Asthma and COVID-19: is asthma a risk factor for severe outcomes?

When I first read the manuscript that accompanies this editorial, upon its online publication on February 19th 2020(1), COVID-19 had already killed 2118 people in China, but only one person in Europe - an 80-year-old tourist from China, who died in France on the 15th February. I read the manuscript with grim fascination, as it was clear that SARS-CoV-2 had spread very rapidly in China which already had 74,576 cases and in South Korea which already had 58 cases, and that it was then invading Europe also, as France already had 12 cases, Germany 16, the UK 9, Italy 3, Spain 2 and other countries too

Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care.

BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1-3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses

Connecting low- and high-mass star formation: the intermediate-mass protostar IRAS 05373+2349 VLA 2

Until recently, there have been few studies of the protostellar evolution of intermediate-mass (IM) stars, which may bridge the low- and high-mass regimes. This paper aims to investigate whether the properties of an IM protostar within the IRAS 05373+2349 embedded cluster are similar to that of low- and/or high-mass protostars. We carried out Very Large Array as well as Combined Array for Research in Millimeter Astronomy continuum and 12CO(J=1–0) observations, which uncover seven radio continuum sources (VLA 1–7). The spectral index of VLA 2, associated with the IM protostar is consistent with an ionized stellar wind or jet. The source VLA 3 is coincident with previously observed H2 emission line objects aligned in the north–south direction (P.A. −20 to −12◦), which may be either an ionized jet emanating from VLA 2 or (shock-)ionized cavity walls in the large-scale outflow from VLA 2. The position angle between VLA 2 and 3 is slightly misaligned with the large-scale outflow we map at ∼5-arcsec resolution in 12CO (P.A. ∼30◦), which in the case of a jet suggests precession. The emission from the mm core associated with VLA 2 is also detected; we estimate its mass to be 12–23 M , depending on the contribution from ionized gas. Furthermore, the large-scale outflow has properties intermediate between outflows from low- and high-mass young stars. Therefore, we conclude that the IM protostar within IRAS 05373+2349 is phenomenologically as well as quantitatively intermediate between the low- and high-mass domains

Reprogramming of lysosomal gene expression by interleukin-4 and Stat6.

BACKGROUND: Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological contexts in which lysosomal genes are coordinately regulated and to identify transcription factors involved in this control. RESULTS: As transcription factors and their target genes are often co-regulated, we performed meta-analyses of array-based expression data to identify regulators whose mRNA profiles are highly correlated with those of a core set of lysosomal genes. Among the ~50 transcription factors that rank highest by this measure, 65% are involved in differentiation or development, and 22% have been implicated in interferon signaling. The most strongly correlated candidate was Stat6, a factor commonly activated by interleukin-4 (IL-4) or IL-13. Publicly available chromatin immunoprecipitation (ChIP) data from alternatively activated mouse macrophages show that lysosomal genes are overrepresented among Stat6-bound targets. Quantification of RNA from wild-type and Stat6-deficient cells indicates that Stat6 promotes the expression of over 100 lysosomal genes, including hydrolases, subunits of the vacuolar H⁺ ATPase and trafficking factors. While IL-4 inhibits and activates different sets of lysosomal genes, Stat6 mediates only the activating effects of IL-4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL-4. CONCLUSIONS: The current data establish Stat6 as a broadly acting regulator of lysosomal gene expression in mouse macrophages. Other regulators whose expression correlates with lysosomal genes suggest that lysosome function is frequently re-programmed during differentiation, development and interferon signaling

Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae

Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans