Allergic Conditions Research Articles

Machine learning methods for low-cost pollen monitoring – Model optimisation and interpretability

Pollen is a major issue globally, causing as much as 40 % of the population to suffer from hay fever and other allergic conditions. Current techniques for monitoring pollen are either laborious and slow, or expensive, thus alternative methods are needed to provide timely and more localised information on airborne pollen concentrations. We have demonstrated previously that low-cost Optical Particle Counter (OPC) sensors can be used to estimate pollen concentrations when machine learning methods are used to process the data and learn the relationships between OPC output data and conventionally measured pollen concentrations.This study demonstrates how methodical hyperparameter tuning can be employed to significantly improve model performance. We present the results of a range of models based on tuned hyperparameter configurations trained to predict Poaceae (Barnhart), Quercus (L.), Betula (L.), Pinus (L.) and total pollen concentrations. The results achieved here are a significant improvement on results we previously reported: the average R2 scores for the total pollen models have at least doubled compared to using previous parameter settings.Furthermore, we employ the explainable Artificial Intelligence (XAI) technique, SHAP, to interpret the models and understand how each of the input features (i.e. particle sizes) affect the estimated output concentration for each pollen type. In particular, we found that Quercus pollen has a strong positive correlation with particles of optical diameter 1.7–2.3 μm, which distinguishes it from other pollen types such as Poaceae and may suggest that type-specific subpollen particles are present in this size range.There is much further work to be done, especially in training and testing models on data obtained across different environments to evaluate the extent of generalisability. Nevertheless, this work demonstrates the potential this method can offer for low-cost monitoring of pollen and the valuable insight we can gain from what the model has learned.

Clinical Profile of Vernal Keratoconjunctivitis (VKC) Patients: A Retrospective Study at a Peripheral Combined Military Hospital in Bangladesh

Background: Vernal keratoconjunctivitis (VKC) is an allergic eye disease that especially affects young boys. The most common symptoms are itching, photophobia, burning, and redness. This study was conducted to assess the clinical profile of vernal keratoconjunctivitis (VKC) among the local population reported at a peripheral combined military hospital over 1 year. This study aimed to analyze the cases of vernal keratoconjunctivitis at a peripheral combined military hospital. Material & Methods: This is a retrospective study carried out in the Department of Ophthalmology at Combined Military Hospital, Saidpur. A total number of 110 patients with VKC were diagnosed based on their history, clinical features, and characteristic symptoms and sign over a period of 1 year from Jan 2021 to Dec 2021. Best-corrected visual acuity (VCVA) was assessed and each patient was thoroughly examined with a Slit Lamp Bi microscope, Fluorescein staining, and Tear film break-up time. Follow-up was done every 4 weeks, 3 months, and 6 months for 01 year. A purposive sampling technique was used in this study. Data was collected by a pre-designed questionnaire. All data were analyzed using SPSS version 20 (IBM Corp, Armonk, NY, USA) results were compiled in the frequency distribution table. Informed written consent was taken from all participants. Ethical clearance was obtained by the ethical committee of CMH. Results: Out of 110 patients, 80 (72.72%) were male and 30 (27.27%) were female. The highest incidence of VKC occurred in the age group of 11–15 years. In maximum cases 70 (63.63%) had palpebral form followed by mixed form 25 (22.72%) and then bulbar form 15 (13.63%). Corneal complications occurred in 27 (24.54%) patients; Out of 27, 25 patients had minor complications and 2 had major complications. The minor complications were usually superficial punctate keratopathy (SPK) or other epithelial disturbance. Major complications were superior pannus and pseudogerontoxon. Although patients with VKC often give a history of allergies or atopic diseases such as allergic rhinitis, asthma, or hay fever, in the present study, coexisting allergic conditions could be detected only 40 (36.36%) patients. Conclusion: VKC is a common form of allergic conjunctivitis among the age group of 11–15 years of male patients. The most common is the palpebral form followed by mixed and then bulbar forms. Some cases showed a history of atopy and other allergic conditions.

DEVELOPMENT OF ORODISPERSIBLE TABLETS OF LORATADINE CONTAINING AN AMORPHOUS SOLID DISPERSION OF THE DRUG IN SOLUPLUS® USING DESIGN OF EXPERIMENTS

Objective: The objective of the present work was to develop an orodispersible tablet of loratadine, an orally active, non-sedating anti-histaminic, belonging to BCS Class II. The drug was prepared as a solid dispersion using Soluplus® as carrier and formulated into an optimal tablet using Design of Experiments. Methods: Solid dispersions of loratadine with varying ratios of Soluplus® were prepared by solvent evaporation and subjected to solubility study in simulated salivary fluid. Selected composition was characterized by differential scanning calorimetry and X-ray diffraction and formulated into an orodispersible tablet by direct compression after addition of suitable excipients. DOE based on a full factorial design was used to optimize the product using a trial version of JMP software, so as to obtain a tablet with low friability, rapid disintegration and maximal drug dissolution within 5 min. The optimized tablet was prepared and evaluated for several attributes, including in vivo disintegration and palatability. Results: A solid dispersion prepared with a 1: 4 ratio of loratadine: Soluplus® was found to show a 130-fold increase in drug solubility in the simulated salivary fluid. X-ray diffraction revealed loratadine in amorphous form. The exercise using DOE for optimization of the orodispersible tablet formula served to balance the proportion of crospovidone as super disintegrant and PVP as dry binder and yielded a formulation with good mechanical strength, rapid in vitro disintegration (39 sec) and dissolution of 93.78% of the drug within 5 min. When evaluated in vivo, the tablets were found to disintegrate in about 60 secs and were reported to be palatable. Conclusion: A patient-friendly dosage form containing a highly soluble form of loratadine was prepared and could be of potential benefit in offering quick relief from allergic conditions.

Sputum Neurturin Levels in Adult Asthmatic Subjects.

Neurturin (NRTN) is a neurotrophic factor that was originally identified in the development and maintenance of neural cells. Recent studies involving NRTN knockout mice have reported its anti-inflammatory effects in allergic airway conditions. However, the role of NRTN in human asthma has not yet been identified. The purposes of the present study were to confirm the presence of NRTN in the airways and to investigate the clinical and pathogenetic roles of NRTN in asthma. The NRTN levels in the induced sputum were measured by enzyme-linked immunosorbent assay (ELISA). Relationships between NRTN and clinical characteristics, asthma control status, and airway inflammation were assessed. Sixty-four asthmatic subjects were enrolled in the study. All asthmatic subjects had detectable sputum NRTN levels, with a mean (SD) level of 2.03 (1.29) ng/mL. The sputum NRTN levels had significant positive correlations with sputum eosinophil and exhaled nitric oxide levels and were significantly higher in the atopic subjects than in the non-atopic subjects. No significant difference in sputum NRTN levels were observed for asthma control status and asthma exacerbation. In sputum inflammatory analyses, sputum NRTN level was positively correlated with interleukin (IL)-5 and IL-13 levels, and negatively correlated with matrix metalloproteinase (MMP)-9 level. It is plausible that sputum NRTN could serve as a new marker for Type 2 airway inflammation, implicating its role in the process of airway remodeling in asthma. Future studies should investigate the clinical relevance of sputum NRTN level in prospective analyses.

COVID-19 and Pregnancy: Interrelationships With Asthma and Allergy

Pregnant individuals are at higher risk of complications from respiratory viruses such as coronavirus-19 disease (COVID-19). Altered lung function, vaccine hesitancy, and resistance to taking necessary medications because of a lack of safety data in pregnancy make this population especially vulnerable to the effects of COVID-19. Like many medical conditions, the treatment of allergic conditions, including asthma and allergic rhinitis, were affected during the pandemic, with decreased numbers of in-person visits and interruptions in medical treatment. There were initially no data to allow pregnant women with asthma know whether the condition put them at higher risk of complications from COVID-19. There are now increasing data for the efficacy and safety of vaccines for COVID-19 in at-risk populations, including pregnant women. Vaccine studies show no increased risk for spontaneous abortion, congenital anomalies, or pregnancy complications. Furthermore, infants of individuals vaccinated during pregnancy have been shown to obtain protective antibodies via the placenta, providing protection against COVID-19 after birth. Although overall risks are low, pregnant women who become infected with COVID-19 are at higher risk for maternal and pregnancy complications. Antiviral treatment is available for pregnant women with mild to moderate symptoms of COVID-19, with reassuring safety data to date. Dexamethasone is the mainstay of inpatient therapy.

