Allergy Asthma & Clinical Immunology
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Published By Springer (Biomed Central Ltd.)

1710-1492, 1710-1492

2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Leila Khani ◽  
Mir Hadi Jazayeri ◽  
Reza Nedaeinia ◽  
Mahmood Bozorgmehr ◽  
Seyed Masood Nabavi ◽  
...  

Abstract Background Multiple sclerosis (MS) and neuromyelitis optica syndrome disease (NMOSD) are inflammatory diseases of the central nervous system. The pathogenesis and treatments for these two conditions are very different. Natural killer (NK) and natural killer T (NKT) cells are immune cells with an important role in shaping the immune response. B cells are involved in antigen presentation as well as antibody and cytokine production. There is conflicting evidence of the roles of NK, NKT, and B cells in the two conditions. We aimed to compare the frequency of CD3−CD16+CD56+NK, CD3+ CD56+ NKT, and CD5+CD19+ B cells in the peripheral blood and serum Interleukin-10 (IL-10) in patients with MS and NMOSD. Methods CD19+CD5+ B, CD3− CD16+CD56+ NK, and CD3+CD56+ NKT cells were quantitated by flow cytometry in 15 individuals with Interferon-Beta (IFN-β) treated relapsing–remitting MS (RRMS), 15 untreated RRMS, and 15 NMOSD patients as well as 30 healthy controls (HC). Serum IL-10 was measured using an enzyme-linked immunosorbent assay (ELISA). Results The percentage of CD3−CD56+CD16+ NK cells in the peripheral blood of IFN-treated MS (1.81 ± 0.87) was significantly lower than for untreated RRMS (4.74 ± 1.80), NMOSD (4.64 ± 1.26) and HC (5.83 ± 2.19) (p < 0.0001). There were also differences for the percentage of CD3−CD16+ and CD3−CD56+ cells (p < 0.001 and p < 0.0007; respectively). IFN-treated RRMS (2.89 ± 1.51) had the lowest proportion of CD3+CD56+ among the study groups (p < 0.002). Untreated RRMS (5.56 ± 3.04) and NMOSD (5.47 ± 1.24) had higher levels of CD3+CD56+ than the HC (3.16 ± 1.98). The mean percentage of CD19+CD5+ B cells in the peripheral blood of untreated RRMS patients (1.32 ± 0.67) was higher compared to the patients with NMOSD (0.30 ± 0.20), HC (0.5 ± 0.22) and IFN-treated RRMS (0.81 ± 0.17) (p < 0.0001). Serum interleukin-10 was significantly higher in the IFN-treated RRMS (8.06 ± 5.39) and in HC (8.38 ± 2.84) compared to untreated RRMS (5.07 ± 1.44) and the patients with NMOSD (5.33 ± 2.56) (p < 0.003). Conclusions The lower proportion of CD3−CD56+ CD16+ NK and CD3+CD56+ cells in peripheral blood of IFN-treated RRMS compared to other groups suggests the importance of immunomodulation in patients with RRMS disorder. Based on the differences in CD19+CD5+ B cells and serum IL-10 between patients and HC, supplementary assessments could be of value in clarifying their roles in autoimmunity.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Marcus Maurer ◽  
Markus Magerl ◽  
Emel Aygören-Pürsün ◽  
Konrad Bork ◽  
Henriette Farkas ◽  
...  

