Non-asthmatic Patients Research Articles

Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with lower airway disease. However, only few studies of CRSwNP from outside secondary/tertiary care centres have been published. We recently reported an asthma frequency of 44% and 65% in primary and secondary care patients respectively. Therefore, we hypothesise that inflammation of the lower airways could be present in all CRSwNP patients, even without asthma. Here, we assessed the degree of lower and upper airway inflammation using exhaled and nasal nitric oxide (NO) in primary care CRSwNP patients with and without asthma. Fifty-seven patients who met the EPOS criteria for CRSwNP were prospectively recruited from primary care ear, nose and throat clinics. Nasal endoscopy was performed by an ear, nose and throat specialist upon enrolment. Additionally, 30 healthy controls were enrolled. Expiratory and nasal NO measurements and thorough pulmonary evaluation were performed. Pulmonary disease was diagnosed by a respiratory physician. Fifty-nine percent of CRSwNP patients with asthma showed elevated expiratory NO; the same was seen in 29% of non-asthmatic CRSwNP patients. Compared with controls, a high level of exhaled NO was significantly more prevalent in CRSwNP irrespective of asthma-status. Nasal NO was significantly lower in patients with CRSwNP compared with controls. Subclinical eosinophilic lower airway inflammation is common in CRSwNP in the primary sector, even in the absence of asthma.

TWEAK/Fn14 interaction induces proliferation and migration in human airway smooth muscle cells via activating the NF-κB pathway.

Asthma, an increasingly common chronic disease among children, are characterized by airway remodeling, which is partly attributed to the proliferation and migration of airway smooth muscle cell (ASMC). The purpose of the present study was to investigate potential roles and mechanisms of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis on cell proliferation and migration in HASMCs. Compared to HASMCs from non-asthmatic patients, those from asthmatic patients showed elevated expression levels of both Fn14 and TWEAK. Additionally, similar to the response triggered by platelet-derived growth factor-BB, stimulation with recombinant TWEAK strongly induced cell proliferation and migration in HASMCs. However, depletion of Fn14 remarkably abrogated the enhancement of TWEAK on the cell proliferation and migration of HASMCs. Furthermore, treatment with TWEAK led to the activation of NF-κB. This effect was eliminated by silencing Fn14, indicating that TWEAK-induced NF-κB signaling was mediated via Fn14. Moreover, the TWEAK/Fn14 interaction promoted cell proliferation and migration. These effects were blocked by NF-κB inhibitor SN50, which suggest that the TWEAK/Fn14 signaling system partially depends on NF-κB activity. Collectively, we demonstrated that the TWEAK/Fn14 axis accelerated HASMC cell proliferation and migration by activating the NF-κB pathway, thereby exacerbating airway remodeling in asthma. Altogether, these findings indicate a novel role for the TWEAK/Fn14/NF-κB pathway as a potent option for limiting airway remodeling in asthma.

Eustachian Tube dysfunction in chronic rhinosinusitis: pre and post-operative results following endoscopic sinus surgery, a prospective study.

Prospective study investigating the incidence of concurrent Eustachian Tube dysfunction (ETD) in patients with CRS refractory to medical therapy, and the effect of Endoscopic Sinus Surgery (ESS) on ETD in this patient group. Prospective study of 57 CRS patients. Outcome measures were SNOT-22 and ETDQ-7 questionnaires, tympanometry and Valsalva manoeuvre recorded pre-operatively and at 3 and 9 months post ESS. There was a moderate positive correlation between pre-operative ETDQ-7 and SNOT 22 scores (r equals 0.5715, p less than 0.0001). 68% of patients recorded positive ETDQ-7 scores pre-operatively, mean equals 20.6 (SD plus or minus 10.34). Mean ETDQ-7 scores were significantly lower at 3 months; mean equals 11.4 (SD plus or minus 5.65) (P less than 0.0001) and 9 months mean equals 11.4 (SD plus or minus 6.15) (P less than 0.0001) following ESS. Type A tympanograms increased form 76.6% pre-operatively, to 94.5% at 3 months and 96% at 9 months. Reported positive Valsalva increased from 38% pre-operatively to 96% at 3 and 9 months. Mean ETDQ-7 scores were higher in the CRSwNP group; 24.34 (SD plus or minus 9.2) compared to the CRSsNP group; 18.11 (SD plus or minus 10.3), (p equals 0.6101). 16 patients in the cohort had existing diagnoses of asthma, of which 4 had documented aspirin sensitivity. The mean pre-operative SNOT-22 score in this overall subgroup was 64.81 (SD equals plus or mins 20.13) compared with 49.07 (SD equals plus or minus 21.37) in non-asthmatic patients (p equals 0.0168). We found a high incidence of concurrent ETD symptoms in patients with severe CRS, which improve following ESS. Further research is required to better understand the association between CRS and ETD in order to provide effective treatments.

