Intermittent Asthma Research Articles

Increased IL‐17A secreting CD4+ T cells, serum IL‐17 levels and exhaled nitric oxide are correlated with childhood asthma severity

Measuring fractional exhaled nitric oxide (FeNO) is a simple and non-invasive method for assessing airway inflammation. IL-17 plays an important role in T cell-dependent inflammatory response that occurs in allergic asthma, it could act as a potent activator of inducible nitric oxide synthase (iNOS) to amplify FeNO levels. To evaluate the differences in the CD4(+) IL-17A(+) T cell counts, serum IL-17 levels, and FeNO levels in children with mild intermittent to moderate to severe persistent asthma classified by using the Global Initiative for Asthma (GINA). One hundred and twenty asthmatic children divided into the mild intermittent (n = 42), mild persistent (n = 42), and moderate to severe persistent (n = 36) groups, and 20 healthy controls were recruited for the study. Information obtained at visits included the assessment of asthma severity according to GINA guidelines and C-ACT, lung function parameters, FeNO levels, CD4(+) IL-17A(+) T cells counts from PBMCs, iNOS production by sputum cells and serum IL-17 levels. Serum IL-17 and FeNO levels were significantly higher in mild to severe persistent asthmatic patients than in intermittent asthmatics or healthy controls (P < 0.05). The percentage of CD4(+) IL-17A(+) T cells was higher in moderate to severe persistent asthmatics than in mild asthmatics (P < 0.01). Moderate to severe asthmatics (n = 5) exhibited greater iNOS production in sputum cells than mild cases (n = 5). Decreased iNOS expression in sputum cells was noted in all subjects after IL-17 neutralizing antibody (P < 0.05). Serum IL-17 levels were positively correlated with FeNO (rho = 0.74; P < 0.01), negatively correlated with C-ACT (rho = -0.63; P < 0.01) in asthmatics. CD4(+) IL-17A(+) T cells counts and serum IL-17 levels in conjunction with augmented FeNO levels are systemic markers of childhood asthma, using these markers, prediction and potential therapeutics for persistent asthmatics may be developed.

Determine Efficacy of a Short Course of Montelukast in Children with Intermittent Asthma and Viral Infection

Introduction Mild intermittent asthma is common in children and viral infections are responsible for the majority of exacerbations. As leukotrienes are potent inflammatory mediators, some studies have shown that Montelukast, a leukotriene receptor antagonist, may be effective on reduction of asthma symptom. To determine whether a short course of Montelukast in asthmatic children with common cold would modify the severity of an asthma episode. Materials and Methods Children, aged 6-12 years with intermittent asthma participated in this randomized, double-blind, placebo-controlled clinical trial. Treatment with Montelukast or placebo was initiated at the onset of viral upper respiratory tract infection and continued for 7 days. Primary outcomes included the clinical manifestation: duration of episodes, daily symptom, nights symptoms and activity limitation. Secondary outcomes included the need for beta agonist usage, oral prednisolone, physician visit, hospital admission and school absence. Results A total of 187 children with intermittent asthma were randomized, 93 to Montelukast group and 94 to placebo group. Montelukast significantly decreased the cough by 17.3% (P<0.001), nighttime awakenings by 5.4% (P=0.01), interference with normal activity by 6% (P<0.01), time off from school by 6% (P<0.01), β-agonist usage by 17.2% (P<0.001) and doctor visits by12.2% (P<0.01) compared to placebo. Whereas there was a non significant reduction in wheezing, tachypnea, respiratory distress, asthma exacerbation, oral prednisolone and hospitalization (P=0.8). Conclusion A short course of Montelukast, introduced at the first sign of a viral infection, results in a reduction in cough, β-agonist use and nights awakened, time off from school and limitation of activity. More studies are needed to evaluate the optimal dose and duration of treatment.

