Home About us Contact
|
Home About us Contact | ||
|
|
||
Inhaled
Terms modified by Inhaled Selected AbstractsAngiogenesis and lymphangiogenesis in bronchial asthmaALLERGY, Issue 8 2010A. Detoraki To cite this article: Detoraki A, Granata F, Staibano S, Rossi FW, Marone G, Genovese A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy 2010; 65: 946,958. Abstract Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders. [source] Unawareness and undertreatment of asthma: follow-up in a different geographic area in DenmarkALLERGY, Issue 8 2009V. Backer Background:, Early detection and treatment of asthma is important to minimize morbidity and healthcare costs. The objective of this study was to investigate asthma awareness and management in a western society. Methods:, In a random sample of 10 400 subjects aged 14,44 years, 686 (6.6%) reported symptoms of asthma in a standardized screening questionnaire. All 686 were evaluated by respiratory specialists and diagnosed by history, symptoms, lung function tests, bronchial challenges and allergy testing. Of these 686 participants, 69 (10%) had asthma alone, 205 (30%) had rhinitis alone and 217 (32%) had both asthma and rhinitis; 195 (28%) had nonasthmatic respiratory reports. Results:, Awareness of asthma was found among 163 (57%) of the 286 asthmatics, and 204 (95%) had doctor-diagnosed rhinitis as well. In a multivariate regression analysis, comorbidity with rhinitis (, = 0.489, P < 0.001), smoking (, = ,0.116, P < 0.01), doctor-diagnosed bronchitis (, = 0.086, P < 0.05), and earlier emergency visits at hospital (, = 0.147, P < 0.001) was significantly associated with awareness. A difference in awareness was found between those who had asthma and rhinitis (62.2%) and those who had asthma alone (40.6%) (P < 0.01). Inhaled corticosteroids (ICS) were used by 27% of those with asthma, including 12% who used both ICS and long-acting beta-agonist. Conclusions:, More than half of the persons with asthma were aware of their disorder; and the awareness was more likely in those with comorbidity of rhinitis. In general, asthma management was inadequate. [source] Respiratory muscle performance with stretch-shortening cycle manoeuvres: maximal inspiratory pressure,flow curvesACTA PHYSIOLOGICA, Issue 3 2005G. E. Tzelepis Abstract Aim:, To test the hypothesis that the maximal inspiratory muscle (IM) performance, as assessed by the maximal IM pressure,flow relationship, is enhanced with the stretch-shortening cycle (SSC). Methods:, Maximal inspiratory flow,pressure curves were measured in 12 healthy volunteers (35 ± 6 years) during maximal single efforts through a range of graded resistors (4-, 6-, and 8-mm diameter orifices), against an occluded airway, and with a minimal load (wide-open resistor). Maximal inspiratory efforts were initiated at a volume near residual lung volume (RV). The subjects exhaled to RV using slow (S) or fast (F) manoeuvres. With the S manoeuvre, they exhaled slowly to RV and held the breath at RV for about 4 s prior to maximal inspiration. With the F manoeuvre, they exhaled rapidly to RV and immediately inhaled maximally without a post-expiratory hold; a strategy designed to enhance inspiratory pressure via the SSC. Results:, The maximal inspiratory pressure,flow relationship was linear with the S and F manoeuvres (r2 = 0.88 for S and r2 = 0.88 for F manoeuvre, P < 0.0005 in all subjects). With the F manoeuvre, the pressure,flow relationship shifted to the right in a parallel fashion and the calculated maximal power increased by approximately 10% (P < 0.05) over that calculated with the S manoeuvre. Conclusion:, The maximal inspiratory pressure,flow capacity can be enhanced with SSC manoeuvres in a manner analogous to increases in the force,velocity relationship with SSC reported for skeletal muscles. [source] Behavioral and cardiovascular effects of 7.5% CO2 in human volunteersDEPRESSION AND ANXIETY, Issue 1 2005Jayne E. Bailey M.Sc. Abstract The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5,7% CO2 inhaled for 15,20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety. Depression and Anxiety 00:000,000, 2005. © 2005 Wiley-Liss, Inc. [source] Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept studyDIABETES OBESITY & METABOLISM, Issue 5 2006M. Hausmann Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source] Dangers relating to fires in carbon-fibre based composite materialFIRE AND MATERIALS, Issue 4 2005Tommy Hertzberg Abstract Inhalable carbon fibres have been suspected to pose similar threats to human health as asbestos fibres. It is well-known that fibres having a diameter of less than 3 µm might be inhaled and transported deep into the human respiratory system. Some composite