Evolutionary lung function evaluated by impulse oscillometry in preschoolers with asthma. / Función pulmonar evolutiva evaluada por oscilometría de impulso en prescolares con asma.

INTRODUCTION: Impulse oscillometry (IOS) is useful for measuring lung function in preschool children. Our objec tive was to describe the alterations and evolutionary profile of IOS in asthmatic children under 6 years of age after one year of follow-up. PATIENTS AND METHOD: 62 preschoolers performed IOS at the begin ning of the study and after one year. The proportion of altered IOS and bronchodilator response (BR +) at both times was compared, in addition to sub-analysis according to asthma control and presence of atopy. For the statistical analysis, we used McNemar's %2 and the Student's t-test with a 5% a error. RESULTS: The initial IOS was altered in 80.6% and in 64.5%% after one year (p = 0.04). 77.4% of the children presented BR+ at the beginning of the study and 83.9% after one year. The uncontrolled asthma group presented a significant improvement in the X5 and D5-20 means, but the controlled asthma group did not. In atopic patients, only uncontrolled asthmatics improved X5, AX, and D5-20. CONCLUSION: IOS shows alterations in a high percentage of preschoolers with uncontrolled asthma, which decreases significantly at one year, but remains altered and with BR + in most children. Ad ditional studies are required to identify different preschool asthma phenotypes and their evolution with treatment.

Outdoor air pollutants exposure associated with pulmonary function and EBC pH value in atopic asthmatic and non-asthmatic children.

OBJECTIVE: Air pollution is associated with the prevalence of respiratory diseases. This study aimed to evaluate the impacts of outdoor air pollutants and indoor Dermatophagoides pteronyssinus 1 (Der p 1) exposure on levels of fractional exhaled nitric oxide (FeNO), exhaled breath condensate (EBC) pH, and pulmonary function in atopic children. METHODS: This study recruited 59 atopic mild-to-moderate asthmatic children and 23 atopic non-asthmatic children. Data on personal characteristics, FeNO, EBC pH, and pulmonary function were collected. Group 1 allergens of Der p 1 were measured on the tops of mattresses and on bedroom floors in the children's homes, and outdoor air pollutant concentrations were estimated from air quality monitoring stations, using the ordinary kriging method. RESULTS: Exposure levels of outdoor air pollutants, except for particulate matter (PM)2.5, for the recruited children met outdoor air quality standards set by the Taiwan Environmental Protection Agency. The lag effect of outdoor PM10 exposure was negatively associated with the forced expiratory volume in one second (FEV1) [(Lag 1: ß=-0.771, p = 0.028), and O3 (Lag 1-7: ß=-2.02, p = 0.04, Lag 1-28: ß=-3.213, p = 0.029)]. Median pulmonary function parameters differed significantly in forced vital capacity (FVC) (p = 0.004) and FEV1 (p = 0.024) values between atopic asthmatic and non-asthmatic children. No association was found between the FeNO/EBC pH level and exposure to Der p 1 allergen and air pollutants in the recruited children. CONCLUSIONS: Outdoor PM10 and O3 exposure was associated with reduction in FEV1 in atopic asthmatic and non-asthmatic children.

Atopy and pulmonary function among healthy-weight and overweight/obese children with asthma.

INTRODUCTION: Epidemiologic studies have found low/absence of atopy in obese asthmatic children, but the association or lack thereof of atopy with disease morbidity, including pulmonary function, in obese asthma is not well understood. We sought to define the association of atopy with pulmonary function in overweight/obese minority children with asthma. METHODS: In a retrospective chart review of 200 predominantly minority children evaluated at an academic Pediatric Asthma Center over 5 years, we compared the prevalence of atopy, defined as ≥ 1 positive skin prick test or serum-specific immunoglobulin E quantification to environmental allergens, and its association with pulmonary function in overweight/obese (body mass index [BMI] > 85th percentile) (n = 99) to healthy-weight children (BMI, 5th-85th percentile for age) (n = 101). RESULTS: In a cohort comprised of 47.5% Hispanics and 39.5% African Americans, 81% of overweight/obese and 74% of healthy-weight children were atopic. While atopic healthy-weight children had lower percent-predicted forced expiratory volume in the first second (FEV1 ) (93 ± 13.6 vs 107% ± 33.2%, P = .03) and lower percent-predicted forced vital capacity (FVC) (93% ± 12.2% vs 104% ± 16.1%, P = .01) as compared to nonatopic children, atopy was not associated with FEV1 (P = .7) or FVC (P = .17) in overweight/obese children. Adjusting for demographic and clinical variables, atopy was found to be an independent predictor of FEV1 and FVC in healthy-weight (ß = -2.4, P = .07 and ß = -1.7, P = .04, respectively) but not in overweight/obese children (ß = .6, P = .5 and ß = .8, P = .3). CONCLUSIONS: Atopy is associated with lower lung function in healthy-weight asthmatics but not in overweight/obese asthmatics, supporting the role of nonallergic mechanisms in disease burden in pediatric obesity-related asthma.

