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  • A contemporary look at allergic conjunctivitis
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-21
    Pascale Dupuis; C. Lisa Prokopich; Alexander Hynes; Harold Kim

    Allergic eye disease is common, yet often overlooked in North America. In the U.S., up to 40% of the population is deemed to be affected and this number is growing. Symptoms and signs of ocular allergy can lead to decreased productivity and negatively impact quality of life (QoL). Various treatment options exist to achieve symptom control. For allergic conjunctivitis, ophthalmic agents include antihistamines, mast cell stabilizers, dual-activity agents, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and some off-label treatments. Immunotherapy is recommended as a therapeutic option. This review provides a summary of the forms of ocular allergies, with a focus on symptoms and signs, impact on QoL, physical examination, diagnosis and therapeutic options of allergic conjunctivitis. Through multidisciplinary collaborations, a simplified algorithm for the treatment of allergic conjunctivitis is proposed for Canadian clinical practice.

  • Antibiotic hypersensitivity and adverse reactions: management and implications in clinical practice
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-21
    Anthony Jourdan; Brijit Sangha; Eric Kim; Sohrab Nawaz; Vikram Malik; Radhika Vij; Sudhir Sekhsaria

    Studies have shown the discrepancy between self-reported antibiotic allergies and true allergies. Inaccurate reporting of antibiotic hypersensitivities can limit treatment options and result in use of more expensive antibiotics and contribute to resistance. This retrospective cohort chart review obtained data on 16,515 patients after obtaining IRB approval. Patients who had an antibiotic adverse reaction were identified, recorded, and their management reviewed. 7926 patients were selected from inpatient internal medicine clinics, 8042 patients from outpatient internal medicine clinics, and 547 from orthopedic clinics. The prevalence of reported antibiotic sensitivity in our study was 9.89% (n = 1624). Reported antibiotic sensitivity was 8.88% (n = 704) in inpatient settings as compared to 11.2% (n = 902) and 5.12% (n = 28) in medicine and orthopedic outpatient settings respectively. The top five antibiotic adverse reactions reported were penicillins (42%), sulfonamides (25%), fluoroquinolones (4.3%), tetracyclines (4.2%), and macrolides (3.5%). In all settings, penicillins and sulfonamides adverse reactions were the top two reportings. 11.88% (n = 193) of patients with reported adverse reactions reported sensitivities to multiple antibiotics. Our study demonstrated high prevalence of reported antibiotic sensitivity in three clinical settings. However, a significant portion of these patients may not be truly hypersensitive to these antibiotics. There is a need for increased awareness among medical professionals about the importance of detailed history taking and management of self-reported antibiotic allergies to combat unnecessary use of antibiotics.

  • Dust mite ingestion-associated, exercise-induced anaphylaxis: a case report and literature review
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-06
    Mongkhon Sompornrattanaphan; Yanisa Jitvanitchakul; Nat Malainual; Chamard Wongsa; Aree Jameekornrak; Orathai Theankeaw; Torpong Thongngarm

    Oral mite anaphylaxis (OMA) is a condition characterized by severe allergic reactions after ingesting food containing dust mite-contaminated flour. Physical exertion is recognized as a common trigger factor inducing anaphylaxis. The association of OMA with exercise-induced anaphylaxis has rarely been reported. We report a 29-year-old Thai woman who had dust mite ingestion-associated, exercise-induced anaphylaxis who tolerated the same bag of contaminated flour without exercise. A sample of contaminated cooking flour was examined under a light microscope. Living mites, Dermatophagoides farinae, were detected by a medical entomologist based on the morphology. We performed skin test to both mite-contaminated and newly opened Gogi® cooking flour, common aeroallergens, food allergens, and all other ingredients in the fried coconut rice cake 5 weeks after the anaphylactic episode. Specific IgE tests, using ImmunoCAP were also performed. Dust mite ingestion-associated, exercise-induced anaphylaxis may be misdiagnosed as wheat-dependent exercise-induced anaphylaxis and should be suspected in patients with anaphylaxis linked to food intake and exercise, but who have no apparent evidence to the index food ingredients on allergy workup.

  • Use of mepolizumab in adult patients with cystic fibrosis and an eosinophilic phenotype: case series
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-06
    Lijia Zhang; Larry Borish; Anna Smith; Lindsay Somerville; Dana Albon

    Cystic fibrosis (CF) is characterized by inflammation, progressive lung disease, and respiratory failure. Although the relationship is not well understood, patients with CF are thought to have a higher prevalence of asthma than the general population. CF Foundation (CFF) annual registry data in 2017 reported a prevalence of asthma in CF of 32%. It is difficult to differentiate asthma from CF given similarities in symptoms and reversible obstructive lung function in both diseases. However, a specific asthma phenotype (type 2 inflammatory signature), is often identified in CF patients and this would suggest potential responsiveness to biologics targeting this asthma phenotype. A type 2 inflammatory condition is defined by the presence of an interleukin (IL)-4high, IL-5high, IL-13high state and is suggested by the presence of an elevated total IgE, specific IgE sensitization, or an elevated absolute eosinophil count (AEC). In this manuscript we report the effects of using mepolizumab in patients with CF and type 2 inflammation. We present three patients with CF (63, 34 and 24 year of age) and personal history of asthma, who displayed significant eosinophilic inflammation and high total serum IgE concentrations (type 2 inflammation) who were treated with mepolizumab. All three patients were colonized with multiple organisms including Pseudomonas aeruginosa and Aspergillus fumigatus and tested positive for specific IgE to multiple allergens. We examined the effect of mepolizumab on patients’ lung function (FEV1), blood markers of type 2 inflammation, systemic corticosteroid use and frequency of CF exacerbations. One patient had a substantial increase in lung function after starting mepolizumab and all three patients had a substantial benefit in regards to reduced oral CCS use. While none of the patients showed significant changes in the exacerbation rates there was markedly reduced requirements for oral CCS with exacerbations. In addition, mepolizumab had a positive effect on type 2 inflammatory markers, reducing markers of allergic inflammation in all 3 patients. Mepolizumab appears to have a positive effect on clinical course in patients with CF presenting with a type 2 phenotype characterized by allergic sensitization and hyper-eosinophilia.

  • Epidemiology and associated factors of atopic dermatitis in Malagasy children
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-06
    F. A. Sendrasoa; I. M. Ranaivo; N. H. Razanakoto; M. Andrianarison; O. Raharolahy; V. T. Ratovonjanahary; M. Sata; M. F. Rakotoarisaona; L. S. Ramarozatovo; F. Rapelanoro Rabenja

    Little is known about the epidemiology and associated factors of childhood AD in the markedly different, low-income, tropical environment like Madagascar. We aim to assess the epidemiology and associated factors of AD in individuals fewer than 15 years of age in Antananarivo Madagascar. It was a retrospective and descriptive study over a period of 7 years (2010 to 2016) in children 6 months to 14 years in the Department of Dermatology, Joseph Raseta Befelatanana Antananarivo Madagascar. The diagnosis of AD was based on clinical data. The prevalence of AD was 5.6% in children aged 6 months to 14 years. The details of 151 cases of atopic dermatitis were analyzed. The mean age of patients was 4 years. There was a female preponderance (sex ratio: 0.7). A family history of AD was noted in 56 cases (37%). No association between breast-feeding and AD was found. The age of onset of AD was before the age of 3 months in 7.5% and between 6 months to 5 years in 70%. Children born in March (dry season) had the highest risk of AD. Consultations for AD increased during the winter (from July to October; p = 0.005). However, the prevalence of AD was similar in urban and rural areas. Weather may have an impact on the prevalence of atopic dermatitis in Madagascar. No significant correlation was found between the duration of breastfeeding and AD, as well as urbanization.

  • Type II acquired cutis laxa associated with recurrent urticarial vasculitis: brief report
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2020-01-03
    Amelia Nabatanzi; Siqi Da; Musa Male; Siyuan Chen; Changzheng Huang

    Cutis laxa is a connective tissue disease characterized by loose, wrinkled, and redundant skin. It is either inherited or acquired. In most cases, acquired cutis laxa is associated with neoplasms, drugs, and autoimmune diseases. We present a rare case of acquired cutis laxa following a recurrent urticaria-like eruption in the absence of an autoimmune disease, neoplasm, drugs and or syndrome. We report a case of a 45-year-old Chinese lady with a 1-year history of widespread pruritic urticarial eruption and a 6-month history of progressive skin wrinkling. On examination, the patient appeared older than her actual age, with apparent wrinkling on the mid-torso with generalized smooth, erythematous macules and wheals. A family history of similar conditions was absent. Biopsy revealed hypersensitivity and atrophy. Following the Food and Drug Administration (FDA) guidelines, we administered antihistamines, which relieved the itching, but her hyperpigmentation and cutis laxa never improved. Our case shows that the decrease of elastic fibers may be associated with the infiltration of inflammatory cells in the dermis. This supports the hypothesis that chemical mediators may play a major role in the destruction of elastic fibers, thus causing cutis laxa. In addition, we advise practitioners to take a complete clinical and family history to determine if the condition is inherited or acquired.

  • Kimura’s disease affecting multiple body parts in a 57-year-old female patient: a case report
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-30
    Bo Yu; Guoxing Xu; Xiaofan Liu; Wen Yin; Hao Chen; Baoqing Sun

    Kimura’s disease (KD) is a rare chronic inflammatory disease with unknown etiology. It usually manifests as a painless soft tissue mass or subcutaneous nodule on one side of the patient’s head and/or neck and rarely affects multiple parts of the body. The disease is more common among young Asian males. A 57-year-old Chinese woman complained of multiple masses on her body surface. Ultrasonography was used to examine the retroperitoneal, bilateral neck, bilateral supraclavicular, bilateral axillary, and bilateral inguinal superficial lymph nodes. Enlargement of multiple lymph nodes was found in all areas. Many solid nodules were also found in the right parotid gland and right posterior neck area, respectively. Numerous solid nodules were seen on the left chest wall. Laboratory tests showed that the percentage of eosinophils in the whole blood was 39.40%, total immunoglobulin E (IgE) level was > 5000 kU/L, and serum special IgE to Phadiatop (inhaled allergens) and fx5 (food allergens) were 1.01 and 1.04 kUA/L, respectively. After a complete examination, the masses located in the right neck, retroauricular and left axillary regions, and left chest wall were resected directly. Postoperative pathological findings revealed KD. The case discussed in this study is extremely rare and did not meet the common affected areas and age characteristics of KD. This presentation can be used to improve disease awareness among physicians.

  • Expression of COX-1, COX-2, 5-LOX and \(\hbox {CysLT}_2\) in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-26
    Monique Vorsprach; Christoph Arens; Stephan Knipping; Dörte Jechorek; Sabine Stegemann-Koniszewski; Eva Lücke; Jens Schreiber

    Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance. We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ($$\hbox {CysLT}_2$$) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, $$n=23$$) as compared to patients with aspirin tolerant asthma (ATA, $$n=17$$) and a control group with nasal polyps, but without asthma (NPwA, $$n=15$$). Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing. We observed a stronger expression of 5-LOX and $$\hbox {CysLT}_2$$ in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and $$\hbox {CysLT}_2$$ between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups. The AA-metabolizing enzymes and the $$\hbox {CysLT}_2$$ were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.

  • Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-18
    Yahao Ren; Takamichi Ichinose; Miao He; Seiichi Youshida; Masataka Nishikawa; Guifan Sun

    Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS. The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2−/−, TLR4−/−, and adaptor protein myeloid differentiation factor 88 (MyD88)−/− BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2−/−, TLR4−/− and MyD88−/− BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed. In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2−/− mice than in TLR4−/− mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4−/− mice treated with OVA + H-ASD + LPS. In MyD88−/− mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible. These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

  • The impact of perennial allergic rhinitis with/without allergic asthma on sleep, work and activity level
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-06
    Mercedes Rodriguez Romano; Stephanie James; Emily Farrington; Richard Perry; Lisa Elliott

    Allergic respiratory diseases such as allergic rhinitis (AR) and allergic asthma (AA) are common conditions that can influence sleep and daytime functioning. However, the significance of this impact is unclear—particularly in perennial allergy sufferers. This study investigates the impact of perennial allergy on sleep, daily activities and productivity. Adults with self-reported or physician-diagnosed perennial AR aged ≥ 18 years were recruited in Denmark, France, Germany and Sweden. Allergy sufferers were identified using online panels closely matching national population characteristics for each country. Impact on sleep, work, productivity and activity (by the Work, Productivity and Activity Index) were analysed. Descriptive analyses were conducted. In total, 511 subjects with perennial AR (47.4% also with seasonal allergy) completed the survey. Most subjects (77.5%) had a physician-diagnosis of AR; 46.4% were diagnosed with both AA and AR. Most subjects (65.2%) reported sensitisation to house dust mites. Of all subjects, 66.0% reported sleep problems. Subjects with sleep problems woke, on average, 3.8 times per night, with 92.0% taking 15+ min to fall asleep (22.2% took 60+ min). Upon waking at night, 40.8% struggled to get back to sleep, and 69.2% had difficulties waking in the morning due to tiredness. Disturbances in daily functioning due to sleep issues were reported in 85.5–95.0% of subjects with sleep problems across all aspects investigated. Overall work and activity impairment were 53.3% and 47.1%, respectively. Sleep issues were more frequent (78.1% vs 54.7%) in those diagnosed with both AR and AA compared to AR alone, and more burdensome, with a greater impact on daily functioning (47.0% vs 33.3%) and impairment in work and activity (62.0% and 54.9% vs 39.3% and 35.2%, respectively). Of all subjects, 20.5% were receiving AIT at the time of the survey; of these, 36.4% reported moderate or great improvement in sleep due to allergy treatment. In perennial AR sufferers, sleep problems are common and impact on daily functioning, with results indicating a greater burden in those with both AR and AA compared to AR alone.

  • Diagnosis of Vespa affinis venom allergy: use of immunochemical methods and a passive basophil activation test
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-04
    Peshala Gunasekara; S. M. Handunnetti; Sunil Premawansa; Pradeep Kaluarachchi; Chandima Karunatilake; Indra P. Ratnayake; R. K. S. Dias; G. A. S. Premakumara; W. M. D. K. Dasanayake; Suranjith L. Seneviratne; Rajiva de Silva

    Allergy to Vespa affinis venom is common in the Asia Pacific region. Venom preparations for diagnosis are not commercially available for this species. The prominent allergens in V. affinis venom were identifiedusing immunochemical methods. Use of ImmunoCAP of Vespula vulgaris crude venom/its components and a passive basophil activation test (BAT) in the diagnosis of patients who had anaphylaxis to V. affinis venom (n = 30) were also accessed. The IgE double-positivity rates (positive to both hornet and honeybee) in ImmunoCAP and the passive BAT were determined. High IgE reactivity was seen with the five allergens in V. affinis venom; 96% (29/30) for 34 and 24 kDa, 93% (28/30) for 45 kDa and 90% (27/30) reactivity for the 100 and 80 kDa respectively. IgE cross-reactivity was low with ImmunoCAP using V. vulgaris venom (43%; 13/30) and Ves v1 (3%; 1/30), but relatively high with Ves v5 (73%; 22/30). All patients (100%) were positive to V. affinis venom in passive BAT. In ImmunoCAP, a high double-positivity rate (76%; 23/30) was detected while no double-positivity was detected in passive BAT. High IgE reactivity for five allergens of V. affinis points to the potential of using these allergens in component resolved diagnosis (CRD). The passive BAT has shown its importance as a promising diagnostic tool with high accuracy. It would be particularly useful in cases with doubtful double-positive results of other diagnostic tests.

  • Mechanism(s) of prolonged attenuation of allergic responses after modulation of idiotypic regulatory network
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-04
    R. M. Gorczynski; T. Maqbool; G. Hoffmann

    We showed previously that allergic reactivity to ovalbumin (OVA) could be regulated in mice following perturbation of immune networks using combinations of an immune Ig along with anti-idiotypic Ig. We have explored features of this regulation including: its persistence after cessation of administration of combined Igs; the ability of heterologous Igs to produce immunoregulation; a role for Treg induction in regulation; and the ability to attenuate responses in mice pre-sensitized to an allergic stimulus. BALB/c mice were sensitized to OVA. Mice also received 5 weekly injections of immune Ig or anti-idiotype Ig (at separate sites) from either homologous (mouse) or heterologous (human) sources. In the latter case pooled IVIG (given IM, hence hereafter IMIG) was used as a source of anti-idiotype Ig, and human anti-Tet as immune Ig. Injections of the Ig were given from the time of OVA sensitization (to attenuate development of immunity), or after pre-sensitization of mice (to attenuate existing allergic responses). All mice were assayed for development of OVA-specific serum IgE and IgG, as well as the production of OVA-induced IL-2, IL-4, IL-13, IL-31 and IL-33 in splenocytes cultured for 72 h. In studies examining possible mechanism(s) responsible for inhibition of immunity mice received, in addition to the Ig treatments described, infusion of depleting anti-CD4, and/or anti-CD8 antibodies, or a mAb to TNFSFR25, known to expand Tregs implicated in regulation of Allo immunity. Combinations of both heterologous and homologous immune Igs and anti-idiotype Igs attenuated OVA allergic responses in both naïve and pre-sensitized mice. This attenuation persisted in mice greater than 14 weeks after cessation of treatment with the Igs used. Finally, depletion of either CD4 or CD8 cells ameliorated the suppressive effect seen, while the combination of anti-CD4 and anti-CD8 essentially abolished suppression. Suppression was further enhanced by anti-TNFSFR25 mAb. We conclude that the combine Ig treatment protocols used produced a long-lasting suppression of allergic immunity, even in pre-sensitized animals. The effects seem to depend upon induction and expansion of Tregs and represents a novel approach to treatment of allergic disease in humans and other animals.

  • The critical role of histology in distinguishing sarcoidosis from common variable immunodeficiency disorder (CVID) in a patient with hypogammaglobulinemia
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-12-02
    Rohan Ameratunga; Yeri Ahn; Dominic Tse; See-Tarn Woon; Jennifer Pereira; Sinead McCarthy; Hilary Blacklock

    Common variable immunodeficiency disorders (CVID) are a rare group of primary immune defects, where the underlying cause is unknown. Approximately 10–20% of patients with typical CVID have a granulomatous variant, which has closely overlapping features with sarcoidosis. Here we describe a young man who sequentially developed refractory Evans syndrome, cauda equina syndrome and most recently renal impairment. Following immunosuppression, he has made a recovery from all three life-threatening autoimmune disorders. As the patient was hypogammaglobulinemic for most of the time while on immunosuppression, vaccine challenges and other tests were not possible. Histological features were in keeping with sarcoidosis rather than the granulomatous variant of CVID. In the brief period when immunosuppression was lifted between the cauda equina syndrome and renal impairment, he normalised his immunoglobulins, confirming sarcoidosis rather than CVID was the underlying cause. We discuss diagnostic difficulties distinguishing the two conditions, and the value of histological features in our diagnostic criteria for CVID in identifying sarcoidosis, while the patient was hypogammaglobulinemic. The key message from this case report is that the characteristic histological features of CVID can be very helpful in making (or excluding) the diagnosis, particularly when other tests are not possible.

  • Variants in the IL17 pathway genes are associated with atopic asthma and atopy makers in a South American population
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-04-29
    Milca de J. Silva; Maria B. R. de Santana; Bruna R. Tosta; Roberta P. Espinheira; Neuza Maria Alcantara-Neves; Maurício L. Barreto; Camila Alexandrina Figueiredo; Ryan dos S. Costa

    Asthma is a complex disorder with multiple phenotypes which can influence its severity and response to treatment. The TH17 lymphocytes producing IL-17A and IL17-F cytokines, may have a role on asthma inflammation. The aim of our study was to evaluate the association between genetic variants in IL17 pathway genes with asthma and atopy markers. Genotyping was performed using a commercial panel in 1245 participants of SCAALA cohort. The study included 91 SNVs in IL-17 pathway genes. Logistic regressions for asthma and atopy markers were performed using PLINK 1.9. In silico analyses were performed using rSNPbase, RegulomeDB, and Gtex portal for in silico gene expression. The T allele of rs1974226 in IL17A was positively associated with asthma (OR: 1.37; 95% CI 1.02–1.82). Also, the T allele of rs279548 was positively associated with asthma (OR: 1.30; 95% CI 1.02–1.64), atopy (OR: 1.62; 95% CI 1.05–2.50) and increased expression of the IL17RC in lung and whole blood tissues. The others genetic variants in the IL17 pathways genes were associated with both protection and risk for asthma development as well as with IgE levels. The genetic variants in IL-17-related genes are associated with the atopic asthma phenotype and IgE production.

  • Association of molds and metrological parameters to frequency of severe asthma exacerbation
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-04-29
    Mona Al-Ahmad; Edin Jusufovic; Nermina Arifhodzic; Tito Rodriguez; Jasmina Nurkic

    Sensitization to airborne molds may be a risk factor for severe asthma and direct cause of asthma exacerbation (AE). A prospective, 1-year (April 2016–March 2017) study, done in Kuwait Allergy Centre, investigated the link between AEs with exposure to outdoor molds and the role of meteorological parameters in mold sensitized patients and compared with non-allergic asthma patients who had asthma deterioration. The total of 676 adult asthmatics with moderate-severe AEs were included and divided into atopic (85.65%) and non-atopic group. Atopy was defined by positive skin prick test (SPT) to at least one inhalant allergen. Data regarding atopy and asthma severity were collected from patient’s records. Patients with symptoms and signs of acute respiratory infection and patient sensitized to indoor allergens only were excluded. Daily count of local pollens (Salsola kali, Bermuda grass) and molds (Aspergillus, Alternaria and Cladosporium) were obtained from the Aerobiology department. Daily metrological parameters (atmospheric pressure-AP, temperature-T and relative humidity-RH) were provided by Kuwait Environment Public Authority. Count of spores/m3 and weather variable are shown on weekly basis. The year circle was divided into 4 Seasons (1, 2, 3, 4) accordingly to typical desert climate. Sensitization to molds was relatively high but significantly less (25.0%) if compared to the pollens sensitization. The highest number of AEs was in season 4 for both molds and pollens sensitized patients. Seasonal patterns for both allergens were significant and positively correlated with RH and AP. In season 1 only, mold sensitized patients showed higher rate of AEs. Non-atopic patients have been less sensitive to increased RH than atopic. Negative correlation with T was similar in both atopic and non-atopic patients. Despite of high rate of sensitization to molds, their significant role in triggering AE was not found in desert environment. Typical desert climate and high allergencity of local weeds outweigh the influence of the molds.

