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Airway Disease (airway + disease)
Kinds of Airway Disease Selected AbstractsAirway gene therapy and cystic fibrosisJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2005DW Parsons Abstract:, Airway disease in cystic fibrosis (CF) is the major cause of death and is presently inadequately treatable, but genetic therapies offer the hope that such life-long disease will be curable, or at least satisfactorily treated. Normal pathogen defences that have evolved on airway surfaces also prevent the various gene vectors now available from producing effective gene transfer. Nevertheless, findings from basic research and human clinical trials are revealing how these barriers might be overcome or circumvented, with benefits to therapeutic efficacy and patient safety. Though progress is slower than expected or desired, the therapeutic rewards will be great when safe and effective gene therapy for CF airway disease becomes a clinical reality. [source] Editorial: Rhinoconjunctivitis and wheeze in preschool children: a different relationship than in adults (United or Coexistent Airways Disease)?ALLERGY, Issue 4 2007G. Viegi First page of article [source] Inflammatory airway disease: defining the syndrome.EQUINE VETERINARY EDUCATION, Issue 2 2003Conclusions of the Havemeyer Workshop No abstract is available for this article. [source] A region on equine chromosome 13 is linked to recurrent airway obstruction in horsesEQUINE VETERINARY JOURNAL, Issue 3 2007U. JOST Summary Reasons for study: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor , chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. Methods: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1,4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2,4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2,4), age ,7 years. Results: For both sires haplotypes could be established in the order AHT133-LEX047-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2,4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family. Conclusions: This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease. Potential relevance: Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease. [source] Airway inflammation in Michigan pleasure horses: prevalence and risk factorsEQUINE VETERINARY JOURNAL, Issue 4 2006N. E. Robinson Summary Reasons for performing study: Although subclinical airway inflammation is thought to be common in horses, there is little information on its prevalence and none on risk factors. Objective: To determine the prevalence and risk factors for an increased number of inflammatory cells and for mucus accumulation in the trachea of pleasure horses. Methods: Horses (n = 266) in stables (n = 21) in Michigan were examined endoscopically, once in winter and once in summer 2004. Visible tracheal mucoid secretions were graded 0,5 and inflammatory cell numbers counted in a tracheal lavage sample. Information collected about each horse included age, gender, presence of cough, percent time indoors and source of roughage. The repeated measures were analysed by generalised estimating equations and linear mixed models. Results: Horses eating hay, especially from round bales, had the most neutrophils, whereas horses feeding from pasture had the fewest. Being female and being outdoors in winter were associated with increased numbers of inflammatory cells. Older horses had fewer macrophages than young horses. More than 70% of horses had >20% neutrophils in tracheal lavage. Twenty percent of horses had a mucus accumulation score >1; 17% had both a mucus score >1 and >20% neutrophils. The significant risk factors for mucus accumulation >1 were age >15 years, feeding on hay as compared to pasture, and being outdoors for more than 80% time in winter. Even though mucus accumulation score >1 was a risk factor for cough, only half of such horses coughed. Cough and mucus accumulation were associated with increased number of neutrophils. Conclusions: In comparison to pasture feeding, hay feeding, particularly from round bales, was associated with an increased number of neutrophils in the airway. Being outdoors in winter was associated with increased numbers of inflammatory cells and with mucus accumulation. Because 70% of horses have >20% neutrophils, this value should not be used as the sole indicator of airway inflammation. Potential relevance: The study reinforces the importance of hay feeding and older age as risk factors for inflammatory airway disease. Horses that do not have ,heaves' may be best kept indoors when winters are cold. [source] Inflammatory airway disease, nasal discharge and respiratory infections in young British racehorsesEQUINE VETERINARY JOURNAL, Issue 3 2005J. L. N. WOOD Summary Reasons for performing study: Respiratory disease is important in young Thoroughbred racehorses, but the variation in the rates of occurrence between different ages and training groups has not been characterised. Objectives: To determine the rates of respiratory disease, particularly inflammatory airway disease (IAD), as well as evidence of infection, and their variation between age and group. Methods: Horses were examined monthly in 7 British flat training yards over a 3 year