Jellyfish anaphylaxis: A wide spectrum of sensitization routes.

Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock." Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.

Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene.

BACKGROUND: Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies. RESEARCH QUESTION: What is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)? STUDY DESIGN AND METHODS: Four hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included. Comparison groups were defined by atopic and asthma status (neither, atopy alone, atopic asthma, nonatopic asthma, with atopy defined as any positive specific IgE (≥0.35 KU/L) to any of the 10 allergens or mixes and asthma defined as self-report of doctor-diagnosed current asthma). Multivariable regression analyses (linear, logistic, and zero inflated negative binomial where appropriate) adjusted for age, sex, race, lung function, smoking status, pack-years smoked, and use of inhaled corticosteroids were used to determine characteristics of groups and relationship with outcomes (exacerbations, clinical outcomes, CT metrics) separately in COPDGene and SPIROMICS, and then adjusted results were combined using meta-analysis. RESULTS: The prevalence of atopy was 35% and 36% in COPD subjects from SPIROMICS and COPDGene, respectively, and less than 50% overlap was seen between atopic status with asthma in both cohorts. In meta-analysis, individuals with nonatopic asthma had the most impaired symptom scores (effect size for St. George's Respiratory Questionnaire total score, 4.2; 95% CI, 0.4-7.9; effect size for COPD Assessment Test score, 2.8; 95% CI, 0.089-5.4), highest risk for exacerbations (incidence rate ratio, 1.41; 95% CI, 1.05-1.88) compared with the group without atopy or asthma. Those with atopy and atopic asthma were not at increased risk for adverse outcomes. INTERPRETATION: Asthma and atopy had incomplete overlap among former and current smokers with COPD in COPDGene and SPIROMICS. Nonatopic asthma was associated with adverse outcomes and exacerbation risk in COPD, whereas groups having atopy alone and atopic asthma had less risk.

Exposure to diisononyl phthalate promotes atopic march by activating of NF-κB and p38 MAPK.

What factors and underlying mechanisms influence the occurrence of the atopic march remain unclear. Recent studies suggest that exposure to diisononyl phthalate (DINP) might be associated with the occurrence of atopic dermatitis (AD) and asthma. However, little is known about the role of DINP exposure in the atopic march. In this study, we investigated the effect of DINP exposure on the progression from AD to asthma, and explored the potential mechanisms. We built an atopic march mouse model from AD to asthma, by exposure to DINP and sensitization with OVA. Pyrrolidine dithiocarbamate and SB203580 were used to block NF-κB and p38 MAPK respectively, to explore the possible molecular mechanisms. The data showed that DINP aggravated airway remodeling and airway hyperresponsiveness (AhR) in the progression from AD to asthma, induced a sharp increase in IL-33, IgE, Th2 and Th17 cytokines, and resulted in an increase in the expression of thymic stromal lymphopoietin (TSLP) and in the number of inflammatory cells. Blocking NF-κB inhibited AD-like lesions, and the production of IL-33 and TSLP in the progression of AD, while alleviating airway remodeling, AhR, and the expression of Th2 and Th17 cytokines in both the progression of AD and the asthmatic phenotype. Blocking p38 MAPK in the progression of asthma, inhibited airway remodeling, AhR, and the expression of Th2 and Th17 cytokines. The results demonstrated that exposure to DINP enhanced the immune response to memory CD4+ T helper cells through the NF-κB and p38 MAPK signaling pathways, leading to an aggravation of the atopic march.

Alcohol-Related Dermatitis: A Review.