materials use carbon fibres as structural reinforcement. These fibres do not pose any risks as such as they are firmly connected to the laminate and surrounded by a polymer matrix. Also, these fibres typically have diameters >6 µm and thus, are not inhalable. However, if the material is exposed to a fire, the carbon material might be oxidized and fractionated and thereby, inhalable fibres might be generated into the fire smoke. The capability of carbon fibre-based composite material to produce dangerous inhalable fibres from different combustion scenarios has been investigated. It was found that the risk of fires generating inhalable carbon fibres is related to the surface temperature, the oxygen level and the airflow field close to the material surface. The temperatures necessary for oxidation of the carbon fibre is so high that it is possible that only a flashover situation will pose any real danger. Other possible danger scenarios are highly intense fires (e.g. a liquid fuel fire), or situations where structural damage is part of the fire scenario. Copyright © 2005 John Wiley & Sons, Ltd. [source] Trends in hospital-based management of acute asthma from a teaching hospital in South AsiaINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2005S. F. Hussain Summary The aim of this study is to evaluate the hospital-based management of acute asthma in south Asia and to compare practices over a 10-year period. Adult patients (n = 102) admitted at a teaching hospital with acute asthma were studied. Documentation of precipitating factors, family history and physical signs were inadequate in more than half of patients. Pulse oximetry was documented in 95 (93%) patients, but peak flow monitoring was performed only in 50 (49%) patients. Ten-year trend showed deterioration in history and physical examination skills, under use of peak flow readings, and poor pre-discharge instructions. Some aspects of improved care included frequent use of pulse oximeter, preference of inhaled over systemic bronchodilators and increased use of systemic steroids. Significant deficiencies were identified in hospital-based management of acute asthma. Most aspects of asthma care continued to fall short of asthma guidelines. [source] Depleted uranium,the growing concernJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2002Aqel W. Abu-Qare Abstract Recently, several studies have reported on the health and environmental consequences of the use of depleted uranium. Depleted uranium is a heavy metal that is also radioactive. It is commonly used in missiles as a counterweight because of its very high density (1.6 times more than lead). Immediate health risks associated with exposure to depleted uranium include kidney and respiratory problems, with conditions such as kidney stones, chronic cough and severe dermatitis. Long-term risks include lung and bone cancer. Several published reports implicated exposure to depleted uranium in kidney damage, mutagenicity, cancer, inhibition of bone, neurological deficits, significant decrease in the pregnancy rate in mice and adverse effects on the reproductive and central nervous systems. Acute poisoning with depleted uranium elicited renal failure that could lead to death. The environmental consequences of its residue will be felt for thousands of years. It is inhaled and passed through the skin and eyes, transferred through the placenta into the fetus, distributed into tissues and eliminated in urine. The use of depleted uranium during the Gulf and Kosovo Wars and the crash of a Boeing airplane carrying depleted uranium in Amsterdam in 1992 were implicated in a health concern related to exposure to depleted uranium. Copyright © 2002 John Wiley & Sons, Ltd. [source] Metabolic responses in ischemic myocardium after inhalation of carbon monoxideACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009K. AHLSTRÖM Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection. [source] Beta-2 adrenergic receptor genetic polymorphisms and asthmaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009N. Hizawa MD Summary Beta-2-Adrenergic receptors (,2AR) participate in the physiologic responses of the lung, including bronchodilation and bronchoprotection, through mechanisms such as mucociliary clearance, fluid accumulation and mediator release from mast cells and basophils. Thus, these receptors may also play an important role in the pathophysiology of asthma. The gene encoding ,2AR (ADRB2) is extremely polymorphic, and studies of this gene improves our understanding of asthma and possibly lead to new methods to prevent, diagnose and treat it. This review summarizes results from various studies on the possible relationship of ADRB2 polymorphisms to asthma