Use of Saliva-PCR as an alternative diagnostic tool for COVID-19 positive cases.

Objective: To find the presence of SARS-CoV-2 in saliva and oropharyngeal secretions in confirmed cases of COVID 19 to establish them as potential diagnostic alternatives. Study Design: Cross Sectional study. Setting: Hayatabad Medical Complex and Public Reference Lab of Khyber Medical University, Peshawar. Period: April 2022 to September 2022. Material & Methods: Study included SARS-CoV-2 patients confirmed by a positive RT-qPCR diagnosed through nasopharyngeal swab. Data was collected using a digital questionnaire. Saliva was collected using "passive drool" procedure. RNA was extracted from saliva samples and virus was detected through one-step-RT-qPCR using Universal qPCR Master Mix. The data obtained was presented using graphical representation in the form of proportions. Results: The study included 211 individuals with a wide range from 12 to 75 years. There were 146 (69%) males and 65 (31%) females.17% reported being hospitalized or received medical treatment recently. Only six individuals reported regular use of medications for hypertension and diabetes. 30% of participants reported a positive response when asked about their pervious respiratory allergic conditions. Results showed that out of 211 participants 75 (36%) were positive for COVID-19 using saliva-PCR, while the remaining 136 (64%) were negative. The findings showed that saliva-PCR had lower sensitivity than nasopharyngeal-PCR in detecting COVID-19. Conclusion: The results of saliva-PCR diagnosis showed lower sensitivity than nasopharyngeal-PCR in detecting COVID-19. Additional research is required to substantiate the effectiveness of PCR using saliva as an alternative diagnostic option.

Causes of Non-Adherence to Allergen-Specific Immunotherapy: A Foundation towards a Patient-Personalized Approach.

Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report

BackgroundPanic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy.Case presentationThis report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly.ConclusionsThe immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient’s clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Indoor aeroallergens from American cockroaches and mites initiate atopic march via cutaneous contact in a murine model.

The progression of allergic diseases from atopic dermatitis in childhood to other allergic conditions such as asthma in later life is often referred to as the atopic march. In order to study the relationship between cutaneous sensitization by aeroallergen and atopic march, we established a mouse model to test the hypothesis using American cockroaches and house dust mites as the model allergens. Mice were sensitized via skin with native cockroach extract (CraA) or recombinant Per a 2 and Der p 2 proteins without adjuvant. Each mouse was subjected to a total of three 1-week patching sensitizations with a 2-week interval in between each application. The resulting immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of skin lesions and nasal mucosa were evaluated. In mice, application of CraA, rPer a 2, and rDer p 2 aeroallergens through skin patching induced significantly high levels of both total IgE and specific IgEs. The epicutaneous sensitization after a subsequent allergen challenge showed a significant increase in scratch bouts, AHR, epidermal thickness, and eosinophil counts in the skin compared with the control mice. In addition, stimulation of murine splenocytes with allergens increased higher levels of Th2 cytokines, anti-inflammatory cytokines, and chemokines excretion. Our study provides evidence supporting that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. We hope this new allergy model will be useful in the development of new preventive and therapeutic strategies aimed at stopping the atopic march.

Modulation of inflammatory and oxidative stress biomarkers due to dexamethasone exposure in chicken splenocytes