  • Stability of peripheral blood immune markers in patients with asthma
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-04-29
    Nami Shrestha Palikhe; Ana-Maria Bosonea; Cheryl Laratta; Vivek Dipak Gandhi; Drew Nahirney; Angela Hillaby; Miranda Bowen; Mohit Bhutani; Irvin Mayers; Lisa Cameron; Harissios Vliagoftis

    Asthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease. Nineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0. FEV1 (% predicted), FEV1/FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor. Among the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

  • Health effects of diesel engine exhaust emissions exposure (DEEE) can mimic allergic asthma and rhinitis
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-04-29
    Elopy Sibanda; Nancy Makaza

    Patients presenting to Accident and Emergency (A&E) facilities with dyspnoea, coughing, wheezing and nasal blockage are presumed to have allergic asthma and/or rhinitis. Occupational asthma (OA), which has similar symptoms is rarely considered. Triggers of OA include exposure to diesel engine exhaust emissions exposure (DEEEE) that are carcinogenic. We report the case of a patient who presented to an A&E facility with asthma-like symptoms, was treated for allergic asthma. Frequent exacerbations were experienced. Upon investigations it was shown that were symptoms triggered by DEEE exposure. A 36-year-old female bank employee was referred for the evaluation of suspected asthma. She reported a 3-month history of symptoms suggestive of asthma and rhinitis, for which she had previously required A&E treatment. There was no history of atopy. The symptoms only occurred at work or after work. Their onset had coincided with changing offices to one located proximal to a diesel-powered electricity generator. A diagnosis of asthma had been made at the A&E facility and the appropriately used inhaled fluticasone and salbutamol provided limited relief. Skin prick testing was weakly positive for seasonal pollen and house dust mite allergens. Allergen specific IgE tests for 16 regionally relevant aeroallergens were negative. Tests to exclude connective tissue diseases were positive for the anti-Ro-52/TRIM-21 autoantibody. Baseline spirometry values were markedly reduced and bronchodilator administration showed limited reversibility, FEV1 (+ 8%), PEF (+ 5%). Following a 10-day discontinuation of work exposure, the symptoms abated and FEV1 and PEF increased by 10–14% from baseline. The recent onset of asthma, in a non-atopic adult, with workday related symptoms and improvement upon discontinuation of exposure were attributed to passive occupational exposure to DEEE. The diesel generator was relocated, a short course of inhaled fluticasone and oral prednisolone was prescribed and symptoms resolved. This is the first report of the health effects of DEEE mimicking asthma and rhinitis in Zimbabwe. Atypical presentations of adult onset asthma in the absence of a history of either atopy or allergen specific IgE antibody sensitization should trigger in-depth evaluation of occupational exposure in all cases including office workers. Serial monitoring of lung function values should be used for diagnostic and monitoring of the patients.

  • Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-05-16
    Dale L. Bodian; Thierry Vilboux; Natalie S. Hauser

    Hereditary angioedema (HAE) is a potentially life-threatening group of conditions that is often underdiagnosed or misdiagnosed. As HAE is typically diagnosed by detecting C1 inhibitor deficiency, there is a critical need for methods that can identify affected individuals with normal C1 inhibitor. The recent discovery of associations between PLG K330E and ANGPT1 A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing. We analyzed genome sequences from a generally healthy population cohort of 2820 adults and identified PLG K330E in one individual. Subsequent review of this participant’s medical history revealed symptoms clinically attributed to allergy of unknown etiology but that are consistent with published descriptions of HAE patients carrying the PLG K330E variant. The participant, a 31 year old female, reported lip and tongue angioedema, without wheals, which did not respond to treatment with steroids or antihistamines. The genotype-first approach demonstrated that detection of PLG K330E in undiagnosed or misdiagnosed individuals can identify patients actually affected with HAE-U. The genetic diagnosis will facilitate selection of appropriate treatment, discontinuation of therapies ineffective for this condition, and timely diagnosis of affected family members. The results support a role of PLG K330E in the pathogenesis of HAE and suggest that genetic testing be considered as an approach to diagnose patients with unexplained angioedema.

  • Pleiotropic microRNA-21 in pulmonary remodeling: novel insights for molecular mechanism and present advancements
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-05-20
    Congshan Jiang; Yuanxu Guo; Hongchuan Yu; Shemin Lu; Liesu Meng

    MicroRNA-21 (miR-21), probably one of the most studied miRNAs to date, is found pleiotropic in various biological events. Its emerging role in pulmonary remodeling has attracted extensive attention. This review summarizes the genomic information of its primary transcript and various transcriptional regulations on its promoter. In addition, the role of miR-21 in pulmonary remodeling related signaling such as transforming growth factor β (TGF-β), bone morphogenetic protein (BMP), epidermal growth factor receptor (EGFR) and Notch signaling is discussed. Various validated miR-21 target genes participate in controlling of the overactive cell accumulation, smooth muscle contraction, inflammatory stress (trigger for lung epithelium damage), extracellular matrix deposition and hypoxia-induced disorders. Moreover, we focus on its particular implication in events including inflammatory stress-driven epithelium damage, epithelial-to-mesenchymal transition (EMT), transdifferentiation of fibroblasts into myofibroblasts, hypoxia stimuli and ROS response, as well as some other pulmonary remodeling related events such as overactive fibroblast (myofibroblast) accumulation, extracellular matrix deposition, and angiogenesis. Here, we summarize the strong potential of miR-21 in pulmonary remodeling and provide novel clues for further research in this area.

  • Chronic idiopathic systemic capillary leak syndrome: a case report
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-05-28
    Ahmed M. Alkhunaizi; Abdullah H. Kabbani; Mohamed A. ElTigani

    Idiopathic systemic capillary leak syndrome (ISCLS), is a rare disorder characterized by recurrent attacks of varying severity of hypovolemic shock and generalized edema in association with hemoconcentration and hypoalbuminemia in the absence of albuminuria. The chronic form of ISCLS is extremely rare with only a few cases reported in the literature. Here we report the case of a young woman who developed chronic ISCLS characterized by massive, generalized and persistent edema. The work up confirmed the presence of monoclonal gammopathy. She was treated with several agents with no response. Chronic ISCLS is a very rare disease of unknown etiology and results in devastating complications. The medical community should be aware of this disease with the hope that targeted therapy will become available in the future.

  • Sinobronchial allergic mycosis syndrome in an elderly male
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-06-04
    Eisuke Mochizuki; Shun Matsuura; Tsutomu Kubota; Yasutaka Mochizuka; Kyohei Oishi; Hyogo Naoi; Masahiro Uehara; Shinichiro Mikura; Miyuki Nagaoka; Masaru Tsukui; Naoki Koshimizu; Ichirota Nameki

    Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years. An 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy. Despite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

  • Outcomes following mepolizumab treatment discontinuation: real-world experience from an open-label trial
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-06-10
    Hector Ortega; Catherine Lemiere; Jean-Pierre Llanos; Mark Forshag; Robert Price; Frank Albers; Steven Yancey; Mario Castro

    Limited information is available on the clinical course of patients with severe asthma following discontinuation of biologic treatment. Therefore, a post hoc analysis was conducted in patients with severe eosinophilic asthma who participated in the COSMOS trial, where patients received mepolizumab for more than 1 year of continuous therapy. The objective of this post hoc analysis was to evaluate changes in the Asthma Control Questionnaire (ACQ-5) and blood eosinophil counts 12 weeks after the last administration of mepolizumab. Cessation of mepolizumab was associated with a rise in the blood eosinophil count and loss of asthma control after stopping therapy. These data suggest that patients with severe disease require extended and continuous treatment. Further studies evaluating longer duration of continuous treatment with mepolizumab could help understanding of whether changes in the presentation of the disease (disease modification) are possible with the use of biologics, such as mepolizumab.

  • Risk factors and prognosis of recurrent wheezing in Chinese young children: a prospective cohort study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-06-18
    Jing Guo; Wenjing Zhu; Huimin Wang; Patrick G. Holt; Guicheng Zhang; Chuanhe Liu

    Nearly all the investigations into the risk factors for wheezing and asthma were conducted in developed countries with a high prevalence rate of asthma and allergy, but the studies in developing countries are limited. In this study, we aimed to investigate the risk factors for different wheezing phenotypes in Chinese young children and to explore the prognosis of recurrent wheezing. This cohort study contained the recruitment stage and the follow-up stage conducted by phone questionnaire survey. According to the information collected at the follow-up for wheezing episodes and remission age, our cohort was divided into transient wheezing, persistent wheezing and late-onset wheezing. The wheezing symptoms and potential risk factors were compared between these three wheezing groups. From the initial 109 participants, 78.0% completed the follow-up survey. The frequency of current wheezing at followup was significantly reduced in all three groups compared to the recruitment stage (p < 0.01). We observe a trend that the rhinovirus (RV) and respiratory syncytial virus (RSV) infection rates were higher in the persistent wheezing group, and the overall infection rates appear to be the lowest in late-onset wheezing group at recruitment. At follow-up stage, the rates of rhinitis ever and current rhinitis were both higher in the persistent wheezing (63.0%, 50.0%) and late-onset wheezing groups (88.2%, 58.8%), compared to the transient wheezing group (14.3%, 14.3%). The incidence of current wheezing episodes increased cumulatively if the participant had concomitant risk factors of rhinitis ever, aeroallergens sensitization at recruitment, either alone or together with previous RV infection at the time of recruitment. While the incidence of wheezing declined overall with age, but in addition to transient wheezers, additional subsets of children manifest persistent wheeze or late onset wheeze, and moreover the risk factors for wheezing display phenotypic variability between these subgroups. Rhinitis ever and aeroallergens sensitization, either alone or together with previous RV infection, were the most significant predictors for persistent wheezing in children in an eastern environment, such as in China.

  • Inflammatory patterns of antrochoanal polyps in the pediatric age group
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-06-20
    Huiwen Zheng; Lixing Tang; Beibei Song; Xiaojian Yang; Ping Chu; Shujing Han; Pengpeng Wang; Jie Lu; Wentong Ge; Xin Ni

    The pathogenesis and etiology of antrochoanal polyps (ACPs) remains obscure. This study aimed to characterize the inflammatory profiles and investigate the effect of atopy on the pathogenesis of pediatric ACPs. Thirty-three ACP patients and ten control subjects were enrolled from January to December 2017. The severity of individual nasal symptoms was scored on a visual analogue scale (VAS). The serum total immunoglobulin E (IgE) and cytokines level was measured by multiplexed luminex assay. There was no significant difference in VAS scores and counts of inflammatory cells between atopic and nonatopic ACP. No difference in IFNγ, IL-4, IL-5, IL-13, IL-17A and IL-25 was found between control and whole ACP, nonatopic and atopic ACP. Significantly increased levels of IL-6 and IL-10 were found in ACP compared with control. For neutrophil chemotactic factor, significant increases of IL-8 and GRO were observed in ACP, but for eosinophil chemotactic factor, no difference was found in RANTES and GM-CSF. IL-6 level was positively correlated with IL-8, MCP1, and GRO level, and IL-10 level was positively correlated with IL-4 and IL-13 in ACP subjects. Nasal obstruction was the most common symptom in ACPs in children. Allergic condition may have a poor role in the pathogenesis of ACPs. IL-6 plays a crucial role in the pathogenesis of neutrophilic inflammation in patients with ACPs and may provide a new treatment strategy for ACPs in children. Treg cell associated cytokine IL-10 was involved in the inflammatory pathophysiological process of ACPs and played a certain regulatory role.

