Multimodal, open-source big data analysis in asthma: A novel approach to inform public health programming

Asthma is a chronic respiratory disease affecting over 358 million people worldwide; for this reason analysing big data on asthma from different countries could give a more detailed picture of current disease burden. We aim to investigate the correlations between asthma and key socio-demographic parameters from different world databases. We found a direct correlation with the gross domestic product (GDP) per capita and its nominal counterpart, with wealthiest countries seen to have the highest prevalence of asthma, as also confirmed by a similar correlation with the human development index (HDI). A positive correlation was also seen between asthma prevalence and a number of socio-cultural data being representative of a good life quality index and prevalent in more developed and wealthier countries. Concerning medical data, an inverse relationship was seen between asthma prevalence and helminthiasis. Those data indicate a higher prevalence for asthma in more developed countries, where socio-economic status is higher and also the access to medical care is more ubiquitous. The approach used in our study highlighted the role of medical literacy and access to healthcare facilities in the correct diagnosis of asthma and vice versa. Our data appear to be suitable in terms of a health programming approach because of the high burden of disease worldwide

COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019 (COVID-19). It has been hypothesized that patients on immunosuppressive treatments, including biologics, may have an augmented risk of being infected by SARS-CoV-2; however, there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases. Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination. Nevertheless, even in the best-case scenario of apparent elimination, there is concordance about a possible contagion resurgence as late as 2024. Therefore, knowledge of the impact of SARS-CoV-2 on immune-mediated diseases and among patients treated with biologicals, together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response (or both), will help us to best manage our patients during this pandemic over the next few years

Identification and spatial distribution of the mRNA encoding an egg envelope component of the Cyprinid zebrafish, Danio rerio, homologous to the mammalian ZP3(ZPC)

Using degenerate reverse transcription polymerase chain reaction (RT-PCR) techniques we have isolated a cDNA encoding a putative component of the zebrafish Danio rerio egg chorion, homologous to the mammalian ZP3 (ZPC). The predicted protein (zfZPC) has a calculated molecular mass of 58.4 kDa and contains a signal peptide (located in the N-terminal region) composed of 11 hydrophobic amino acid residues followed by a signal peptide cleavage site. The zfZPC contains the ZP domain, a characteristic amino acid sequence shared by all ZP proteins of the mammalian zona pellucida and of both amphibian and bird egg envelope components. The zfZPC also exhibits certain unique features including five N-terminal Q-rich tandem repeats presumably involved in the hardening of the chorion after the fertilization of the egg and a long C-terminal tail containing two potential sites of N-linked type glycosylation. RT-PCR and in situ hybridization revealed a restricted pattern of tissue distribution: the gene encoding zfZPC is transcribed only in the growing oocyte of sexually mature female fish

Eosinophilic granulomatosis with polyangiitis relapse after covid-19 vaccination: A case report

Background: We here describe the case of a 71-year-old Caucasian woman previously diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA) that had been treated with Mepolizumab, an anti-IL5 monoclonal antibody, since 2019 with a good clinical response. Methods: She had a mild COVID-19 in December 2020 and she tested negative for SARS-CoV-2 infection in only late January 2021. In April 2021 she received the first dose of mRNA BNT162b2 vaccine. Ten days later she developed myalgia, dyspnea and numbness of the limbs due to a relapse of EGPA that occurred during Mepolizumab treatment

Genetic susceptibility to Candida infection: A new look at an old entity

In recent years, several studies have shed light on the pathogenesis of many novel immune defects associated with narrow susceptibility to bacterial, viral and fungal infections. Genetically determined forms of susceptibility to Candida species infection, which had been elusive for a long time, have been recognized. Refractory or recurrent infections of skin, nails and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects in the Th17 subset, which is crucial for host response against infections at mucosal and epithelial sites. Here we review the main clinical features and the mechanisms of diseases which share CMC as main phenotype

Fungal allergy in asthma-state of the art and research needs

Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies

Changes in symptoms of asthma and rhinitis by sensitization status over ten years in a cohort of young Chilean adults

