Reversible Airway Obstruction Research Articles

External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease

Fixed airflow limitation can be found both in asthma and chronic obstructive pulmonary disease (COPD), posing a day-to-day diagnostic challenge. We aimed to determine the external validity of metabolomic analysis of exhaled air by electronic nose for distinguishing asthma and COPD in patients with fixed airways obstruction. One hundred patients were included in a cross-sectional design: 60 asthma patients: 21 with fixed airways obstruction (fixed asthma), 39 with reversible airways obstruction (classic asthma) and 40 COPD patients (GOLD stages II-III). Standardized sampling of exhaled breath was performed and volatile organic compounds were captured using an electronic nose resulting in breathprints. External validity in newly recruited patients (validation sets) was tested using a previous and independent training set. Breathprints were analysed by principal component and canonical discriminant analysis and area under the curve (AUC) of receiver operating characteristic curves. External validity of breathprints showed 88% accuracy for distinguishing fixed asthma from COPD (AUC 0.95, 95% CI 0.84-1.00, sensitivity 85%, specificity 90%) and 83% for classic asthma (AUC 0.93, 95% CI 0.87-1.00, sensitivity 91%, specificity 90%) (both P<0.001). Discriminative accuracy was not confounded by current smoking. External validation of exhaled breath molecular profiling shows high accuracy in distinguishing asthma and COPD in newly recruited patients with fixed airways obstruction. Exhaled air analysis may therefore reduce misdiagnosis in obstructive airways diseases, potentially leading to more appropriate management.

Interferon‐lambda as a new approach for treatment of allergic asthma?

Asthma is a heterogeneous inflammatory disorder of the lung caused principally by sensitization and exposure to an allergen, but also influenced by environmental factors such as cigarette smoking, stress, exercise, pollution, respiratory virus infection and certain respiratory bacteria. The cardinal features of asthma include wheeze, shortness of breath, variable and reversible airway obstruction, airway hyperresponsiveness, mucus production and airway inflammation. Allergic asthma is the most common form of asthma, caused by sensitization and exposure via the airways to a number of innocuous allergens including proteins from house dust mites, animals, moulds and tree and grass pollens. Sensitization and challenge elicits a response from Th2 helper T cells and, through the actions of interleukin (IL)‐4, IL‐5 and IL‐13, IgE production, airway eosinophilia, mast cell activation, mucus production and airway hyperreactivity ensues. Mild asthma can be well controlled by inhaled steroid therapies or inhaled steroid‐β2 agonist combinations. However, in moderate to severe asthma, adequate control frequently cannot be achieved with these therapies, and new and better treatments are therefore required. Asthma exacerbations are acute attacks of asthma when an otherwise ‘stable’ asthmatic experiences a rapid increase in symptoms accompanied by decreased lung function, most often precipitated by a respiratory virus infection. Asthma exacerbations are responsible for the vast majority of the morbidity and mortality associated with asthma; and represent an area not well controlled by current therapy regimes. The search for new asthma therapies remains an intensive area of interest, and the last 10 years have seen a number of novel therapeutic strategies applied to both stable asthma and asthma exacerbations, including new formulations of steroids and β2 agonists, anti‐Th2 cytokine therapies, anti‐TNF‐α therapies, etc. The work by Koltsida et al (Koltsida et al, 2011) in this issue of EMBO Molecular Medicine is of outstanding importance in this regard for …

Outdoor Air Pollution and Asthma in Children

Background. Asthma, a chronic inflammatory disease of the airways, is associated with reversible airway obstruction and hyperresponsiveness to triggers; clinical symptoms include wheezing, episodic cough, shortness of breath, and increased mucous production. Ambient or outdoor environmental exposure to ozone, particulate matter, sulfur dioxide, and nitrogen oxides has been well documented to exacerbate asthma. Children appear to be most vulnerable to the harmful effects of ambient air pollutants. As their lungs are not completely developed, children may experience greater exposure to environmental pollutants than adults and the higher doses of varied composition may remain in their lungs for a greater duration. Altogether, the negative effects of air pollutants on pulmonary function place children at a greater risk of air pollutant-induced exacerbation of asthma for the duration of their lives. Objectives. The aim of this review was to assess recently published literature regarding the influence of air pollution on asthma in children. Methods. For this work, we reviewed articles found in PubMed using the key words “outdoor air pollution, asthma, and children” which were published between 2006 and 2009. Only those articles that had a full version available in PubMed were analyzed. Results. We reviewed studies published between 2006 and 2009 examining the effect of outdoor air pollution on asthma in children. In total, we evaluated 25 articles; of these, 9 were published in 2006, 3 in 2007, 8 in 2008, and 5 in 2009. Of these 25 studies, 1 was a clinical trial, 6 were cross-sectional, 4 were case–control (2 with a case-crossover design), 12 were cohort prospective, and 2 were cohort retrospective studies with varied follow-up times ranging from 10 days to 7 years. The ages of children also differed, ranging from birth to 18 years of age. Conclusions. All studies reviewed in this work indicate that outdoor air pollution affects the appearance and exacerbation of asthma in children. Although these findings are of great interest, the limitations of noted works make future investigations of the effect of air pollution on asthma in children essential.