and asthma-related phenotypes, including bronchodilator responses to inhaled ,2 -agonists. At present, it appears that, for asthma, ADRB2 polymorphisms are not aetiologically involved. However, they might affect disease severity and clinical response to both acute and chronic administration of ,2 -agonists. The development is that by assessing the ADRB2 genotype, it might be possible to predict the clinical course of asthma as well as responsiveness to chronic administration of ,2 -agonists. Carefully, performed and adequately powered clinical trials continue to be important for achieving those goals. [source] Noninvasive in vivo electron paramagnetic resonance study to estimate pulmonary reducing ability in mice exposed to NiO or C60 nanoparticlesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Hidekatsu Yokoyama MD Abstract Purpose To develop new methods that can estimate the influences of manufactured nanomaterials on biological systems, the in vivo pulmonary reducing ability of mice that had received inhalation exposures to NiO or C60 nanoparticles was investigated using a 700 MHz electron paramagnetic resonance (EPR) spectrometer. Materials and Methods NiO or C60 suspensions were atomized and mice in exposure chambers inhaled the resulting aerosol particles for 3 hours. The exposure conditions, number-based geometric average diameters, and the average number concentration were precisely controlled at almost the same levels for both NiO and C60 nanoparticles. Two days or 2 weeks after exposure, an EPR study was conducted noninvasively. Temporal changes in EPR signal intensity at the target area (ie, lung field) were obtained by the region-selected intensity determination (RSID) method. Results NiO nanoparticles significantly suppressed pulmonary reducing ability 2 days and 2 weeks after exposure, but C60 nanoparticles had no such effect. Conclusion This is the first in vivo estimation of the reducing ability in experimental animals exposed to manufactured nanoparticles. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [source] Absolute quantification of cerebral blood flow in normal volunteers: Correlation between Xe-133 SPECT and dynamic susceptibility contrast MRIJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Linda Knutsson PhD Abstract Purpose To compare absolute cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast MRI (DSC-MRI) and Xe-133 SPECT. Materials and Methods CBF was measured in 20 healthy volunteers using DSC-MRI at 3T and Xe-133 SPECT. DSC-MRI was accomplished by gradient-echo EPI and CBF was calculated using a time-shift-insensitive deconvolution algorithm and regional arterial input functions (AIFs). To improve the reproducibility of AIF registration the time integral was rescaled by use of a venous output function. In the Xe-133 SPECT experiment, Xe-133 gas was inhaled over 8 minutes and CBF was calculated using a biexponential analysis. Results The average whole-brain CBF estimates obtained by DSC-MRI and Xe-133 SPECT were 85 ± 23 mL/(min 100 g) and 40 ± 8 mL/(min 100 g), respectively (mean ± SD, n = 20). The linear CBF relationship between the two modalities showed a correlation coefficient of r = 0.76 and was described by the equation CBF(MRI) = 2.4 · CBF(Xe),7.9 (CBF in units of mL/(min 100 g)). Conclusion A reasonable positive linear correlation between MRI-based and SPECT-based CBF estimates was observed after AIF time-integral correction. The use of DSC-MRI typically results in overestimated absolute perfusion estimates and the present study indicates that this trend is further enhanced by the use of high magnetic field strength (3T). J. Magn. Reson. Imaging 2007;26:913,920. © 2007 Wiley-Liss, Inc. [source] Effects of indomethacin on cerebral blood flow at rest and during hypercapnia: An arterial spin tagging study in humans,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2002Keith S. St. Lawrence PhD Abstract Purpose To investigate using an arterial spin tagging (AST) approach the effect of indomethacin on the cerebral blood flow (CBF) response to hypercapnia. Materials and Methods Subjects inhaled a gas mixture containing 6% CO2 for two 5-minute periods, which were separated by a 10-minute interval, in which subjects inhaled room air. In six subjects, indomethacin (i.v., 0.2 mg/kg) was infused in the normocapnic interval between the two hypercapnic periods. Results Indomethacin reduced normocapnic gray matter CBF by 36 ± 5% and reduced the CBF increase during hypercapnia from 43 ± 9% to 16 ± 5% in gray matter (P < 0.001) and from 48 ± 11% to 35 ± 9% in white matter (P < 0.025). Conclusion The results demonstrate that an AST approach can measure the effects of indomethacin on global CBF increases