No abstract

SUMMARYThe role of in¯ammatory effector cells in the pathogenesis of airway allergy has been the subject of much investigation. However, whether systemic factors are involved in the development of local responses in both upper and lower airways has not been fully clari®ed. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis in a murine model sensitized to ovalbumin (OVA). Both upper-and lower-airway physiological responsiveness and in¯ammatory changes were assessed, as well as bone marrow progenitor responses, by culture and immunohistological methods. Signi®cant nasal symptoms and hyper-responsiveness appeared after intranasal OVA challenge (P<0 . 0001 and P<0 . 01, respectively), accompanied with signi®-cant nasal mucosal changes in CD4+ cells (P<0 . 001), interleukin (IL)-4 + cells (P<0 . 01), IL-5 + cells (P<0 . 01), basophilic cells (P<0 . 02) and eosinophils (P<0 . 001), in the complete absence of hyper-responsiveness or in¯ammatory changes in the lower airway. In the bone marrow, there were signi®cant increases in CD34 + cells, as well as in eosinophils and basophilic cells. In the presence in vitro of mouse recombinant IL-5, IL-3 or granulocyte±macrophage colony-stimulating factor (GM-CSF), the level of bone marrow eosinophil/basophil (Eo/Baso) colony-forming cells increased signi®cantly in the OVA-sensitized group. We conclude that, in this murine model of allergic rhinitis, haemopoietic progenitors are upregulated, which is consistent with the involvement of bone marrow in the pathogenesis of nasal mucosal in¯ammation. Both local and systemic events, initiated in response to allergen provocation, may be required for the pathogenesis of allergic rhinitis. Understanding these events and their regulation could provide new therapeutic targets for rhinitis and asthma.

IntroductionA major barrier to improving childhood cancer survival is the perception that paediatric oncology services are too costly for low-income and middle-income country (LMIC) health systems. We conducted a systematic review to synthesise existing evidence on the costs and cost-effectiveness of treating childhood cancers in LMICs.MethodsWe searched multiple databases from their inception to March 2019. All studies reporting costs or cost-effectiveness of treating any childhood cancer in an LMIC were included. We appraised included articles using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Where possible, we extracted or calculated the cost per disability-adjusted life year (DALY) averted using reported survival and country-specific life expectancy. Cost/DALY averted was compared with per capita gross domestic product (GDP) as per WHO-Choosing Interventions that are Cost-Effective guidelines to determine cost-effectiveness.ResultsOf 2802 studies identified, 30 met inclusion criteria. Studies represented 22 countries and nine different malignancies. The most commonly studied cancers were acute lymphoblastic leukaemia (n=10), Burkitt lymphoma (n=4) and Wilms tumour (n=3). The median CHEERS checklist score was 18 of 24. Many studies omitted key cost inputs. Notably, only 11 studies included healthcare worker salaries. Cost/DALY averted was extracted or calculated for 12 studies and ranged from US$22 to US$4475, although the lower-end costs were primarily from studies that omitted key cost components. In all 12, cost/DALY averted through treatment was substantially less than country per capita GDP, and therefore considered very cost-effective.ConclusionMany included studies did not account for key cost inputs, thus underestimating true treatment costs. Costs/DALY averted were nonetheless substantially lower than per capita GDP, suggesting that even if all relevant inputs are included, LMIC childhood cancer treatment is consistently very cost-effective. While additional rigorous economic evaluations are required, our results can inform the development of LMIC national childhood cancer strategies.