Application of proteomics in asthma research

Bronchial asthma is caused by allergic airway inflammation, resulting in reversible airway obstruction, characterized by airway hyper-responsiveness, bronchoconstriction, increased mucus secretion and an increase in lung vessel permeability. The pathophysiological changes in asthma have been attributed to the altered expression of biologically plausible proteins associated with transcriptional pathways, inflammatory mediators, chemokines, cytokines, apoptosis and cell proliferation. Such multifactorial diseases characteristically involve an interplay of many genetic variations of molecular and biochemical pathways and their interactions with environmental factors. The complex nature of the asthma phenotype, together with genetic heterogeneity and environmental influences, has made it difficult to uncover the aspects that underlie this common disease. Recently, genomic and proteomic technologies have been developed to identify associations between genes, proteins and disease. This approach, called ‘omics biology’, aims to recognize early onset of disease, institute preventive treatment and identify new molecular targets for novel drugs in multifactorial diseases. This article reviews examples of how proteomic technology can be used to find asthma marker proteins (from the cell model to clinical samples). Identification of protein changes in different stages of asthma could provide further insights into the complex molecular mechanisms involved in this disease. These studies provide new insights for finding novel pathological mediators and biomarkers of asthma.

Detection of volatile organic compounds (VOCs) in exhaled breath of patients with chronic obstructive pulmonary disease (COPD) by ion mobility spectrometry

COPD is a disease characterised by a chronic inflammation of the airways and a not fully reversible airway obstruction. The spirometry is considered as gold-standard to diagnose the disease and to grade its severity. In this study we used the methodology of Ion Mobility Spectometry in order to detect Volatile Organic Compounds (VOCs) in exhaled breath of patients with COPD. The purpose of this study was to investigate if the VOCs detected in patients with COPD were different from the VOCs detected in exhaled breath of healthy controls. 13 COPD patients and 33 healthy controls were included in the study. Breath samples were collected via a side-steam Teflon tube and directly measured by an ion mobility spectrometer coupled to a multi capillary column (MCC/IMS). One peak was identified only in the patients group compared to the healthy control group. Consequently, the analysis of exhaled breath could be a useful tool to diagnose COPD.

NEW PHARMACOLOGICAL TREATMENTS FOR PATIENTS WITH CHRONIC OBSTRUCTIVE PUMONARY DISEASE (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gasses. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. A literature search using PubMed, Science Direct, EBSCO and free patents on line for the years 2000-2010. Recent discoveries in the physiology and pathology of airways diseases have served to generate potential new drugs for the treatment of COPD patients. Several substances that block or activate specific pathways and receptors the aim of which is to decrease inflammation and increase airway obstruction reversibility are being used in different clinical protocols and hopefully will be available for patients in the near future.

Pathogenesis of airway inflammation in bronchial asthma

Bronchial asthma is a chronic disorder characterized by airway inflammation, reversible airway obstruction, and airway hyperresponsiveness. Eosinophils are believed to play important roles in the pathogenesis of asthma through the release of inflammatory mediators. In refractory eosinophilic asthma, anti-IL-5 mAb reduces exacerbations and steroid dose, indicating roles of eosinophils and IL-5 in the development of severe eosinophilic asthma. Even in the absence of IL-5, it is likely that the "Th2 network", including a cascade of vascular cell adhesion molecule-1/CC chemokines/GM-CSF, can sufficiently maintain eosinophilic infiltration and degranulation. Cysteinyl leukotrienes can also directly provoke eosinophilic infiltration and activation in the airways of asthma. Therefore, various mechanisms would be involved in the eosinophilic airway inflammation of asthma. In the pathogenesis of severe asthma, not only eosinophils but also mast cells or neutrophils play important roles. Mast cells are much infiltrated to smooth muscle in severe asthma and induce airway remodeling by release of inflammatory mediators such as amphiregulin. Treatment with anti-IgE Ab, which neutralizes circulating IgE and suppresses mast cell functions, reduces asthma exacerbations in severe asthmatic patients. Furthermore, infiltration of neutrophils in the airway is also increased in severe asthma. IL-8 plays an important role in the accumulation of neutrophils and is indeed upregulated in severe asthma. In the absence of chemoattractant for eosinophils, neutrophils stimulated by IL-8 augment the trans-basement membrane migration of eosinophils, suggesting that IL-8-stimulated neutrophils could lead eosinophils to accumulate in the airways of asthma. In view of these mechanisms, an effective strategy for controlling asthma, especially severe asthma, should be considered.