during hypercapnia and suggest that an AST approach could be used to investigate pharmacological effects on focal CBF increases during functional activation. J. Magn. Reson. Imaging 2002;15:628,635. Published 2002 Wiley-Liss, Inc. [source] "Whippets"-Induced Cobalamin Deficiency Manifesting as Cervical MyelopathyJOURNAL OF NEUROIMAGING, Issue 3 2004Alan L. Diamond ABSTRACT Background. Nitrous oxide (N O) is inhaled in anesthesia and as a recreational drug from whipped cream dispensers. Its abuse reaches ,10% in some age groups. By inactivating cobalamin (Cbl) (vitamin B12), N O can cause neurologic and hematologic manifestations. We present a case of N O-induced Cbl deficiency presenting as cervical myelopathy. Case History. After regularly inhaling N O for many months, a 31-year-old man developed limb paresthesiae and ataxia over 3 months. Examination revealed finger pseudoathetosis, hyporeflexia, decreased sensation, and gait ataxia. Brain magnetic resonance imaging (MRI) was normal, but the posterior columns of the cervical and upper thoracic cord revealed patchy nonenhancing hyperintense lesions. Serum Cbl was 98 pg/mL (normal = 170,900 pg/mL). Cbl replacement led to recovery within 3 months.Discussion. This patient presented with the symptoms and signs of Cbl deficiency. The MRI lesions in the posterior columns aided the diagnosis. Physicians need to have a high level of suspicion in cases of unexplained Cbl deficiency and myelopathy. [source] Economic evaluation of BDP/formoterol fixed vs two single inhalers in asthma treatmentALLERGY, Issue 9 2010B. Brüggenjürgen To cite this article: Brüggenjürgen B, Ezzat N, Kardos P, Buhl R. Economic evaluation of BDP/formoterol fixed vs two single inhalers in asthma treatment. Allergy 2010; 65: 1108,1115. Abstract Background:, Asthma treatment costs are substantial, the largest proportion being incurred by medications. Combination therapy with inhaled corticosteroids (ICS) and long-acting beta2 -agonists (LABA) is recommended in patients not adequately controlled by ICS alone. Aim of this study was to compare costs and health outcomes of a fixed ICS,LABA combination of beclomethasone dipropionate (BDP) and formoterol fumarate (FF) vs the same drugs delivered via separate inhalers in Germany. Methods:, A cost-minimization analysis, a cost-effectiveness analysis, as well as a threshold analysis were undertaken. Efficacy results were obtained from a recent clinical trial. Cost inputs include medical costs, physician costs, and hospital admission costs. Medical costs, health outcomes, and treatment costs were also varied to assess their impact on results. Results:, Beclomethasone dipropionate/FF fixed combination was less costly compared to BDP + FF delivered as separate inhalers, costs totaling ,525 and ,637, respectively, over a 24-week treatment period. The incremental cost-effectiveness ratio was ,,9.77 per additional day free of asthma symptoms. Equal cost-effectiveness ratios would still be obtained at a price of the fixed combination increased by 3.4-fold. Conclusion:, A cost-minimization analysis as well as a cost-effectiveness analysis for Germany based on different product price calculations show that BDP/FF fixed combination is superior to BDP + FF delivered via separate inhalers. [source] Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthmaALLERGY, Issue 7 2010N. Scichilone To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternņ A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897,902. Abstract Background:, Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. Aim:, To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. Methods:, After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 ,g daily or fluticasone propionate/salmeterol (FP/S) 500/100 ,g daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Results:, Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV1) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV1 in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD20FEV1 Mch improved significantly from 90.42 (±30.08) ,g to 432.41 (±122.71) ,g in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN2 test parameters. Conclusion:, The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN2 tests. [source] Persistence with asthma treatment is low in Germany especially for controller medication , a population based study of 483 051 patientsALLERGY, Issue 3 2010J. Hasford To cite this article: Hasford J, Uricher J, Tauscher M, Bramlage P, Virchow JC. Persistence with asthma treatment is low in Germany especially for controller medication , a population based study of 483 051 patients. Allergy 2010; 65: 347,354. Abstract Background:, The objective of the present analysis was to evaluate treatment patterns and persistence with treatment of an unselected patient population with a diagnosis of asthma. Methods:, The database of the Bavarian statutory health insurance physician's association (Kassenärztliche Vereinigung) covering 83% of the population was analyzed for an index period from April 2005 to March 2006. Defined daily doses (DDDs) were used to quantify treatment persistence. Results were compared with recent guidelines. Results:, The prevalence of physician diagnosed asthma in Bavaria was 4.8% in females and 4.5% in males; only 61.4% of these patients (of a total of n = 483 051) received any anti-asthmatic pharmacotherapy; 68.3% received medical care from their general practitioner, and 8.3% from a pulmonologist alone. Most patients (65.1%) received no more than 90 DDDs of controller medication in the index period of 365 days, only about 1% received medication for the complete index period. Long- (40.1%) and short-acting ,2 -agonists (65.6%) were used more frequently than inhaled corticosteroids (ICS). 52.8% of asthma patients were treated in accordance with guidelines. Conclusions:, Persistence of asthma patients with medical treatment is low, especially for controller medication. The discrepancy between current knowledge, guidelines and clinical practice is substantial and may question the value of current guidelines for the treatment of patients with asthma in ambulatory care. In addition, the results of this study cast doubt on the impact of contemporary treatment on the decline of asthma mortality seen in recent years in Germany. [source] The role of small airways in monitoring the response to asthma treatment: what is beyond FEV1?ALLERGY, Issue 11 2009N. Scichilone The definition of asthma has evolved from that of an episodic disease characterized by reversible airways constriction to a chronic inflammatory disease of the airways, with at least partially reversible airway constriction. Increasing evidence supports the notion that small and large airways play a central role in asthma pathophysiology with regard to inflammation, remodeling and symptoms. The contribution of the distal airways to the asthma phenotype carries implications for the delivery of inhaled medications to the appropriate areas of the lung and for the monitoring of the response to asthma treatment. Asthma control is evaluated on the basis of symptoms, lung function and exacerbations. However, evidence suggests that dissociation between lung function and respiratory symptoms, quality of life and airway inflammation exists. In this study, common spirometric parameters offer limited information with regard to the peripheral airways, and it is therefore necessary to move beyond FEV1. Several functional parameters and inflammatory markers, which are discussed in the present study, can be employed to evaluate distal lung function. In this study, extrafine formulations deliver inhaled drugs throughout the bronchial tree (both large and small airways) and are effective on parameters that directly or indirectly measure air trapping/airway closure. [source] Regular vs prn nebulized treatment in wheeze preschool childrenALLERGY, Issue 10 2009A. Papi Background:, International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze. Methods:, Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1,4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 ,g beclomethasone bid plus 2500 ,g salbutamol prn; (2) placebo bid plus 800 ,g beclomethasone/1600 ,g salbutamol combination prn; (3) placebo bid plus 2500 ,g salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency. Results:, As compared with prn salbutamol (61.0 ± 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes. Conclusions:, Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study. [source] Decreased FOXP3 protein expression in patients with asthmaALLERGY, Issue 10 2009S. Provoost Background:, T-regulatory cells (Treg) are important in balancing immune responses and maintaining peripheral tolerance. Current evidence suggests that asthma is characterized by a relative deficiency in Treg, allowing T helper 2 cells to expand. In this study, we aimed to evaluate circulating Treg, defined by the protein FOXP3, in both control subjects and patients with stable asthma. Methods:, Peripheral blood mononuclear cells (PBMC) of control (n = 14) and asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3 and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and representative cytokines were studied. Results:, In control subjects and asthmatic patients, numbers of peripheral blood CD4+CD25high and CD4+CD25highFOXP3+ T-cells were similar. However, FOXP3 protein expression within CD4+CD25high T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4+CD25high T-cells in glucocorticosteroid-treated patients when compared to steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T-bet, and FOXP3/RORc2. Conclusion:, Asthmatic patients have decreased FOXP3 protein expression within their CD4+CD25high Treg. Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4+CD25high T-cell population. [source] Persistent airflow obstruction in asthma of patients with Churg,Strauss syndrome and long-term follow-upALLERGY, Issue 4 2009V. Cottin Background:, Little is known about the long-term outcome of airflow obstruction in asthma of patients with Churg,Strauss syndrome (CSS). Methods:, We conducted a retrospective study of 24 consecutive patients (aged 41.1 ± 13.5 years) with CSS in a single center. All had asthma (starting 8.1 ± 9.5 years prior to the diagnosis of CSS), blood eosinophilia (6.1 ± 4.4 × 109/l) and systemic manifestations of CSS. Antineutrophil cytoplasmic antibodies were found in 7 of 22 tested patients. Seven patients had smoked (a mean of 10 pack-years). All patients received oral corticosteroids, 11 cyclophosphamide and 23 inhaled corticosteroids. Results:, Airflow obstruction was found in 14 patients (70%) at diagnosis, and in 11 of 22 patients (50%) at the time of the clinical remission of CSS. The mean postbronchodilator FEV1/FVC and FEV1 were 69 ± 12% and 74 ± 21% of predicted at diagnosis (n = 20); 71 ± 10% and 92 ± 19% of predicted at the clinical remission (n = 22); and 64 ± 13% and 80 ± 21% at last visit (n = 13), respectively. During follow-up, postbronchodilator FEV1 increased by 30 ± 28% in six patients with FEV1/FVC < 70% despite inhaled therapy who received higher dose of oral corticosteroids. At last visit, 5 of 13 patients (38%) with more than 3 years of follow-up had persistent airflow obstruction as defined by postbronchodilator FEV1/FVC < 70% and FEV1 < 80% of predicted. Conclusion:, Airflow obstruction due to uncontrolled asthma is present despite corticosteroids in many patients at diagnosis and at clinical remission of CSS, and during follow-up. It may be still partly reversible with increased oral corticosteroid treatment. [source] Plasma protein profiles in early asthmatic responses to inhalation allergen challengeALLERGY, Issue 1 2009T. Rhim Although mediators, such as lipids, cytokines, and chemokines, are related to the appearance of an IPR, there has been no reliable indicator to predict conditions for the appearance of an IPR. In this study, we adopted a proteomic approach to investigate the pathogenesis at the level of the plasma proteins and to develop plasma markers to predict the appearance of an IPR following an inhalation challenge with Dermatophagoides pteronyssinus (D.p.). Sixteen mild asthmatics were recruited. Plasma was obtained before challenge and when a decline in forced expiratory volume in 1 s (FEV1) values greater than 20% from the phosphate-buffered saline value was achieved during D.p. allergen challenge (positive responders), or at 60 min after the highest concentration of D.p. allergen was inhaled (negative responders). After comparing normalized volumes of the spots in the two groups, differentially expressed spots were identified using intra-gel digestion and mass spectrometric analysis. Before D.p. antigen challenge, four spots of gamma fibrinogen and its isoforms were significantly decreased and two spots of complement C3 fragments were significantly increased in the positive responders compared to the negative responders. After D.p. antigen challenge, complement C3 fragment was persistently higher, while gamma fibrinogen was lower in the positive responders than in the negative responders. A validation study using Western blotting showed that gamma fibrinogen expression in the IPR-positive asthmatics was significantly decreased compared to the average of the IPR-negative asthmatic control group. These results indicate that alterations in the complement cascade and fibrinogen may predispose patients to the appearance of an immediate response to D.p. allergen challenge and may provide plasma markers to predict the appearance of an IPR. [source] Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LENALLERGY, Issue 7 2007T. Werfel Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow's milk and hen's eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to ,classical' food allergens, such as hen's eggs and cow's milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed. [source] Therapeutic doses of glucocorticoids: implications for oral medicineORAL DISEASES, Issue 5 2006SK Baid Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic,pituitary,adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. [source] Parental