  • Maternal diet before and during pregnancy and risk of asthma and allergic rhinitis in children
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-06-22
    Nour Baïz; Jocelyne Just; Julie Chastang; Anne Forhan; Blandine de Lauzon-Guillain; Anne-Marie Magnier; Isabella Annesi-Maesano

    Consumption of certain foods during pregnancy has been shown to have beneficial effects on childhood asthma and allergic disease development and aggravation. However, most studies provide conflicting results and the relationships between maternal preconceptional diet and risks of childhood asthma and allergic disease have not previously been explored. The objective of this study was to assess maternal diet during the year before pregnancy and the last 3 months of pregnancy and investigate their associations with the risks of asthma, wheezing, allergic rhinitis and atopic dermatitis in young children. The study sample consisted of 1140 mother–child pairs from the EDEN cohort. Mothers had responded to the food frequency questionnaires used to assess diet before and during pregnancy. Children were followed up using health questionnaires. The health outcomes studied were: asthma, wheezing, allergic rhinitis and atopic dermatitis by the age of 3 years. Using multivariable-adjusted logistic regression models, significant inverse associations were observed between cooked green vegetable consumption before pregnancy and childhood asthma; consumption of eggs and raw vegetables before and during pregnancy, consumption of grains before pregnancy, and consumption of cooked green vegetables during pregnancy and allergic rhinitis. For the first time, a significant positive association was found between meat intake during the preconceptional period and a risk of wheezing, allergic rhinitis and atopic dermatitis. Based on our findings, preconceptional and prenatal maternal intake of certain type of food groups may be preventive against asthma, wheezing and allergic rhinitis, whereas higher maternal intake of meat before pregnancy may increase the risk of wheezing, allergic rhinitis and atopic dermatitis in young children.

  • 更新日期:2019-11-28
  • Clinical and pulmonary function changes in cough variant asthma with small airway disease
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-07-02
    Honglei Yuan; Xiaojing Liu; Li Li; Gang Wang; Chunfang Liu; Yuzhen Zeng; Ruolin Mao; Chunling Du; Zhihong Chen

    It is known that small airway disease is present across all asthma severities; however, its prevalence and clinical characteristics in cough variant asthma (CVA) have not been fully illuminated. A total of 77 CVA patients with preserved proximal airway function (FEV1/FVC > 70%) were enrolled in this study. The correlation between forced expiratory flow at 50% (FEF50%) and FEF25–75% in the CVA population was first evaluated. FEF50% was determined to be an easy and feasible parameter for identifying small airway disease. CVA with small airway disease is defined as FEF50% < 70%, whereas CVA with normal small airways is identified as FEF50% > 70%. Demographic features, clinical characteristics, lung function and induced sputum test results were determined at the initial visit and at the final visit 1 year later. FEF50% is a good marker for small airway disease. The cutoff value of 70% is more sensitive than the previously published 60% for identifying more patients with small airway problems early. Nearly half of the CVA population (45.4%) in our cohort had small airway disease. In both group, symptoms improved greatly after anti-asthmatic treatment. Interestingly, the changes in symptom scores [Asthma Control Test (ACT) and ACQ] were even greater in the CVA with small airway disease group than in the control group because of the higher medication usage in this subpopulation in real life. However anti-asthmatic therapy can not reverse small airway dysfunction. At last visit, FEF50% of CVA with small airway diseases was 57.2% ± 10.5%, still much lower than the control group (FEF50% = 92.6% ± 16.5%). In our cohort, nearly half of the CVA population had small airway disease. Their demographic features, clinical characteristics, airway eosinophils and drug responsiveness were quite similar between two groups, which means these indices can not be used as markers to identify small airway obstruction. We found FEF50% is an easy and feasible marker for early identification. Regular anti-asthmatic medication helped to improve clinical scores in patients with small airway disease, but the obstruction could not be reversed over 1-year period.

  • Allergen sensitization pattern of allergic adults and children in southern China: a survey based on real life data
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-07-24
    Wenting Luo; Haisheng Hu; Wangbing Tang; Xiangwei Zou; Huimin Huang; Zhifeng Huang; Yong Liu; Baoqing Sun

    Allergic diseases are increasing yearly. We aimed to evaluate the difference in allergen sensitization pattern between adults and children in southern China by analyzing a large sample size of real-life data, and to provide the evidence for formulating the prevention and management strategies. Retrospective analysis was conducted on 39,813 serum allergen-specific IgE (sIgE) results collected in southern China from January to December in 2017. Sensitization patterns and how these allergens could lead to the allergic diseases were analyzed for adults and children respectively. The difference of allergen positive rate between groups was calculated using the Chi square test. The top five most sensitized allergens in southern China were house dust mite (28.1%), cockroach (24.3%), shrimp (19.2%), crab (15.5%) and egg white (9.9%). While cockroach had the highest positive rate in adults (29.2%), the most sensitized allergen in children was house dust mite (29.7%). The positive rates of egg white and cow’s milk in children were higher than in adults for the whole year (p < 0.001); whereas for adults, the positive rate to cockroach, shrimp and crab were higher than in children (p < 0.001). The positive rate of house dust mite in coastal cities (32.4%) was higher than that in landlocked cities (24.0%) in children, but in adults, the rate in landlocked cities (31.1%) was higher than that in coastal cities (25.3%). Optimal scaling analysis showed that the sIgEs of crab and shrimp had the closest correlation with cockroach-sIgE (Cronbach’s α = 0.891). The positive rate to mold allergens increased from summer to autumn, reaching its plateau in October (6.2%). Patients with skin diseases were found to receive the highest sIgE prescription from doctors (56.9%). Doctors tend to prescribe more sIgE tests for patients with skin disorders in southern China. In addition to house dust mite, cockroach was found to be another important allergen. Adults with multiple sensitization always showed co-sensitization with shrimp, crab and house dust mite. These should be taken into consideration when giving allergen avoidance advice to patients.

  • Epigenome-wide association study of asthma and wheeze characterizes loci within HK1
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-07-24
    Todd M. Everson; Hongmei Zhang; Gabrielle A. Lockett; Akhilesh Kaushal; Melinda Forthofer; Susan L. Ewart; Kimberley Burrows; Caroline L. Relton; Gemma C. Sharp; A. John Henderson; Veeresh K. Patil; Faisal I. Rezwan; S. Hasan Arshad; John W. Holloway; Wilfried Karmaus

    To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood. We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort. We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (ORIOW = 0.17, 95% CI 0.04–0.57) (ORALSPAC = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82). We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze.

  • Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-01
    Maria Gonzalez-Orozco; Rosa E. Barbosa-Cobos; Paola Santana-Sanchez; Lizbeth Becerril-Mendoza; Leonardo Limon-Camacho; Ana I. Juarez-Estrada; Gustavo E. Lugo-Zamudio; Jose Moreno-Rodriguez; Vianney Ortiz-Navarrete

    Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA.

  • 更新日期:2019-11-28
  • Sestrin2 is involved in asthma: a case–control study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-14
    Yanfang Kang; Chen Chen; Xiaotian Hu; Xiaohua Du; Huifen Zhai; Yan Fang; Xiulin Ye; Weimin Yang; Shibo Sun

    Asthma is a chronic disease that seriously harms the health of patients. Oxidative stress is involved in asthma. As an oxidative stress-inducible protein, sestrin2 is elevated in oxidative stress-related diseases. We aimed to explore whether sestrin2 was involved in asthma. Seventy-six subjects (44 in the asthma group, 32 in the control group) were recruited in this study. Plasma sestrin2 levels, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio were measured in controls and in asthmatics both during an exacerbation and when controlled after the exacerbation. The asthma group had a significant higher sestrin2 level than the control group (asthmatics during exacerbation, 1.75 ± 0.53 ng/mL vs. 1.32 ± 0.48 ng/mL, p < 0.001; asthmatics when controlled after the exacerbation, 1.56 ± 0.46 ng/mL vs. 1.32 ± 0.48 ng/mL, p = 0.021, respectively). In addition, sestrin2 was negatively correlated with FEV1% predicted and FEV1/FVC ratio in asthmatics during exacerbation (r = − 0.393, p = 0.008; r = − 0.379, p = 0.011; respectively). Moreover, negative correlations between sestrin2 and FEV1% predicted and FEV1/FVC ratio also existed in asthmatics when controlled after the exacerbation (r = − 0.543, p < 0.001; r = − 0.433, p = 0.003 respectively). More importantly, multiple linear regression analysis demonstrated that FEV1% predicted was independently associated with sestrin2 in asthmatics both during exacerbation and when controlled after the exacerbation. Sestrin2 is involved in asthma. Sestrin2 levels increase in asthmatics both during exacerbation and when controlled after the exacerbation. In addition, sestrin2 is independently associated with FEV1% predicted.

  • Graft versus host disease and microchimerism in a JAK3 deficient patient
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-22
    Zahra Shahbazi; Nima Parvaneh; Shirin Shahbazi; Hamzeh Rahimi; Mohammad Hamid; Davoud Shahbazi; Samaneh Delavari; Hassan Abolhassani; Asghar Aghamohammadi; Reza Mahdian

    The lymphohematopoietic cells originating from feto-maternal trafficking during pregnancy may cause microchimerism and lead to materno-fetal graft versus host disease (GVHD) in severe combined immunodeficiency (SCID) patients. However, definitive diagnosis between GVHD and Omenn’s syndrome is often difficult based on clinical and immunological phenotypes particularly in the patients with hypomorphic mutations. A 3-year-old girl with a history of erythroderma and immunodeficiency was studied. The whole exome sequencing method was used to find the disease-causing variants, and T-A cloning and Quantitative Florescence Polymerase Chain Reaction (QF-PCR) methods were utilized to detect the presence of mosaicism or microchimerism. We identified a homozygous missense Janus Kinase 3 mutation (JAK3, c.2324G>A, p.R775H) as a new disease-causing variant in the patient, and the presence of microchimerism with maternal origin was proven as an underlying cause of her clinical presentation. The findings highlighted the importance of appropriate diagnostic approach in GVHD cases with hypomorphic JAK3 mutations. When analyzing the results of the next generation sequencing, the possibility of microchimerism should be considered based on the context of the disease.

  • Short-term pulmonary infiltrate with eosinophilia caused by asthma: a phenotype of severe, eosinophilic asthma? Five cases and a review of the literature
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-23
    Min Song; Shan Cai; Hong Luo; Yi Jiang; Min Yang; Yan Zhang; Hong Peng; Ping Chen

    Asthma is often accompanied by peripheral eosinophilia and eosinophilic airway inflammation. This article explores the relationship between asthma and short-term pulmonary infiltrate with eosinophilia, which results from irregular asthma treatment. We report five unique cases of asthma-induced short-term eosinophilic pneumonia encountered at our pulmonary and critical care centre in Hunan, China, from January 1, 2014, to August 31, 2018. The 5 asthma patients were women with persistent dyspnoea symptoms, an increased peripheral eosinophil count and a high level of exhaled nitric oxide (FeNO). Chest CT revealed multiple infiltrates and ground-glass opacities in both lung fields in all 5 patients. Four of the 5 patients had increased eosinophils in bronchoalveolar lavage (BAL). Three were positive for reversibility in lung function testing, and two had eosinophil infiltration as revealed by lung biopsy. No antibiotic treatment was given, and after a short period of glucocorticoid therapy and inhaled corticosteroid plus long-acting β2-agonist (ICS + LABA) treatment, the symptoms of all of the patients disappeared. In addition, their blood eosinophils returned to normal, and their lung lesions were quickly absorbed and improved. These cases show a unique association between short-term eosinophilic pneumonia and asthma. The occurrence of eosinophilic pneumonia can prove fatal during a serious asthma attack. Additionally, the presence of peripheral eosinophilia with lung infiltrates poses a diagnostic challenge for clinicians by creating suspicion of pulmonary infiltrate with eosinophilia when present in asthmatic patients.

  • Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-28
    H. Henry Li; Bruce Zuraw; Hilary J. Longhurst; Marco Cicardi; Konrad Bork; James Baker; William Lumry; Jonathan Bernstein; Michael Manning; Donald Levy; Marc A. Riedl; Henrike Feuersenger; Subhransu Prusty; Ingo Pragst; Thomas Machnig; Timothy Craig

    Hereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment effects by subgroups, onset of effect, and other exploratory analysis have not been reported. This is a post hoc exploratory analysis on data from the randomized, placebo-controlled COMPACT study. 90 patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH (SC) 40 or 60 IU/kg of body weight twice weekly for 16 weeks, preceded or followed by a placebo period. The pre-specified primary efficacy endpoint was the time-normalized number of HAE attacks, and pre-specified secondary efficacy endpoints were the percentage of patients with a certain treatment response (≥ 50% reduction on C1-INH (SC) versus placebo in the time-normalized number of attacks) and the time-normalized number of use of rescue medication. Pre-specified exploratory endpoints included severity of attacks, alone and combined with rescue medication use. Post hoc analyses included exploration of onset of effect and clinical assessment of patients with < 50% of response. Subgroup findings by various patient characteristics showed a consistent preventive effect of C1-INH (SC). In a post hoc analysis of attacks, the onset of the preventive effect within the first 2 weeks after treatment initiation in COMPACT showed that 10/43 patients (23%) experienced attacks of any severity with 60 IU/kg versus 34/42 patients (81%) with placebo. The need for rescue medication was tenfold lower with 60 IU/kg (35 treated attacks) versus placebo (358 treated attacks). A qualitative analysis of the 4 patients treated with 60 IU/kg and with < 50% reduction of attacks demonstrated a reduction in severity of attacks, rescue medication use, and symptom days which was considered a clinically meaningful treatment effect. C1-INH (SC) prophylaxis demonstrated a preventive treatment effect with evidence of benefit within 2 weeks. A consistent treatment effect at recommended C1-INH (SC) dosing was evident in all subgroups of patients with type I/II HAE and by various measures of disease and treatment burden. Trial registration EU Clinical Trials Register, 2013-000916-10, Registered 10 December 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000916-10 ; ClinicalTrials.gov Register, NCT01912456, Registered 31 July 2013, https://clinicaltrials.gov/ct2/show/NCT01912456 .

  • Structural alterations and markers of endothelial activation in pulmonary and bronchial arteries in fatal asthma
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-28
    Renata Calciolari Rossi; Raquel Anonni; Diogenes Seraphim Ferreira; Luiz Fernando Ferraz da Silva; Thais Mauad

    There is interest in better understanding vessel pathology in asthma, given the findings of loss of peripheral vasculature associated with disease severity by imaging and altered markers of endothelial activation. To date, vascular changes in asthma have been described mainly at the submucosal capillary level of the bronchial microcirculation, with sparse information available on the pathology of bronchial and pulmonary arteries. The aim of this study was to describe structural and endothelial activation markers in bronchial arteries (BAs) and pulmonary arteries (PAs) of asthma patients who died during a fatal asthma attack. Autopsy lung tissue was obtained from 21 smoking and non-smoking patients who died of an asthma attack and nine non-smoking control patients. Verhoeff–Masson trichrome staining was used to analyse the structure of arteries. Using immuno-histochemistry and image analyses, we quantified extracellular matrix (ECM) components (collagen I, collagen III, versican, tenascin, fibronectin, elastic fibres), adhesion molecules [vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)] and markers of vascular tone/dysfunction [endothelin-1 (ET-1) and angiotensin II type 2 receptor (AT2)] in PAs and BAs. There were no significant differences in ECM components, ICAM-1, ET-1 or AT2 between asthma patients and controls. Smoking asthma patients presented with decreased content of collagen III in both BA (p = 0.046) and PA (p = 0.010) walls compared to non-smoking asthma patients. Asthma patients had increased VCAM-1 content in the BA wall (p = 0.026) but not in the PA wall. Our data suggest that the mechanisms linking asthma and arterial functional abnormalities might involve systemic rather than local mediators. Loss of collagen III in the PA was observed in smoking asthma patients, and this was compatible with the degradative environment induced by cigarette smoking. Our data also reinforce the idea that the mechanisms of leukocyte efflux via adhesion molecules differ between bronchial and pulmonary circulation, which might be relevant to understanding and treating the distal lung in asthma.

  • Hypersensitivity reactions to high osmolality Total Parenteral Nutrition: a case report
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-08-30
    Steph A. Pang; Shaun Eintracht; Jesse M. Schwartz; Belinda Lobo; Elizabeth MacNamara

    The full range of allergic reactions to Total Parenteral Nutrition (TPN) remains unknown. Additionally, beyond individual allergens, there may be other factors contributing to TPN hypersensitivity reactions. We present a case of a patient with negative skin testing to common TPN allergens who had recurrent urticarial reactions to TPN. Her skin reactions resolved once TPN was stopped. Following a literature review, we postulated that the reactions could be due to the high osmolality of her TPN. Consequently, lowering her TPN from 2785 to 1928 mOsm/kg and premedicating with cetirizine resulted in resolution of her urticaria. When looking at patients who have hypersensitivity reactions to TPN, one must consider that their reactions may be due to factors other than allergens. More studies are needed to clarify the relationship between high osmolality TPN infusions and non-IgE mediated hypersensitivity reactions.

  • Shared prenatal impacts among childhood asthma, allergic rhinitis and atopic dermatitis: a population-based study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-03
    Ching-Heng Lin; Jiun-Long Wang; Hsin-Hua Chen; Jeng-Yuan Hsu; Wen-Cheng Chao

    Increasing prevalence of childhood allergic diseases including asthma is a global health concern, and we aimed to investigate prenatal risk factors for childhood asthma and to address the potential shared prenatal impacts among childhood asthma, allergic rhinitis (AR) and atopic dermatitis (AD). We used two claim databases, including Taiwan Birth Cohort Study (TBCS) and National Health Insurance Research Database (NHIRD), to identify independent paired mother–child data (mother–child dyads) between 2006 and 2009. The association between prenatal factors and asthma was determined by calculating adjusted odds ratio (aOR) with 95% confidence interval (CI) using conditional logistic regression analysis. A total of 628,878 mother–child dyads were included, and 43,915 (6.98%) of children developed asthma prior to age 6. We found that male gender (aOR 1.50, 95% CI 1.47–1.53), maternal asthma (aOR 1.80, 95% CI 1.71–1.89), maternal AR (aOR 1.33, 95% CI 1.30–1.37), preterm birth (aOR 1.32, 95% CI 1.27–1.37), low birth weight (aOR 1.14, 95% CI 1.10–1.19) and cesarean section (aOR 1.10, 95% CI 1.08–1.13) were independent predictors for childhood asthma. A high urbanization level and a low number of older siblings were associated with asthma in a dose–response manner. Notably, we identified that the association between maternal asthma and childhood asthma (aOR 1.80, 95% CI 1.71–1.89) was stronger compared with those between maternal asthma and childhood AR (aOR 1.67, 95% CI 1.50–1.87) as well as childhood AD (aOR 1.31, 95% CI 1.22–1.40). Similarly, the association between maternal AR and childhood AR (aOR 1.62, 95% CI 1.53–1.72) was higher than those between maternal AR and childhood asthma (aOR 1.33, 95% CI 1.30–1.37) as well as childhood AD (aOR 1.35, 95% CI 1.31–1.40). Furthermore, the number of maternal allergic diseases was associated with the three childhood allergic diseases in a dose–response manner. In conclusion, this population-based study provided evidence of prenatal impacts on childhood asthma and demonstrated the shared maternal impacts among childhood asthma, AR, and AD. These findings highlight the shared prenatal impacts among allergic diseases, and studies are warranted to address the pivotal pathway in allergic diseases.

  • Efficacy of add-on mepolizumab in adolescents with severe eosinophilic asthma
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-03
    Steven W. Yancey; Hector G. Ortega; Oliver N. Keene; Eric S. Bradford

    Adolescents (12–17 years of age) with severe eosinophilic asthma experience frequent exacerbations and reduced lung function leading to poor health-related quality of life. Mepolizumab is approved for add-on maintenance therapy in patients with severe eosinophilic asthma ≥ 6 years of age in the EU and ≥ 12 years of age in other regions (including the USA), based on a Phase II/III program demonstrating reduced exacerbation rates with 4-weekly treatment. A total of 34 adolescent patients were recruited across the Phase III mepolizumab trials. Consistent with outcomes in the overall population, there was a reduction in the annual rate of clinically significant exacerbations, along with a reduction in blood eosinophil counts in response to mepolizumab in adolescent patients. The safety profile in adolescent patients was consistent with that seen in the overall population. Data from the Phase III clinical development program provide evidence for comparable efficacy and safety of mepolizumab between adolescents with severe eosinophilic asthma and the overall population. Clinical trial registration DREAM, NCT01000506 [MEA112997]; MENSA, NCT01691521 [MEA115588]; SIRIUS, NCT01691508 [MEA115575]; MUSCA, NCT02281318 [200862]; COSMOS, NCT01842607 [MEA115661].

  • Food allergy-related concerns during the transition to self-management
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-05
    Jennifer Lisa Penner Protudjer; Roelinde Middelveld; Sven-Erik Dahlén; Staffan Ahlstedt

    Compared to non-allergic individuals, food allergic individuals have impaired health-related quality of life (HRQL). However, effects of gender and age are unclear. The objective of our study was to describe associations between allergies to common foods and HRQL with consideration to gender and age. Adolescents and adults (N = 137; 49.6% males) with specialist-diagnosed allergy to milk, egg and/or wheat completed age-appropriate versions of the Food Allergy Quality of Life Questionnaire (FAQLQ). We pooled common questions and calculated overall- and domain-specific HRQL in association with number and severity of symptoms and time elapse since worst reaction. In the entire study population, HRQL was not affected by gender or age, whereas gender-specific age categories affected HRQL among males only. For example, males 18–39 years had worse overall- (β = 0.77; 95% CI 0.08–1.45) and domain-specific HRQL vs. males < 18 years. Among participants with 1–3 food allergy symptoms, no associations were found. Among participants with 4–6 symptoms, the domain allergen avoidance and dietary restrictions was worse among older participants (e.g. 40+ years: β = 0.71; 95% CI 0.05–1.37 vs. < 18 years), and males 18–39 vs. < 18 years. Among participants with severe symptoms, females vs. males, and participants 18–39 vs. < 18 years had worse HRQL. At least 4 years since worst reaction was associated with worse HRQL for participants 40+ years vs. < 18 years, and older males vs. males < 18 years. Nearly all differences exceeded the clinical relevance threshold of ≥ 0.5. Associations between allergies to common foods and HRQL are affected by gender and age. Most affected are males 18–39 years. Among females, HRQL is more stable across age groups.