Association of Alveolar Nitric Oxide Levels with Pulmonary Function and Its Reversibility in Stable Asthma

Background: Inflammation of peripheral airways is implicated in the pathophysiology of severe asthma. However, contributions of peripheral airway inflammation to airway caliber/function in patients with stable asthma, including those with mild to moderate disease, remain to be confirmed. Objectives: To determine whether peripheral airway inflammation affects airway function in patients with asthma. Methods: In 70 patients with mild to severe asthma, alveolar nitric oxide [CANO(TMAD)] levels were examined as a noninvasive biomarker of peripheral airway/alveolar inflammation. CANO(TMAD) and maximal nitric oxide (NO) flux in the airway compartment, J’awNO, were estimated with a model that incorporated trumpet-shaped airways and axial diffusion using exhaled NO output at different flow rates. Measures of pulmonary function were then assessed by spirometry and an impulse oscillometry system, and their bronchodilator reversibility was examined. Results: CANO(TMAD) levels were not correlated with pre- or postbronchodilator spirometric values, but were significantly associated with prebronchodilator reactance at low frequency (Xrs5) (rho = –0.31, p = 0.011), integrated area of low-frequency Xrs (AX) (rho = 0.35, p = 0.003) and negative frequency dependence of resistance (Rrs5-Rrs20) (rho = 0.35, p = 0.004). Furthermore, CANO(TMAD) levels were associated with bronchodilator reversibility of FEV₁, FEF_25–75%, Xrs5 and AX (rho = 0.35, 0.31, –0.24 and –0.31, respectively; p ≤ 0.05 for all). No variables were related to J’awNO. Conclusions: Elevated CANO(TMAD), but not J’awNO, partly reflects reversible airway obstruction originating in the peripheral airway. These findings indicate the involvement of peripheral airway inflammation in physiological abnormalities in asthma.

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.

Usefulness of Exhaled Nitric Oxide for Diagnosing Asthma

Rationale. A standard asthma diagnosis is made based on clinical history, reversibility of airway obstruction, and bronchial hyperresponsiveness. Fractional exhaled nitric oxide (FeNO) is a noninvasive airway inflammatory marker that has been suggested as a diagnostic tool for asthma. The aim of this study was to establish a FeNO cut-off value for asthma diagnosis. Methods. One hundred and fourteen consecutive adult patients (mean age 34 ± 13 years) reporting symptoms consistent with asthma, with normal spirometric parameters and a negative bronchodilator test, were included in the study. All underwent a methacholine challenge test following the five-breath dosimeter protocol. FeNO was measured with a portable device (NioxMino, Aerocrine AB, Sweden) just before the methacholine challenge. The sensitivity, specificity, and diagnostic performance of FeNO measurement were calculated. Results. Thirty-five out of the 114 patients (30.7%) were diagnosed with asthma. A positive methacholine challenge was associated with higher FeNO levels and with lower forced expiratory volume in one second (FEV1) at baseline. No correlation was found between methacholine provocative concentration causing a decrease of 20% in FEV1 (PC20) and FeNO levels. A receiver-operating characteristic curve was constructed for FeNO levels (area under the curve [AUC]: 0.762; 95% confidence interval [CI]: 0.667-0.857; p < .001). The FeNO cut-off point with maximal specificity and sensitivity for asthma diagnosis was 40 ppb. Conclusions. Patients with confirmed asthma showed higher FeNO levels. A cut-off value of 40 ppb was calculated as the most efficient for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool to rule out a diagnosis of asthma, especially in patients in whom a methacholine challenge is not feasible or available.