period. IAD was defined as increased mucus in the trachea with increased proportions of neutrophils in tracheal wash samples. Frequencies of disease outcomes were estimated from the data. Results: The prevalence of IAD was 13.8% and the incidence was 8.9 cases/100 horses/month. Rates varied with training and age groups, decreasing in older animals. The prevalence of nasal discharge (ND) was 4.1%. Rates of bacterial isolation were more common than viral infections. The incidence and prevalence of several bacterial species decreased with age. Conclusions: IAD and ND were common in young racehorses, varying significantly between training groups and decreasing with age, consistent with infection playing a role in aetiology. Potential relevance: The high prevalence of IAD in 2-year-old horses in Britain suggests that routine endoscopic examination may be helpful in providing early diagnosis and appropriate therapy. The transmission of bacteria and viruses within and between groups of young animals and the role of infection, stable environment and factors inherent to each horse, including their genetic make-up, in the multifactorial aetiology of the disease all merit further study. [source] IL-5-induced airway eosinophilia , the key to asthma?IMMUNOLOGICAL REVIEWS, Issue 1 2001Eckard Hamelmann Summary: Bronchial asthma is a chronic inflammatory airway disease defined by reversible airway obstruction and non-specific airway hyper-responsiveness (AHR). Although profound insights have been made into the pathophysiology of asthma, the exact mechanisms inducing and regulating the disease are still not fully understood. Yet, it is generally accepted that the pathological changes in asthma are induced by a chronic inflammatory process which is characterized by infiltration of the bronchial mucosa with lymphocytes and eosinophils, increased mucus production and submucosal edema. There is increasing evidence that an imbalance in the T-helper (Th) cell response of genetically predisposed individuals to common environmental antigens plays a pivotal role in the pathogenesis of allergic bronchial asthma and other atopic disorders. Following allergic sensitization, T cells from atopic patients tend to produce elevated levels of Th2-type cytokines, especially interleukin (IL)-4, IL-13, IL-5 and IL-6, which induce and regulate IgE production and eosinophil airway infiltration. In this review, the role of Th2-type cytokines, IgE and airway eosinophils in the induction of airway inflammation and AHR is discussed, and animal studies of asthma and AHR, mainly in rodents will be considered. A better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease which is increasing worldwide. I thank the many colleagues in the laboratory of Dr. E. W. Gelfand, National Jewish Research Center, Denver CO, USA, for continuous support and encouragement. E.H. is a fellow of the Deutsche Forschungsgemeinschaft (DFG Ha 2162/1-1 and 2-1). [source] TAP1 gene AccI polymorphism is associated with atopic bronchial asthmaJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2003Liang-Wen Hang Abstract Asthma is a hyperresponsive airway disease that may involve inflammation responses. A transporter associated with the antigen processing 1 gene (TAP1) is involved in antigen processing, and is therefore considered to play a role in the pathogenesis of bronchial asthma. The aim of this study was to test whether the polymorphisms of the TAP1 gene are a genetic marker for susceptibility to bronchial asthma. A normal control group comprised of 43 healthy people, and 116 patients with allergic asthma were examined in this study. The polymorphism was detected by polymerase chain reaction (PCR)-based restriction analysis. Associations between atopic bronchial asthma and TAP1 polymorphisms were evaluated. The results revealed no significant differences between normal individuals and asthmatics in regard to the TAP1 gene DpnII polymorphism (P=0.752). However, there was a significant difference between the control and asthma groups as regards the TAP1 gene AccI polymorphism (P=0.020). The odds ratio (OR) of GG homozygotes of the TAP1 AccI polymorphism was 229.8 compared with the AA homozygote group. The results show that the AccI polymorphism may be an indicator for atopic bronchial asthma. J. Clin. Lab. Anal. 17:57,60, 2003. © 2003 Wiley-Liss, Inc. [source] An unusual dematiaceous fungal infection of the skin caused by Fonsecaea pedrosoi: a case report and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2003Sate H. Hamza Background:, A case of an unusual dematiaceous fungal infection of the skin in a 43-year-old man with diabetes mellitus treated with steroids for reactive airway disease is presented. He developed chromoblastomycosis in the left wrist and was treated with antifungals and multiple surgical excisions. Results:, Histologic examination of the excised tissue revealed widespread suppurative granulomatous inflammation in the dermis and subcutaneous tissue. Thick-walled internally septated brown fungal cells were found both inside multinucleated giant cells and extracellularly. Non-to-lightly pigmented septate hyphal elements, however, were also identified with special stains and, in retrospect, on one of