Epidemiology and outcomes of adults with asthma who were hospitalized or died with 2009 pandemic influenza A (H1N1) – California, 2009

Asthma was the most common chronic condition among adults hospitalized for 2009 pandemic influenza A (H1N1) (pH1N1). We describe the epidemiology and factors for severe outcomes among adults with asthma who were hospitalized or died from pH1N1 in California. We reviewed California Department of Public Health pH1N1 reports from April 23, 2009 through August 11, 2009. Reports were included if the patient had pH1N1 (or non-subtypeable influenza A) infection by polymerase chain reaction in an adult (age≥18 years) with asthma who was hospitalized or died. Patients were classified as having intermittent or persistent asthma on the basis of regular medications. Risk factors associated with severe outcomes (i.e., intensive care unit admission or death) vs those with less severe outcomes were assessed by chi-square tests and logistic regression. Among 744 identified patients, 170 (23%) had asthma (61% intermittent, 39% persistent). 132 of 142 (93%) patients had other chronic medical conditions. Severe outcomes occurred in 54 of 162 (33%), more commonly among those with renal disease (64% versus 31%; P=0.04) and chest radiograph infiltrates (54% versus 11%; P<0.01), less commonly among those who received antivirals within 48 hours of symptom onset (22% versus 44%; P=0.02). In multivariable analysis, chest radiograph infiltrates were associated with severe outcomes (adjusted odds ratio 9·38, 95% confidence interval 3·05-28·90). One third of adults with asthma who died or were hospitalized with pH1N1 experienced severe outcomes. Early empiric antiviral therapy should be encouraged, especially among asthma patients.

The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking.

Airway inflammation and bronchial hyperreactivity in steroid naive children with intermittent and mild persistent asthma

Intermittent and mild persistent asthma are defined according to symptom frequency and spirometry and treated differently. To our knowledge, there is no study comparing airway inflammation between intermittent and mild persistent asthmatic children. Children aged 7-16 years, referred to our pediatric allergy clinic for recurrent respiratory complaints underwent a detailed clinical history and spirometry with reversibility. None of the subjects had been using regular anti-inflammatory treatment. After a 2-week run-in period during which asthma symptoms were recorded, exhaled NO measurement, bronchial provocation test with adenosine monophosphate and methacholine and sputum induction were performed. Data of patients with intermittent and mild persistent asthma and a control group were compared. Thirty intermittent, 26 mild persistent asthmatic children, and 21 control subjects were studied. Sputum was obtained from 19 of intermittent asthmatics (63.3%), 18 of mild persistent asthmatics (69.2%), and 13 of control subjects (61.9%). Eosinophil count and exhaled nitric oxide were not different between asthmatic groups. Neutrophil count of children with mild persistent asthma was higher than the intermittent asthmatic group (P = 0.003). Geometric mean of PC20 methacoline values were not different between groups (P = 0.058). Geometric mean of PC20 AMP was lower among patients with mild persistent asthma (P = 0.102). Eosinophilic airway inflammation and direct BHR may not be significantly different in intermittent asthmatic children from their peers with mild persistent disease. Neutrophilic airway inflammation and BHR to an indirect stimuli are more pronounced in the mild persistent group.

Management of asthma in French schoolchildren: The 6C study

Abstract Objectives To describe the severity of asthma in schoolchildren in six cities in France in order to evaluate asthma management, observance and therapeutic education of both parents and children. Participants and methods Nine thousand six hundred and forty one schoolchildren in 401 CM1 and CM2 classrooms in 108 randomly selected primary schools participated in a multicentre epidemiological cross-sectional survey in six French cities (the 6C study). A standardized questionnaire provided information on: (1) symptoms and severity of their asthma; (2) control and management of the asthma by parents and children. Results Nine hundred and three children out of the 9641 participants were asthmatics. Of these asthmatic children, 22.3% had had no previous medical diagnosis of asthma. Among the asthmatic children, 77.3% suffered from intermittent asthma, 9.9% from mild persistent asthma and 12.8% from moderate persistent asthma. The asthmatic children were being followed mainly by pediatricians or general practitioners. Nearly a third (30%) of the parents knew how to prevent an asthma attack and more than half said that they knew how to use asthma medication in the event of severe attacks. Few parents knew the cause of the attacks. Peak flow-meters were rarely used. The positive effects of physical exercise were poorly known, especially by parents whose children suffered from mild asthma. Conclusion Guidelines for asthma control and management in France can be improved. The parents of children with mild or un-diagnosed asthma should be targeted. Guidelines for treatment and care must be adapted to the culture, the socioeconomic context and to the family's level of knowledge (or ignorance) of the disease.