BACKGROUND: We investigated the net changes in prevalence of symptoms of asthma and rhinitis over 10 years in a cohort of young by baseline sensitization status. METHODS: One thousand one hundred ninety three Chilean adults subjects aged 22-28 living in a semi-rural area of central Chile answered a lifestyle and the European Community Respiratory Health Survey (ECRHS) questionnaires. Bronchial hyper-responsiveness (BHR) and skin prick test (SPT) to eight allergens were measured at baseline in 2001. Ten years later, 772 participants completed the questionnaires again. Estimates of adjusted net changes in prevalence of symptoms by sensitization status at baseline and association between sensitization status at baseline and respiratory symptoms ten years later were assessed. RESULTS: A quarter of the participants were sensitized to at least one allergen in 2001. Prevalence of wheeze had a net change per year of -0.37 % (95 % Confidence Interval -0.71 to 0.02 %; p = 0.067). Self-reported nasal allergies in the last 12 months increased by 0.83 % per year (95 % CI 0.49 to 1.17 %; p < 0.001). Those sensitized to either cat fur (OR 1.76; CI 1.01 to 3.05), cockroach, (OR 2.09; 1.13 to 3.86) blend of grass and pollens (1.78; 95 % CI 1.08 to 2.92), or weeds (OR 1.77; 95 % CI 1.01 to 3.12) in 2001 were more likely to have wheeze in the last 12 months 10 years later. CONCLUSION: Symptoms of asthma remained stable or slightly changed over 10 years in adults, whilst rhinitis and nasal allergies greatly increased. Being sensitized to at least one allergen is a risk factor for persistent symptoms of asthma and rhinitis, but not for determining net changes of symptoms over time. The underlying causes for the contrasting trends between asthma and nasal allergy are unknow

A Traditional Diet Is Associated with a Reduced Risk of Eczema and Wheeze in Colombian Children

Background: Diet might influence the risk of allergic diseases. Evidence from developing countries with high prevalence of childhood asthma is scant. Methods: Information on wheeze, rhinitis, and eczema was collected from 3209 children aged 6–7 years in 2005, who were taking part in the International Study on Asthma and Allergy in Children (ISAAC) in Colombia. Intake frequency of twelve food groups was assessed. Associations between each food group and current wheeze, rhino-conjunctivitis, and eczema were investigated with multiple logistic regressions, adjusting for potential confounders. Simes’ procedure was used to test for multiple comparisons. Results: 14.9% of children reported wheeze in the last 12 months, 16% rhino-conjunctivitis, and 22% eczema. Eczema was negatively associated with consumption of fresh fruits and pulses three or more times per week (adjusted Odds ratio (aOR): 0.64; 95% Confidence Interval (CI): 0.49 to 0.83; p value = 0.004; and aOR: 0.62, 95% CI: 0.47 to 0.80; p value < 0.001, respectively). Current wheeze was negatively associated with intake of potatoes (aOR: 0.44, 95% CI: 0.31 to 0.62, p value = 0.005), whilst this outcome was positively associated with consumption of fast food (aOR: 1.76, 95% CI: 1.32 to 2.35, p value = 0.001). These associations remained statistically significant after controlling for multiple comparisons. Conclusions: A traditional diet might have a protective effect against eczema and wheeze in Colombian children, whilst intake of fast foods increases this risk

Chronic spontaneous urticaria: a low-grade disseminated intravascular coagulation only partially reversed by Omalizumab

Chronic spontaneous urticaria (CSU) is a disorder characterized by wheals and/or angioedema. The coagulation cascade and inflammation pathways are closely linked together. The aim of our study was first to investigate the dynamics of clot formation in plasma (Clot Waveform Analysis, CWA) in a group of 47 patients with CSU along with other coagulative parameters dedicated to the study of hypercoagulability, such as D-Dimer, F 1 + 2 peptide, Fibrinogen, Platelet count and Mean Platelet Volume (MPV). Secondly, 23 out of 47 patients were treated with Omalizumab at four administration intervals from T0 to T4. A statistically significant increase in Activated Partial Thromboplastin (aPTT) ratio, D-Dimer, F1 + 2, Platelet count and MPV was found when compared with 53 healthy controls (HC). In contrast, the 2nd Derivative of aPTT showed lower values than those of the HC. No differences were found between 1st derivative of aPTT and Fibrinogen. D-Dimer only showed a significant difference between T0 and T3. An activation of both coagulation and fibrinolysis along with a weaker clot acceleration may be in agreement with a low-grade DIC. The accelerated turnover of platelets expressed by both an increase in platelet count and MPV further supports this pathway in CSU. Omalizumab does not affect the relationship between the immune and the hemostatic systems

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab

Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%