Asthma is the most common chronic respiratory disease in the UK; however, the misdiagnosis rate is substantial. The lack of consistency in national guidelines and the paucity of data on the ...performance of diagnostic algorithms compound the challenges in asthma diagnosis. Asthma is a highly rhythmic disease, characterised by diurnal variability in clinical symptoms and pathogenesis. Asthma also varies day to day, seasonally and from year to year. As much as it is a hallmark for asthma, this variability also poses significant challenges to asthma diagnosis. Almost all established asthma diagnostic tools demonstrate diurnal variation, yet few are performed with standardised timing of measurements. The dichotomous interpretation of diagnostic outcomes using fixed cut-off values may further limit the accuracy of the tests, particularly when diurnal variability straddles cut-off values within a day, and careful interpretation beyond the 'positive' and 'negative' outcome is needed. The day-to-day and more long-term variations are less predictable and it is unclear whether performing asthma diagnostic tests during asymptomatic periods may influence diagnostic sensitivities. With the evolution of asthma diagnostic tools, home monitoring and digital apps, novel strategies are needed to bridge these gaps in knowledge, and circadian variability should be considered during the standardisation process. This review summarises the biological mechanisms of circadian rhythms in asthma and highlights novel data on the significance of time (the fourth dimension) in asthma diagnosis.
Shift work causes misalignment between internal circadian time and the external light/dark cycle and is associated with metabolic disorders and cancer. Approximately 20% of the working population in ...industrialised countries work permanent or rotating night shifts, exposing this large population to the risk of circadian misalignment-driven disease. Analysis of the impact of shift work on chronic inflammatory diseases is lacking. We investigated the association between shift work and asthma.
We describe the cross-sectional relationship between shift work and prevalent asthma in >280000 UK Biobank participants, making adjustments for major confounding factors (smoking history, ethnicity, socioeconomic status, physical activity, body mass index). We also investigated chronotype.
Compared with day workers, 'permanent' night shift workers had a higher likelihood of moderate-severe asthma (OR 1.36 (95% CI 1.03 to 1.8)) and all asthma (OR 1.23 (95% CI 1.03 to 1.46)). Individuals doing any type of shift work had higher adjusted odds of wheeze/whistling in the chest. Shift workers who never or rarely worked on nights and people working permanent nights had a higher adjusted likelihood of having reduced lung function (FEV
<80% predicted). We found an increase in the risk of moderate-severe asthma in morning chronotypes working irregular shifts, including nights (OR 1.55 (95% CI 1.06 to 2.27)).
The public health implications of these findings are far-reaching due to the high prevalence and co-occurrence of both asthma and shift work. Future longitudinal follow-up studies are needed to determine if modifying shift work schedules to take into account chronotype might present a public health measure to reduce the risk of developing inflammatory diseases such as asthma.
COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly ...understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14
monocyte phenotype and function. Modified features of CD14
monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker K
-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.
Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response ...in these patients presently remains ill-defined.
Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence.
We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology.
Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.
Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving.
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Lymphocytes were examined during COVID-19 and at up to 6 months of convalescenceB cell changes seen during acute COVID-19 were largely restored in convalescenceT cells from convalescent COVID-19 patients displayed persistent changesLymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes
The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in >100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health.
Shuwa et al. examine lymphocyte characteristics in acute and convalescent COVID-19 patients, detailing persistent alterations in lymphocyte phenotype up to 6 months following hospital discharge. In this report, they identify 3 subgroups of convalescent patients based on distinct lymphocyte signatures, with 1 subgroup associated with poorer clinical outcomes.
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