Allergy Asthma and Clinical Immunology最新文献

Background: Childhood atopic dermatitis can have a negative effect on caregivers' quality of life and stress levels due to the burdensome nature of its treatment. Given that the condition often emerges in infancy, atopic dermatitis-related stress also carries the potential to negatively affect the developing mother-infant bond. While it is plausible that atopic dermatitis has a negative impact on maternal-infant bonding, these relationships have not been studied directly. In light of this gap, the current study investigated the association between infantile atopic dermatitis and the maternal-infant bond using a mixed-method design.

Methods: Mothers of infants (< 19 months) with atopic dermatitis were recruited from social media and medical clinics between October 2021 and May 2022. Mothers with infants unaffected by inflammatory skin conditions were also recruited to serve as a control group. Participants were asked to complete questionnaires related to their demographics, child's health, and mother-infant bond. Multiple linear regression analyses were used to assess bonding quality among cases and controls. A subset of cases were also asked to participate in semi-structured interviews focused on infantile atopic dermatitis and the maternal-infant bond.

Results: The final sample consisted of 32 cases and 65 controls. Scores on the impaired bonding and risk of abuse subscales did not significantly differ between cases and controls. However, mothers of infants with atopic dermatitis did report lower levels of caregiving anxiety (b = - 1.47, p < 0.01) and pathological anger/rejection (b = - 1.74, p = 0.02) relative to controls. Qualitative findings suggest that the topical therapies required to manage atopic dermatitis may strengthen the bond between some mothers and infants.

Conclusion: Findings suggest that atopic dermatitis does not have a negative impact on maternal-infant bonding and may actually improve bonds in some cases. In light of this finding, clinicians may leverage the potentially positive impact of atopic dermatitis-related caregiving on the maternal-infant bond to encourage caregivers to remain adherent to their child's topical treatments.

Background: Human placental extract (HPE) has been documented to facilitate the healing of certain disorders including allergy. However, the effects of HPE on the functionality of mast cells, a critical cell type in allergic diseases, have not been reported.

Methods: To investigate the effects of HPE on the regulation of allergy with respect to the biological functions of mast cells, the mast cell line C57 or HMC-1 cells were treated with HPE followed by the assessment of cell proliferation, apoptosis, activation, chemotaxis and phagocytosis. Mouse peritoneal mast cells were also investigated for their responses to induction of apoptosis by HPE in vivo. Furthermore, the effect of HPE on mast cell degranulation was confirmed using the passive cutaneous anaphylaxis (PCA) assay, an acute allergy model.

Results: HPE was capable of suppressing mast cell proliferation and inducing mast cell apoptosis. Mast cell degranulation in response to compound 48/80- or anti-DNP IgE and DNP-mediated activation was suppressed. In addition, treatment with HPE compromised the production of cytokines by mast cells and cell chemotaxis. These observations were consistent with the dampened passive cutaneous anaphylaxis (PCA) assay following treatment with HPE.

Conclusion: This study revealed a suppressive effect of HPE on overall mast cell activities, suggesting a potential regulatory role of HPE on the alleviation of allergic diseases through mast cells.

Introduction: Food allergies (FA) can detrimentally impact physical, emotional, and psychological quality of life (QoL) among pediatric patients. Given the changes from childhood into adolescence, the impact of FA on QoL likely evolves with age. The purpose of this study was to determine whether QoL differed between adolescents and children with FA who participated in a Food Allergy Symposium (FAS).

Methods: Patients with confirmed FA were recruited at an educational community symposium in September 2018 and September 2019. Patients and/or their parents were invited to complete the Food Allergy Quality of Life Questionnaires (FAQLQ). The Food Allergy Independent Measure (FAIM) reflects concerns about accidental food exposure and disease severity. Higher FAIM and FAQLQ scores reflect worse QoL. Summary scores were compared using the Wilcoxon rank sum test, Fisher's exact test, or the Chi-square test.