Evaluation the clinical effects of short –course montelukast on asthma symptoms due to viral upper respiratory tract infection in children with intermittent Asthma

زمینه و هدف: آسم یک اختلال تنفسی مزمن است که میلیونها کودک در جهان به آن مبتلا می باشند. شایعترین شکل آسم در کودکان آسم متناوب است. حملات آسم معمولا به دنبال عفونتهای تنفسی ویروسی اتفاق می افتند. مشاهده شده است كه در بيماران مبتلا به آسم شروع زود هنگام مونته لوكاست (آنتاگونيست اختصاصي گيرنده لكوترين) در ابتدای عفونتهاي تنفسي ويروسي موجب كاهش شكايات و علائم آسم گرديده است. هدف از این مطالعه ارزیابی اثربخشی مونته لوکاست در کاهش علائم بالینی آسم بدنبال عفونتهای تنفسی فوقانی در کودکان مبتلا به آسم متناوب است. مواد و روش کار: این تحقیق به صورت کارآزمایی بالینی دوسو کور در دو گروه مداخله و شاهد انجام گرفت. تعداد 187 کودک 6 تا 12 ساله مبتلا به آسم متناوب به صورت تصادفی در دو گروه مداخله و شاهد قرار گرفتند. این کودکان در ابتدای بروز علائم بالینی عفونت تنفسی فوقانی مورد معاینه قرار گرفته و به گروه مداخله 7 عدد قرص جویدنی 5 میلی گرمی مونته لوکاست و به گروه کنترل 7 عدد دارونما داده شد تا هر شب یک عدد استفاده شود. به کودکان در دو گروه تاکید شد از برانگیزننده های حمله آسم ومصرف داروهای برطرف کننده علائم عفونت تنفسی فوقانی از جمله آنتی هیستامین ها طی مدت بررسی پرهیز کنند. این کودکان به مدت دو ماه از نظربروز علائم بالینی آسم بررسی شدند . داده ها حاصل از مشاهدات دموگرافيك و باليني بيماران بررسي شده و توسط نرم افزار SPSS تجزيه و تحليل شد. براي مقايسه تغييرات متغيرهاي مورد بررسي در دو گروه براي متغير هاي كيفي از آزمون كاي دو و براي متغييرهاي كمي از آزمون chi-square استفاده شد. در تمامي محاسبات 05/0 P< به عنوان سطح معني دار در نظرگرفته شد. یافته ها: دراین مطالعه استفاده از مونته لوکاست در مقایسه با پلاسبو باعث کاهش میزان سرفه (3/17% کاهش) و کاهش بروزبیداری ازخواب شبانه (4/5% کاهش) شداما بر بروز ویزینگ، تاکی پنه و دیسترس تنفسی نسبت به پلاسبو تاثیر مهمی نداشت. نتيجه‌گيري: این مطالعه نشان داد داروی مونته لوکاست علائم آزار دهنده بیماری شامل: سرفه و بیداری از خواب شبانه راکاهش داد. براساس مطالعات معتبر انجام شده، این دارو عارضه اندکی داشته و در حال حاضر در دسترس می باشد. با این حال جهت توصیه به مصرف روتین مونته لوکاست در حین سرماخوردگی کودکان آسماتیک مطالعات بیشتر و با حجم نمونه بالاتر نیاز است. واژه های كليدي: آسم متناوب، عفونت تنفسی ویروسی، مونته لوکاست

A 35-Year-Old Woman With Unusual Behavior and Prolonged Respiratory Failure

A 35-year-old woman was brought to the ED by family members with a 3-day history of behavioral changes. The patient exhibited confusion, confabulation, and occasional combativeness. Her family denied any recent flu-like symptoms, sick contacts, or recent travels. Her medical history was significant for mild intermittent asthma. The patient had no history of psychiatric illness. Her medications included occasional albuterol use for well-controlled asthma. She worked as a registered nurse and was married with three children.

A phase 1 study of heat/phenol‐killed, E. coli‐encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP‐123) for the treatment of peanut allergy

Immunotherapy for peanut allergy may be limited by the risk of adverse reactions. To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg. There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA /l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA /l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4. Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%.