Association between lipid profile and the prevalence of asthma: a meta-analysis and systemic review

Objective: To explore the association of asthma with serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglyceride.Methods: PubMed, Cochrane, and Embase databases were systematically searched through November 2015 using the following search terms: dyslipidemia, HDL, LDL, triglyceride, cholesterol, and asthma. Eligible studies included randomized controlled trials (RCTs), retrospective, cohort, and cross-sectional studies. Sensitivity analysis and publication bias were performed.Results: Twenty studies were included in the analysis, with a total 32,604 patients (3,458 in the asthma group and 29,146 in the control group). The pooled analysis found that the mean difference between groups was significantly higher in the asthma group for levels of LDL (6.026 mg/dL, 95% CI = 2.696–9.356, p < .001) and total cholesterol (8.161 mg/dL, 95% CI = 3.006–13.316, p = .002) compared with the control group. No association was observed between asthma and control groups for levels of HDL (mean difference = –0.728, 95% CI = –3.146–1.691, p = .555) or triglycerides (mean difference = 1.436, 95% CI = –2.768–5.640, p = .503).Conclusions: Levels of LDL and total cholesterol were higher in patients with asthma than non-asthmatic patients.

Eosinophilic otitis media diagnosis using flow cytometric immunophenotyping

Objectives: (1) To assess the ability of flow cytometric immunophenotyping to detect and quantitate eosinophils in patients with eosinophilic otitis media (EOM). (2) to evaluate the association of EOM to bronchial asthma.Methods: Twenty-one patients with chronic otorrhea or middle ear effusion (MEE) were included in this prospective cohort study. Group I composed of 10 patients (14 ears) and associated to bronchial asthma. Group II included 11 patients (11 ears) without bronchial asthma. Samples of MEE were sent for flow cytometric analysis at initial presentation. Patients with positive eosinophils on flow cytometric immunophenotyping were analyzed after one-month course of dexamethasone eardrops.Results: EOM was diagnosed in all patients of group I and in three patients of group II. The mean eosinophils percentage was 43.5% and 14.2% for group I and group II, respectively (p = .006). Those patients showed a significant response to dexamethasone eardrops, both on clinical examination and on flow cytometric analysis with a decrease in eosinophil levels post-treatment. However, this improvement was temporary and symptoms recurred after treatment cessation. Bronchial asthma was not associated to all patients with EOM.Conclusion: Diagnosis of EOM remained mostly clinical; flow cytometry immunophenotyping of MEE may be helpful as an additional tool in diagnosis and monitoring the response to treatment, particularly in non-asthmatic patients.

Oral Corticosteroids for Nonasthmatic Patients with Probable Viral Bronchitis

If one excludes pneumonia, acute lower respiratory tract infections (LRTIs) usually are viral in origin (often labeled as “viral bronchitis”). Patients

Asthma and influenza vaccination in elderly hospitalized patients: Matched case-control study in Spain

