 allogeneic hematopoietic cell transplant (allo-HCT) recipients, that can predict the risk of progression to lower respiratory tract infection (LRTI) and RSV-associated mortality. A weighted index was calculated using adjusted hazard ratios for immunodeficiency markers. Based on the ISI-RSV (range, 0-12), patients were stratified into low (0-2), moderate (3-6), and high (7-12) risk groups. A significant trend of increasing incidence of LRTI and RSV-associated mortality was observed as the risk increased from low to moderate to high (P < .001). Patients in the high-risk group had the greatest benefit of ribavirin-based therapy at the upper respiratory tract infection stage and the highest risk for progression to LRTI and death when antiviral therapy was not given (6.5 [95% confidence interval (CI), 1.8-23.6] and 8.1 [95% CI, 1.1-57.6], respectively). The ISI-RSV is designed to stratify allo-HCT recipients with RSV infection into groups according to their risk for progression to LRTI and RSV-associated mortality. Identification of high-risk groups using this index would distinguish patients who would benefit the most from antiviral therapy, mainly with aerosolized ribavirin. The ISI-RSV should be validated in a multi-institutional study.

Respiratory syncytial virus infections in children with cancer.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in children, especially those with cancer. Data on RSV infections in this vulnerable population is limited. We conducted a retrospective study of all RSV infections in children with cancer from 1998 to 2009 to determine characteristics and outcomes of these infections, identify risk factors for LRTI and mortality, and the effect of antiviral therapy on these outcomes. We identified 59 patients with a median age of 5 years; 53% had hematologic malignancy, 32% were hematopoietic stem cell transplant recipients, 39% had received corticosteroids, and 76% cytotoxic chemotherapy within 1 month before RSV infection. LRTI developed in 22 (37%) patients with a trend of higher rate in males (odds ratio=2.57 [0.86-7.62], P=0.09) and children with lymphocytopenia (odds ratio=2.95 [0.86-10.12], P=0.085). No significant differences were observed in the rates of progression to LRTI (3/10 [30%] vs. 19/49 [39%], P=0.729) and RSV-associated mortality (0/10 [0%] vs. 3/49 [6%], P=0.422) for patients receiving antiviral therapy at upper respiratory tract infection stage compared with those who did not. However, patients with LRTI had significantly better outcomes when treated with aerosolized ribavirin plus immunomodulators (mainly palivizumab) when compared with aerosolized ribavirin alone (mortality rates: 0/6 [0%] vs. 3/4 [75%], P=0.03). Ribavirin did not show any benefit in reducing LRTI or mortality; however, addition of palivizumab to the treatment regimen may be potentially beneficial, especially for children with LRTI.

Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections.

OBJECTIVES: Respiratory syncytial virus (RSV) infections are well recognized as a significant cause of morbidity and mortality in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients. We evaluated the spectrum of clinical manifestations, management (including ribavirin-based antiviral therapy) and outcomes of RSV infections and determined the risk factors associated with RSV lower respiratory tract infection (LRTI) and all-cause mortality. METHODS: In this retrospective study, we analysed clinical data from all laboratory-confirmed RSV infections in allo-HSCT recipients (n = 280) who presented at our institution from January 1996 to May 2009. RESULTS: Of the 280 patients, 80 (29%) developed LRTI within 20 days (median 1 day, range 0-19 days) and 44 (16%) died within 90 days (median 26 days, range 1-82 days) from RSV diagnosis. Multivariable logistic regression analyses identified several significant risk factors associated with RSV LRTI and all-cause mortality, including age, male sex, neutropenia, lymphocytopenia and lack of ribavirin-based antiviral therapy at the upper respiratory tract infection (URTI) stage. Aerosolized ribavirin-based therapy at the URTI stage was the single most significant factor in reducing the risk of RSV LRTI (83%), all-cause mortality (57%) and RSV-associated mortality (87%) in these patients (P < 0.05), irrespective of the year of RSV diagnosis. CONCLUSIONS: Our results demonstrate that RSV infections are a significant cause of morbidity and mortality in high-risk allo-HSCT recipients and ribavirin-based antiviral therapy at the URTI stage had a positive impact on both outcomes in this vulnerable population with multiple risk factors.

Characteristics and outcomes of pandemic 2009/H1N1 versus seasonal influenza in children with cancer.

BACKGROUND: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. METHODS: Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. RESULTS: When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. CONCLUSIONS: Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.