Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

支气管哮喘患者血清嗜酸性粒细胞阳离子蛋白（ECP）在特异性免疫治疗中的变化

目的通过观察支气管哮喘患者接受特异性免疫治疗前后血清嗜酸性粒细胞阳离子蛋白（eosinophilcationicprotein,ECP）的变化,评价免疫治疗的效果,探讨其治疗机制。方法60例支气管哮喘患者随机分为治疗组40例,对照组20例,治疗组用阿罗格变应原浸液特异性免疫治疗（specificimmu．notherapy,SIT）,对照组吸人布地奈德,在治疗前后抽静脉血查ECP。结果两组治疗后患者血清ECP均有降低,有显著性差异（治疗组P〈0．01,对照组P〈0．05）,但治疗组明显优于对照组（P〈0．01）。结论特异性免疫治疗能有效降低患者血清ECP,其可能的免疫机制是有效地抑制了嗜酸性粒细胞在气管的聚集与活化,降低其释放ECP的能力,起到治疗作用。     

Extracorporeal photopheresis for the treatment of severe,refractory steroid dependent pediatric Crohn's Disease

Crohn's disease is a chronic, inflammatory disease of the gastrointestinal tract, affecting both children and adults. Extracorporeal photopheresis (ECP) has been used in steroid dependent adults with moderate to severely active Crohn's disease, with response rates up to 50%, with up to 25% complete responses. A 12‐year‐old male patient had severe unremitting Crohn's disease for one year, despite treatment with anti‐inflammatory, immunosuppressive, and biologic agents. He failed elemental enteral nutrition and required total parenteral nutrition (TPN). A diverting colostomy for perforation was required. He required frequent hospitalizations and required homebound schooling. Endoscopy revealed severe inflammation and ulcerations of the entire colon. ECP was begun twice weekly for 4 weeks, then twice per week every 14 days for a total of 28 weeks. ECP was well tolerated and prednisone was gradually discontinued. He continued daily azathioprine and infliximab at 6 week intervals. TPN was weaned as enteral intake improved. Disease abatement allowed a return to school and normal activities. Endoscopy at completion of ECP course revealed normal upper tract, normal ano‐rectum, and decreased, although significant, colonic disease. This response has continued for at least 16 months since completion of ECP. We conclude that ECP is useful for pediatric patients with steroid dependent Crohn's disease and prospective evaluation is warranted. J. Clin. Apheresis 28:381–386, 2013. © 2013 Wiley Periodicals, Inc.     

Polymorphism of the eosinophil cationic protein-gene is related to the expression of allergic symptoms

BACKGROUND: We have found a polymorphism in the ECP (eosinophil cationic protein)-gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C). OBJECTIVE: To investigate the prevalence of the ECP-polymorphism and to screen for disease associations. METHODS: DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis. RESULTS: The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non-allergic subjects (P = 0.0056). Of the students who were Phadiatop-positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non-allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy. CONCLUSION: The 434(G > C) polymorphism in the ECP-gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.     

Markers of inflammation in the feces of infants with cow's milk allergy

Growing evidence exists that exposure to cow's milk elicits inflammation in the gut of infants with cow's milk allergy, irrespective of symptoms. To demonstrate inflammation and increased protein leakage from the gut during a cow's milk elimination‐challenge test in fecal samples of infants presenting with different symptoms suggestive of cow's milk allergy, we measured the concentrations of α₁‐antitrypsin (AT), eosinophil cationic protein (ECP), immunoglobulin (Ig) A, and cow's milk‐specific IgA antibodies, in fecal samples of 208 infants with a mean age of 7 months. Prechallenge samples were collected after a mean 3‐week elimination period, and post‐challenge samples were obtained 4 days after starting the challenge. Fecal levels of prechallenge total IgA (p = 0.02) and post‐challenge AT (p = 0.001) were higher in infants with a positive challenge. Of these infants, pre‐ and post‐challenge levels of ECP were higher in those reacting after 24 h than in those reacting within 1 h (p = 0.006 and p = 0.045). Prechallenge levels of ECP were higher in those showing intestinal symptoms (p = 0.008), and both pre‐ and post‐challenge levels of total IgA were higher in those with an IgE‐mediated reaction to cow's milk (p = 0.04 and p = 0.008). Regardless of the challenge result, total IgA increased during the challenge (p < 0.001 for both challenge‐positive and ‐negative infants) and was higher in those breast‐fed until the challenge than in those fed formula only (p < 0.01). Hence, in infants reacting to the cow's milk challenge, higher prechallenge levels of fecal IgA indicate increased antigenic stimuli in the gut, and higher post‐challenge levels of AT reflect increased protein loss as a result of intestinal inflammation. In infants with slowly evolving gastrointestinal symptoms, increased fecal ECP may help in distinguishing patients from those who tolerate cow's milk. Individual serial follow‐up of fecal IgA and ECP can be used to estimate the degree of inflammation in the gut and an appropriate time for a challenge test, but are not diagnostic tools for cow's milk allergy.     