the routinely stained sections. In culture, the organism was reported to initially grow as soft white colonies that soon turned to black and velvety. Conclusions:, The two unusual features of this case include the controversial report of the organism's initial growth in culture as soft white colonies and the presence of hyphal elements in addition to the sclerotic bodies in the dermis and subcutaneous tissue. This has not been reported before in human cases of dermal infection by Fonsecaea pedrosoi. [source] Airway gene therapy and cystic fibrosisJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2005DW Parsons Abstract:, Airway disease in cystic fibrosis (CF) is the major cause of death and is presently inadequately treatable, but genetic therapies offer the hope that such life-long disease will be curable, or at least satisfactorily treated. Normal pathogen defences that have evolved on airway surfaces also prevent the various gene vectors now available from producing effective gene transfer. Nevertheless, findings from basic research and human clinical trials are revealing how these barriers might be overcome or circumvented, with benefits to therapeutic efficacy and patient safety. Though progress is slower than expected or desired, the therapeutic rewards will be great when safe and effective gene therapy for CF airway disease becomes a clinical reality. [source] Alcohol Functionally Upregulates Toll-Like Receptor 2 in Airway Epithelial CellsALCOHOLISM, Issue 3 2009Kristina L. Bailey Background:, Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria. Methods:, Airway epithelial cells [primary bronchial epithelial cells (NHBE) and 16HBE 14o-] were exposed to 0 to 100 mM alcohol for 0 to 24 hours. Real time PCR was used to quantify TLR2 mRNA. Protein levels of TLR2 were determined using Western blots and fluorescence activated cell sorting (FACS) on cells exposed to 0, 50, and 100 mM alcohol. Finally, cells were "primed" with alcohol, stimulated with a TLR2 agonist (peptidoglycan), and interleukin 8 (IL-8) release was measured. Results:, Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells. Conclusions:, Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics. [source] Ethanol Treatment Reduces Bovine Bronchial Epithelial Cell MigrationALCOHOLISM, Issue 4 2005John R. Spurzem Background: Chronic ethanol abuse is associated with significant lung disease. Excessive alcohol intake increases risk for a variety of respiratory tract diseases, including pneumonia and bronchitis. Damage to airway epithelium is critical to the pathogenesis of airway disorders such as chronic bronchitis and chronic obstructive pulmonary disease. The ability of the airway epithelium to repair itself is an important step in the resolution of airway inflammation and disease. Ethanol exposure is known to modulate signaling systems in bronchial epithelial cells. We hypothesize that chronic ethanol exposure down-regulates the adenosine 3,:5,-cyclic monophosphate signaling cascade in airway epithelial cells, resulting in decreased epithelial cell migration and repair. Methods: We evaluated the effect of ethanol on primary cultures of bovine bronchial epithelial cells in in vitro models of cell migration, wound repair, cell attachment, and cell spreading. Results: Ethanol causes a concentration-dependent effect on closure of mechanical wounds in cell monolayers. Pretreatment of cells with 100 mm ethanol for 24 hr further slows wound closure. Ethanol pretreatment also reduced the protein kinase A response to wounding and made the cells unresponsive to stimuli of protein kinase A that accelerate wound closure. The effects of ethanol on cell migration in wound closure were confirmed in another assay of migration, the Boyden chamber cell migration assay. Prolonged treatment with ethanol also reduced other cell functions, such as spreading and attachment, which are necessary for epithelial repair. Conclusions: Ethanol modulates signaling systems that are relevant to airway injury and repair, suggesting that chronic, heavy ethanol ingestion has a detrimental impact on airway repair. Impaired response to inflammation and injury may contribute to chronic airway disease. [source] Reproducibility of Airway Responsiveness in Horses Using Flowmetric Plethysmography and Histamine BronchoprovocationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009R. D. Nolen-Walston Background: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. Hypothesis: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. Animals: Twenty-nine healthy adult horses from 2 university herds. Methods: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase ,flow by 35%) as a measure of airway responsiveness. Each horse was re-tested 1,4 weeks after BL (short-term [ST]) and again at 3,12 months after BL (long-term [LT]). Results: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26,0.79, range 0,2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45,1.17, range 0.14,3.10). There was no significant difference in reproducibility between the 2 groups of subjects. Conclusions and Clinical Importance: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low. [source] Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?ALLERGY, Issue 