Abstract Background Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects. As better tolerated targeted therapies become available, attenuated androgen withdrawal is increasingly considered by physicians and their patients with HAE. Attenuated androgens withdrawal has not been systematically studied in HAE, although examination of other disorders indicates that attenuated androgen withdrawal may result in mood disturbances and flu-like symptoms. Standardized protocols for attenuated androgen discontinuation that continue to provide control of attacks while limiting potential attenuated androgen withdrawal symptoms are not established as the outcomes of different withdrawal strategies have not been compared. We aim to describe the challenges of attenuated androgen discontinuation in patients with HAE and how these may continue into the post-androgen period. Case presentation We present a retrospective case series of 10 patients with confirmed type I HAE who have discontinued prophylactic treatment with attenuated androgens. The most common reason for attenuated androgen discontinuation was side effects. Attenuated androgens were either immediately withdrawn, tapered and/or overlapped with another treatment. The major challenge of discontinuation was the management of an increased frequency and severity of HAE attacks in some patients. Conclusions Healthcare teams need to undertake careful planning and monitoring after attenuated androgens discontinuation, and modify treatment strategies if HAE control is destabilized with an increased number of attacks. Discontinuation of attenuated androgens is definitively an option in an evolving HAE treatment landscape, and outcomes can be favourable with additional patient support and education.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Mayra D. Álvarez-Santos ◽  
Marisol Álvarez-González ◽  
Elizabeth Eslava-De-Jesus ◽  
Angel González-López ◽  
Ivonne Pacheco-Alba ◽  
...  

Abstract Background Airway obstruction (AO) in asthma is driven by airway smooth muscle (ASM) contraction. AO can be induced extrinsically by direct stimulation of ASM with contractile agonists as histamine, or by indirect provocation with antigens as ovalbumin, while the airway tone is dependent on intrinsic mechanisms. The association of the ASM phenotypes involved in different types of AO and airway tone in guinea pigs was evaluated. Methods Guinea pigs were sensitized to ovalbumin and challenged with antigen. In each challenge, the maximum OA response to ovalbumin was determined, and before the challenges, the tone of the airways. At third challenge, airway responsiveness (AR) to histamine was evaluated and ASM cells from trachea were disaggregated to determinate: (a) by flow cytometry, the percentage of cells that express transforming growth factor-β1 (TGF-β1), interleukin-13 (IL-13) and sarco-endoplasmic Ca2+ ATPase-2b (SERCA2b), (b) by RT-PCR, the SERCA2B gene expression, (c) by ELISA, reduced glutathione (GSH) and, (d) Ca2+ sarcoplasmic reticulum refilling rate by microfluorometry. Control guinea pig group received saline instead ovalbumin. Results Antigenic challenges in sensitized guinea pigs induced indirect AO, AR to histamine and increment in airway tone at third challenge. No relationship was observed between AO induced by antigen and AR to histamine with changes in airway tone. The extent of antigen-induced AO was associated with both, TGF-β1 expression in ASM and AR degree. The magnitude of AR and antigen-induced AO showed an inverse correlation with GSH levels in ASM. The airway tone showed an inverse association with SERCA2b expression. Conclusions Our data suggest that each type of AO and airway tone depends on different ASM phenotypes: direct and indirect AO seems to be sensitive to the level of oxidative stress; indirect obstruction induced by antigen appears to be influenced by the expression of TGF-β1 and the SERCA2b expression level plays a role in the airway tone.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Mongkhon Sompornrattanaphan ◽  
Ranista Tongdee ◽  
Chamard Wongsa ◽  
Anupop Jitmuang ◽  
Torpong Thongngarm

Abstract Background Nodular regenerating hyperplasia (NRH) is the most common liver involvement in common variable immunodeficiency (CVID). Most patients are asymptomatic with gradually increasing alkaline phosphatase (ALP) and mildly elevated transaminase enzymes over the years. We report the first case of fatal liver mass rupture in a CVID patient with probable NRH. Case presentation A 24-year-old man was diagnosed with CVID at the age of 1.25 years. Genetic testing revealed a transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI) mutation. He had been receiving intravenous immunoglobulin (IVIg) replacement therapy ever since then. The trough level of serum IgG ranged between 750–1200 mg/dL. However, he still had occasional episodes of lower respiratory tract infection until bronchiectasis developed. At 22 years old, computed tomography (CT) chest and abdomen as an investigation for lung infection revealed incidental findings of numerous nodular arterial-enhancing lesions in the liver and mild splenomegaly suggestive of NRH with portal hypertension. Seven months later, he developed sudden hypotension and tense bloody ascites. Emergency CT angiography of the abdomen showed NRH with intrahepatic hemorrhage and hemoperitoneum. Despite successful gel foam embolization, the patient died from prolonged shock and multiple organ failure. Conclusions Although CVID patients with NRH are generally asymptomatic, late complications including portal hypertension, hepatic failure, and hepatic rupture could occur. Therefore, an evaluation of liver function should be included in the regular follow-up of CVID patients.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Jingjing Wang ◽  
Zeyi Zhang ◽  
Ou Chen

