Benralizumab improves patient reported outcomes and functional parameters in difficult-to-treat patients with severe asthma: Data from a real-life cohort

In the last decade, an increasing number of randomized controlled trials (RCTs) on biologic therapy in patients with severe asthma have included patient-reported outcomes (PROs) as secondary efficacy measures. The majority of these RCTs showed a benefit in symptoms and quality of life. However, the magnitude of this benefit remains uncertain, because it rarely exceeded the minimal important difference (MID), owing to a significant improvement in the control group (placebo effect). Real-life studies on biologic therapies assessing PRO are scarce. They may support and integrate RCT results through their different experimental design. This real-life retrospective study provides data on 15 patients with difficult-to-treat severe eosinophilic asthma treated with benralizumab up to 6 months. Asthma quality of life questionnaire (AQLQ) and asthma control test (ACT) were assessed and administered at each visit to minimize the Hawthorne effect. Changes in general accepted efficacy measures, such as forced expiratory volume in 1 s (FEV1), peak expiratory flux (PEF), exacerbation rate and blood eosinophils, from baseline were also assessed. AQLQ and ACT improved from 3.9 ± 0.4 to 5.2 ± 0.4 and from15.6 ± 5.7 to 18.1 ± 5.6, respectively. FEV1 increased of about 250 ml (+14%). PEF increased from 288 ± 107 to 333 ± 133 l/min. The number of exacerbations requiring OCS courses decreased from 2.8 ± 2.2 to 0.5 ± 0.8. Eosinophil counts dropped to 25.6 ± 15 cells/microliter. In conclusion, most patients reported improvements in AQLQ and ACT greater than MID, suggesting that these outcome represent a sensitive tool in real-life effectiveness studies. Our approach reduced the limitations of transition questions and the Hawthorne effect, increasing findings reliability

The Employment of Leukotriene Antagonists in Cutaneous Diseases Belonging to Allergological Field

Leukotrienes (LTs) are potent biological proinflammatory mediators. LTC4, LTD4, and LTE4 are more frequently involved in chronic inflammatory responses and exert their actions binding to a cysteinyl-LT 1 (CysLT1) receptor and a cysteinyl-LT 2 (CysLT2) receptor. LTs receptor antagonists available for clinical use demonstrate high-affinity binding to the CysLT1 receptor. In this paper the employment of anti-LTs in allergic cutaneous diseases is analyzed showing that several studies have recently reported a beneficial effects of these agents (montelukast and zafirlukast as well as zileuton) for the treatment of some allergic cutaneous related diseases-like chronic urticaria and atopic eczema although their proper application remains to be established

erythema multiforme like rash in a patient sensitive to ofloxacin

and increase matrix metalloproteinases-1 of dermal 10. Farrell AM. Acquired perforating dermatosis in renal and broblasts in three-dimensional cultures. J Dermatol Sci diabetic patients. Lancet 1997; 349: 895–896. 2000; 24: 99–104. 11. Golub LM, Ramamurthy NS, McNamara TF, Greenwald 9. Ryan ME, Usman A, Ramamurthy NS, Golub LM, RA, Rifkin BR. Tetracyclines inhibit connective tissue Greenwald RA. Excessive matrix metalloproteinase activbreakdown: new therapeutic implications for an old family ity in diabetes: inhibition by tetracycline analogues with of drugs. Crit Rev Oral Biol Med 1991; 2: 297–321. zinc reactivity. Curr Med Chem 2001; 8: 305–316

Acquired angioedema with C1 inhibitor deficiency associated with anticardiolipin antibodies.

Acquired angioedema (AAE) with C1 inhibitor deficiency is often associated to B cell lymphoproliferative disorders or autoimmune diseases. We report a case of AAE associated with IgM anti-cardiolipin antibodies, with frequent edematous attacks, that disappeared completely after a slight immunosuppression and danazol therapy

acute allergic reactions to anisakis simplex after ingestion of anchovies

symptoms after ingestion of esh. The etiological role of The study population also comprised 33 controls grouped as: Anisakis simplex was evaluated in 49 adult subjects with ‐ 24 individuals who never ate raw or undercooked esh during acute allergic symptoms after ingestion of anchovies. their lifetime, of whom 5 were non-atopic healthy subjects, Serum-specie c IgE and prick tests to anchovy were nega- 9 were non-atopic patients with physical urticarias, and 10 tive in each patient. Specie c IgE reactions to Anisakis had a personal history of atopy (atopic dermatitis, allergic asthma and/or rhinitis); were positive in 45 patients and skin tests in 43. Only 3 ‐ 9 regular consumers of raw-esh products with no antepatients with allergy to the nematode were atopic. cedents of atopy or any allergic reactions. However, IgE responses to Anisakis were also observed After an adequate washout period from active treatments, in in habitual consumers of raw e sh, without any clinical vivo tests were performed in both patients and controls: manifestations, suggesting that the relevance of results of ‐ skin-prick tests (SPTs) with common aeroallergens conventional tests has to be interpreted on the basis of (Stallergenes Italia, Saronno, Varese, Italy)

Allergenius, an expert system for the interpretation of allergen microarray results