  • Successful management of severe asthma in a young boy with eosinophilic chronic rhinosinusitis who received omalizumab: a case report
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-05
    Yasuho Shoda; Misa Watanabe; Kota Wada; Takehiko Soutome; Yumiko Komine; Tetsuo Mikami; Tetsuo Nemoto; Akira Ohara

    The incidence of chronic rhinosinusitis with nasal polyps has recently increased in Japan and other East Asian countries, and this disease is called eosinophilic chronic sinusitis (ECRS) in Japan. ECRS usually occurs in adults and is frequently accompanied by refractory bronchial asthma. However, its occurrence in children under 10 years of age is rare. Here, we present an unusual case of ECRS complicated by intractable asthma in an 8-year-old boy. Oral administration of prednisolone (10 mg/day) initially relieved the ECRS and bronchial asthma, but both returned during prednisolone dose reduction. Because nasal cavity-opening surgery was ineffective, oral administration prednisolone at 10 mg/day was continued. Pancytopenia was observed 16 months after the start of treatment, and the patient was admitted to our hospital. He was diagnosed with refractory cytopenia in childhood, but gradually improved after cyclosporine treatment. Although the dose of cyclosporine was therapeutic for asthma, it did not alleviate the asthma attacks, and the patient’s quality of life markedly decreased. We administered omalizumab even though its use was contraindicated by negative results in an inhalable antigen test. After the third administration of omalizumab, the asthma was better controlled and respiratory function improved; however, the nasal symptoms of ECRS persisted. Attempts to relieve these symptoms by increasing the therapeutic dose of omalizumab were only partially successful. We replaced omalizumab with mepolizumab; doing so slightly improved the sinusitis symptoms, but quality of life remained unsatisfactory. We repeated the nasal cavity-opening surgery. After surgery, the asthma and sinusitis were unchanged. Omalizumab effectively treated the severe combined asthma in a young patient, but its effect on sinusitis was insufficient. More cases and long-term follow-up data are needed to better evaluate the effectiveness of mepolizumab for treatment of ECRS.

  • Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-11
    Ciara Jade Bansal; Amolak Singh Bansal

    Chronic spontaneous urticaria (CSU) is often associated with organ specific autoimmunity but is rarely caused by food allergy. Colourings and preservatives in pre-packaged foods, so called pseudoallergens, have also been implicated. Factors that promote inflammation or reduce anti-inflammatory mechanisms may however, predispose susceptible individuals to CSU. Chronic underlying infection and mental and emotional stress can sometimes precede the onset of CSU and once established can exacerbate the symptoms. There is early evidence of dysbiosis within the gastrointestinal tract in people with CSU and reduced levels of vitamin D are also evident. The latter may be related to the importance of vitamin D3 in increasing T regulatory function which can control a tendency to autoimmunity. It is quite possible that a state of on-going chronic inflammation with reduced anti-oxidant mechanisms may underlie the not infrequent association between CSU and metabolic syndrome. Effective treatment of CSU should involve the use of anti-histamines, intermittent steroids and anti-IgE therapy. For recalcitrant disease immune modulatory therapy has a place. However, talking therapies that reduce stress and anxiety, vitamin D3 supplementation, correction of intestinal dysbiosis and treatment of any chronic infection should also be considered.

  • Maternal food allergy is associated with daughters’ menarche in early adolescence
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-11
    Jennifer Lisa Penner Protudjer; Elissa Michelle Abrams; Anita Luba Kozyrskyj; Allan Barry Becker

    Associations between allergic disease and puberty amongst females have been widely studied. However, this association has received less attention in multigenerational populations. To this end, we sought to examine maternal allergic disease status ever, and daughters’ menarche. In a cohort of children born in 1995, in Manitoba, Canada, we considered maternal allergic disease ever to daughters’ age 7–8 years, and daughters’ menarche at ages 12–14 years. We included all participants for whom we had information on both the exposure and the outcome of those eligible. Data were analysed using descriptive statistics and logistic regression, with adjustment for confounding variables. Overall, the prevalences of maternal allergic diseases were 28.6% for asthma 18.8% for food allergy, 27.3% for eczema and 45.5% for rhinitis. By age 12–14 years, 41.6% (64/159) girls had reached menarche. Maternal food allergy was significantly associated with daughters’ menarche (OR 4.39, 95% CI 1.51–12.73), whereas no association was found for maternal asthma, eczema or rhinitis. With consideration to comorbid disease, a combination of maternal asthma + food allergy was associated with daughters’ menarche by age 12–14 years (OR 6.41; 95% CI 1.32–31.01). Maternal food allergy ever is associated with daughters’ menarche by age 12–14 years.

  • Serum IL-1β can be a biomarker in children with severe persistent allergic rhinitis
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-18
    Myung Woul Han; Song Hee Kim; Inbo Oh; Yang Ho Kim; Jiho Lee

    Allergic rhinitis (AR) is one of the most common diseases globally and usually persists throughout life. In the present study, we aimed to determine whether the expression of inflammatory biomarkers has a relationship with the severity of allergic rhinitis and with comorbid asthma or other allergic diseases in children. For diagnosis of AR, the skin prick test was performed to measure the responses to 18 allergens. Blood levels of eosinophils and immunoglobulin E (IgE) were examined. We classified the patients into 2 groups based on the severity of the condition as Group 1 [intermittent AR (IAR) or mild persistent AR (PAR)] and Group 2 (moderate to severe PAR). To determine the expression of inflammatory biomarkers, in serum and several biomarkers (caspase-1, IL-1β, CCL-11, CCL-24 and IL-33) were measured in the serum using enzyme-linked immunosorbent assay (ELISA). Additionally, we analyzed the correlation between clinical variables and the expression of biomarkers (eosinophils count, IL-1β and CCL-24) and the severity of AR. We found that eosinophils count, IL-1β, a marker of activation of inflammasomes, and CCL-24 were significantly increased in the moderate to severe PAR group (p = 0.008, p = 0.003, p = 0.039). Additionally, the expressions of eosinophil count, IL-1β and CCL-24 were significantly higher in patients with active asthmatic symptoms than in those without these conditions. On univariate analysis, allergic rhinitis in sibling, paternal allergic rhinitis, high expression of eosinophils count, IL-1β and CCL-24, history of active asthma and atopy correlated with severity of AR. Multivariate analysis showed only paternal allergic rhinitis and high expression of IL-1β as significant risk factors of moderate to severe PAR with 6.4 fold and 4.7 fold-increase in risk, respectively (p = 0.011 and p = 0.030). In conclusion, this study provides the first evidence that an excessive release of biologically active IL-1β may promote inflammation in severe PAR. It demonstrates that IL-1β can be a biomarker for active allergic diseases such as AR, asthma, and atopy. Moreover, this finding suggests that IL-1B should be investigated as a therapeutic target in severe PAR and other allergic diseases.

  • Haemopoietic stem cell transplantation in Systemic lupus erythematosus: a systematic review
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-18
    Nipun Lakshitha de Silva; Suranjith L. Seneviratne

    Despite advances in treating Systemic lupus erythematosus (SLE), a proportion of patients continue to face significant morbidity and mortality. Haemopoietic stem cell transplant (HSCT) has been recognized as an option for such patients. We analysed the evidence on efficacy and safety of HSCT in patients with SLE. A database search was done for articles on HSCT in SLE up to July 2017 in PUBMED, Cochrane library, LILACS and clinical trial registration databases to select prospective or retrospective studies with 8 or more patients. Of the 732 search results from the PUBMED, Cochrane and LILACS database search, following duplicate removal, 15 studies were eligible for detailed assessment. Findings of an additional trial were obtained from the clinical trial registration database. Data were extracted on study design, patient characteristics, nature of intervention, outcomes, complications and study quality. Case reports and small case series were summarised without detailed qualitative analysis. Most of the studies showed remission in the majority of patients. Relapse of the original disease increased with longer follow-up. Common adverse effects included: infections and secondary autoimmune disorders. Short follow up period and lack of randomised controlled trials were the main limitations restricting the generalizability of study results. A meta-analysis was not performed due to heterogeneity of studies. Although HSCT is a viable option in SLE, its exact clinical utility needs to be further evaluated in well-designed studies.

  • Oral immunotherapy with peach juice in patients allergic to LTPs
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-09-24
    Begoña Navarro; Eladia Alarcón; Ángela Claver; Mariona Pascal; Araceli Díaz-Perales; Anna Cisteró-Bahima

    To assess the safety and efficacy of an oral immunotherapy regimen in patients with allergy to lipid transfer proteins (LTPs). Prospective study of 24 patients allergic to LTP with positive skin test and a history of anaphylaxis. All patients underwent a desensitization protocol with commercial peach juice. Rising doses of peach juice were administered, starting with an initial dose of seven drops of a 1/1000 dilution and finishing with a dose of 5 ml at visit 17. At visit 18, all patients performed an open challenge with whole juice at a cumulative dose of 200 ml. All adverse reactions occurring during the administration of the different doses were recorded. Levels of rPru p 3 in the juice were quantified. There were no severe reactions during the desensitization process in the 24 patients. Seven patients (29%) reported mild oral symptoms, and two patients (8%) had urticaria associated with co-factors (one due to exercise and another due to non-steroidal anti-inflammatory drugs). Nineteen patients were able to swallow 5 ml of juice and five withdrew from the study. In two pregnant patients the final challenge was not performed. In all, 17/24 patients were able to consume 200 ml peach juice without developing symptoms. Oral immunotherapy with the regimen used in this study is an effective and safe short-term therapeutic option for patients with allergy to LTPs. Commercial peach juice appears to be suitable for this treatment.

  • CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-10-01
    Michael N. Fein; David A. Fischer; Andrew W. O’Keefe; Gord L. Sussman

    Oral H1-antihistamines (AHs) are the most commonly used therapy to treat allergic rhinitis and chronic urticaria. Older, first-generation AHs (e.g. diphenhydramine, hydroxyzine) have significant and common side effects including sedation, impairment with decreased cognitive function, poor sleep quality, dry mouth, dizziness, and orthostatic hypotension. These drugs have also been found to result in death from accidents, intentional or unintentional overdoses, and sudden cardiac death. The unfavourable risk–benefit profile of first-generation AHs led to the development of newer, less-sedating second- and third-generation AHs, which first became available in Canada in the 1980s. High-quality trials have proven that newer generation AHs are superior in safety compared to older first-generation AHs. On average, they have improved potency and efficacy. Second- and third-generation AHs are the recommended first-line treatment for mild allergic rhinitis and acute and chronic urticaria. Despite this evidence, older first-generation AHs continue to be over-utilized because of their over-the-counter (OTC) status and long history of use. The Canadian Society of Allergy Clinical Immunology (CSACI) recommends that newer generation AHs should be preferred over first-generation AHs for the treatment of allergic rhino-conjunctivitis and urticaria. To promote this recommendation, education of health professionals and the public is necessary. Further, given the dangers of older first-generation AHs, we believe they should be used only as a last resort with eventual consideration given to having them only available behind the counter in pharmacies.