Th17 Immunity in Children with Allergic Asthma and Rhinitis: A Pharmacological Approach

Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss), nasal wash (NW) and plasma (P) from Healthy Controls (HC) and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t) and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested “in vitro” on IL-17A, RORγ(t) and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of 12 weeks of treatment with Budesonide and Formoterol was tested “in vivo” in T-lymphocytes from mild-moderate asthma/persistent rhinitis patients. IL-17A was increased in Ss, NW and P from children with mild-moderate asthma compared with intermittent and HC. In cultured T-lymphocytes IL-17A and RORγ(t) expression were higher in mild-moderate asthma/persistent rhinitis than in mild-moderate asthma/intermittent rhinitis, while FOXP3 was reduced. Budesonide with Formoterol reduced IL-17A and RORγ(t), while increased FOXP3 in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis, and reduced the IL-8 release mediated by IL-17A present in NW and Ss from mild-moderate asthma/persistent rhinitis in nasal and bronchial epithelial cells. Finally, Budesonide with Formoterol reduced IL-17A levels in P and Ss, CD4+IL-17A+T-cells, in naïve children with mild-moderate asthma/persistent rhinitis after 12 weeks of treatment. Th17 mediated immunity may be involved in the airway disease of children with allergic asthma and allergic rhinitis. Budesonide with Formoterol might be a useful tool for its therapeutic control.

Improving Health status of bronchial asthma patients in Nuclear Materials Authority

Background: Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness and shortness of breath. Asthma can result in variable restriction in the physical, emotional, and social aspects of the patient's life. Setting: out patient clinic in Nuclear materials Authority Objectives: This study was done mainly to Improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority Method: The study was carried out on 51 subjects, they were chosen from those attendants of the out patients clinic in Nuclear Materials Authority in el Katamya in the period from January to May 2012, by measurement of lung function and bronchial hyperresponsiveness as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids (ICS) and other controller medications in asthmatic employees. Results: the asthmatic patients were 51 patients (36 males and 15 females), their ages ranged from 27-59 (46.2±7.3) years, they weredetected from those attendants of the out patient clinic in Nuclear Materials Authority in El Katamya representing (2.1% ) of workers. 15 (29.4%) patients were smoker, and 36 (70.6%) patients never smoked, 21 patients (41.2%) were exposed to radioactive materials in their labs in the form of radioactive substances and30 patients (58.8%)patients were not exposed.19 (37.3%) patients had intermittent asthma, 11 (21.6%) patients had mild persistent asthma 9 (17.6%) patients had moderate persistent asthma and 12(23.5%) patients had sever persistent asthma. 11(21.6%) patient used long acting anti-inflammatory medications, 23 (45.1%) patients received other controller medication in the form of short acting steroids as Clenil inhaler and ketotifen as zaditen while the majority of patients received rescue medication 34(66.7%) in the form of short acting bronchodilators and oral steroids. Conclusion: Patient education, measurement of lung function and review of the treatment plan as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids and other controller medications in asthmatic employees improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority.

Improving Health status of bronchial asthma patients in Nuclear Materials Authority

Background: Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness and shortness of breath. Asthma can result in variable restriction in the physical, emotional, and social aspects of the patient's life. Setting: out patient clinic in Nuclear materials Authority Objectives: This study was done mainly to Improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority Method: The study was carried out on 51 subjects, they were chosen from those attendants of the out patients clinic in Nuclear Materials Authority in el Katamya in the period from January to May 2012, by measurement of lung function and bronchial hyperresponsiveness as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids (ICS) and other controller medications in asthmatic employees. Results: the asthmatic patients were 51 patients (36 males and 15 females), their ages ranged from 27-59 (46.2±7.3) years, they weredetected from those attendants of the out patient clinic in Nuclear Materials Authority in El Katamya representing (2.1% ) of workers. 15 (29.4%) patients were smoker, and 36 (70.6%) patients never smoked, 21 patients (41.2%) were exposed to radioactive materials in their labs in the form of radioactive substances and30 patients (58.8%)patients were not exposed.19 (37.3%) patients had intermittent asthma, 11 (21.6%) patients had mild persistent asthma 9 (17.6%) patients had moderate persistent asthma and 12(23.5%) patients had sever persistent asthma. 11(21.6%) patient used long acting anti-inflammatory medications, 23 (45.1%) patients received other controller medication in the form of short acting steroids as Clenil inhaler and ketotifen as zaditen while the majority of patients received rescue medication 34(66.7%) in the form of short acting bronchodilators and oral steroids. Conclusion: Patient education, measurement of lung function and review of the treatment plan as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids and other controller medications in asthmatic employees improve health status including symptoms and quality of life in bronchial asthma patients in Nuclear Materials Authority.