Dexamethasone (DEXA) is a potent corticosteroid, commonly used for treating inflammatory, hypersensitive and allergic conditions. It is administered to birds with tumours. Many studies were conducted on its immunosuppressive effects; however none of the similar study is available employing chicken splenocytes culture system. The present study was conducted to assess DEXA induced alterations in inflammatory and oxidative stress biomarkers in chicken splenocytes due to its in vitro exposure. The maximum non-cytotoxic dose (MNCD) was evaluated and was further used for conducting lymphocytes proliferation assay (LPA), antioxidant assays (lipid peroxidation, GSH, superoxide dismutase and nitric oxide assays) and assessment of mRNA levels of various genes (IL-1β, IL-6, IL-10, LITAF, iNOS, NF-κB1, Nrf-2, Caspase-3 and -9) through qPCR. The MNCD was determined to be 30 ng/ml in chicken splenocytes culture system. DEXA caused reduction in B and T lymphocytes proliferation indicating its immunosuppressive effects, however improved the antioxidant status of the exposed splenocytes. The expression levels of IL-1β, IL-6, iNOS, LITAF and NF-κB1 were significantly reduced while IL-10 was enhanced, which signify potent anti-inflammatory potential of DEXA. NF-κB is a major transcription factor that regulates genes responsible for both, innate and adaptive immune responses and elicits inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf-2) level was found to be up-regulated. Nrf-2 plays important role in combating the oxidant stress and its increased expression could be the reason of improved antioxidant status of DEXA exposed cells. Present findings indicated that DEXA exhibited modulation in anti-inflammatory, immunomodulatory and antioxidant mediators in chicken splenocytes.

Patterns in the Development of Pediatric Allergy.

Describe clinical and epidemiologic patterns of pediatric allergy using longitudinal electronic health records (EHRs) from a multistate consortium of US practices. Using the multistate Comparative Effectiveness Research through Collaborative Electronic Reporting EHR database, we defined a cohort of 218 485 children (0-18 years) who were observed for ≥5 years between 1999 and 2020. Children with atopic dermatitis (AD), immunoglobulin E-mediated food allergy (IgE-FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) were identified using a combination of diagnosis codes and medication prescriptions. We determined age at diagnosis, cumulative incidence, and allergic comorbidity. Allergic disease cumulative (and peak age of) incidence was 10.3% (4 months) for AD, 4.0% (13 months) for IgE-FA, 20.1% (13 months) for asthma, 19.7% (26 months) for AR, and 0.11% (35 months) for EoE. The most diagnosed IgE-FAs were peanut (1.9%), egg (0.8%), and shellfish (0.6%). A total of 13.4% of children had ≥2 allergic conditions, and respiratory allergies (ie, asthma, AR) were commonly comorbid with each other, and with other allergic conditions. We detail pediatric allergy patterns using longitudinal, health care provider-based data from EHR systems across multiple US states and varied pediatric practice types. Our results support the population-level allergic march progression and indicate high rates of comorbidity among children with food and respiratory allergies.

Ocular surface inflammation and ectatic corneal disorders.

Inflammatory mediators are a focus of recent corneal ectasia (CE) research and are a profound, modifiable contributor to CE in general and keratoconus (KC) in particular, opening a path to explore new methods of control. As advanced imaging technology and expanded population screening allow for earlier detection, the possibility of early intervention can profoundly change the prognosis of CE. Significant increases in the inflammatory mediators and immune components have been observed in the cornea, tear fluid, and blood of ectasia patients, while inflammation dampeners such as vitamin D and their receptors are reduced. Atopy and allergy have a strong association with KC, known to increase itch factors and stimulate eye rubbing, a risk factor in ectasia pathogenesis. Management of atopy or allergic conditions and topical anti-inflammatories has helped stabilize CE disease. Strategies such as monitoring inflammatory factors and using immune or inflammatory modulators, including managing subclinical inflammation, may be clinically beneficial in stabilizing the disease and improving outcomes. The detected factors are biomarkers, but as yet unproven to be sensitive or specific enough to be considered biomarkers for early detection of CE. The establishment of such biomarkers could improve the therapeutic outcome.

Atopic allergic conditions and prostate cancer risk and survival in the Multiethnic Cohort study