Chlorogenic acid suppresses pulmonary eosinophilia, IgE production, and Th2-type cytokine production in an ovalbumin-induced allergic asthma: Activation of STAT-6 and JNK is inhibited by chlorogenic acid

Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction, airway hyperreactivity, and remodeling of the airways. Chlorogenic acid (CGA), an ester of caffeic acid with quinic acid, is one of the most abundant polyphenol compounds in various agricultural products. CGA shows various biological properties, such as anti-oxidant, anti-viral, anti-carcinogenic and anti-inflammatory activities. We investigated suppressive effects of CGA on ovalbumin (OVA)-induced allergic asthma in mice and underlying mechanisms of them. CGA significantly reduced pulmonary eosinophilia and expression of IL-4, IL-5 and TNF-α in the lung as well as the serum levels of total and OVA-specific IgE, while CGA enhanced those of total and OVA-specific IgG3, of which isotype switching is down-regulated by IL-4. In vitro IgE production from LPS/IL-4-stimulated splenocytes was remarkably reduced by CGA, while that of IgG3 was enhanced. The Cε germ line transcription, which is necessary for IL-4 mediated IgE isotype switching, was reduced by CGA in LPS/IL-4-stimulated splenocytes. IgE isotype switching is mediated via several transduction pathways, activating several molecules including STAT-6, NF-κB, ERK1/2, and JNK. Among the molecules, which were activated by IL-4/LPS, activation of STAT-6 and JNK was inhibited by CGA.

Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

BackgroundThe budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear.MethodsThe acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted) who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg), formoterol (4.5 μg), salbutamol (2 × 100 μg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day.ResultsIn the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1.ConclusionsA single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma.Trial RegistrationClinicalTrials.gov number NCT00272753

Role of CCR4 inCD4+CD25+Regulatory T cell on Asthma

Asthma is a chronic disease characterized by airway inflammation, airway hyperresponsiveness (AHR) and reversible airway obstruction. This study was conducted to examine the relative contribution of the chemokine receptors CCR4 in regulatory T cells on a murine model of allergic asthma and to determine chemotactic response and specific expression of CCR4 by CD4+CD25+ regulatory T cells. After ovalbumin (OVA) sensitization, we used adoptive transfer experiments to compare the effect of wild‐type CCR4 Treg cells with CCR4‐deficient Treg cells and then IL‐4,5,13, serum IgE were evaluated by ELISA. Additionally, stained lung tissue with H&amp;E(Hematoxylin &amp; Eosin), PAS(Periodic acid‐Schiff ) and IHC(Immuniohistochemistry) was observed. Sensitization with OVA mice led to increased levels of IL‐4, 5, 13 in BAL fluid and in serum IgE. Also, damage to epithelium, and hyperplasia of goblet cells, smooth muscle and fibroblasts were examined whereas the adoptive transfer of wild‐type CD4+CD25+ Treg cells to asthmatic recipient markedly down‐regulated the inflammation. In contrast, the transfer of CCR4‐deficient Treg cells was unable to significantly decrease the cytokine expression and structural remodeling of the airway. These result suggest that CCR4 is required for enhancing the role of CD4+CD25+ regulatory T cells and Tregs may attract CCR4 preferentially to suppress allergic asthma.

Natural killer T cells are important in the pathogenesis of asthma: The many pathways to asthma

The pathogenesis of bronchial asthma, a complex trait associated with a number of environmental factors (eg, allergens, infection, air pollution, exercise, and obesity), involves multiple cell types and several distinct cellular and molecular pathways. These pathways include adaptive and innate immunity and involve T(H)2 cells, mast cells, basophils, eosinophils, neutrophils, airway epithelial cells, and subsets of a newly described cell type called natural killer T (NKT) cells. A role for subsets of NKT cells in asthma has been suggested by extensive studies in animal models of asthma induced with allergen, viral infection, ozone exposure, or bacterial components, suggesting that NKT cells function in concert with T(H)2 cells or independently of adaptive immunity in causing airway hyperreactivity. The clinical relevance of NKT cells in human asthma is supported by the observation that NKT cells are present in the lungs of some patients with asthma, particularly patients with severe, poorly controlled asthma, although additional research is required to more precisely define the specific role of NKT cells in human asthma. These studies of NKT cells greatly expand our understanding of possible mechanisms that drive the development of asthma, particularly in the case of asthma associated with neutrophils, viral infection, and air pollution.