Abstract Background Asthma is a common multifactorial disease affecting millions worldwide. The Barker hypothesis postulates an association between later onset disease risk and energy exposure in utero. Birth weight corrected for gestational age is better for measuring the infant size, which reflects energy exposure in utero. Findings on asthma and birth weight corrected for gestational age have been inconclusive. We conducted a meta-analysis to further clarify the relationship between birth weight corrected for gestational age and later onset asthma. Methods A systematic literature search of the PubMed, Web of Science, MEDLINE, and Scopus databases up to January 2021 was conducted. The subject terms were used as follows: “asthma”, “allerg*”, “respiratory”, “birth weight”, “gestational age”, “birth outcomes”, “intrauterine growth retardation”, and “fetal growth restriction”. Results We included 12 articles with data from a total of 6,713,596 people. Compared with non-SGA infants, infants small for gestation age (SGA) were not associated with an increased risk of asthma (OR = 1.07; 95% CI 0.94–1.21). However, in the subgroup analysis, we found an increased risk of later onset asthma among SGA in studies conducted in Asia, with a large sample size, and defined asthma through medical records rather than questionnaires. Large for gestational age (LGA) was not associated with an increased risk of asthma when non-LGA or appropriated for gestational age (AGA) infants were used as the reference (OR = 1.02; 95% CI 0.90–1.16; OR = 1.01; 95% CI 0.88–1.15). Conclusion These results indicated that neither SGA nor LGA was associated with an increased risk of asthma. However, considering the limitations of the research, these results should be interpreted with caution.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Julia A. Cahill ◽  
Preena Simritpreet Sahota ◽  
Manstein Kan

Abstract Background True allergy to metronidazole, a common anti-infective in clinical practice, is rarely reported in the literature. In the case of Trichomonas, there are few alternatives to the nitrimidazole class of drugs, and the alternatives that do exist are associated with worse clinical outcomes. Accordingly, for the rare patients with Type 1 hypersensitivity reactions to metronidazole but compelling need, desensitization protocols have been adapted previously. Reactions during these protocols appear common. Patients in previous regimens have required higher level care for observation, which is costly and resource-intensive. Case presentation We report here on a successful outpatient two-day regimen for metronidazole desensitization. Our patient had compelling indication for metronidazole, but reacted after receiving the very first dose of a previously described desensitization protocol. Accordingly, the protocol was adapted further. Despite this, she went on to develop objective hives prior to reaching the full intended dose. With appropriate symptom management and pre-medication on the second day in clinic, she was successfully desensitized and able to complete a week of full-dose metronidazole. No acute care resources were needed. Conclusion We propose this two-day desensitization regimen for patients who react during the previously described desensitization protocols. This regimen was effective and safe, and did not necessitate the use of acute-care resources. Two-day desensitization protocols while relatively uncommon, can be successful.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Erika Yue Lee ◽  
Christine Song ◽  
Peter Vadas ◽  
Matthew Morgan ◽  
Stephen Betschel