Results: Seventy-four surveys (82% children, 18% adolescents) were included. The FAQLQ total score was higher among adolescents than children (median 5.2 vs 4.2; p = 0.045), and the FAIM was lower in adolescents (median 2.2 vs 2.8; p = 0.037). More adolescents reported previous anaphylaxis than children (91.7% vs 51.8%; p = 0.011). The percentage reassured by having epinephrine was higher in adolescents (81.8% vs 45.8%; p = 0.046). No other QoL scores and survey responses were significantly different.

Discussion: In this study, adolescents were more concerned about their disease and more reassured by epinephrine carriage than younger children, which may reflect increased autonomy and responsibility. Community events are an important way to assess QoL and provide FA-related education to pediatric patients.

Background: Although numerous studies have suggested a negative correlation between Helicobacter pylori (H. pylori) infection and allergies, there has been limited research on the relationship between H. pylori infections and atopic dermatitis (AD). The present study aimed to investigate the effects of H. pylori infection in an AD mouse model and identify potential mechanisms related to type 2 immunity, skin barrier defects, and pruritus.

Methods: A model of AD-like symptoms was established with 2,4-dinitrochlorobenzene (DNCB) after infection of the gastric cavity with H. pylori. Analysis of the expression of key inflammatory cytokines and serum levels of immunoglobulin E (IgE) was based on enzyme-linked immunosorbent assay (ELISA). The expression of filaggrin (FLG) and loricrin (LOR) were analyzed by immunohistochemistry staining. The evaluation of STAT1, STAT3, phosphorylated STAT1 (phospho-STAT1), and phosphorylated STAT3 (phospho-STAT1) expression levels in skin lesions was performed using western blot.

Results: The present study showed that the H. pylori-positive AD group (HP+AD+) exhibited milder skin lesions, including erythema, erosion, swelling, and scaling, than the H. pylori-negative AD group (HP-AD+). Additionally, HP+AD+ displayed lower levels of IgE in serum, and downregulated expression of interleukins 4 and 31 (IL-4 and IL-31) in serum. Furthermore, HP+AD+ demonstrated higher expression of filaggrin and loricrin than HP-AD+. Notably, H. pylori significantly reduced the amount of phosphorylated STAT1 and STAT3.

Conclusion: Helicobacter pylori infection negatively regulates the inflammatory response by affecting inflammatory factors in the immune response, and repairs the defective epidermal barrier function. In addition, H. pylori infection may reduce IL-31, thereby alleviating pruritus. These effects may be associated with the inhibition of JAK-STAT signaling activation.

Introduction: Hypersensitivity pneumonitis (HP) is usually caused by the inhalation of avian and fungal proteins. The present study assesses a cohort of Urban Pest Surveillance and Control Service (UPSCS) workers with high exposure to avian and fungal antigens, in order to identify their degree of sensitization and the potential risk of developing HP.

Methods: Workers were divided according to their work activity into Nest pruners (Group 1) and Others (Group 2). All individuals underwent a medical interview, pulmonary function tests and the determination of specific IgG antibodies. Antigenic proteins of pigeon sera were analysed using two-dimensional immunoblotting. Proteins of interest were sequenced by liquid-chromatography-mass spectrometry (LC-MS).

Results: 101 workers were recruited (76 men, average age: 42 yrs); (Group 1 = 41, Group 2 = 60). Up to 30% of the study population exhibited increased levels of IgGs to pigeon, small parrot and parrot, and up to 60% showed high levels of Aspergillus and Penicillium IgGs. In Group 1, specific parakeet and Mucor IgGs were higher (p = 0.044 and 0.003 respectively) while DLCO/VA% were lower (p = 0.008) than in Group 2. Two-dimensional immunoblotting showed protein bands of 20-30 KDa recognized by HP patients but not by workers. LC-MS analysis identified Ig Lambda chain and Apolipoprotein A-I as candidate proteins for distinguishing HP patients from exposed workers.

Conclusions: Two pigeon proteins were identified that may play a role in the development of pathological differences between HP patients and exposed workers. DLCO/VA may have a predictive value in the development of HP disease.

Background: Most asthma diagnoses and patient care take place in primary care settings. Electronic medical records (EMRs) offer an opportunity to utilize technology to improve asthma diagnosis and care. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in primary care EMRs, to enable surveillance, benchmarking, and quality improvement in primary care settings. The objective of this study was to develop a case definition for suspected and confirmed asthma for use in a primary care sentinel surveillance system.