Web-Based Asthma Management for Urban Teens

Joseph CLM, Ownby DR, Havstad SL, et al. Evaluation of a web-based asthma management intervention program for urban teenagers: reaching the hard to reach [published online ahead of print September 27, 2012]. J Adolesc Health; doi: 10.1016/j.jadohealth.2012.07.009[OpenUrl][1][CrossRef][2] Investigators from multiple institutions in Michigan and Georgia sought to determine whether using Puff City,1 a web-based asthma intervention developed by the authors and aimed at African American teenagers, improves asthma outcomes. Students in grades 9 through 12 were recruited from 6 public high schools for the study if they had a diagnosis of asthma made by a health care provider, current symptoms, and use of asthma medications. Students without a formal asthma diagnosis were also included if they had symptoms consistent with a diagnosis of intermittent asthma or more severe asthma (based on the International Survey of Asthma and Allergies in Childhood questionnaire). ### PICO Question: Among urban African American teenagers with asthma, does a tailored, web-based asthma management program improve clinical outcomes? Question type: Intervention Study design: Randomized controlled At enrollment, participants were randomized to the intervention (Puff City) or … [1]: {openurl}?query=rft.jtitle%253DJ%2BAdolesc%2BHealth%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.jadohealth.2012.07.009%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/j.jadohealth.2012.07.009&link_type=DOI

Passive Smoking Induces Leukotriene Production in Children: Influence of Asthma

Background. Passive smoking is associated with poor asthma control in children, but the mechanism is unknown. Leukotrienes are involved in the asthma pathogenesis and their synthesis is increased in adult subjects who actively smoke. Objective. To evaluate whether passive smoking, as assessed by urinary cotinine levels, increases leukotriene production in children with or without asthma. Methods. This was a prospective, cross-sectional study in which children with stable intermittent asthma (without exacerbation) and healthy control children were studied through spirometry and urinary concentrations of cotinine and leukotriene E4 (LTE4). Both groups were balanced to include children with and without passive smoking. Results. Ninety children (49 with asthma and 41 controls, 54.4% females) aged 9 years (range, 5–13 years) were studied. Urinary LTE4 concentrations were progressively higher as cotinine levels increased (rS = 0.23, p = .03). LTE4 also correlated with body mass index (BMI) (rS = 0.30, p = .004), and multiple regression analysis revealed that BMI was even more influential than cotinine for determining LTE4 levels. LTE4 concentrations were unrelated with gender, age, or spirometry. In turn, cotinine inversely correlated with forced expiratory volume in one second (FEV1) (rS = −0.22, p = .04) and forced vital capacity (FVC) (rS = −0.25, p = .02), but when analyzed by groups, these relationships were statistically significant only in children with asthma. Conclusions. Exposure to environmental tobacco smoke, as assessed by urinary cotinine levels, was associated with an increased urinary concentration of LTE4, although BMI exerted more influence in determining its concentration. Urinary cotinine was associated with decreased lung function, mainly in children with asthma.

Asthma and Risk of Community-Acquired Blood Stream Infection Caused by Escherichia Coli: A Population-Based Case-Control Study

M O N D A Y 537 Asthma and Risk of Community-Acquired Blood Stream Infection Caused by Escherichia Coli: A Population-Based Case-Control Study Hyeon Jong Jong Yang, MD, Duk Won Bang, Eell Ryoo, Larry Baddour, Majdi Al-Hasan, Barbara Yawn, MD, MSc, FAAFP, Young J. Juhn, MD, MPH; Soonchunhyang University Hospital, Seoul, Mayo Clinic, Gil Hospital, South Korea, University of Kentucky Medical Center, Olmsted Medical Center, Rochester, MN, Mayo Clinic, Rochester, MN. RATIONALE: Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli blood stream infection (BSI). We assessed whether asthma status is associated with risk of developing community-acquired E.coli BSI. METHODS: The study was designed as a population-based retrospective case-control study, which enrolled 259 eligible communityacquired E. coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-, genderand residency-matched controls. We excluded nosocomial and health care-associated E. coli BSI cases and non-Olmsted County, MN residents. Asthma status was ascertained by predetermined criteria for asthma. Data were fitted to a conditional logistic regression model to calculate adjusted odds ratio and 95% confidence interval (CI). RESULTS: Of 259 eligible patients, 179 (69 %) were female and mean age was 61622 years. Thirty-six (14 %) of 259 cases and 16 (6 %) of 259 controls had a prior history of asthma (adjusted OR, 2.84; 95%CI, 1.14-7.09, p50.026) controlling for ethnicity, educational level, statistically significant comorbid conditions, and immunosuppressive therapy. Asthma severity was associated with risk of E. coli BSI (OR:0.94, 95% CI: 0.31-2.80 for intermittent asthma; OR 3.17; 95% CI, 1.15-8.75 for mild persistent asthma; and OR 7.0; 95%CI 1.59-30.80 for moderate persistent asthma) compared to non-asthmatics. Sixteen (6.2%) cases and 6 controls (2.3%) had food allergy (adjusted OR 3.24, 95%CI, 0.92-11.38, p50.067). CONCLUSIONS: The study results suggest that a history of asthma may be a risk factor associated with the development of E. coli BSI.