10 2010J. Bogefors To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Mĺnsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; 65: 1222,1226. Abstract Background:, Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study:, To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods:, The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results:, Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion:, Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease. [source] Single-scan acquisition of registered hyperpolarized 3He ventilation and ADC images using a hybrid 2D gradient-echo sequenceMAGNETIC RESONANCE IN MEDICINE, Issue 6 2007Jim M. Wild Abstract The pulse sequences for hyperpolarized 3He lung MRI that have made the most clinical impact to date are 1) those that supply regional apparent diffusion coefficient (ADC) measurements, which provide insight into early emphysematous destruction of the alveoli in the lungs, and 2) high-resolution ventilation images that provide regional indicators of airway obstruction in obstructive airway disease, such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). In this work a hybrid 2D ADC-ventilation sequence was used with low flip angles to acquire both sets of data in the same breath-hold. The performance of the sequence was investigated in vivo in a healthy subject and a subject with mild emphysema, and compared with conventional 2D gradient-echo (GRE) 3He ventilation and ADC imaging sequences. Acquisition of the ADC and ventilation images in one breath-hold provides ventilation images with equal or better SNR (,20) and the same spatial resolution (3.75 mm × 3.3 mm in plane) with simultaneous accurate, high-resolution ADC images. The hybrid sequence offers a means of conserving gas by using two-thirds of the 3He gas needed for separate ADC and ventilation exams, and saves the subject from having to perform an extra breath-hold. The data are inherently spatially and temporally registered, allowing quantitative cross-correlation between high-spatial-resolution ADC and ventilation data. Magn Reson Med 57:1185,1189, 2007. © 2007 Wiley-Liss, Inc. [source] CRTH2 mediates the activation of human Th2 cells in response to PGD2 released from IgE/anti-IgE treated nasal polyp tissueALLERGY, Issue 3 2010C. A. Pérez-Novo To cite this article: Pérez- Novo CA, Holtappels G, Vinall SL, Xue L, Zhang N, Bachert C, Pettipher R. CRTH2 mediates the activation of human Th2 cells in response to PGD2 released from IgE/anti-IgE treated nasal polyp tissue. Allergy 2010; 65: 304,310. Abstract Background:, Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D2 (PGD2) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue. Methods:, Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD2. Supernatants were assayed for PGD2 content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP1), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD2 synthase were analysed by real time PCR. Results:, Increased release of PGD2 by nasal polyp tissue treated with IgE/anti-IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD2 synthase, DP1 and CRTH2 receptors increased after stimulation with IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD2 produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. Conclusion:, These data suggest that in immunologically activated nasal polyp tissue, PGD2 produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism. [source] The small airways and distal lung compartment in asthma and COPD: a time for reappraisalALLERGY, Issue 2 2010M. Contoli To cite this article: Contoli M, Bousquet J, Fabbri LM, Magnussen H, Rabe KF, Siafakas NM, Hamid Q, Kraft M. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy 2010; 65: 141,151. Abstract The involvement of small airways in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been debated for a long time. However, a proper definition of small airway disease is still lacking, and neither a widely accepted biomarker nor a functional parameter to assess small airway abnormalities and to explore the effect of tested compounds on small airways is available. Aiming towards increased knowledge and consensus on this topic, this perspective paper intends to (i) strengthen awareness among the scientific community on the role of small airways in asthma and COPD; (ii) examine the pros and cons of some biological, functional and imaging parameters in the assessment of small airway abnormalities; and (iii) discuss the evidence for distal airway pharmacological targeting in asthma and COPD. [source] Serum eosinophil granule proteins predict asthma risk in allergic rhinitisALLERGY, Issue 5 2009L. P. Nielsen Background:, Allergic rhinitis is a common disease, in which some patients will deteriorate or develop asthma. It is important to characterize these patients, thereby offering the possibility for prevention. This study evaluated eosinophil parameters as potential indicators of deteriorating allergic airway disease. Methods:, The subjects of the study included all patients who suffered seasonal allergic rhinitis and had participated in a study 6 years earlier, in which blood eosinophils, serum eosinophil cationic protein (ECP) serum eosinophil peroxidase (EPO), nasal