BACKGROUND: An in vitro procedure based on a microarray containing many different allergen components has recently been introduced for use in allergy diagnosis. Recombinant and highly purified allergens belonging to different allergenic sources (inhalants, food, latex and hymenoptera) are present in the array. These components can either be genuine or cross-reactive, resistant or susceptible to heat and low pH, and innocuous or potentially dangerous. A large number of complex and heterogeneous relationships among these components has emerged, such that sometimes these interactions cannot be effectively managed by the allergist. In the 1960s, specialized languages and environments were developed to support the replacement of human experts with dedicated decision-making information systems. Currently, expert systems (ES) are advanced informatics tools that are widely used in medicine, engineering, finance and trading. METHODS: We developed an ES, named Allergenius ®, to support the interpretation of allergy tests based on microarray technology (ImmunoCAP ISAC ®). The ES was implemented using Flex, a LPA Win-Prolog shell. Rules representing the knowledge base (KB) were derived from the literature and specialized databases. The input data included the patient’s ID and disease(s), the results of either a skin prick test or specific IgE assays and ISAC results. The output was a medical report. RESULTS: The ES was first validated using artificial and real life cases and passed all in silico validations. Then, the opinions of allergists with experience in molecular diagnostics were compared with the ES reports. The Allergenius reports included all of the allergists’ opinions and considerations, as well as any additional information. CONCLUSIONS: Allergenius is a trustable ES dedicated to molecular tests for allergy. In the present version, it provides a powerful method to understand ISAC results and to obtain a comprehensive interpretation of the patient’s IgE profiling

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

sensitivity to rubber chemicals and latex among hemodialysis patients

test. A history of atopic disease was reported by 6 subjects patients undergoing long-term hemodialysis. (7.2%), pruritus by 35 (42.2%) and dermatitis by 22 (26.5%). Sixteen patients (19.3%), exhibited positive patch tests to PATIENTS AND METHODS rubber antigens (Table I). For 9 of them, the rubber allergy We enrolled 154 consecutive hemodialysis patients (66 women and 88 was considered clinically relevant, as these patients had previmen). The median time of dialysis was 53O 44 months, with a range ously had episodes of allergic contact dermatitis following of 1± 205 months. Skin-prick tests were performed with a standardized exposure to the rubber allergens. However, it was not possible commercial extract of non-ammoniated latex (StallergeA nes, Paris, to assess whether the sensitivity to the rubber chemicals was France) and with glove extracts prepared as previously reported (3). Brie y, twenty 1 cm2 (400mg total weight) freshly cut glove pieces induced by hemodialysis or prior to treatment. The most (Le Petit, Gradate, Como, Italy) were incubated for 30min in 5ml of common sensitizers were thiuram mix (12 cases) and carba sterile 0.9% NaCl saline solution. The incubation uid was used as a mix (5 cases) We did not ® nd any signi® cant diŒerences stock solution for prick testing. Histamine hydrochloride (10mg/ml) concerning age, sex, durationof hemodialysis, history of atopy, and 0.9% NaCl saline solution served as positive and negative controls, respectively. Wheals of 3 mm or greater were regarded as positive in prior or current pruritus among patients with either positive the absence of a reaction to saline. A glove user test was performed or negative patch tests (Table I ). Statistical analysis showed, as follows: a ® ngertip was cut from a surgical glove, dampened with however, a signi® cant association between positive patch water, and placed on one ® nger for 15± 30min. If the reaction was test results and the presence of prior or current dermatitis negative, the whole glove was worn for the same amount of time. One ( p 5 0.004). vinyl glove was used as control. Urticaria on the ® nger/hand exposed to latex was regarded as a positive reaction. Only 83 patients accepted to undergo the patch test. These tests were performed with a series of 32 rubber additives (4). The allergens were applied in Finn Chambers DISCUSSION with Scampor tape to each patient's back. Readings were taken after 2 and 4 days. The reactions were scored in accordance with the Recent data have demonstrated that non-atopic hemodialysis recommendations of the International Contact Dermatitis Research patients, despite continued exposure, are not at risk of developGroup. Any drug that could have interfered with the allergic tests was ing latex allergy (6). Moreover, allergic contact dermatitis due stopped at least 2 weeks prior to testing. Laboratory evaluation to substances used in manufacturing hemodialysis devices is included measurement of total IgE level by the PRIST (Pharmacia, Uppsala, Sweden) and serum-speci® c IgE to latex by a uorescence rarely reported (7). However, we observed a positive patch enzyme-linked immunoassay (CAP-FEIA system; Pharmacia). The test in 16 patients (19.3%), and 9 reactions were considered threshold of positivity for the CAP test was set at 0.35kU/l. Atopy clinically relevant. Most of the sensitizations were towards was assessed by a careful clinical history of atopic dermatitis and/or allergens normally employed in the European standard patchseasonal or perennial rhinitis or asthma, and by increased IgE levels. test series. Therefore, contact allergy can be a relevant clinical Informed consent was given by subjects prior to participation in the study. problem in hemodialysis patients. Statistical analysis of data was performed by two-tailed chi-squared The exposure to rubber products can vary according to test and Fisher exact test when necessary. Mean values of continuous method of dialysis. Furthermore, the allergenicity can vary variables were compared using Student's t-test. Probability ( p) values from one product to another based on the allergen content less than 0.05 were considered signi® cant. (7, 8)