  • The association between caesarean section and childhood asthma: an updated systematic review and meta-analysis
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-10-29
    Behzad Darabi; Shoboo Rahmati; Mohammad Reza HafeziAhmadi; Gholamreza Badfar; Milad Azami

    Investigating the association between caesarean section (SC) and childhood asthma has shown contradictory results in different studies. The present study was conducted to determine the association between SC and childhood asthma. The present study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. All the steps of the study were conducted independently by two reviewers from the inception until February 1, 2019. In case of disagreement, the third reviewer resolved it. We searched international online databases, including Scopus, Cochrane Library, PubMed/Medline, Embase, Web of Science (ISI), Science Direct, and Google scholar. The results of studies were combined using random effects model, and heterogeneity was measured through I2 index and Cochran’s Q test. Comprehensive Meta-Analysis Software was used for meta-analysis. The significance level of all tests was considered to be P < 0.05. The heterogeneity rate was high (I2 = 67.31%, P < 0.001) in 37 studies. The results showed that SC increased the risk of childhood asthma (RR (relative risk) = 1.20 [95% CI 1.15–1.25, P < 0.001]). The association between emergency and elective SC and childhood asthma was significant with RR of 1.18 (95% CI 1.07–1.29, P < 0.001) in 13 studies and 1.23 (95% CI 1.20–1.26, P < 0.001) in 13 studies, respectively. The subgroup analysis for RR of childhood asthma in SC indicated that study design (P = 0.306), prospective/retrospective studies (P = 0.470), quality of studies (P = 0.514), continent (P = 0.757), age of diagnosis (P = 0.283) and year of publication (P = 0.185) were not effective in the heterogeneity of studies. Sensitivity analysis by removing one study at a time indicated that the overall estimate is robust. According to the meta-analysis, SC (overall, elective, and emergency) increased the risk of childhood asthma. Therefore, it is hoped that developing clinical guidelines and implementing appropriate management plans would diminish the risk of asthma.

  • Plasma cytokine profiles associated with rhodesiense sleeping sickness and falciparum malaria co-infection in North Eastern Uganda
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-10-30
    Julius Nsubuga; Charles Drago Kato; Ann Nanteza; Enock Matovu; Vincent Pius Alibu

    Immunological Human African Trypanosomiasis (HAT) studies often exclude malaria, although both infections overlap in specific endemic areas. During this co-infection, it is not known whether this parasitic interaction induces synergistic or antagonistic cytokine response among humans. This study determined prevalence of Plasmodium falciparum malaria among Trypanosoma brucei rhodesiense HAT and plasma cytokine profile levels associated with HAT and/or malaria infections. Participants were recruited at Lwala hospital in north eastern Uganda: healthy controls (30), malaria (28), HAT (17), HAT and malaria (15) diagnosed by microscopy and PCR was carried out for parasite species identification. Plasma cytokine levels of Interferon-gamma (IFN-γ), Tumour Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6, IL-10 and Transforming Growth Factor-beta (TGF-β) were measured by sandwich Enzyme-Linked Immuno Sorbent Assay and data statistically analysed using Graphpad Prism 6.0. The prevalence of P. falciparum malaria among T. rhodesiense HAT cases was high (46.8%). Malaria and/or HAT cases presented significant higher plasma cytokine levels of IFN-γ, TNF-α, IL-6, IL-10 and TGF-β than healthy controls (P < 0.05). Levels of IFN-γ, IL-6 and IL-10 were significantly elevated in HAT over malaria (P < 0.05) but no significant difference in TNF-α and TGF-β between HAT and malaria (P > 0.05). Co-infection expressed significantly higher plasma IFN-γ, IL-6, and IL-10 levels than malaria (P < 0.05) but no significant difference with HAT mono-infection (P > 0.05). The TNF-α level was significantly elevated in co-infection over HAT or malaria mono-infections (P < 0.05) unlike TGF-β level. Significant positive correlations were identified between IFN-γ verses TNF-α and IL-6 verses IL-10 in co-infection (Spearman’s P < 0.05). The T. b. rhodesiense significantly induced the cytokine response more than P. falciparum infections. Co-infection led to synergistic stimulation of pro-inflammatory (IFN-γ, TNF-α), and anti-inflammatory (IL-6, and IL-10) cytokine responses relative to malaria mono-infection. Level of TNF-α partially indicates the effect induced by T. b. rhodesiense and P. falciparum mono-infections or a synergistic interaction of co-infections which may have adverse effects on pathogenesis, prognosis and resolution of the infections. Trial registration VCD-IRC/021, 26/08/2011; HS 1089, 16/01/2012

  • Differential expression of CCR2 and CX3CR1 on CD16+ monocyte subsets is associated with asthma severity
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-04
    Reem Al-Rashoudi; Gillian Moir; Mohamed S. Al-Hajjaj; Monther M. Al-Alwan; Heather M. Wilson; Isabel J. Crane

    Monocytes play an important role in immune and inflammatory diseases and monocyte subsets are predictors of disease in certain conditions. Expression of the chemokine receptors, CCR2 and CX3CR1 on monocyte subsets relates to their function and can be used in their characterization. Our objective was to determine whether CD14, CD16, CCR2 and CX3CR1 on monocyte subsets are potential indicators of asthma severity. Blood samples were collected from Saudi Arabian patients with asthma and normal healthy individuals. Six-color flow-cytometry phenotypic analysis was used to identify human blood monocyte subsets, based on their expression of CD14 and CD16 following CD45 gating. Expression of CCR2 and CX3CR1 was analysed on classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) subsets and correlated with disease severity. We demonstrated a significant increase in percentage of total CD45-positive monocytes in the blood of patients with severe asthma, but the proportion of the individual monocyte subsets was not significantly changed when patients with mild, moderate and severe asthma were compared with healthy individuals. CD16 expression (mean fluorescence intensity, MFI) was decreased on intermediate and non-classical subsets in patients with severe asthma compared to healthy controls. CX3CR1 expression was also lower, with a lower percentage of cells expressing CX3CR1 in the non-classical CD14+CD16++ subset in all patients with asthma and this was inversely related to the percentage of cells expressing CCR2. CCR2 expression on monocytes indicated a tendency toward more phagocytic monocytes in patients with asthma. The differential expression of CD16, CX3CR1 and CCR2 on monocyte subsets in peripheral blood indicates modulation of the inflammatory response and suggests a role for monocytes in asthma pathogenesis.

  • Gender differences in asthma perception and its impact on quality of life: a post hoc analysis of the PROXIMA (Patient Reported Outcomes and Xolair® In the Management of Asthma) study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-06
    Delia Colombo; Emanuela Zagni; Fabio Ferri; Giorgio Walter Canonica

    Gender differences in asthma perception and control have been reported. The PROXIMA observational study assessed these outcomes in a cohort of Italian severe allergic asthma (SAA) patients. This post hoc analysis of the PROXIMA results was aimed at assessing gender differences in SAA in a real-world setting, focusing on disease perception and impact on quality of life (QoL). The PROXIMA study was an observational, multicenter study, consisting of a cross-sectional and a prospective longitudinal phase, including adult outpatients diagnosed with SAA at step 4 requiring a therapeutic step-up. Patients on omalizumab treatment at baseline were included in the 12-month longitudinal phase. Disease control was assessed by the Asthma Control Questionnaire (ACQ) score, patients’ disease perception by the Brief Illness Perception Questionnaire (BIPQ), and QoL by the EuroQoL five-dimensional three-level questionnaire (EQ-5D-3 L) at baseline and after 6 and 12 months. Two regression models were used to evaluate the association between gender and BIPQ total score and EQ-5D-3L score, respectively. 357 patients (65% females) were analyzed for the cross-sectional phase and 99 (62.6% females) for the longitudinal phase. The prevalence of perennial and seasonal aeroallergens was similar between genders. ACQ score decreased similarly during omalizumab treatment at 6 and 12 months in both genders; no gender differences were observed in control rates. Asthma perception was worse among females at all study visits reaching statistical significance at 12 months (mean (SD) B-IPQ total score 41.8 (9.4) vs 35.6 (12.0); T test p-value (males vs females) < 0.05). Statistically significant gender differences were observed for some specific items, with males reporting less symptom experience, concern about the disease, and emotional impact at 12-months. The results of the multivariate regression model for repeated measures showed that overall treatment with omalizumab improved disease perception overtime regardless from gender. Males reported a significantly better QoL compared to females at both 6 and 12 months. In this real-world setting, females confirmed to have a worse perception of asthma, feel it as more symptomatic and suffer a greater impact on their QoL, even though having similar baseline severity and obtaining similar level of control.

  • Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-12
    Lundy McKibbin; Colin Barber; Chrystyna Kalicinsky; Richard Warrington

    Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema. The underlying pathophysiology and diagnostic criteria continues to evolve. There is a significant overlap between HAE-nC1 INH and idiopathic nonhistaminergic angioedema, ultimately this may be found to be the same condition. Characterization of cohorts suspected to have either of these conditions is warranted to help refine diagnosis, pathophysiology, and treatment response. A retrospective chart review of 418 patients diagnosed with angioedema was conducted. The following inclusion criteria was used: lack of response to antihistamines, steroids, and epinephrine; normal C4, C1 inhibitor (C1 INH) level and function; lack of urticaria or pruritus; occurrence without offending drugs; and positive family history. Enzyme immunoassays for C1 INH function were performed at the Mayo Clinic. Charts meeting these criteria were reviewed for frequency and type of episodes as well as use and response to therapies. 6 patients met the above criteria. 3 of these completed genetic testing, none were found to have factor XII abnormalities. None had angiopoietin 1 or plasminogen gene sequencing. 5 of 6 patients were successfully treated with C1 INH or tranexamic acid for acute treatment of attacks (4 with C1 INH and 1 with tranexamic acid). 4 patients have used Icatibant with good response (typically under 40 min for near full recovery); of these, 3 required Icatibant as acute treatment after other therapies (C1 inhibitor and tranexamic acid) were ineffective. There were 9 patients who otherwise met criteria, but due to a lack of family history were classified as having idiopathic non-histaminergic angioedema. This retrospective chart review found 6 HAE-nC1 INH patients in Manitoba. 1 responded to tranexamic acid and not C1 INH, 4 typically responded to C1 INH, and 1 responded exclusively to Icatibant. All patients—4 total—who used Icatibant responded; of these 4 patients, 3 required Icatibant after other therapies had failed.

  • Whole blood vs PBMC: compartmental differences in gene expression profiling exemplified in asthma
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-21
    Daniel He; Chen Xi Yang; Basak Sahin; Amrit Singh; Casey P. Shannon; John-Paul Oliveria; Gail M. Gauvreau; Scott J. Tebbutt

    Blood has proven to be a useful resource for molecular analysis in numerous biomedical studies, with peripheral blood mononuclear cells (PBMCs) and whole blood being the major specimen types. However, comparative analyses between these two major compartments (PBMCs and whole blood) are few and far between. In this study, we compared gene expression profiles of PBMCs and whole blood samples obtained from research subjects with or without mild allergic asthma. Whole blood (PAXgene) and PBMC samples were obtained from 5 mild allergic asthmatics and 5 healthy controls. RNA from both sample types was measured for expression of 730 immune-related genes using the NanoString nCounter platform. We identified 64 uniquely expressed transcripts in whole blood that reflected a variety of innate, humoral, and adaptive immune processes, and 13 uniquely expressed transcripts in PBMCs which were representative of T-cell and monocyte-mediated processes. Furthermore, analysis of mild allergic asthmatics versus non-asthmatics revealed 47 differentially expressed transcripts in whole blood compared to 1 differentially expressed transcript in PBMCs (FDR < 0.25). Finally, through simultaneous measurement of PBMC proteins on the nCounter assay, we identified CD28 and OX40 (TNFRSF4), both of which are critical co-stimulatory molecules during T-cell activation, as significantly upregulated in asthmatics. Whole blood RNA preserved in PAXgene tubes is excellent for producing gene expression data with minimal variability and good sensitivity, suggesting its utility in multi-centre studies requiring measurement of blood gene expression.