lavage ECP and nasal lavage EPO levels were measured. Patients in the present study were interviewed on occurrence of rhinitis symptoms during the last season, rhinitis outside season, asthma-like symptoms and asthma diagnosis, and were skin-prick tested for common aeroallergens. Eosinophil parameters from the study 6 years earlier were then tested for the ability to predict occurrence of new allergies, worsening of rhinitis and occurrence of asthma. Results:, Forty-four patients participated in the study. In four patients seasonal rhinitis symptoms had deteriorated, 10 had experienced perennial rhinitis symptoms, 14 reported asthma-like symptoms and seven had been diagnosed with asthma. Thirteen had developed additional sensitization. Patients developing asthma-like symptoms compared with patients with no such symptoms had significantly higher serum ECP (16.7 ,g/l vs 8.2 ,g/l; P , 0.01) and serum EPO (17.9 ,g/l vs 8.8 ,g/l; P , 0.05). Results were similar, considering patients diagnosed with asthma. Blood eosinophils and nasal lavage parameters were not related to development of asthma and asthma-like symptoms. No eosinophil parameter was related to deterioration of rhinitis or additional sensitization. Conclusion:, Serum ECP and EPO in patients with seasonal rhinitis demonstrated a high predictive ability for later development of asthma. [source] Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis , a GA2LEN studyALLERGY, Issue 4 2009C. Bachert Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets. [source] Cigarette smoke facilitates allergen penetration across respiratory epitheliumALLERGY, Issue 3 2009K. Gangl Background:, The association between cigarette smoke exposure and allergic airway disease is a matter for debate. We sought to investigate in an in vitro system whether active smoking reduces the integrity and barrier function of the respiratory epithelium and thus facilitates allergen penetration. Methods:, We cultured the human bronchial epithelial cell line 16HBE14o, in a transwell culture system as a surrogate for the intact respiratory epithelium. The cell monolayer was exposed to standardized cigarette smoke extract (CSE). The extent and effects of trans-epithelial allergen penetration were measured using 125I-labelled purified major respiratory allergens (rBet v 1, rPhl p 5 and rDer p 2) and histamine release experiments. Results:, Exposure of cells to concentrations of CSE similar to those found in smokers induced the development of para-cellular gaps and a decrease in trans-epithelial resistance. CSE exposure induced a more than threefold increase in allergen penetration. Increased subepithelial allergen concentrations provoked a substantial augmentation of histamine release from sensitized basophils. Conclusions:, Our results indicate that cigarette smoke is a potent factor capable of reducing the barrier function of the respiratory epithelium for allergens and may contribute to increased allergic inflammation, exacerbation of allergic disease and boosting of IgE memory. [source] Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challengeALLERGY, Issue 10 2008A. Inal Background:, There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. Methods:, Four study groups were formed: rhinitis only, without bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. Results:, The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T24, the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T24. Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T24. Conclusions:, This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms. [source] The effects of allergens in outdoor air on both atopic and nonatopic subjects with airway diseaseALLERGY, Issue 5 2008P. G. J. Burney Background:, Reports on air pollution and asthma exacerbations have been inconsistent, although effects of airborne allergen can be spectacular. With no generalized test for allergen in air, it is not known how far allergen is responsible for nonepidemic exacerbations of the disease. Methods:, Two hundred and ninety-seven patients using bronchodilators aged 18,64 years attending a London practice provided serum samples and were asked to report any acute respiratory events over the coming months. Small particles with a mean aerodynamic diameter <10 ,m (PM10) were collected using a high volume sampler on the roof of the practice. The ability of airborne particles to bind IgE from the patients was compared for particles sampled on the weekend before their reported exacerbation with particles sampled on the weekend 2 weeks before or after. Results:, Exacerbations were associated with a 25% increase in IgE binding to particles collected on the previous weekend compared with the control weekends (95% confidence interval: 10,43%; P = 0.00089). This increase was not higher in patients with positive skin tests or in those sensitized to grass or tree pollens. Conclusions:, Airborne allergen is an important cause of exacerbations even in those with ,intrinsic' asthma. It is important to identify the allergens responsible, as some of these may be controllable. Interpretation of associations of asthma exacerbations with other air pollutants is difficult in the light of these findings. [source] Allergic