ABSTRACTObjectives: Influenza infection is an exacerbating factor for asthma, and its prevention is critical in managing asthmatic patients. We investigated the effect of influenza vaccination on asthmatic and non-asthmatic patients hospitalized with laboratory-confirmed influenza in Spain. Methods: We made a matched case-control study to assess the frequency of hospitalization for influenza in people aged ≥65 years. Hospitalized patients with unplanned hospital admissions were recruited from 20 hospitals representing seven Spanish regions. Cases were defined as those hospitalized due to a laboratory-confirmed influenza infection and controls were matched by age, sex, and hospital. Data were obtained from clinical records, and patients stratified by clinical asthma history. Vaccination status and asthma due to influenza infection were analyzed according to sociodemographic variables and medical risk conditions. Multivariable analysis was made using conditional logistic regression models. Results: 582 hospitalized patients with influenza (15.8% asthmatic) and 1,570 hospitalized patients without influenza (7.9% asthmatic) were included. In the multivariable conditional logistic regression using unvaccinated and non-asthmatic patients as the reference group, vaccination significantly prevented influenza in non-asthmatic patients (aOR = 0.63; 95% CI: 0.45, 0.88) and also showed a trend for a possibly protective effect in asthmatic patients (aOR = 0.79; 95% CI: 0.34, 1.81). Conclusion: Our results suggest that influenza vaccination could be a protective factor for asthmatic patients, although the results are inconclusive and further research is required. Practically, given the better clinical evolution of vaccinated asthma cases, and the lack of better evidence, the emphasis on vaccination of this group should continue.

SiMA: A simplified migration assay for analyzing neutrophil migration.

In lung inflammation, neutrophils are the first leukocytes migrating to an inflammatory site, eliminating pathogens by multiple mechanisms. The term "migration" describes several stages of neutrophil movement to reach the site of inflammation, of which the passage of the interstitium and basal membrane of the airway are necessary to reach the site of bronchial inflammation. Currently, several methods exist (e.g., Boyden Chamber, under-agarose assay, or microfluidic systems) to assess neutrophil mobility. However, these methods do not allow for parameterization on single cell level, that is, the individual neutrophil pathway analysis is still considered challenging. This study sought to develop a simplified yet flexible method to monitor and quantify neutrophil chemotaxis by utilizing commercially available tissue culture hardware, simple video microscopic equipment and highly standardized tracking. A chemotaxis 3D µ-slide (IBIDI) was used with different chemoattractants [interleukin-8 (IL-8), fMLP, and Leukotriene B4 (LTB4 )] to attract neutrophils in different matrices like Fibronectin (FN) or human placental matrix. Migration was recorded for 60 min using phase contrast microscopy with an EVOS® FL Cell Imaging System. The images were normalized and texture based image segmentation was used to generate neutrophil trajectories. Based on these spatio-temporal information a comprehensive parameter set is extracted from each time series describing the neutrophils motility, including velocity and directness and neutrophil chemotaxis. To characterize the latter one, a sector analysis was employed enabling the quantification of the neutrophils response to the chemoattractant. Using this hard- and software framework we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB4 , the effect of the matrices FN versus HEM as well as the response to different medications (Prednisolone). Additionally, a comparison of four asthmatic and three non-asthmatic patients gives a first hint to the capability of SiMA assay in the context of migration based diagnostics. Using SiMA we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB4 , the effect of the matrices FN versus HEM as well as the response to different medications, that is, Prednisolone induced a change of direction of migrating neutrophils in FN but no such effect was observed in human placental matrix. In addition, neutrophils of asthmatic individuals showed an increased proportion of cells migrating toward the vehicle. With the SiMA platform we presented a simplified but yet flexible platform for cost-effective tracking and quantification of neutrophil migration. The introduced method is based on a simple microscopic video stage, standardized, commercially available, µ-fluidic migration chambers and automated image analysis, and track validation software. © 2017 International Society for Advancement of Cytometry.

Brain-derived neurotrophic factor and airway fibrosis in asthma

Airway remodeling in asthma driven by inflammation involves proliferation of epithelial cells and airway smooth muscle (ASM), as well as enhanced extracellular matrix (ECM) generation and deposition, i.e., fibrosis. Accordingly, understanding profibrotic mechanisms is important for developing novel therapeutic strategies in asthma. Recent studies, including our own, have suggested a role for locally produced growth factors such as brain-derived neurotrophic factor (BDNF) in mediating and modulating inflammation effects. In this study, we explored the profibrotic influence of BDNF in the context of asthma by examining expression, activity, and deposition of ECM proteins in primary ASM cells isolated from asthmatic vs. nonasthmatic patients. Basal BDNF expression and secretion, and levels of the high-affinity BDNF receptor TrkB, were higher in asthmatic ASM. Exogenous BDNF significantly increased ECM production and deposition, especially of collagen-1 and collagen-3 (less so fibronectin) and the activity of matrix metalloproteinases (MMP-2, MMP-9). Exposure to the proinflammatory cytokine TNFα significantly increased BDNF secretion, particularly in asthmatic ASM, whereas no significant changes were observed with IL-13. Chelation of BDNF using TrkB-Fc reversed TNFα-induced increase in ECM deposition. Conditioned media from asthmatic ASM enhanced ECM generation in nonasthmatic ASM, which was blunted by BDNF chelation. Inflammation-induced changes in MMP-2, MMP-9, and tissue inhibitor metalloproteinases (TIMP-1, TIMP-2) were reversed in the presence of TrkB-Fc. These novel data suggest ASM as an inflammation-sensitive source of BDNF within human airways, with autocrine effects on fibrosis relevant to asthma.

Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs

ABSTRACTObjective: Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Methods: Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Results: Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E2 and PGI2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE2, KCl, sodium nitroprusside, and acetylcholine. Conclusion: Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI2 analogs through the impairment of cAMP pathway.

Asthma and Risk of Appendicitis in Children: A Population-Based Case-Control Study

ObjectiveTo assess whether asthma is associated with risk of appendicitis in children. MethodsWe used a population-based case-control study design using a comprehensive medical record review and predetermined criteria for appendicitis and asthma. All children (age younger than 18 years of age) who resided in Olmsted County, Minnesota, and developed appendicitis between 2006 and 2012 were matched to controls (1:1) with regard to birthday, gender, registration date, and index date. Asthma status was ascertained using predetermined criteria. Active (current) asthma was defined as the presence of asthma symptoms or asthma-related events (eg, medication use, clinic visits, emergency department, or hospitalization) within 1 year before the index date. Inactive asthma was defined as subjects without these events. A conditional logistic regression model was used. ResultsAmong the 309 appendicitis cases identified, when stratified according to asthma status, active asthma was associated with significantly increased risk of appendicitis compared with inactive asthma (odds ratio [OR] = 2.48; 95% confidence interval [CI], 1.22–5.03) and to no asthma (OR = 1.88; 95% CI, 1.07–3.27; overall P = .035). When controlling for potential confounders such as gender, age, and smoking status, active asthma was associated with a higher odds of developing appendicitis compared with nonasthmatic patients (adjusted OR = 1.75; 95% CI, 0.99–3.11) whereas inactive asthma was not (overall P = .049). Tobacco smoke exposure within 3 months was associated with an increased risk of appendicitis (adjusted OR = 1.66; 95% CI, 1.02–2.69). Among asthma medications, leukotriene receptor antagonists reduced the risk of appendicitis (OR = 0.18; 95% CI, 0.04–0.74). ConclusionsActive asthma might be an unrecognized risk factor for appendicitis in children whereas a history of inactive asthma does not pose such risk. Further investigation exploring the underlying mechanisms is warranted.

Possible association between -954G/C iNOS polymorphism in nasal polyposis. A case-control study in a population group of Northern Romania

Abstract BACKGROUND. Polymorphisms for genes encoding chemosensitive signalling proteins like NOS2 might contribute to the variability in individual susceptibility to nasal polyposis. NO produced by the inducible NO synthase enzyme NOS2A is generated at high levels in certain types of inflammation, so that the role of NOS2 might also be important in nasal polyposis etiopathogeny. MATERIAL AND METHODS. This is a cross-sectional, randomized, case-control study for the evaluation of the frequency of -954G/C NOS2A2 alleles among patients with nasal polyposis. The study included 91 cases of nasal polyposis diagnosed patients (nasal endoscopy and CT scan examination), and 117 healthy unrelated controls. NOS2 genotyping was carried out using PCR amplification of relevant gene fragment and it was followed by restriction enzyme digestion. Detection of the variant alleles was determined through analysis of resulting restriction fragment length polymorphism (RFLP) followed by gel electrophoresis. RESULTS. Molecular analysis revealed an increased frequency of NOS2 variant allele in the study group compared to the control group (p=0.019, OR=1.991, CI=1.08-3.67). A statistically significant finding was highlighted among allergic and nonallergic patients with nasal polyposis (p=0.046, OR=0.449. CI=0.208-0.969) and a relationship between nasal polyposis patients with asthma and non-asthmatic patients (p=0.119, OR=1.825, CI=0.875-3.80). CONCLUSION. The main finding of our study is that -954G/C polymorphism of NOS gene seems to be associated with an increased risk for nasal polyposis.

465 - Protein S-Acylation in Pulmonary Disease

Obesity is a major risk factor for asthma. Obese asthmatics exhibit poor symptom control, frequent exacerbation, and increased levels of reactive oxygen species (ROS). The consumption of a western diet, high in fat and carbohydrates, can both induce obesity and increase ROS. Oxidation of critical cysteine resides, due to high ROS, may hinder post-translational modifications required for proper protein function. Previous studies reported that increased cysteine oxidation, due to consumption of a high-fat diet (HFD), coincided with decreased protein S-acylation. Protein S-acylation is regulated by acyltransferases (zDHHCs) and thioesterases (PPT/APTs). To date, there have been no reports of the S-acylated protein profile in the lung and how it may be modified by comorbid disease. We hypothesize that identifying the pulmonary ‘palmitoylome’ will provide critical information and insight into pathogenesis of lung disease, including the pathophysiology of asthma. The lung ‘palmitoylome’ was profiled by LC-MS analysis of S-acylated proteins isolated from murine whole lung tissue. Additionally, to measure alterations of pulmonary S-acylation in obesity and asthma, we used whole lung tissue of lean and obese, or house dust mite (HDM) allergic, C57BL/6 mice. To assess whether gene expression of zDHHC or PPT/APT enzymes was altered in obesity or asthma, RT-PCR was performed from lung tissue cDNA from the aforementioned mice. Furthermore, a microarray was conducted from human nasal epithelial cells isolated from obese asthmatic and non-asthmatic patients. We identified several S-acylated proteins in murine lung tissue. Differences in protein S-acylation as a result of feeding a HFD, as well as HDM-induced asthma, were observed. Although, gene expression of zDHHC enzymes was not altered in lung tissue, PPT/APT genes were significantly altered in lean vs. obese and healthy vs. allergic lung tissue. PPT and zDHHC gene expression was differentially expressed in the nasal epithelial cells from obese control vs. obese asthmatic patients. In conclusion, both obesity and asthma exhibit an altered protein S-acylation profile in murine lung tissue and in primary nasal epithelial cells from human subjects, which may contribute to pulmonary pathophysiology.

Differential association of plasma monocyte chemoattractant protein-1 with systemic inflammatory and airway remodeling biomarkers in type-2 diabetic patients with and without asthma.

BackgroundChronic inflammation is a hallmark of type-2 diabetes (T2D) and asthma. Monocyte chemoattractant protein (MCP)-1 or CCL-2 is a key regulator of monocytic infiltration into the sites of inflammation. The changes in systemic MCP-1 levels and its relationship with other inflammatory/immune markers in T2D patients with asthma remain unclear and have been addressed in this study.MethodsPlasma samples from 10 asthmatic T2D patients (Group I: BMI = 37.82 ± 9.75 kg/m2), 13 non-asthmatic T2D patients (Group II: BMI = 32.68 ± 4.63 kg/m2), 23 asthma patients without T2D (Group III: BMI = 30.14 ± 6.74 kg/m2), and 25 non-asthmatic non-diabetic controls (Group IV: BMI = 27.99 ± 5.86 kg/m2) were used to measure levels of MCP-1 and multiple cytokine/chemokine biomarkers with bead-based multiplex assays using Luminex technology. IgE/ECP were measured using commercial ELISA kits. Data (mean ± SEM) were compared using unpaired Student’s t-test and linear dependence between two variables was assessed by Pearson’s correlation coefficient (r) and P ≤ 0.05 was considered as significant.ResultsPlasma MCP-1 levels were significantly higher in Group I (337.95 ± 46.40 pg/mL) as compared with Group II (216.69 ± 17.30 pg/mL), Group III (251.76 ± 19.80 pg/mL), and Group IV (223.52 ± 133.36 pg/mL). MCP-1 showed differential association with tested biomarkers by correlating positively with: (i) IFN-α2, IL-10, fractalkine, and VEGF in T2D patients with asthma; (ii) IL-6 and GRO-α in T2D patients without asthma; (iii) MDC, IP-10, GM-CSF, FGF-2, and PDGF-AA/BB in patients with asthma only; and (iv) FPG and TG in non-asthmatic non-diabetic controls. MCP-1 associated with IL-1RA only in subjects with asthma.ConclusionThe systemic MCP-1 levels were significantly elevated in T2D patients with asthma as compared with those without asthma and/or diabetes while these changes correlated differentially with important biomarkers of inflammation and airway remodeling.

Infant lung function predicts asthma persistence and remission in young adults.

Asthma in adults is associated with a persistent reduction in lung function from childhood, but this link has not been assessed back to infancy. Reduced infant lung function (ILF), a measure of antenatal and infant lung growth, is associated with asthma into adolescence. Our aim was to assess whether this link persists into adulthood and whether ILF can predict the remission of asthma symptoms in young adults. The study cohort was an unselected full-term birth cohort of 253 subjects enrolled antenatally with lung function assessments at 1, 6 and 12 months (maximum expiratory flow at functional residual capacity, V'maxFRC), and 6, 11, 18 and 24 years (spirometry) of age. Infants with V'maxFRC in the lowest quartile at 1 month had an OR of 5.1 (95% CI: 2-13, P = 0.001) for asthma at 24 years. Subjects with asthma at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 48-90%) versus 110% (95% CI: 101-119%) in non-asthmatic patients (P = 0.001). Subjects with current versus resolved asthma symptoms at 24 years had a mean V'maxFRC at 1 month of 69% predicted (95% CI: 53-84%) versus 105% (88-123%), respectively (P = 0.003). Subjects with current asthma at 24 years had persistently lower lung function from infancy with a mean reduction of 16.2% (95% CI: 8.1-24.3%, P < 0.0001). Reduced lung function in early infancy is predictive of persistent asthma in young adults and a persistent reduction in lung function, suggesting abnormal lung development and growth in utero or very early in life.

Depressive Symptoms Among Asthmatic and Non-Asthmatic Patients Attending Khyber Teaching Hospital (KTH), Peshawar

&#x0D; &#x0D; &#x0D; The purpose of the present research was to investigate the difference between the depressive symptoms among asthmatic and non-asthmatics. The total sample consisted of sixty (n=60) participants that included thirty (n=30) asthmatics and thirty (n=30) non-asthmatics both males and females. Convenient sampling technique was used in sample selection. The Beck Depression scale was used. Data was collected from the asthmatic patients in the Khyber Teaching Hospital. It was hypothesized that asthmatics will have more depressive symptoms than the non-asthmatics. The results supported the hypothesis (p&lt;0.01). The female asthmatics scored slightly higher on scale of depression than male asthmatics.&#x0D; &#x0D; &#x0D;

Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges

Oral food challenges (OFCs) are routinely used to confirm ongoing food allergy. Serum-specific IgE (sIgE) and skin prick testing (SPT) are imperfect predictors of which patients will pass OFCs. The objective of this study was to describe the design and implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) to study and iteratively improve sIgE and SPT thresholds to determine when and where to conduct OFCs for patients. Allergists consulted recommended sIgE and SPT thresholds when ordering challenges although diversions were permitted. Criteria were iteratively improved after periodic analyses of challenge outcome and diversions. Over 3 years, allergists ordered 2368 food challenges for 1580 patients with histories of IgE-mediated reactions to food: 1386 in an outpatient clinic and 945 in a higher resource infusion center. Reactions to challenge were observed in 13% of clinic and 23% of infusion center challenges. Six patients challenged in clinic required treatment with epinephrine compared with 22 in the infusion center. The need for epinephrine was more common in patients with asthma-5% of asthmatic patients required epinephrine compared with 1% of nonasthmatic patients (P < .01). Recommended sIgE and SPT thresholds were incrementally changed and, using the control chart methodology, a significant decrease was noted in the proportion of challenges ordered in the higher resource location. By setting and continually refining sIgE and SPT recommendations using the SCAMP method, allergists can better determine the risk of severe reaction and triage patients to the appropriate setting for an OFC.

IgE anti-Haemophilus influenzae type b (Hib) antibodies detected in serum of Hib-vaccinated asthmatic and non-asthmatic pediatric patients.