Abstract Rationale There exists a geographic barrier to access CIA care for patients who live in rural communities; telemedicine may bridge this gap in care. Herein we characterized the use of telemedicine in CIA at a population-based level and single centre. Methods Before the COVID-19 pandemic, telemedicine care was provided via the Ontario Telemedicine Network (OTN) in Ontario, Canada. Descriptive data were collected from the OTN administrative database and from electronic medical records at a single academic centre during 2014 to 2019. The potential distance travelled and time saved by telemedicine visits were calculated using postal codes. Results A total of 1298 telemedicine visits was conducted over OTN, with an average of 216 visits per year. Only 11% of the allergists/immunologists used telemedicine to provide care before the COVID-19 pandemic. In the single centre that provided the majority of the telemedicine care, 66% patients were female and the overall mean age was 46. The most common diagnosis was immunodeficiency (40%), followed by asthma (13%) and urticaria (11%). Most patients required at least one follow-up via telemedicine. The average potential two-way distance travelled per visit was 718 km and the average potential time travelled in total was 6.6 h. Conclusion Telemedicine was not widely used by allergists/immunologists in Ontario, Canada before the COVID-19 pandemic. It could offer a unique opportunity to connect patients who live in remote communities and allergists/immunologists who practice in urban centres in Canada. Independent of the current pandemic, our study further highlights the need for more physicians to adopt and continue telemedicine use as well as for healthcare agencies to support its use as a strategic priority once the pandemic is over.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan Benes ◽  
Roman Skulec ◽  
Dalibor Jilek ◽  
Ondrej Fibigr ◽  
Vladimir Cerny

AbstractRefractory status asthmaticus is the cause of rare cases of in-hospital death due to acute bronchial asthma. The most severe cases unresponsive to first, second and next line treatment may be fatal despite aggressive organ support with invasive ventilation and extracorporeal membrane oxygenation. Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, is an approved add-on biological treatment for severe asthma. However, it is not indicated in an acute setting. Here, we report the case of a young patient with status asthmaticus fully dependent on extracorporeal membrane oxygenation refractory to any therapy for six days, who was successfully treated with omalizumab.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Peter Stepaniuk ◽  
Amin Kanani

Abstract Background Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent angioedema episodes which is caused by deficiency or dysfunction of C1 inhibitor. Although complement dysregulation has historically been shown to be associated with various malignancy and immune disorders, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions. Case presentation We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren’s syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients. Conclusions Our case series identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions and that in patients with angioedema, C1 inhibitor deficiency and malignancy, a diagnosis of HAE should still be considered in addition to acquired angioedema (AAE).


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Zainab Ridha ◽  
Marc-Antoine Bédard ◽  
Anna Smyrnova ◽  
Olivier Drouin ◽  
Aniela Pruteanu ◽  
...  

Abstract Background The Global Initiative for Asthma has only recently added tiotropium bromide as adjunct controller therapy in severe asthma (Step 4 or 5) in adults (2015) and children (2019). Although not yet approved for pediatric use by Health Canada, it has been occasionally offered by asthma specialists as a therapeutic trial in children with troublesome asthma or treatment for adverse effects. The objective of this study was to describe the indications and real-life clinical experience in initiating tiotropium in children with asthma. Methods We designed a retrospective mixed-method case series study of children aged 1–17 years who initiated tiotropium in our tertiary-care centre between 2013 and 2020. Clinical information was extracted from electronic medical records and tiotropium dispensing, from drug claims. Parents/children and physicians independently completed a questionnaire about treatment goals, perceived efficacy, safety, satisfaction, and lessons learned. Results The 34 (11 females; 23 males) children had a median (range) age of 9.1 (1.4–17.8) years. Children were primarily on Step 4 (85%) or 5 (6%) prior to tiotropium initiation, yet most (84%) did not increase their treatment step after tiotropium initiation. The physicians’ treatment goals were to improve asthma control, alleviate adverse effects of current therapy, and/or improve lung function. The most improved symptoms were coughing/moist cough, difficulty breathing, whistling breath, and bronchial secretions/mucus. Although most parents and physicians reported a significant benefit with tiotropium bromide, physicians particularly remarked, as their “lesson learned’, on the improvement in chronic symptoms in asthmatic children, particularly those with prominent moist cough and in lung function, in those with seemingly none (or incompletely) reversible obstruction as well as the ability to decrease the ICS and/or LABA dose to lessen adverse effects. A few physicians raised caution on the risk of lower adherence with an additional inhaler. Conclusion In children with severe asthma on Step 4 or 5, tiotropium bromide was primarily used as substitute, rather than additional, adjunct therapy to improve asthma control, alleviate adverse effects, and/or to improve lung function. The latter two indications, combined with its perceived effectiveness in children with prominent moist cough, also suggest additional indications of tiotropium to be formally explored.


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