: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Is atopic sensitization associated with indicators of early vascular ageing in adolescents?

BACKGROUND: Chronic systemic inflammation accelerates early vascular ageing. Atopic sensitization and allergic diseases may involve increased inflammatory activity. This study aimed to assess whether atopic sensitization and allergic diseases were associated with altered vascular biomarkers in Norwegian adolescents. METHODS: Distensibility coefficient of the common carotid arteries, carotid intima-media thickness and atopic sensitization (serum total and specific IgEs) were assessed in 95 Norwegian adolescents, who participated in the RHINESSA generation study. Symptoms of allergic disease were assessed by an interviewer-led questionnaire. RESULTS: Atopic sensitization was found in 33 (34.7%) of the adolescents. Symptomatic allergic disease was found in 11 (33.3%) of those with atopic sensitization. Distensibility coefficient of the common carotid arteries appeared to be lower in participants with atopic sensitization than in those without (46.99±8.07*10-3/kPa versus 51.50±11.46*10-3/kPa; p>0.05), while carotid intima-media thickness did not differ between these groups (0.50±0.04mm versus 0.50±0.04mm; p>0.05). Crude, as well as age- and sex-adjusted multiple regression, revealed no significant association, neither of atopic sensitization nor of allergic disease, with distensibility coefficient of the common carotid arteries and carotid intima-media thickness. CONCLUSIONS: Our results do not support the assumption of an adverse impact of atopic sensitization and/or allergic disease on distensibility coefficient of the common carotid arteries and carotid intima-media thickness in Norwegian adolescents. Further research is necessary to study whether the clinical severity of allergic diseases might be more important than the status of allergic disease or atopic sensitization.

Setting definitions of childhood asthma in epidemiologic studies.

BACKGROUND: The definitions of childhood asthma differ among epidemiological studies. We aimed to compare the diagnostic accuracy and agreement of previous asthma definitions and to evaluate questionnaire-driven asthma definition patterns. METHODS: Data on 808 participants aged 7-12 years from 20 schools were analyzed. Asthma definitions based on symptoms assessed by questionnaire, parent-reported medical asthma diagnosis, current use of asthma medication, airway reversibility after bronchodilatation, and increased (≥35 ppb) levels of exhaled nitric oxide (eNO) were compared with a gold standard (medical diagnosis of asthma with asthma symptoms in the past 12 months and/or airway reversibility). Concordance was assessed by Cohen's kappa. Data-driven analysis was applied to the questionnaire, and six scores were determined "asthma," "rhinitis," "cough," "non-specific respiratory symptoms," "treated asthma," and "uncontrolled asthma." Tree decisions were built using these scores. RESULTS: Definitions of asthma based on respiratory symptoms, airway reversibility, and parent-reported medical diagnosis had a low sensitivity but high specificity. Agreement between reported and objective measures was poor. Parent-reported medical asthma diagnosis, but not reversibility or eNO, was able to predict questionnaire-driven symptom patterns. Decision trees indicated that those with recent non-specific respiratory symptoms had a higher probability of positive bronchodilation. CONCLUSION: A standardized operational definition of asthma should include a composite score based on reported asthma medical diagnosis, symptoms, and lung function.

Microfibrillar-associated protein 4 in serum is associated with asthma in Danish adolescents and young adults.

BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily, which plays multifaceted roles in innate immunity and normal endothelial function. It has been proposed that MFAP4 promotes the development of asthma in vivo and proasthmatic pathways of bronchial smooth muscle cells in vitro. The aim of this study was to investigate the significance of serum MFAP4 in adolescents and young adolescents with persistent asthma. METHODS: Prospective, observational study including adolescents and young adults (age 11-27 years) previously diagnosed with asthma during childhood 2003 to 2005 (0-15 years) at the four pediatric outpatient clinics in the Region of Southern Denmark (n = 449). Healthy controls were recruited at follow-up (n = 314). Detection of serum MFAP4 was performed by AlphaLISA technique. RESULTS: Current asthma was associated to a 14% higher mean level of serum MFAP4 compared with controls (expß 1.14, 95% confidence intervals [CI], 1.05-1.23) and a 6% higher mean level compared with subjects with no current asthma (expß 1.06, 95% CI, 0.99-1.13). No association was found at follow-up between serum MFAP4 and self-reported atopic symptoms (other than asthma), Asthma Control Test-score, fractional exhaled nitric oxide (FeNO), nor to flow rate at 1 second, forced vital capacity, and forced expiratory flow 25% to 75%, response to short-acting beta 2 agonist or mannitol. CONCLUSIONS: We found a significantly higher mean level of serum MFAP4 in adolescent and young adults with mild to moderate asthma compared with healthy controls but no association to FeNO and lung function nor to the response to short-acting beta 2 agonist or mannitol. The result supports the hypothesis that MFAP4 plays a role in the pathogenesis of asthma although the marker did not demonstrate any obvious potential as an asthma biomarker in adolescents and young adults with asthma. To understand the possible proasthmatic functions of MFAP4, further investigation in specific asthma phenotypes and the underlying molecular mechanisms is warranted.

Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction.

Mast cell activation syndrome (MCAS) is a rare condition defined by a severe systemic reaction to mast cell (MC)-derived mediators. Most cases present with clinical signs of anaphylaxis, and some have an underlying IgE-dependent allergy. A primary MC disease (mastocytosis) may also be detected. Severe recurrent MCAS episodes requiring intensive care or even resuscitation are typically found in patients who suffer from both mastocytosis and allergy against certain triggers, such as hymenoptera venom components. A less severe form and a local form of MC activation (MCA) also exist. For these patients, diagnostic criteria are lacking. Moreover, a number of different, unrelated, conditions with overlapping symptoms may be confused with MCAS. As a result, many patients believe that they are suffering from MCAS but have in fact a less severe form of MCA or another underlying disease. In the current article, we review the potential differential diagnoses of MCA and MCAS and discuss available diagnostic criteria and diagnostic tools. These criteria and assays may be useful in daily practice and help avoid unnecessary referrals and unjustified fears in patients.

Effect of Creatine Supplementation on the Airways of Youth Elite Soccer Players.

INTRODUCTION: Owing to its well-established ergogenic potential, creatine is a highly popular food supplement in sports. As an oral supplement, creatine is considered safe and ethical. However, no data exist on the safety of creatine on lung function in athletes. The aim of this project was to evaluate the effects of a standard course of creatine on the airways of youth elite athletes. METHODS: Nineteen elite soccer players, 16-21 yr old, completed a stratified, randomized, double-blind, placebo-controlled, parallel-group trial. The creatine group (n = 9) ingested 0.3 g·kg⋅d of creatine monohydrate (CM) for 1 wk (loading phase) and 5 g·d for 7 wk (maintenance phase), and the placebo group (n = 10) received the same dosages of maltodextrin. Airway inflammation (assessed by exhaled nitric oxide, FENO) and airway responsiveness (to dry air hyperpnoea) were measured pre- and postsupplementation. RESULTS: Mild, unfavorable changes in FENO were noticed by trend over the supplementation period in the CM group only (P = 0.056 for interaction, η = 0.199), with a mean group change of 9 ± 13 ppb in the CM group versus -5 ± 16 ppb in the placebo group (P = 0.056, d = 0.695). Further, the maximum fall in forced expiratory volume in 1 s after dry air hyperpnoea was larger by trend postsupplementation in the CM group compared with the placebo group: 9.7% ± 7.5% vs 4.4% ± 1.4%, respectively (P = 0.070, d = 0.975). These adverse effects were more pronounced when atopic players only (n = 15) were considered. CONCLUSION: On the basis of the observed trends and medium to large effect sizes, we cannot exclude that creatine supplementation has an adverse effect on the airways of elite athletes, particularly in those with allergic sensitization. Further safety profiling of the ergogenic food supplement is warranted.

Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome.

Mast cell activation (MCA) accompanies diverse physiologic and pathologic processes and is one of the more frequently encountered conditions in medicine. MCA-related symptoms are usually mild and often transient. In such cases, histamine receptor blockers and other mediator-targeting drugs can usually control MCA. In severe cases, an MCA syndrome (MCAS) may be diagnosed. However, overt MCAS is an unusual condition, and many patients referred because of suspected MCAS are diagnosed with other diseases (autoimmune, neoplastic, or infectious) unrelated to MCA or suffer from MCA-related (eg, allergic) disorders and/or comorbidities without fulfilling criteria of an overt MCAS. These considerations are important as more and more patients are informed that they may have MCA or even MCAS without completing a thorough medical evaluation. In fact, in several instances, symptoms are misinterpreted as MCA/MCAS, and other clinically relevant conditions are not thoroughly pursued. The number of such referrals is increasing. To avoid such unnecessary referrals and to prevent misdiagnoses, we here propose a diagnostic algorithm through which a clinically relevant (systemic) MCA can be suspected and MCAS can subsequently be documented or excluded. In addition, the algorithm proposed should help guide the investigating care providers to consider the 2 principal diagnoses that may underlie MCAS, namely, severe allergy and systemic mastocytosis accompanied by severe MCA. Although validation is required, we anticipate that this algorithm will facilitate the management of patients with suspected MCAS.

Vaccine Allergy? Skin Testing and Challenge at a Tertiary Pediatric Hospital in Melbourne, Australia.

BACKGROUND: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. OBJECTIVE: We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy. METHODS: A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented. RESULTS: There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis. CONCLUSIONS: The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI.

Association between asthma control and Interleukin-17F expression levels in adult patients with atopic asthma.

OBJECTIVES: To investigate the correlation between Interleukin 17 (IL-17F) and the level of asthma control. METHODS: This is a cross-sectional study of 40 subjects who were diagnosed with atopic asthma. All participants were recruited from the Allergy and Immunology Clinic, Prof. R.D. Kandou General Hospital, Manado, Indonesia, between April 2015 and April 2016. Total serum IL-17F measured by using Enzyme-Linked Immunosorbent Assay methods; and mRNA IL-17F was obtained by using real-time reverse transcriptase polymerase chain reaction. Level of asthma control was quantified by using asthma control test (ACT) scoring system. The correlation between IL-17F, mRNA, and level of asthma control was analyzed by using Pearson's correlation coefficient (r). RESULTS: There is a strong positive correlation between IL-17F serum level and Nathan's ACT-score (r=0.969) which is statistically significant (p less than 0.001). Analysis of the correlation between mRNA IL-17F serum level and Nathan's ACT-score revealed a strong positive correlation (r=0.963), which is statistically significant (p less than 0.001). CONCLUSION: These findings suggest that IL-17F plays an important role in asthma control. However, the role played by IL-17F in asthma pathogenesis are still questions to be answered.

Associations between factors related to atopic disease and glaucoma in the National Health and Nutrition Examination Survey.

INTRODUCTION: Previous studies have suggested associations between glaucoma and serum sensitization to specific allergens. The purpose of this study was to examine associations between inciting factors for atopic disease, atopic diseases and symptoms, and glaucoma in the 2005-2006 National Health and Nutrition Examination Survey. METHODS: The study population included adult participants of National Health and Nutrition Examination Survey 2005-2006. Inciting factors for atopic disease included pet ownership, mildew/musty smell in home, cockroaches in home, use of water treatment devices, and crowded living conditions. Atopic diseases and symptoms included hay fever, eczema, any allergy, sneezing problems, and sinus infections. The outcome was glaucoma defined by the Rotterdam criteria. Covariates included age, gender, ethnicity, and allergy-related medication use. Logistic regression was used to examine associations between each exposure and glaucoma prevalence, controlling for all covariates. Statistical analyses were weighted by the National Health and Nutrition Examination Survey multistage sampling design. RESULTS: The weighted study population included 83,205,587 subjects, of whom 2,657,336 (3.2%) had glaucoma. After adjusting for covariates, factors associated with increased glaucoma included cat ownership (odds ratio =1.99, 95% confidence interval = 1.02-3.87) and mildew/musty smell in home (odds ratio = 1.95, 95% confidence interval = 0.99-3.84; borderline significance), while history of eczema was associated with decreased glaucoma (odds ratio = 0.27, 95% confidence interval = 0.02-0.99). CONCLUSION: In National Health and Nutrition Examination Survey, self-reported cat ownership is associated with increased glaucoma prevalence, while a mildew/musty smell in home may have a borderline association with increased glaucoma prevalence. These findings are possibly related to laboratory associations identified in the same population and further studies are needed to identify potential mechanisms to explain these associations.

Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.

