The morbidity and mortality related to respiratory tract diseases is enormous, with hundreds of millions of individuals afflicted and four million people dying each year. Understanding the immunological processes in the mucosa that govern outcome following pathogenic encounter could lead to novel therapies. There is a need to study responses at mucosal surfaces in humans for two reasons: (i) Immunological findings in mice, or other animals, often fail to translate to humans. (ii) Compartmentalization of the immune system dictates a need to study sites where pathogens reside. In this manuscript, we describe two novel non-invasive nasal mucosal microsampling techniques and their use for measuring immunological parameters: 1) using nasal curettes to collect cells from the inferior turbinate and; 2) absorptive matrices to collect nasal lining fluid. Both techniques were well tolerated and yielded reproducible and robust data. We demonstrated differences in immune populations and activation state in nasal mucosa compared to blood as well as compared to nasopharyngeal lumen in healthy adults. We also found superior cytokine detection with absorptive matrices compared to nasal wash. These techniques are promising new tools that will facilitate studies of the immunological signatures underlying susceptibility and resistance to respiratory infections.

Rationale-The Global Burden of Disease Study suggests almost 3.5 million people die as a consequence of household air pollution every year. Respiratory diseases including chronic obstructive pulmonary disease and pneumonia in children are strongly associated with exposure to household air pollution. Smoke from burning biomass fuels for cooking, heating, and lighting is the main contributor to high household air pollution levels in low-income countries like Malawi. A greater understanding of biomass fuel use in Malawi should enable us to address household air pollution-associated communicable and noncommunicable diseases more effectively.Objectives-To conduct a cross-sectional analysis of biomass fuel use and population demographics among adults in Blantyre, Malawi.Methods-We used global positioning system-enabled personal digital assistants to collect data on location, age, sex, marital status, education, occupation, and fuel use. We describe these data and explore associations between demographics and reported fuel type. Measurements and MainResults-A total of 16,079 adults participated (nine households refused); median age was 30 years, there was a similar distribution of men and women, 60% were married, and 62% received secondary school education. The most commonly reported occupation for men and women was "salaried employment" (40.7%) and "petty trader and marketing" (23.5%), respectively. Charcoal (81.5% of households), wood (36.5%), and electricity (29.1%) were the main fuels used at home. Only 3.9% of households used electricity exclusively. Lower educational and occupational attainment was associated with greater use of wood.Correspondence and requests for reprints should be addressed to Kevin Mortimer, M.A., M.B., B.Chir., M.Sc., Ph.D., Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Kevin.Mortimer@liverpool.ac.uk. Author Contributions: M.J.N., principal investigator; K.M., investigator; S.B.G., investigator; K.C.P., analysis of enumeration data; A.N., project manager; M.M., data manager; G.N., project advisor; K.J.D., epidemiology advisor.Author disclosures are available with the text of this article at www.atsjournals.org. Conclusions-This large cross-sectional study has identified extensive use of biomass fuels in a typical sub-Saharan Africa periurban population in which women and people of lower socioeconomic status are disproportionately affected. Biomass fuel use is likely to be a major driver of existing communicable respiratory disease and the emerging noncommunicable disease (especially respiratory and cardiovascular) epidemic in this region. Our data will help inform the rationale for specific intervention studies and the development of appropriately targeted public health strategies to tackle this important and poverty-related global health problem. Europe PMC Funders Group Keywordsbiomass fuel use; noncommunicable diseases; household air pollution Household air pollution is an important health risk that is intrinsically linked with poverty. Analysis from...

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules.Trial registrationThe study was registered on EudraCT (2014-004634-26)FundingThe study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.

BackgroundIn developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at primary health care level are weak and patients turn to unskilled informal health providers to seek health care. Delayed diagnosis and treatment of these diseases facilitates increased severity and tuberculosis transmission.The World Health Organisation developed the Practical Approach to Lung Health strategy which has been shown to improve the management of both tuberculosis and chronic airways disease. The guidelines address the need for integrated guidelines for tuberculosis and chronic airways disease. Engaging with informal health providers has been shown to be effective in improving health services uptake. However, it is not known whether engaging community informal health providers would have a positive impact in the implementation of the Practical Approach to Lung Health strategy. We will use a cluster randomised controlled trial to determine the effect of using the two interventions to improve case detection and treatment of patients with tuberculosis and chronic airways disease.MethodsA three-arm cluster randomised trial design will be used. A primary health centre catchment population will form a cluster, which will be randomly allocated to one of the arms. The first arm personnel will receive the Practical Approach to Lung Health strategy intervention. In addition to this strategy, the second arm personnel will receive training of informal health providers. The third arm is the control. The effect of interventions will be evaluated by community surveys. Data regarding the diagnosis and management of chronic cough will be gathered from primary health centres.DiscussionThis trial seeks to determine the effect of Informal Health Provider and Practical Approach to Lung Health interventions on the detection and management of chronic airways disease and tuberculosis at primary care level in Malawi.Trial registrationThe unique identification number for the registry is PACTR201411000910192 – 21 November 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1068-4) contains supplementary material, which is available to authorized users.

No abstract

No abstract

Background Cardiotoxic therapy causes significant morbidity and mortality in patients (pts) treated for Hodgkin lymphoma (HL). Cardiovascular (CVS) risk calculators do not include cancer therapy despite epidemiological data demonstrating increased risk. We have assessed modifiable CVS risk factors and predicted risk of CVS disease in a cohort of HL survivors. Hypothesis Cardiovascular risk calculators will not identify high risk in young HL survivors. Methods Pts now aged ≤50 treated with doxorubicin and/or radiotherapy (RT) to cardiac tissue for HL >5 years ago were identified. Telephone review of CVS risk factors was offered to pts taking statins or already diagnosed with cerebrovascular or CVS disease. Remaining pts were offered clinical review to assess BMI, blood pressure, cholesterol and HbA1c. Carotid-radial pulse wave velocity (PWV) was measured if available. CVS risk was predicted using international risk calculators (European SCORE, QRISK3, Framingham). Results 160 eligible pts were identified. Median age was 43 years (26–50) and 52% were female. Median time since treatment was 182 months (61–367). Pts received doxorubicin (n=150), with RT (n=97) or RT alone (n=10). Pts were excluded from study due to severe medical condition (n=8), recurrence (n=1), relocation (n=3) or death (n=1). Data were gathered at clinical review (n=70) or telephone review (n=26). Existing cardiovascular diagnoses included hypertension (n=5), transient ischaemic attack (n=2), valvular disease (n=3), heart failure (n=1), atrial fibrillation (n=2), complete heart block (n=1) and coronary artery disease (n=1). At clinical review 51% pts had 3 or more modifiable risk factors with a median of 3 (0–5) per pt. Total cholesterol was >5.0 mmol/L in 58% of patients with a median of 5.2 mmol/L (3.2–8.6). Median systolic blood pressure was 125.5 mmHg (103–164). Median body mass index was 26.3 kg/m-2 (18.6–56.1) with 60% of patients classed as overweight or obese.Advice was offered to all smokers (9%), pts that drank alcohol above UK recommended levels (20%) or exercised below the recommended amount (60%). Risk calculators classified 1.4% (QRISK3) and 10% (Framingham) of pts at high risk of CVS disease and 0% (European SCORE) at high risk of CVS mortality. Pulse wave velocity measured in 34 pts was elevated (>8 m/s) in 76% of cases with a median 10.2 m/s (2.3–16.8). Conclusions Numerous modifiable CVS risk factors were identified in an HL survivor population known from epidemiological studies to be at high risk of CVS morbidity/mortality. None of the CVS risk calculators identified this high risk. Intriguing data indicate PWV may represent an accessible early indicator of CVS dysfunction. These data prompt comprehensive assessment and management of CVS risk factors in cancer survivors and review of the use of risk calculators in this population. Acknowledgement/Funding The Christie NHS Foundation Trust

No abstract