rhinitis and its impact on otorhinolaryngologyALLERGY, Issue 6 2006P. W. Hellings Allergic rhinitis (AR) is a disease with growing impact on everyday medical practice, as its prevalence has steadily increased during the last decades. Immunoglobulin-E (IgE)-mediated airway inflammation may manifest itself as AR, asthma or both. Allergic inflammation in upper and lower airways is now considered as one airway disease, with manifestation of symptoms in upper, lower or global airway. This insight into allergic inflammation of the whole respiratory tract has consequences for the diagnostic and therapeutic approach of affected patients, as highlighted in the ARIA document. In contrast to asthma, the link between AR and associated conditions in the upper airways like rhinosinusitis, nasal polyps, recurrent viral infections, adenoid hypertrophy, tubal dysfunction, otitis media with effusion and laryngitis remains less explored. It is however of utmost importance to consider the aetiological role of IgE-mediated inflammation of the nasal mucosa in several diseases of the upper respiratory tract, as they represent a large body of patient population seen by the general practitioner as well as the paediatrician, allergologist and otorhinolaryngologist. We here aim at reviewing the current literature on the relationship between AR and conditions in upper airways frequently encountered in everyday clinical practice, and highlight the need for further studies exploring the role of allergic inflammation in the development of these diseases. [source] The bronchial circulation,worth a closer look: A review of the relationship between the bronchial vasculature and airway inflammationPEDIATRIC PULMONOLOGY, Issue 1 2010Angela McCullagh MBBS Abstract Until recently, the bronchial circulation has been relatively ignored in the research and clinical arenas, perhaps because of its small volume and seeming dispensability relative to the pulmonary circulation. Although the bronchial circulation only receives around 1% of the cardiac output in health, it serves functions that are critical to maintaining airway and lung function. The bronchial circulation also plays an important role in many lung and airway diseases; through its ability to increase in size, the bronchial circulation is able to provide lung parenchymal perfusion when the pulmonary circulation is compromised, and more recently the role of the bronchial circulation in the pathogenesis of inflammatory airway disease has been explored. Due to the anatomic variability and small volume of the bronchial circulation, much of the research to date has necessitated the use of animal models and invasive procedures. More recently, non-invasive techniques for measuring bronchial blood flow in the mucosal microvascular network have been developed and offer a new avenue for the study of this circulation in humans. In conjunction with molecular research, measurement of airway blood flow (Qaw) may help elucidate the role of the bronchial circulation in inflammatory airway disease and become a useful tool for monitoring therapy. Pediatr Pulmonol. 2010; 45:1,13. © 2009 Wiley-Liss, Inc. [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] Physiologic, bronchoscopic, and bronchoalveolar lavage fluid findings in young children with recurrent wheeze and cough,PEDIATRIC PULMONOLOGY, Issue 8 2006John Saito MD Abstract Assessing airway disease in young children with wheeze and/or cough is challenging. We conducted a prospective, descriptive study of lung function in children <3 years old with recurrent wheeze and/or cough, who had failed empiric antiasthma and/or antireflux therapy and subsequently underwent flexible bronchoscopy. Our goals were to describe radiographic, anatomical, microbiological, and physiological findings in these children, and generate hypotheses about their respiratory physiology. Plethysmography and raised-volume rapid thoracoabdominal compression (RVRTC) techniques were performed prior to bronchoscopy. Mean Z-scores (n,=,19) were ,1.34 for forced expiratory volume at 0.5 sec (FEV0.5), ,2.28 for forced expiratory flows at 75% of forced vital capacity (FVC) (FEF75), ,2.25 for forced expiratory flows between 25,75% of FVC (FEF25,75), 2.53 for functional residual capacity (FRC), and 2.23 for residual volume divided by total lung capacity (RV/TLC). Younger, shorter children had markedly depressed FEF75 and FEF25,75 Z-scores (P,=,0.002 and P,=,<0.001, respectively). As expected, lower airway anatomical abnormalities, infection, and inflammation were common. Elevated FRC was associated with anatomical lower airway abnormalities (P,=,0.03). FVC was higher in subjects with neutrophilic inflammation (P,=,0.03). There was no association between other physiologic variables and bronchoscopic/bronchoalveolar lavage fluid findings. Half of those with elevated RV/TLC ratios (Z-score >2) had no evidence of chest radiograph hyperinflation. We conclude that in this population, plethysmography and RVRTC techniques are useful in identifying severity of hyperinflation and airflow obstruction, and we hypothesize that younger children may have relatively small airways caliber, significantly limiting airflow, and thus impairing secretion clearance and predisposing to lower airway infection. Pediatr Pulmonol. 