BackgroundPrevious studies investigating relationship between atopic allergic conditions (AACs)—a highly reactive immune state—and prostate cancer (PCa) risk were inconclusive, and few have studied diverse racial/ethnic populations.MethodsWe analysed 74,714 men aged ≥45 years at enrollment in Multiethnic Cohort study. Using multivariable Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for self-reported AAC status on PCa outcomes.ResultsThrough 2017, 8697 incident PCa and 1170 related deaths occurred. Twenty-one percent of men reported a history of AACs. AACs were not associated with incident PCa (HR = 0.98, 95% CI: 0.93–1.03) but were significantly inversely associated with PCa mortality (HR = 0.79, 95% CI: 0.67–0.92). This inverse association was consistently observed across all racial/ethnic groups (HR range: 0.60–0.90). Among men diagnosed with PCa, AACs were inversely associated with PCa-specific death (HR = 0.75, 95% CI: 0.63–0.89). Adjusting for potential confounding effect of PSA screening did not meaningfully change the results. No significant heterogeneity was observed in the effect of AACs on PCa incidence or mortality by Dietary Inflammatory Index.ConclusionsHyper-allergic conditions were not associated with PCa incidence but were inversely associated with PCa mortality, suggesting a potential role in reducing tumour progression. Further aetiological research is warranted to understand underlying mechanisms.

Global Impact of Monoclonal Antibodies (mAbs) in Children: A Focus on Anti-GD2.

Monoclonal antibodies (mAbs), as the name implies, are clonal antibodies that bind to the same antigen. mAbs are broadly used as diagnostic or therapeutic tools for neoplasms, autoimmune diseases, allergic conditions, and infections. Although most mAbs are approved for treating adult cancers, few are applicable to childhood malignancies, limited mostly to hematological cancers. As for solid tumors, only anti-disialoganglioside (GD2) mAbs are approved specifically for neuroblastoma. Inequities of drug access have continued, affecting most therapeutic mAbs globally. To understand these challenges, a deeper dive into the complex transition from basic research to the clinic, or between marketing and regulatory agencies, is timely. This review focuses on current mAbs approved or under investigation in pediatric cancer, with special attention on solid tumors and anti-GD2 mAbs, and the hurdles that limit their broad global access. Beyond understanding the mechanisms of drug resistance, the continual discovery of next generation drugs safer for children and easier to administer, the discovery of predictive biomarkers to avoid futility should ease the acceptance by patient, health care professionals and regulatory agencies, in order to expand clinical utility. With a better integration into the multimodal treatment for each disease, protocols that align with the regional clinical practice should also improve acceptance and cost-effectiveness. Communication and collaboration between academic institutions, pharmaceutical companies, and regulatory agencies should help to ensure accessible, affordable, and sustainable health care for all.

Interaction of promethazine hydrochloride with TX-165 in aqueous, NaCl and urea media: a tensiometry and FTIR analysis

An experiment using surface tension was conducted to investigate the interactions of promethazine hydrochloride (PMT), with TX-165, at the interface in different ratios and solvents (water/50 mmol/kg NaCl, and 500 mmol/kg urea) at 298.15 K. A thorough FTIR study of the employed pure and mixed system was also conducted in the aqueous solution. PMT is a medication employed to manage and cure allergic conditions. Usually, NaCl media improved the surface properties of singular and mixed components over aqueous media, resulting in synergistic/attractive interactions among ingredients. TX-165’s composition at mixed monolayer ( ), surface excess concentration (Γ max), pC 20, activity coefficient, and so on were evaluated. The achieved activity coefficient values are attained below one in each case, indicating the attractive interactions amongst ingredients. A negative Gibbs energy of adsorption was obtained all through, indicating spontaneity in the process. A negative excess free energy ( ) was found at the mixed interface of PMT + TX-165, showing a higher surface stability of mixed monolayer than pure component monolayer. FTIR spectroscopy is used to study the spectrum of single and mixed amphiphiles to validate the interaction between PMT and TX-165. This study suggested that TX-165 surfactant might behave as an able antidepressant drug delivery agent.

Complement-mediated immune mechanisms in allergy.