knowledge and use of epinephrine auto-injector for children with food allergyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2006G. Pouessel Epinephrine should be prescribed for patients at risk of anaphylaxis. Our purpose was to determine the use of Anapen® prescribed for food-allergic children, to assess parental knowledge regarding Anapen, and to evaluate the arrangements for emergency kits and personalized care projects in everyday life. A prospective study was performed with a questionnaire sent to families with a food-allergic child previously prescribed Anapen. One hundred and fifty two families were contacted and finally 111 children included (median age 6.5 yrs). Main food allergens were peanuts (n = 89), egg (n = 39) and cow's milk (n = 10). The use of Anapen had been demonstrated to 90% of parents (by prescribing physician, 69%; pharmacist, 25%; general practitioner, 5%; nurse 1%), with a training device (76%) and/or written instructions (49%). When asked to list symptoms requiring injection, 48% of parents cited more than one response: breathing difficulties only (23%), or with angio-edema (41%), collapse or faintness (38%), anaphylactic shock (48%). Of 107 children attending school, 54% had a personalized care project, 72% an Anapen device, and 60% a complete emergency kit (epinephrine, inhaled , -agonist, corticosteroid, anti-H1 drug). , -Agonists were forgotten at school by 34 children (13 asthmatics). Anapen was used in one child for angio-edema and dyspnea after inadvertent ingestion of egg at home. In our population, epinephrine auto-injectors and emergency kits were insufficiently available at schools and in daily life. The use of auto-injectors was not adequately demonstrated. The prescription of epinephrine for food-allergic children at risk of anaphylaxis requires accurate diagnosis, educational programs, information, and follow up. [source] Delivery characteristics of a combined nitric oxide nasal continuous positive airway pressure systemPEDIATRIC ANESTHESIA, Issue 6 2002DEAA, R. Lindwall MD Summary Background: Nitric oxide (NO), when inhaled, has a synergistic effect with airway recruitment strategies such as positive endexpiratory pressure (PEEP) or continuous positive airway pressure (CPAP) in improving oxygenation in lung injury. Methods: We modified a commercially available nasal CPAP (nCPAP) system to enable the concomitant delivery of inhaled NO (iNO) and nCPAP to neonates and term babies. Oxygen, NO and nitrogen dioxide (NO2) concentrations were measured, comparing the effects of using 50 or 1000 parts per million (p.p.m.) NO stock gas cylinders. Results: Stable and accurate delivery of iNO was found for both stock gas concentrations. Using a 50 p.p.m. NO stock gas resulted in limited NO2 formation, with a maximum inspired NO2 concentration of , 0.3 p.p.m. (dose range up to 37 p.p.m. iNO), which was interpreted as the result of progressive dilution with nitrogen. In contrast, using a 1000 p.p.m. NO stock gas cylinder, inspired NO2 levels increased nonlinearly as expected with an increasing inspired concentration of NO. Conclusions: Inhaled NO can be safely and reliably delivered by the system we describe. The NO2 levels generated by the system are low, at least up to a dose of 37 p.p.m. NO, regardless of a stock gas concentration of 50 or 1000 p.p.m. NO. Using a 50 p.p.m. NO stock gas concentration, up to 80% oxygen can be given at 10 p.p.m. iNO. [source] The science of aerosol delivery in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue S9 2008David E. Geller MD Abstract Aerosolized drugs are universally used for treatment of cystic fibrosis airway disease. Inhalation can increase topical efficacy and reduce systemic exposure and toxicity of many drugs. A wide variety of inhaled drugs already exist with many more in the therapeutic pipeline. Understanding the principles of aerosol delivery and how aerosol devices function is important in designing the best therapeutic regimens for CF patients. The variables that determine where an aerosol deposits are numerous and complex. Important aerosol-related variables include particle-size distribution, hygroscopic properties, viscosity and surface tension of the drug. Patient-related variables include inspired flow rate, tidal volume, respiratory rate, breath-holding, upper airway anatomy, lower airways obstruction, and the cognitive and physical ability to use the device. These factors vary widely between patients of different age groups and disease severities, and cause the high variability in drug delivery seen with aerosol drugs. Classic aerosol delivery devices like metered dose inhalers and dry-powder inhalers are small, portable, and have short treatment times. However, they are limited by small drug payloads and user technique problems. Jet nebulizers are commonly used for CF drugs, are easy to operate, require no special breathing pattern, and can deliver very large quantities of drug. However, they require a power or air source, cleaning and sanitizing, and are relatively time consuming. Recently, novel aerosol delivery systems and formulations have been developed to improve delivery efficiency and reduce variability and delivery time. These new systems can ease the treatment burden and improve adherence and outcomes in cystic fibrosis. Pediatr Pulmonol. 