  • A novel mutation in NCF2 resulting in very-early-onset colitis and juvenile idiopathic arthritis in a patient with chronic granulomatous disease
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-21
    Suzan AlKhater

    Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease primarily presents with recurrent infections, and patients may also present with inflammatory conditions, including noninfectious colitis, and an increased frequency of autoimmunity. We report here a patient with CGD in whom the presentation, unlike the classical presentation of CGD, was predominantly of an inflammatory and autoimmune phenotype. A 3-year-old Pakistani female presented with bloody diarrhea since the age of 7 days, followed by the development of perianal abscesses and fistula. There was no other history of recurrent infections. The patient subsequently developed joint pain and stiffness with persistently elevated inflammatory markers and elevated anti-cyclic citrullinate peptide (anti-CCP) antibody titer. She was diagnosed with oligoarticular juvenile idiopathic arthritis and colitis. The diagnosis of CGD was later made and was based on the absence of NADPH oxidase activity in the patient’s neutrophils upon phorbol myristate acetate (PMA) stimulation using the dihydrorhodamine-1,2,3 (DHR) flow cytometry test. Targeted next-generation sequencing revealed an unreported deletion mutation in exon 10 as a homozygous loss-of-function variant of the human neutrophil oxidase factor 2 (NCF2) (NCF2: NM_001190789, nucleotide change: c.855_856del:p.T285fs). The gene encodes a protein subunit, p67phox, in the NADPH enzyme complex. The case emphasizes the importance of maintaining high clinical suspicion of immunodeficiency and CGD in patients with very-early-onset colitis and autoimmune disorders. This case is important due to its rarity and because it might represent a previously undiscovered mutation, which is possibly more common in the patient’s ethnic group. Other mutations in NCF2 have been linked to inflammatory bowel disease and autoimmunity, but without CGD, suggesting similarities in the pathogenesis.

  • Methodological evaluation of human research on asthmagenicity and occupational cleaning: a case study of quaternary ammonium compounds (“quats”)
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-21
    Judy S. LaKind; Michael Goodman

    In this paper, we review methodological approaches used in studies that evaluated the association between occupational exposure to quaternary ammonium compounds (quats) and occupational asthma. This association is of interest because quats are a common active ingredient of disinfectants and have been linked to work-related asthma in some circumstances. However, any evidence-based assessment of an exposure-outcome association needs to consider both strengths and limitations of the literature. We focus on publications cited by various US and international organizations. Eighteen investigations included in the review fall into two broad categories: case reports and challenge studies of individual patients and population studies that examined the association between quats and asthma occurrence in groups of subjects. We evaluated these studies guided by questions that address whether: exposure data on specific quat(s) and other agents that may cause asthma were included, new asthma cases were differentiated from asthma exacerbation, and information on respiratory sensitivity versus irritation was given. We also assessed consistency across studies. Studies of individual patients, particularly those that provided detailed information on challenge test results, document cases of asthma induced by exposure to quats. By contrast, studies of occupational groups with the highest potential for quats exposure (e.g., cleaners and farmers) do not consistently report increased incidence of asthma due specifically to quats. The unresolved methodological issues include: poor understanding of exposure pathways considering that quats are non-volatile, lack of quantitative data allowing for identification of an asthmagenicity threshold, insufficient information on whether quats are sensitizers or act via dose-dependent irritation or some other mechanism, and inability to quantify risk of new-onset asthma attributable to quats. Another important area of uncertainty is the lack of information on the specific quats being used. There is also a lack of data capable of distinguishing the effects of quats from those of other chemical and biological workplace exposures. The current state-of-the-science does not allow a proper assessment of the potential link between quats and occupational asthma.

  • Agreement between self-reported asthma symptoms and exhaled nitric oxide levels: impact on inhaled corticosteroid prescribing in general practice. An observational study
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-21
    Raj Gill; E. Mark Williams

    The National Review of Asthma Deaths UK highlighted that 46% of deaths could be avoided and recommended that all sufferers receive a structured asthma annual review which assess asthma control. In primary care this is commonly achieved using symptom-based questionnaires such as the Asthma Control Test (ACT). A newer method of assessing asthma control is Fractional Exhaled Nitric Oxide (FeNO) testing, which is currently recommended for the diagnosis of asthma, but not for monitoring of asthma control. The study aim was to assess the correlation between self-reported symptoms as measured by the ACT and FeNO testing and the subsequent impact of FeNO testing on prescribing of asthma medication. A retrospective review of 65 patients who had received both ACT and FeNO testing as part of their asthma annual review. A spearman correlation was used to estimate the correlation between ACT scores and FENO levels. A χ2 test was used to compare prompting frequency of the measures and Kendalls τ statistic was made to estimate their concordance and influence on subsequent ICS medication prescription. The mean age of the participants was 41 years (4–93 years). There was no statistically significant correlation between ACT and FeNO (ρ = 0.195, p = 0.120). The median FeNO was 26 ppb (range 8–279 ppb), and the ACT score 20 (range 5 to 25 points). Furthermore, FeNO more frequently prompts a change in medication than ACT, 66% versus 42% (p = 0.005). A low concordance between the measures was found (Kendall’s τ statistic − 0.321). FeNO should be considered for monitoring of control in asthma. To balance the cost of implementing this technology into primary care a risk stratified approach could be applied to testing.

  • Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-21
    Jingyun Li; Jian Jiao; Yunbo Gao; Yuan Zhang; Luo Zhang

    This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.

  • The International/Canadian Hereditary Angioedema Guideline
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-25
    Stephen Betschel; Jacquie Badiou; Karen Binkley; Rozita Borici-Mazi; Jacques Hébert; Amin Kanani; Paul Keith; Gina Lacuesta; Susan Waserman; Bill Yang; Emel Aygören-Pürsün; Jonathan Bernstein; Konrad Bork; Teresa Caballero; Marco Cicardi; Timothy Craig; Henriette Farkas; Anete Grumach; Connie Katelaris; Hilary Longhurst; Marc Riedl; Bruce Zuraw; Magdelena Berger; Jean-Nicolas Boursiquot; Henrik Boysen; Anthony Castaldo; Hugo Chapdelaine; Lori Connors; Lisa Fu; Dawn Goodyear; Alison Haynes; Palinder Kamra; Harold Kim; Kelly Lang-Robertson; Eric Leith; Christine McCusker; Bill Moote; Andrew O’Keefe; Ibraheem Othman; Man-Chiu Poon; Bruce Ritchie; Charles St-Pierre; Donald Stark; Ellie Tsai

    This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

  • Use of a vibrating mesh nebulizer for allergen challenge
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-26
    Donald W. Cockcroft; Beth E. Davis; Christianne M. Blais; Louis-Philippe Boulet; Marie-Éve Boulay; Hélène Villeneuve; Gail M. Gauvreau; Paul M. O’Byrne; Karen J. Howie; Caitlin D. Obminski

    Allergen inhalation tests are a valuable research tool. The allergen dose producing an early asthmatic response (EAR) can be predicted from methacholine responsiveness and allergen skin test endpoint (STE). The Wright® jet nebulizer, which is both inefficient and increasingly difficult to obtain, has been used historically. We assessed the Solo® vibrating mesh nebulizer as an alternative for allergen and methacholine challenges. Eighteen mild atopic asthmatics completed the study. Doubling concentration allergen prick skin tests were performed to determine the STE in allergen units/mL. The Wright® protocol was used to measure the methacholine provocation dose causing a 20% forced expired volume in one second (FEV1) fall (PD20) (μg) and the allergen PD20 (units). The Solo® protocol (0.5 mL nebulized to completion, tidal breathing inhalation) was used to determine both methacholine PD20 and allergen PD20. The nebulizer order was randomized and separated by ≥ 2 weeks. All data were log transformed. The allergen PD20, predicted from the methacholine PD20 and the STE, was within 2 doubling doses of the PD20 measured with the Wright® and 2.64 doubling doses of that measured with Solo®. The Wright® allergen PD20 correlated with the Wright® methacholine PD20 (r = 0.74) and the STE (r = 0.78) and more strongly with the product of the two (Wright® methacholine PD20 × STE, r = 0.91, p < 0.00001). The Solo® allergen PD20 showed similar relationships with the Solo® methacholine PD20 (r = 0.61), the STE (r = 0.75) and the product of the two (Solo® methacholine PD20 × STE, r = 0.83, p < 0.00002). The Wright® and the Solo® methacholine geometric mean PD20s were not significantly different (49.3 and 54.5 μg respectively, p = 0.62). The Wright® allergen PD20 was slightly but significantly lower than the Solo® allergen PD20 (geometric means 6.7 and 10.5 units respectively, p = 0.003). The Solo® allergen PD20 showed the same relationship with methacholine responsiveness and STE as did the Wright®. The Solo® allergen PD20 was slightly but significantly higher than the Wright® allergen PD20. The Solo® vibrating mesh nebulizer was well tolerated and is an acceptable alternative for allergen challenge. Trial registration clinicaltrials.gov: NCT03491358

  • Short-term skin problems in infants aged 0–3 months affect food allergies or atopic dermatitis until 2 years of age, among infants of the general population
    Allergy Asthma Clin. Immunol. (IF 2.664) Pub Date : 2019-11-26
    Kaori Yonezawa; Megumi Haruna

    This study examined whether infants aged 0–3 months exhibited long-term effects of using a moisturizer skincare intervention and whether a short-term skin problem resulted in the subsequent development of food allergies or atopic dermatitis (AD) until the age of 2 years. This study was a follow-up of a completed randomized control trial (RCT) of moisturizer skincare for infants aged 0–3 months. A self-reported questionnaire was mailed to the parents of children aged 1–2 years who had participated in the RCT. Data were analyzed using a Chi square test, by intention to treat analysis, and by multiple logistic regression. Of 155 infants, 22 (14.2%) and 28 (18.1%) had food allergies and AD/eczema until 2 years of age, respectively. No significant difference was seen in food allergies or AD between the group that received moisturizer skincare intervention and the control group. On the contrary, food allergies until 2 years of age were significantly associated with short-term (4–7 days) and long-term (more than 7 days) body skin problems occurring in the first 3 months of life, a family history of AD, and the time of starting complementary food. High value of face transepidermal water loss at 3 months of age was also associated with food allergies. Moreover, a short duration of severe diaper dermatitis during the first 3 months, a family history of AD, and being male were significantly associated with AD/eczema until the age of 2 years. After adjusting for family history of AD, a short-term skin problem in the first 3 months of life was significantly associated with the development of food allergies or AD/eczema until the age of 2 years. Prevention or prompt treatment of skin problems in newborns is essential for preventing future allergic diseases. Trial registration This was a follow-up study conducted 2 years after the completed RCT of a moisturizer skincare intervention for early infants, which was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013260)

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上海纽约大学William Glover