Among traditional Chinese medicine injections, intravenous Shuang-Huang-Lian (IV-SHL) has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). The precise mechanisms of IV-SHL-induced IHRs remain ambiguous. In this study, we investigated the mechanisms of SHL injection (SHLI)-induced IHRs. Our data showed that serum total IgE and mouse mast cell protease 1 (MMCP1) levels were higher in the SHLI antiserum; however, these effects of SHLI disappeared in the antibiotic-treated mice. SHLI caused intraplantar vasopermeability and shock during the first local or systemic injection. SHLI-induced nonallergic IHRs were attributed to its intermediate fraction F2 (the extract of Lonicerae Japonicae Flos and Fructus forsythiae), and could be blocked by antagonists for histamine or C5a, rather than PAF or C3a. Eight constituents of F2 were able to directly activate C5 to promote local vasopermeability at the mg/mL level. In conclusion, SHLI-induced IHRs are not mediated by IgE. SHLI or its F2 can directly activate blood C5. Subsequently, C5a is likely to provoke histamine release from its effector cells (e.g., mast cells and basophils), indicating that histamine is a principal effector of IHRs induced by SHLI.

Atopy Is Associated with Age at Asthma Onset in Elderly Patients.

BACKGROUND: Asthma in the elderly population (60 years of age and older) is frequently underdiagnosed, as well as atopy. Atopy, although more prevalent in younger patients, can be a major cause of asthma in the elderly. Chronic obstructive pulmonary disease (COPD) and cardiovascular disease are common differential diagnoses, especially in elderly smokers. OBJECTIVE: The objective of this study was to assess atopy and comorbidities in elderly patients with asthma. METHODS: This was an observational and retrospective study involving elderly asthmatic patients followed up at a tertiary center. Patients were assessed for severity of asthma, frequency of atopy, and frequency of comorbidities concomitant with asthma. Then, they were classified according to their age at asthma onset and the groups compared with each other for atopy, spirometric parameters, and comorbidities. RESULTS: This study included 243 elderly asthmatic patients, 71.8% of them presenting severe disease and 82.3% forced expiratory volume in 1 second (FEV1) < 80%. Gastroesophageal reflux disease, obesity, and asthma-COPD overlap syndrome were observed, respectively, in 64%, 37%, and 13% of these patients. Atopy was observed in 63%, mainly in those with early onset disease, and its frequency decreased as the age of asthma onset increased (P < .05). Total serum IgE was higher for allergic patients and FEV1 values were lower for patients with long-term asthma. Aspirin-exacerbated respiratory disease was more frequent in patients with nonallergic asthma. CONCLUSIONS: Most elderly asthmatic patients followed up in our tertiary center were atopic and higher values of total serum IgE suggest atopy. Atopy was inversely correlated with age of asthma onset. The diagnosis of allergic asthma in the elderly population is essential to treat patients more properly, improving their quality of life and decreasing asthma morbidity and mortality.

Maternal hemoglobin and hematocrit levels during pregnancy and childhood lung function and asthma. The Generation R Study.

OBJECTIVE: To examine the associations of maternal hemoglobin and hematocrit levels during pregnancy with childhood lung function and asthma, and whether adverse pregnancy outcomes and atopic predisposition modify the associations. METHODS: In a population-based prospective cohort study among 3672 subjects, we measured maternal hemoglobin and hematocrit levels in early pregnancy, and lung function by spirometry and current asthma by questionnaire at age 10 years. RESULTS: Higher maternal hematocrit levels, both continuously and categorized into clinical cut-offs, were associated with lower forced expiratory flow at 75% of forced vital capacity (FEF75 ) in children (Z-score (95%CI): -0.04 (-0.07, -0.01), per increase of 1 SDS in hematocrit level; Z-score (95%CI) difference: -0.11 (-0.20, -0.03) compared with normal hematocrit levels, respectively), taking lifestyle and socio-economic factors into account. Adverse pregnancy outcomes and atopic predisposition did not modify the results. No associations of maternal hemoglobin and hematocrit with current asthma were observed. CONCLUSION: Higher maternal hematocrit levels during pregnancy are associated with lower childhood lung function but not with risk of asthma. Adverse pregnancy outcomes and atopic predisposition do not modify these associations. Underlying mechanisms need to be further studied.