2008; 43:S5,S17. © 2008 Wiley-Liss, Inc. [source] Bronchodilator effect of salbutamol from two different spacer devicesPEDIATRIC PULMONOLOGY, Issue 4 2006Albert M. Li MB Abstract Our aim was to compare the bronchodilator effect of salbutamol delivered via a new holding chamber (Volumatic Soft, VS) with that of an established device (Volumatic, V) in asthmatic children. Children with stable asthma were recruited. They inhaled 100 µg, and 10 min later, 300 µg of salbutamol aerosol delivered via VS or V on day 1, and vice versa on day 2. Spirometry was measured at baseline, 10 min after 100 µg, and 15 min after 300 µg of salbutamol were given. The preference for either device was assessed by visual analogue score. Forty-four children with a median age of 9.2 years (interquartile range, 8.0,10.7) completed the study. There were significant improvements in forced expired volume in 1 sec (FEV1) with time throughout the study period for both V and VS (linear and quadratic trend P,<,0.001). There was a statistically significant difference in postbronchodilator FEV1 between V and VS (P,=,0.013). VS gave an overall greater change in FEV1 than V, by 1.8%. The preference scores for V and VS were 7.0 (IQR 5.0,8.0) and 9.0 (IQR 8.0,10.0) (p,<,0.0005), respectively. In conclusion, comparable clinical efficacy was found for V and VS with respect to changes in FEV1 after salbutamol. Patients also showed a strong preference for the new device. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Alcaligenes infection in cystic fibrosis,PEDIATRIC PULMONOLOGY, Issue 2 2002Kenneth Tan MBBS Abstract The aim of this study was to investigate the effect of chronic Alcaligenes species infection of the respiratory tract on the clinical status of patients with cystic fibrosis. We conducted a retrospective case-controlled study. The microbiological records of all patients attending the Leeds Regional Pediatric and Adult Cystic Fibrosis Units from 1992,1999 were examined. Chronic Alcaligenes infection was defined as a positive sputum culture on at least three occasions over a 6-month period. These patients were compared with controls matched for age, gender, respiratory function, and Pseudomonas aeruginosa infection status. Respiratory function tests, anthropometric data, Shwachman-Kulczycki score, Northern chest x-ray score, intravenous and nebulized antibiotic treatment, and corticosteroid treatment were compared from 2 years before to 2 years after Alcaligenes infection. From a clinic population of 557, 13 (2.3%) fulfilled the criteria for chronic infection. The median age at acquisition of infection was 17.2 years (range, 6.5,33.6). There was no significant difference in the changes of percentage predicted values for FEV1, FVC, FEF25,75, or Shwachman-Kulczycki and Northern chest x-ray scores, or in weight, height, and body mass index z-scores between Alcaligenes -infected cases and controls. There was also no significant difference in the use of antibiotics (intravenous and nebulized) or corticosteroids (inhaled and oral). We conclude that in our clinic, chronic infection with Alcaligenes species was uncommon. Chronically infected patients showed no excess deterioration in clinical or pulmonary function status from 2 years before to 2 years after primary acquisition. Pediatr Pulmonol. 2002; 34:101,104. © 2002 Wiley-Liss, Inc. [source] Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: A pilot study,PEDIATRIC PULMONOLOGY, Issue 2 2001B.J. Thio MD Abstract A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8,16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7,14 days. After inhalation, airway caliber (FEV1) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV1). A significant increase in FEV1 was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV1 from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV1 after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P,=,0.038 and AUC 92.0%,min vs. 205.7%,min, respectively, P,=,0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children. Pediatr Pulmonol. 2001; 32:115,121. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||