Bacterial antigen-induced release of white cell- and platelet-derived bioactive substances in vitro

Summary Objectives. Poor prognosis after resection of primary colorectal cancer may be related to the combination of perioperative blood transfusion and subsequent development of infectious complications. Various white cell- and platelet-derived cancer-growth substances may be involved in this process. Therefore, we studied the in vitro release of substances from white cells and platelets stimulated by bacterial antigens and supernatants from stored red-cell components. Methods. Eight units of whole blood (WB) and 8 U of buffy-coat-depleted red-cell (SAGM) blood were donated by healthy blood donors. Subsequently, one-half of each unit was leucocyte-depleted by filtration, and all 32 half-units were stored under standard conditions for 35 d. Just after storage, and on d 7, 21, and 35 during storage, aliquots of the supernatants were removed from the units and frozen at −80°C. WB from other healthy donors was stimulated for 2 h with sodium chloride (controls), with Escherichia coli (E. coli) lipopolysaccharide (LPS) alone, or with LPS plus supernatants from the WB units (diluted 1:10), or from the SAGM units (diluted 1:20) stored for 0, 7, 21, or 35 d, respectively. Similar assays were performed using Staphylococcus aureus-derived protein A as a stimulatory antigen. The concentration of eosinophil cationic protein (ECP), myeloperoxidase (MPO), histamine (HIS), and plasminogen-activator inhibitor-1 (PAI-1) were determined in supernatants from the stored blood and in assay supernatants by using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) methods. Results. The extracellular concentration of ECP, MPO, and HIS increased significantly in a storage-time-dependent manner in nonfiltered WB and SAGM blood, and the increase was abrogated by prestorage leukofiltration. Similarly, PAI-1 increased significantly in nonfiltered WB, and the increase was abrogated by prestorage leukofiltration. The supernatant concentrations of the four substances were significantly increased in LPS-stimulated (0.5-4 fold) and in protein A-stimulated (0.5-13.5-fold) assays compared with controls. The addition of supernatants from stored nonfiltered WB or SAGM blood significantly increased the assay supernatant of ECP, MPO, HIS, and PAI-1 concentrations storage--time-dependently in LPS-stimulated assays. Prestorage leukofiltration abrogated the additional effect of supernatants from stored blood. Similar results were observed for ECP and HIS through the addition of supernatants from stored blood to protein A-stimulated assays. Protein A stimulation did not lead to increased PAI-1 release in assays diluted by supernatants from stored blood. However, the MPO concentrations were significantly (p=0.004), and independent of storage time and leukofiltration, increased in protein A-stimulated assays diluted by supernatants from stored blood compared with sodium chloride dilution. Conclusion. Extracellular ECP, MPO, HIS, and PAI-1 accumulate during storage of nonfiltered red-cell components, but the accumulation can be prevented by prestorage leukofiltration. In addition, bacterial antigens appear to induce significant release of the substances from white cells and platelets. Addition of supernatants from stored, nonfiltered WB and SAGM blood may increase the substance levels in a storage-time-dependent manner, and prestorage leukofiltration may prevent further increase by supernatants, except for MPO.     

Exhaled NO and eosinophil markers in blood, nasal lavage and sputum in children with asthma after withdrawal of budesonide

BACKGROUND: There is a need for controlled trials among children with asthma to evaluate and compare different markers of inflammation. OBJECTIVE: Our goal was to investigate the effect of withdrawal of inhaled budesonide on repeated measurements of exhaled NO (ENO), peripheral blood eosinophils (PBE), sputum/NAL/serum-eosinophil cationic protein (ECP), bronchial hyperresponsiveness (BHR) and forced expiratory volume in 1 s (FEV(1)) in children with allergic asthma. METHODS: Eighteen asthmatic children were randomly allocated to continue or discontinue use of inhaled budesonide. They were followed up, at six visits for 4 months with regular blood, serum, sputum, and NAL samples. Sixteen age-matched healthy children served as controls. RESULTS: ENO, PBE, and S-ECP increased significantly in the withdrawal group (p < 0.05) but not in the continuous treatment group. No trend could be observed during the study for markers in sputum or in NAL in either group. CONCLUSION: The present data provide evidence for the clinical usefulness of measuring ENO, PBE, and S-ECP and when combined they could help to avoid over- and undertreatment with corticosteroids in the growing child.     