2006; 41: 709,719. © 2006 Wiley-Liss, Inc. [source] Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infectionPEDIATRIC PULMONOLOGY, Issue 1 2005Sitthivuddhi Futrakul MD Abstract The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased ,20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased ,20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P,<,0.05) by chi-square test or Fisher's exact test, or Student's t -test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68,25), maternal history of asthma (OR, 3.45; 95% CI, 1.34,9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26,8.12), and passive smoking (OR, 3; 95% CI, 1.15,7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1,5 years of age (P,,,0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not statistically significant. In conclusion, a history of reactive airway disease, maternal history, breastfeeding less than 3 months, and passive smoking were significant risk factors for BHR. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Circulating adhesion molecules in sera of asthmatic childrenPEDIATRIC PULMONOLOGY, Issue 4 2002Ren-Bin Tang MD Abstract Infiltration of cells into the lung in asthma is regulated by several expressions of cell adhesion molecules (CAMs) on cells present in the airways, and may play a role in the pathogenesis of bronchial asthma. We sought to evaluate the role of serum concentrations of the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in the control of disease activity in acute asthma. Circulating levels of sICAM-1, sVCAM-1, and sE-selectin in sera from 15 normal control subjects and from 20 allergic asthmatic children with acute exacerbations who had returned to stable condition were determined by using commercially available enzyme-linked immunosorbent assay kits. The mean concentration of serum sICAM-1 levels was significantly higher during an acute exacerbation of asthmatic children than in those with stable asthma (19.41,±,10.65 ng/mL vs. 13.46,±,5.44 ng/mL; P,<,0.001) or in control subjects (9.83,±,2.02 ng/mL; P,<,0.001). For sVCAM-1 and sE-selectin, the mean serum concentration of sVCAM-1 was slightly higher in children during an acute exacerbation asthma than when stable. However, the differences did not reach statistical significance. The mean serum concentrations of sVCAM-1 and sE-selectin in acute asthma or stable asthma were significiantly higher than in control subjects. This study provides further evidence that serum concentrations of sICAM-1, sVCAM-1, and sE-selectin are increased in acute asthma. These findings further confirm that leukocyte endothelial adhesion plays a role in inflammmatory airway disease. Pediatr Pulmonol. 2002; 33:249,254. © 2002 Wiley-Liss, Inc. [source] Use and adherence to beta-blockers for secondary prevention of myocardial infarction: who is not getting the treatment?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2004Li Wei Abstract Purpose To characterise those who receive beta-blocker therapy after MI and to estimate the effect of adherence to beta-blocker use on subsequent mortality and recurrent MI. Methods A community-based observational cohort study was done using a record linkage database. Patients were those discharged from hospitals after their first MI between January 1994 and December 1995 and who also survived for at least 1 year. The outcome was all cause mortality and recurrent MI. Results were adjusted for age, sex, social deprivation, airways disease, peripheral vascular disease (PVD), diabetes mellitus, cardiovascular drug use, steroid use and hospitalisation for cardiovascular disease using a logistic regression model and a Cox regression model. Results A total of 865 patients were included in this study. 386 (44.6%) were on beta-blocker treatment during the year after MI. Beta-blocker use was lower amongst high-risk patients (older patients, patients with obstructive airway disease, PVD and those with a previous hospitalisation for heart failure). Mortality was lower in patients treated with beta-blockers compared with those untreated. Good adherence (,80%) was associated with a lower adjusted relative risk of mortality compared with unexposed patients (0.49, 95%CI 0.30,0.80, p,<,0.01). Within the high-risk subgroup of patients, the adjusted relative risk of mortality with good adherence was 0.40 (0.17,0.93, p,=,0.03). Conclusions Beta-blocker use was lower in older patients, patients with airways disease, PVD and heart failure, but these patients appeared to have the greatest benefit from beta-blockers. Good adherence to beta-blocker treatment after MI was associated with a lower risk of mortality. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effect of the proteolytic enzyme serrapeptase in patients with chronic airway diseaseRESPIROLOGY, Issue 3 2003Seiichi NAKAMURA Objectives: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. Methods: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. Results: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 ± 1.8 to 24.4 ± 2.5 (P = 0.0103). Conclusions: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases. [source] | ||||||||||||||||||||||||||||||||||||||||