Atypical Bacteria and Macrolides in Asthma

<p/> <p><it>Chlamydophila pneumoniae </it>and <it>Mycoplasma pneumoniae </it>are common pathogens causing acute illness in both the upper and lower airways. Several observations are supportive of a possible causative role of these pathogens in asthma; however, more evidence is required before this becomes meaningful in clinical practice. Atypical bacteria can enhance airway hyperresponsiveness and inflammation, both of which have been associated with exacerbations in patients with preexisting asthma. It is less clear whether the above mechanisms might also be responsible for the development of asthma. Difficulties in accurately diagnosing these infections contribute to such uncertainty. In the present report, evidence of the involvement of <it>Chlamydophila </it>and <it>Mycoplasma </it>infection in the development and the progression of asthma are reviewed.</p

IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy

Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma

Impact of COVID-19 on Pediatric Asthma : Practice Adjustments and Disease Burden

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters. (C) 2020 American Academy of Allergy, Asthma & Immunology.Peer reviewe

Two-loop non-planar hexa-box integrals with one massive leg

Based on the Simplified Differential Equations approach, we present results for the two-loop non-planar hexa-box families of master integrals. We introduce a new approach to obtain the boundary terms and establish a one-dimensional integral representation of the master integrals in terms of Generalised Polylogarithms, when the alphabet contains non-factorisable square roots. The results are relevant to the study of NNLO QCD corrections for $W,Z$ and Higgs-boson production in association with two hadronic jets.Comment: Ancillary files attached. Mathematica notebook files updated. Accepted for publication in JHE

Synthesis of inositol phosphate-based competitive antagonists of inositol 1,4,5-trisphosphate receptors.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels that are widely expressed in animal cells, where they mediate the release of Ca(2+) from intracellular stores evoked by extracellular stimuli. A diverse array of synthetic agonists of IP3Rs has defined structure-activity relationships, but existing antagonists have severe limitations. We combined analyses of Ca(2+) release with equilibrium competition binding to IP3R to show that (1,3,4,6)IP4 is a full agonist of IP3R1 with lower affinity than (1,4,5)IP3. Systematic manipulation of this meso-compound via a versatile synthetic scheme provided a family of dimeric analogs of 2-O-butyryl-(1,3,4,6)IP4 and (1,3,4,5,6)IP5 that compete with (1,4,5)IP3 for binding to IP3R without evoking Ca(2+) release. These novel analogs are the first inositol phosphate-based competitive antagonists of IP3Rs with affinities comparable to that of the only commonly used competitive antagonist, heparin, the utility of which is limited by off-target effects.Supported by a Senior Investigator Award from the Wellcome Trust 101844 (to C.W.T.), Biotechnology and Biological Sciences Research Council UK and the German Academic Exchange Service (to V.K.). A.E.K. thanks the Research Committee of AUTh for financial support. C.W.T. and V.K. thank Dr S. B. Shears (N.I.E.H.S, U.S.A.) for his helpful advice.This is the final version of the article. It first appeared from the Royal Chemistry Society via http://dx.doi.org/10.1039/C5OB02623

Evolution of airway inflammation in preschoolers with asthma : results of a two-year longitudinal study

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4-6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0-8.6; 6.0, CI: 2.8-12.0; 8.0, CI: 4.0-14.0; 8.5, CI: 4.4-14.5 ppb, respectively) increased with age (correlation p <= 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma