Long-term air pollution exposure and risk of SARS-CoV-2 infection: A UK-wide cohort study.

BACKGROUND: The association between air quality and risk of SARS-CoV-2 infection is poorly understood. We investigated this association using serological individual-level data adjusting for a wide range of confounders, in a large population-based cohort (COVIDENCE UK). METHODS: We assessed the associations between long-term (2015-19) nitrogen dioxide (NO2) and fine particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), exposures with SARS-CoV-2 infection, level of antibody response among those infected, and COVID-19 disease severity. We used serological data from 10,489 participants in the COVIDENCE UK cohort, and estimated annual average air pollution exposure at each participant's home postcode. RESULTS: After controlling for potential confounders, we found a positive association between 5-year NO2 and PM2.5 exposures and the risk of seropositivity: 10 unit increase in NO2 (µg/m3) was associated with an increasing risk of seropositivity by 1.092 (95% CI 1.02 to 1.17; p-for-trend 0.012). For PM2.5, 10 unit increase (µg/m3) was associated with an increasing risk of seropositivity by 1.65 (95% CI 1.015-2.68; p-for-trend 0·049). In addition, we found that NO2 was positively associated with higher antibody titres (p-for-trend 0·013) among seropositive participants, with no evidence of an association for PM2.5. CONCLUSION: Our findings suggest that the long-term burden of air pollution increased the risks of SARS-CoV-2 infection and has important implications for future pandemic preparedness. This evidence strengthens the case for reducing long-term air pollution exposures to reduce the vulnerability of individuals to respiratory viruses.

Characteristics of patients with asthma overprescribed short-acting beta-agonist (SABA) reliever inhalers stratified by blood eosinophil count in North East London: a cross-sectional observational study.

BACKGROUND: Overprescription of short-acting beta-agonist (SABA) inhalers and blood eosinophil count have strong associations with exacerbation risk in asthma. However, in the authors' recent publication only a minority of patients overprescribed SABA (≥6 inhalers in 12 months) were eosinophilic (≥0.3 x 109 cells/l). AIM: To compare the characteristics of eosinophilic and non-eosinophilic patients with asthma overprescribed SABA inhalers, and identify latent classes using clinical variables available in primary care. DESIGN & SETTING: Cross-sectional analysis of patients with asthma in North East London, England, using primary care electronic health record data. METHOD: Unadjusted and adjusted multi-variate regression models and latent class analysis. RESULTS: Eosinophilia was significantly less likely in female patients (P = 0.004), those with multiple mental health comorbidities (P<0.001), and those with SABA on repeat prescription (P<0.001). Latent class analysis identified the following three classes of patients overprescribed SABA: class 1, which represents classical uncontrolled asthma (oral steroids required for exacerbations, step 2-3 asthma medications, high probability of being eosinophilic); class 2, which represents mild asthma (low exacerbation frequency, low asthma medication step, low probability of being eosinophilic); and class 3, which represents difficult asthma (high exacerbation frequency despite high-strength preventer inhalers, low probability of being eosinophilic). The mild asthma class was the largest. CONCLUSION: Many patients being overprescribed SABA were non-eosinophilic with a low exacerbation frequency, suggesting disproportionately high SABA prescription compared with other asthma control markers. Potential reasons for high SABA prescription in these patients included repeat prescription (being dispensed but not taken) and use of SABA for non-asthma breathlessness (for example, breathing pattern disorders with anxiety). Further research is needed into management of SABA overuse in patients without other markers of uncontrolled asthma.

Reducing short-acting beta-agonist overprescribing in asthma: lessons from a quality-improvement prescribing project in East London.

BACKGROUND: Excess prescription and use of short-acting beta-agonist (SABA) inhalers is associated with poor asthma control and increased risk of hospital admission. AIM: To quantify the prevalence and identify the predictors of SABA overprescribing. DESIGN AND SETTING: A cross-sectional study using anonymised clinical and prescribing data from the primary care records in three contiguous East London boroughs. METHOD: Primary care medical record data for patients aged 5-80 years, with 'active' asthma were extracted in February 2020. Explanatory variables included demography, asthma management, comorbidities, and prescriptions for asthma medications. RESULTS: In the study population of 30 694 people with asthma, >25% (1995/7980), were prescribed ≥6 SABA inhalers in the previous year. A 10-fold variation between practices (<6% to 60%) was observed in the proportion of patients on ≥6 SABA inhalers/year. By converting both SABAs and inhaled corticosteroids (ICSs) to standard units the accuracy of comparisons was improved across different preparations. In total, >25% of those taking ≥6 SABAs/year were underusing ICSs, this rose to >80% (18 170/22 713), for those prescribed <6 SABAs/year. Prescription modality was a strong predictor of SABA overprescribing, with repeat dispensing strongly linked to SABA overprescribing (odds ratio 6.52, 95% confidence interval = 4.64 to 9.41). Increasing severity of asthma and multimorbidity were also independent predictors of SABA overprescribing. CONCLUSION: In this multi-ethnic population a fifth of practices demonstrate an overprescribing rate of <20% a year. Based on previous data, supporting practices to enable the SABA ≥12 group to reduce to 4-12 a year could potentially save up to 70% of asthma admissions a year within that group.

Understanding flow properties of mannitol powder at a range of temperature and humidity.

Inadequate flowability of powders in industries during handling can cause many problems. For example, lack of flow from hoppers, poor tablet weight consistency, and low production rate in tableting. Many factors are known to commonly affect flow properties of powders, such as temperature, humidity and conditioning duration. In this paper, flow properties of a mannitol powder, which was conditioned between 24 and 72 h at various high relative humidities and temperature, were measured using a shear tester. A statistical model was developed to investigate the relative importance of these variables on the mannitol flow properties. The developed model showed all independent variables are significant in estimating bulk cohesion. Two separate approaches were used to evaluate inter-particle forces in the bulk, and how these changed with environmental conditions. First, inter-particle forces were inferred from the measured bulk properties using the Rumpf model approach. Secondly, inter-particle forces were predicted based on a model of moisture present on the particle surface using a combination of Kelvin model with the Laplace-Young (KLY) equation. The second approach also involved a new method to measure surface energy of mannitol powder based on measurements using Finite Dilution Inverse Gas Chromatography (FD-IGC). The surface energies of the mannitol powder were measured at high temperature (35 °C) and at different range of relative humidities. In spite of the fundamentally different approaches to the two ways of inferring inter-particles forces, these forces came out within less than 1.5:1 in magnitude. The Rumpf approach from bulk behaviour data obviously reflected the measured change in behaviour with humidity in particular, but this was not predicted from the KLY approach, however the likely reasons for this are postulated and recommendations for improvement are made.