Effect of inhaled corticosteroids on the microbiology of the respiratory tract

See article, page 272

Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge. To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure. Exosomes were isolated from BALF from healthy control subjects (n=10) and patients with mild intermittent asthma (n=10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling. The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2)=0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles. These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.

Use of Impulse Oscillometry System in Assessment of Asthma Severity for Preschool Children

Objective. The National Asthma Education and Prevention Program/Expert Panel Report (NAEPP/EPR)-3 Guidelines for asthma treatment categorize asthma severity based on impairment and risks and on medications administered. The objective of this study was to determine whether impulse oscillometry system (IOS) measures in preschool children are consistent with asthma severity as defined by NAEPP/EPR-3 Guidelines. Methods. Asthma severity of the 162 subjects (aged 2–5 years) was classified by impairment and risks for exacerbations requiring oral systemic corticosteroids, by medication usage, and by combination classification (higher severity of impairment and risks or medication usage). An experienced pediatrician determined the appropriate medications for each child and parents completed structured questionnaires regarding day and night symptoms and interference with normal activity over the preceding 4 weeks. All children were tested by IOS. Results. The mean age was 3.7 ± 0.9 years and 91 (56%) of the total patients were males. When asthma severity was based on (1) impairment and risks and (2) medication usage, asthma was “intermittent” in 17.9% and 11.1% of the total patients, “mild persistent” in 42.0% and 50.6% of total patients, and “moderate–severe persistent” in 40.1% and 38.3% of total patients, respectively. The agreement between severity based on impairment and risks and medication usage was not significant. Xrs5 z-scores differed between intermittent asthma and mild/moderate–severe persistent asthma, as determined by medication usage and combination classification, but not by impairment and risks. As asthma severity (assessed by medication usage) increased, the duration of asthma increased. Conclusions. Xrs5 can be used to discriminate intermittent and persistent asthma in preschool children. Further studies with larger sample sizes are warranted to confirm this finding and to determine the underlying mechanism.

Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1&amp;#945; in obese patients with different severity of asthma

Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.

Trend in asthma severity in steroid naive asthmatic children in Benin city, Nigeria

Asthma imposes heavy health burden on children and families worldwide. It is a chronic inflammatory airway disease and as such, treatment of the asthmatics is aimed at relieve of bronchoconstriction and inflammation. Until about a decade ago, emphasis was on the bronchoconstriction rather than the inflammation. To determine the trend in severity of asthma in steroid naive children, in an era when steroid use in the treatment of asthma was uncommon. Case notes of patients managed for asthma from 1985 to 1995 and age 5 - 16 years were retrieved and reviewed (these case notes are usually stored in Prof. O. Oviawe's office). Information extracted included age of onset of asthma, severity of asthma and drug medication at presentation and at 1 year. The GINA Guideline (2006) was used in classifying the asthma severity. A total of 77 patients satisfied the criteria for the study. Of these, 53 were males and 24 females. Males: Female ratio was 2.3:1; age range 5 - 16 years; mean age ± SD (8.5 ± 3.13 years). At presentation, 48 (62.3%) patient had intermittent, 29 (37.7%) had persistent asthma, of these, 25 (86.2%) had mild persistent and 4 (13.8%) had moderate persistent. None had severe persistent asthma. At 1 year follow-up, 29 (37.7%) now had intermittent asthma, while 44 (57.1%) had persistent asthma, of these, 23 (52.3%) had mild persistent, 20 (45.5%) had moderate persistent, while 1 (2.3%) had severe persistent. Medication therapy was β2-agonist in 72 (93.5%) patients. The study supports progressive pathologic process possibly inflammatory in origin. It is opined that steroid naivity led to the trend seen in this study and judicious use of corticosteroids would have arrested the trend.