Assessment of the allergic reaction in seasonal rhinitis: acoustic rhinometry is a sensitive and objective method

Background Seasonal allergic rhinitis constitutes an excellent in vivo model of an allergic mucosal inflammatory reaction. This offers the opportunity of studying the fundamentals of allergic inflammation in addition to improvement of knowledge on the basal pathophysiological mechanisms of the disease. So far, monitoring methods of disease activity and treatment efficacy have mainly been based upon subjective assessments, illustrating the impact of introducing reliable objective methods. Objective To investigate the allergic inflammatory reaction of seasonal rhinitis through different objective methods and evaluate these as indicators of disease activity and treatment efficacy. Methods Functional parameters, i.e. acoustic rhinometry and nasal metacholine challenge, and biological markers, i.e. blood eosinophil count, eosinophil cationic protein in serum (s-ECP) and nasal lavage fluid (n-ECP), were assessed before and at peak pollen season in 27 patients with grass pollen induced rhinitis. Patients were randomized to either nasal corticosteroid or placebo treatment and recorded nasal symptom scores. Results Acoustic rhinometry revealed a significant difference in favour of steroid treatment (P < 0.05) comparing nasal volumes before and during season. This difference primarily relied upon a decrease in the placebo group (P= 0.05). A reduction from baseline of s-ECP in the steroid group (P < 0.01) was obtained. N-ECP demonstrated a difference between treatment groups, although not significant. Symptom scores increased in all patients during the pollen season, although this was only significant in the placebo treated patients (P < 0.01). The remaining methods applied did not demonstrate further differences, either within or between treatment groups. Conclusion Our results demonstrate acoustic rhinometry to be a sensitive and objective method of assessment of nasal obstruction. Furthemore, acoustic rhinometry and s-ECP reflect the impact of nasal steroid therapy on seasonal allergic rhinitis.     

Advances in the Management of Pediatric Asthma: A Review of Recent FDA Drug Approvals and Label Updates

Children have the highest prevalence of asthma of any age group. In the United States during 2001, there were 12.6 million physician and hospital outpatient visits for asthma treatment, of which almost 5 million involved children 18 years and younger. Therapeutic advances in pediatric asthma could improve patient outcomes and potentially reduce the burden on health care systems. Efforts to obtain efficacy and safety data in pediatric populations and develop pediatric formulations of asthma treatments have been encouraged by the FDA and clinicians. This article reviews the newest additions to asthma therapies approved for use in children, including an inhaled corticosteroid, some long-acting β₂-agonists, some leukotriene-receptor blockers, and a single-isomer, short-acting β₂-agonist.     

沙美特罗替卡松粉吸入剂联合孟鲁司特对支气管哮喘患儿细胞免疫及血清瘦素、嗜酸性粒细胞趋化因子、ECP、LPO的影响

目的探讨沙美特罗替卡松粉吸人剂联合孟鲁司特对支气管哮喘患儿细胞免疫及血清瘦素、嗜酸性粒细胞趋化因子、嗜酸性粒细胞阳离子蛋白（ECP）和脂质过氧化物（LPO）的影响。方法将榆林市儿童医院2011年10月-2012年12月收治的90例支气管哮喘患儿根据治疗方法分为研究组和对照组,每组各45例,研究组给予沙美特罗替卡松粉吸入剂联合盂鲁司特治疗,对照组给予沙美特罗替卡松粉吸入剂治疗。比较两组患儿治疗前后细胞免疫及血清瘦素、嗜酸性粒细胞趋化因子、ECP、LPO的变化情况。结果治疗前两组患儿的CD3＋、CD4＋、CD8’及CD4／CD8水平,差异无统计学意义（均P〉0．05）。治疗6：12周时研究组患儿的CD3＋、CD4＋、CD4／CD8f（64．35±7．55）％,（36．42±4．22）％,（1．69±0．15）;（68．56±8．11）％,（39．01±4．77）％,（1．85±0．17）]明显高于对照组[（60．02±6．04）％,（32．96±3．23）％,（1．25±0．14）;（63．31±6．87）％,（34．82±3．88）％,（1．42±0．16）],差异有统计学意义（均P〈0．05）;而研究组CD8±[（28．66±2．45）％]明显低于对照组[（25．21±5．43）％],差异有统计学意义（P〈0．05）。治疗前两组患儿的血清瘦素、嗜酸性粒细胞趋化因子、ECP、LPO比较,差异无统计学意义（均P〉0．05）。治疗6、12周后研究组患儿的血清瘦素、嗜酸性粒细胞趋化因子、ECP、LPO水平[（7．05±0．48）μg／L,（16．35±1．94）ng／L,（11．03±1．35）pg／L,（9．46±0．10）nmol／L;（6．52±0．47）μg／L,（6．48±O．90）ng／L,（6．05±0．79）pg/L,（7．03：t0．55）nmol／L]均低于对照组[（8．73±0．72）μg／L,（25．24±3．15）ng／L,（16．25±1．76）pg/L,（12．83±1．50）nmol／L;（7．95±0．55）μg/L,（9．25±1．03）ng／L,（10．09±1．24）pg／L,（10．22±1．09）nmol／L],差异有统计学意义（P〈0．05）。结论沙美特罗替卡松粉吸人剂联合孟鲁司特对支气管哮喘患儿细胞免疫及血清瘦素、嗜酸性粒细胞趋化因子、ECP、LPO水平的改善有重要作用。