Methods: A single chart abstractor conducted a manual audit of 776 randomly selected patient charts from an academic primary care practice EMR in Kingston, Ontario. Following the single chart abstractor classification, a consensus on chart classification as "not asthma", "suspected asthma", or "confirmed asthma" was achieved between the abstractor, a family physician, and a respirologist using Canadian Thoracic Society (CTS) criteria. Case definition algorithms based on billing codes, clinical data elements and medications were applied to the site's Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data for the same charts and compared to abstractor classifications to determine each algorithm's measurement properties.

Results: The prevalence of suspected and confirmed asthma were 7.3% (n = 54) and 2.4% (n = 18), respectively. None of the proposed case definitions could differentiate between suspected and confirmed asthma. One algorithm consisting of billing, clinical, and medication elements had the highest Youden's Index for either suspected or confirmed asthma. The algorithm had a sensitivity of 81%, a specificity of 96%, positive predictive value of 71%, negative predictive value of 98%, and a Youden's Index of 0.77 for combined suspected or confirmed asthma cases.

Conclusion: An EMR case definition for suspected or confirmed adult asthma has been validated for use in CPCSSN. Implementation of this case definition will enable the development of a surveillance electronic tool (eTool) for adult asthma that can foster quality improvement.

Background: Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders.

Methods: Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented.

Results: One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2-4 foods after 3, 6, and 12 months of the food ladder compared to baseline.

Conclusion: The Canadian food ladders are safe tools for children with cow's milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline.

Background: Osimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically.

Case presentation: We present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it.

Conclusion: This case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but severe and sometimes fatal adverse drug reaction that is known to occur with a number of antiepileptic drugs. It often follows a prolonged clinical course, which can worsen even after discontinuing the causative drug and administering steroid treatment. Failure to promptly identify the delayed involvement of vital organs, such as the heart and liver, may result in irreversible organ failure and death. We report a case of a presumed sudden death of a young woman who had a documented history of a protracted intermittent hypersensitivity reaction to lamotrigine. Postmortem examination revealed the presence of eosinophilic myocarditis and submassive hepatic necrosis diagnostic of fatal DRESS syndrome that progressed despite early discontinuation of the medication and improvement of dermatologic and hematologic symptoms following steroid therapy.

Background: There is an urgent need to understand the interplay between SARS-CoV-2 and HIV to inform risk-mitigation approaches for HIV-infected individuals.

Objectives: We conclude that people living with HIV (PLWH) who are antiretroviral therapy (ART) naïve could be at a greater risk of morbidity or mortality once co-infected with SARS-CoV-2.

Methods: Here, we performed extensive immune phenotyping using flow cytometry. Moreover, to compare the range of values observed in the co-infected case, we have included a larger number of mono-infected cases with SARS-CoV-2. We also quantified soluble co-inhibitory/co-stimulatory molecules in the plasma of our patients.

Results: We noted a robust immune activation characterized by the expansion of CD8⁺ T cells expressing co-inhibitory/stimulatory molecules (e.g. PD-1, TIM-3, 2B4, TIGIT, CD39, and ICOS) and activation markers (CD38, CD71, and HLA-DR) in the co-infected case. We further found that neutrophilia was more pronounced at the expense of lymphopenia in the co-infected case. In particular, naïve and central memory CD8⁺ T cells were scarce as a result of switching to effector and effector memory in the co-infected case. CD8⁺ T cell effector functions such as cytokine production (e.g. TNF-α and IFN-γ) and cytolytic molecules expression (granzyme B and perforin) following anti-CD3/CD28 or the Spike peptide pool stimulation were more prominent in the co-infected case versus the mono-infected case. We also observed that SARS-CoV-2 alters T cell exhaustion commonly observed in PLWH.

Conclusion: These findings imply that inadequate immune reconstitution and/or lack of access to ART could dysregulate immune response against SARS-CoV-2 infection, which can result in poor clinical outcomes in PLWH. Our study has implications for prioritizing PLWH in the vaccination program/access to ART in resource-constrained settings.