Noninvasive positive pressure ventilation in acute asthmatic attack

Asthma is characterised by reversible airway obstruction. In most patients, control of disease activity is easily achieved. However, in a small minority, asthma may be fatal. Between the two extremes lie patients with severe asthmatic attacks, refractory to standard treatment. These patients are at an increased risk of recurrent severe attacks, with respiratory failure, and mechanical ventilation. Invasive mechanical ventilation of the asthmatic patient is associated with a higher risk of complications and, therefore, is a measure of last resort. Noninvasive positive pressure ventilation (NPPV) is another treatment modality that may be beneficial in patients with severe asthmatic attack who are at an increased risk of developing respiratory failure. These patients have the potential to benefit from early respiratory support in the form of NPPV. However, reports of NPPV in asthmatic patients are scarce, and its usage in asthmatic attacks is, therefore, still controversial. Only a few reports of NPPV in asthma have been published over the last decade. These studies mostly involve small numbers of patients and those who have problematic methodology. In this article we review the available evidence for NPPV in asthma and try to formulate our recommendations for NPPV application in asthma based on the available evidence and reports.

Possible involvement of smoking in the development of asthma-like conditions in patients with chronic obstructive pulmonary disease

Indicies of asthma were measured in smokers with chronic bronchitis (CB) + pulmonary emphysema (PE), smokers with CB only, and non-smokers with CB, to examine whether smoking is involved in the development of asthma-like condition in patients with chronic obstructive pulmonary disease (COPD). Airway hypersensitivity was measured with an Astrograph method, and the reversibility of airway obstruction was measured as improvement in FEV1.0 and as percent change in FEV1.0 after inhalation of a beta-agonist. Both hypersensitivity and reversibility were significantly higher in smokers with CB+PE and in smokers with CB only than in non-smokers with CB. The number of eosinophils in sputum, but not in peripheral blood, was slightly higher in the smokers than in the non-smokers. The serum levels of IgE were significantly higher in the smokers than in the non-smokers. No significant difference in the rate of positive skin tests for common allergens was observed among the three groups, but the rate of positive tests for Broncasma Berna was very high in the smokers, and all such tests were negative in the non-smokers. These results indicate that among patients with COPD an asthmatic component is more frequently found in smokers than in non-smokers, and suggest that smoking plays some part in the development of asthma-like condition in these diseases.

Reversible airway obstruction in children with ataxia telangiectasia

Lung disease is a significant cause of the short life span of ataxia telangiectasia (A-T) patients. Objective lung function measurements are difficult to achieve in A-T. To assess lung function by spirometry in relation to the clinical characteristics of A-T patients followed up at the Israeli Ataxia Telangiectasia National Clinic. Medical and spirometry data were collected from 27 A-T patients during 2004-2007. Laboratory, nutritional condition, mode of treatment, pulmonary status, and malignancies were assessed. The spirometry values FVC, FEV(1), FEV(0.5), FEF(25-75), PEF and time rise to peak flow were analyzed individually and values were compared to those of healthy age-matched children. Eleven patients (40.7%) were found to suffer from asthma according to clinical symptoms and response to bronchodilators. We found significant reduction in FEV(1) and FEV(0.5) (z-scores: -0.84 + or - 0.7 SD, -0.7 + or - 0.6 SD; P = 0.0014 and P = 0.003, respectively), in relation to healthy predicted values. FEF(25-75) was significantly lower than that in healthy children in 5 of 11 asthmatic patients. All 27 patients showed higher than healthy FEV(1)/FVC and FEV(0.5)/FVC ratios (z-scores 0.68 + or - 0.99 SD, P < 0.0015, and 2.12 + or - 1.50 SD, P < 0.0015, respectively). The rise time to peak flow was three-fold longer than that of healthy children. Obstructive lung disease is common among A-T patients. Maximal peak flow reduction and prolonged rise time to peak flow may be the first signs of pulmonary involvement in these patients. Early treatment with anti-asthma therapy, bronchodilators, and steroids, may prevent further pulmonary deterioration and improve the prognosis of A-T patients.