Allergic conditions are associated with canonical and non-canonical activation of the complement system leading to the release of several bioactive mediators with inflammatory and immunoregulatory properties that regulate the immune response in response to allergens during the sensitization and/or the effector phase of allergic diseases. Further, immune sensors of complement and regulator proteins of the cascade impact on the development of allergies. These bioactive mediators comprise the small and large cleavage fragments of C3 and C5. Here, we provide an update on the multiple roles of immune sensors, regulators and bioactive mediators of complement in allergic airway diseases, food allergy and anaphylaxis. A particular emphasis is on the anaphylatoxins C3a and C5a and their receptors, which are expressed on many of the effector cells in allergy such as mast cells, eosinophils, basophils, macrophages and neutrophils. Also, we will discuss the multiple pathways, by which the anaphylatoxins initiate and control the development of maladaptive type 2 immunity including their impact on innate lymphoid cell recruitment and activation. Finally, we briefly comment on the potential to therapeutically target the complement system in the different allergic conditions. Canonical and non-canonical cleavage of complement factors C3 and C5 generates C3a, C5a and C5adesArg (C5adR), activating the anaphylatoxin receptors C3aR, C5aR1 and C5aR2. Activation of such receptors on multiple innate immune cells and consecutive activation of Type 2 innate lymphoid cells controls the development of several allergic diseases. This article is protected by copyright. All rights reserved.

Update meta-analysis on the efficacy and safety issues of fexofenadine

BackgroundFexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. MethodsDouble blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. ResultsFrom the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) –0.33; 95% CI–0.47 to −0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to −0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88–1.21), with no detection of heterogeneity across these 12 studies. ConclusionsAccording to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.

SCD14 and Intestinal Fatty Acid Binding Protein Are Elevated in the Serum of Patients With Idiopathic Anaphylaxis.

Intestinal epithelial integrity compromise has been identified in gastrointestinal (GI), atopic, and autoimmune diseases. Episodes of idiopathic anaphylaxis (IA) are often accompanied by GI manifestations. We, therefore, sought to determine whether surrogate markers of GI permeability were aberrant in this patient population. Serum concentrations of zonulin, intestinal fatty acid binding protein (I-FABP), and soluble CD14 (sCD14) measured in 54 patients with IA were compared with concentrations in healthy controls (HCs); and correlated with clinical and laboratory parameters. The I-FABP was elevated in sera of patients with IA compared with HCs (median 1,378.0 pg/mL vs 479.0 pg/mL, respectively; P < .001). The sCD14 was also elevated compared with HCs (median 2,017.0 ng/mL and 1,189.0 ng/mL, respectively; P < .001), whereas zonulin was comparable between patients with IA and HCs (median 49.6 ng/mL vs 52.4 ng/mL, respectively; P= .40). The I-FABP was elevated in patients with IA who experienced vomiting and/or diarrhea compared with patients with IA who did not (P= .0091). The I-FABP and sCD14 are elevated in the serum of patients with IA. Elevations in these biomarkers of IA provides evidence that increased GI permeability, as is observed in other allergic conditions such as food allergy, is a common finding in those with IA and offers possible insight into the pathogenesis of this disease.

Potential sex differences in human milk fatty acids and their association with atopic dermatitis: Results of the Ulm SPATZ health study.

Polyunsaturated fatty acids (PUFAs) in human milk are essential in immune system maturation and might play a role in the development of allergic conditions, such as atopic dermatitis (AD) in infants. Immune system responses are modulated by sex, but data on the sex-specific associations with PUFAs are limited. We therefore explored sex-specific differences in human milk PUFAs and their association with AD up to 2 years. PUFAs were measured in human milk samples from the Ulm SPATZ Health Study at 6 weeks (n = 512) and 6 months (n = 367). Associations with AD up to 2 years were evaluated using crude and multivariable logistic regression. Interactions between infant sex and PUFAs were explored by including the product term. No significant associations were observed with 6-week data. At 6 months, the median relative proportion of docosahexaenoic acid (DHA) was significantly higher in milk for female than male infants (p = .001). Female infants whose milk was lower in quintile proportions of alpha-linolenic acid (ALA) at 6 months had lower odds of AD compared to males [first vs. fifth quintile OR (95% confidence interval): 0.13 (0.02, 0.66), p = .02]. This interaction was not significant when correcting for multiple testing (α threshold: p = .004). No other statistically significant associations were observed. Individual quintile PUFA proportions in human milk were not associated with AD, overall and in a sex-specific manner. More comprehensive and statistically powered longitudinal studies are needed to determine whether potential sex differences in human milk, if any, could be of clinical relevance for infants including the investigation of mediating factors.

The Promise of Gut Microbiota

The Promise of Gut Microbiota