Haemophilus influenzae type b (Hib) bacterium causes severe illness in infants and children, but has largely been eliminated by introducing a universal Hib conjugate vaccine. While effects of certain vaccinations on atopic disease have been studied, little is known about the relationship between Hib vaccination and diseases of altered immunoglobulin E (IgE) regulation (asthma or atopy). As such, it is necessary to provide more evidence concerning Hib vaccination as a possible risk factor for atopic disease. Total serum IgE and IgE-and IgG-anti-Hib antibody responses were studied in Hib vaccinated asthmatic (N.=14) and non-asthmatic children (N=26) (VaccZyme™ Human Anti Hib Enzyme Immunoassay Kit). Data are reported as mean optical density (OD) values. We found that: 1) total serum IgE levels were higher in asthmatic compared with non-asthmatic subjects (389±125 vs. 125±129, P<0.001); 2) IgE and IgG anti-Hib antibody responses were similar in both asthmatic and non-asthmatic subjects (0.722±0.279 and 0.681±0.280, respectively; P=0.65; 0.450±0.505 and 0.573±0.779, respectively; P=0.580). The universal Hib vaccine antigen did not result in either increased IgE, or IgG anti-Hib antibody responses in asthmatic or non-asthmatics subjects. Thus, in this cohort, no association between Hib vaccination and asthma status was identified.

Importance of fractional exhaled nitric oxide in diagnosis of bronchiectasis accompanied with bronchial asthma.

Fractional exhaled nitric oxide (FeNO) measurement is a simple, rapid, highly reproducible, and noninvasive method of airway inflammation assessment. Therefore, FeNO is extensively used for the diagnosis and management of asthma. The feasibility of using FeNO as an alternative to conventional pulmonary function test to differentiate patients with bronchiectasis (BE) and bronchial asthma from those with BE only remains unclear. From February 2013 to February 2015, 99 patients diagnosed with BE through high-resolution computed tomography (HRCT) were subjected to FeNO measurement, bronchial challenge test (BCT), or bronchodilator test. Bronchial hyperreactivity and/or reversible airway obstruction was used to define asthma. The receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in the diagnosis of asthmatic patients with BE, and the optimal operating point was also determined. Of 99 patients with BE, 20 patients presented asthma, and 12 of these patients received regular treatment, which were given with budesonide (200 µg, bid) for 12 weeks to evaluate changes in the concentration and assess the role of FeNO in the treatment. The area under the ROC curve was estimated as 0.832 for FeNO. Results also revealed a cut off value of >22.5 part per billion (ppb) FeNO for differentiating asthmatic from non-asthmatic (sensitivity, 90.0%; specificity, 62.5%) patients with BE. FeNO and forced expiratory volume for 1 second significantly improved after the treatment. Clinical FeNO measurement is a simple, noninvasive, and rapid method used to differentiate asthmatic from nonasthmatic patients with BE. This technique exhibits potential for asthma management.

Fraction of exhaled nitric oxide measurements in the diagnoses of asthma in elderly patients.

ObjectiveTo assess the value of fraction of exhaled nitric oxide (FeNO) measurements in the diagnosis of asthma in elderly patients.MethodsThe clinical symptoms of 202 elderly patients were assessed with the asthma module of the International Study of Asthma and Allergies in Childhood test, which had been modified for the elderly patients, and the diagnostic routine for chronic obstructive pulmonary disease (COPD), which was based on the Global initiative for chronic Obstructive Lung Disease criteria. Of the 202 patients assessed, 43 were subjected to pulmonary function evaluations (spirometry) and FeNO measurements.ResultsOf the 202 elderly patients, 34 had asthma (23 definite and eleven probable), 20 met COPD criteria, 13 presented with an overlap of asthma and COPD, and 135 did not fit the criteria for obstructive pulmonary disease. Among the 43 elderly patients who were subjected to FeNO measurements, ten showed altered results (23.2%) and 33 had normal results (76.7%). The average value of FeNO in patients with definite and probable asthma undergoing this procedure was 29.2 parts per billion whereas that in nonasthmatic patients was 17.5 parts per billion (P=0.0002).ConclusionWe show a clear relationship between FeNO levels and asthma symptoms and previous asthma diagnoses in elderly patients.