Usefulness Of Exhaled Nitric Oxide In Asthma Diagnosis

RATIONALE: Inflammation is known to underlie the pathogenesis of asthma. Nevertheless, diagnosis is made by clinical history, reversible airway obstruction and bronchial hyperresponsiveness according to international guidelines. Exhaled nitric oxide is a non-invasive inflammatory marker. The aim of the study was to assess the sensitivity and specificity of FeNO in asthma diagnosis.METHODS: Sixty-four consecutive patients reporting asthma symptoms were included in the study. All of them underwent methacholine challenge test following the five-breath dosimeter protocol, after measurement of exhaled nitric oxide with a portable device.RESULTS: Twenty-three of the 64 patients were diagnosed with asthma. A positive MCh challenge was correlated with higher FeNO levels and with basal FEV1. No correlation was found between PC20 and FeNO levels. ROC curves were built for FeNO levels (AUC: 0.79). A cut-off point for FeNO level was calculated with maximal specificity and sensitivity for asthma diagnosis (39.5 ppb).CONCLUSIONS: FeNO as marker of inflammation is highly correlated with functional parameters (MCh) in asthmatic patients. A cut-off point of 39.5 ppb was calculated for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool for asthma diagnosis in patients not able of performing MCh challenges. RATIONALE: Inflammation is known to underlie the pathogenesis of asthma. Nevertheless, diagnosis is made by clinical history, reversible airway obstruction and bronchial hyperresponsiveness according to international guidelines. Exhaled nitric oxide is a non-invasive inflammatory marker. The aim of the study was to assess the sensitivity and specificity of FeNO in asthma diagnosis. METHODS: Sixty-four consecutive patients reporting asthma symptoms were included in the study. All of them underwent methacholine challenge test following the five-breath dosimeter protocol, after measurement of exhaled nitric oxide with a portable device. RESULTS: Twenty-three of the 64 patients were diagnosed with asthma. A positive MCh challenge was correlated with higher FeNO levels and with basal FEV1. No correlation was found between PC20 and FeNO levels. ROC curves were built for FeNO levels (AUC: 0.79). A cut-off point for FeNO level was calculated with maximal specificity and sensitivity for asthma diagnosis (39.5 ppb). CONCLUSIONS: FeNO as marker of inflammation is highly correlated with functional parameters (MCh) in asthmatic patients. A cut-off point of 39.5 ppb was calculated for asthma diagnosis in our population. The use of FeNO measurement may be a helpful tool for asthma diagnosis in patients not able of performing MCh challenges.

Anesthesia for patients with severe chronic obstructive pulmonary disease

Patients with chronic obstructive lung disease experience an increased risk of perioperative pulmonary complications. This review presents an evidence-based approach to perioperative care designed to optimize management. Recent research has provided guidance regarding intraoperative and postoperative administration of oxygen and the selective use of volatile agents. The significance of preoperative malnutrition and postoperative epidural analgesia on outcomes has also been explored further. The opportunity for anesthesiologists to engage in tobacco interventions and the benefits of addressing smoking cessation have been studied. Optimization for surgery includes preoperative treatment of reversible airway obstruction and respiratory infections, smoking cessation, and possibly nutritional interventions. Meticulous intraoperative monitoring combined with a sound understanding of pathophysiological mechanisms underlying air trapping will help clinicians strike a balance between permissive hypercapnia and adequate ventilation.

Leukotriene A4Hydrolase Inhibition Attenuates Allergic Airway Inflammation and Hyperresponsiveness

Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and airway hyperresponsiveness (AHR). Previous studies using leukotriene B(4) (LTB(4)) receptor 1-deficient mice and adoptive transfer experiments have suggested that LTB(4) plays a role in lung inflammation and AHR. In this study, we used a leukotriene A(4) hydrolase (LTA(4)H) inhibitor as a pharmacological tool to directly examine the role of LTB(4) in a mast cell-dependent murine model of allergic airway inflammation. We used the forced oscillation technique to test the effects of an LTA(4)H inhibitor dosed during the challenge phase on AHR. Lung tissue and lavage were collected for analysis. Treatment with an LTA(4)H inhibitor improved multiple parameters encompassing AHR and lung function. Significant decreases in inflammatory leukocytes, cytokines, and mucin were observed in the lung lumen. Serum levels of antigen-specific IgE and IgG1 were also decreased. Labeled antigen uptake by lung dendritic cells and subsequent trafficking to draining lymph nodes and the lung were decreased on LTA(4)H inhibitor treatment. Provocatively, inhibition of LTA(4)H increased lipoxin A(4) levels in lung lavage fluid. These data suggest that LTB(4) plays a key role in driving lung inflammation and AHR. Mechanistically, we provide evidence that inhibition of LTA(4)H, affects recruitment of both CD4(+) and CD8(+) T cells, as well as trafficking of dendritic cells to draining lymph nodes, and may beneficially modulate other pro- and antiinflammatory eicosanoids in the lung. Inhibition of LTA(4)H is thus a potential therapeutic strategy that could modulate key aspects of asthma.