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Airway Function (airway + function)
Selected AbstractsEnvironment and prednisone interactions in the treatment of recurrent airway obstruction (heaves)EQUINE VETERINARY JOURNAL, Issue 5 2000C. A. Jackson Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function. [source] Airway function in infants treated with inhaled nitric oxide for persistent pulmonary hypertensionPEDIATRIC PULMONOLOGY, Issue 3 2008Aparna U. Hoskote MD Abstract Rationale Inhaled nitric oxide (iNO), used for treatment of persistent pulmonary hypertension of newborn (PPHN), is an oxygen free radical with potential for lung injury. Deferring ECMO with iNO in these neonates could potentially have long-term detrimental effects on lung function. We studied respiratory morbidity (defined as occurrence of respiratory infections requiring treatment, episodes of wheezing, and/or need for ongoing medications following discharge) and airway function at 1 year postnatal age in term neonates treated with iNO but not ECMO for PPHN, and compared data from similar infants recruited to the UK ECMO Trial randomized to receive ECMO or conventional management (CM). Methods Maximal expiratory flow at FRC (V'maxFRC) was measured in infants treated with iNO for PPHN (oxygenation index ,25) at birth. Results V'maxFRC was measured in 23 infants and expressed as z -scores, to adjust for sex and body size and compared to data from 71 (46 ECMO, 25 CM) infants studied at a similar age in the ECMO Trial. Respiratory morbidity was low in iNO group. V'maxFRCz -score was lower than predicted in all groups (P,<,0.001), with no significant difference between those treated with iNO [mean (SD) z -score: ,1.65 (1.2)] and those treated with ECMO [,1.59 (1.2)] or CM [,2.1(1.0)]. Within iNO, ECMO and CM groups; 26%, 37% and 56%, respectively, had V'maxFRCz -scores below normal. Conclusions Respiratory outcome at 1 year in iNO treated neonates with moderately severe PPHN is encouraging, with no apparent increase in respiratory morbidity when compared to the general population. Sub-clinical reductions in airway function are evident at 1 year, suggesting that continuing efforts to minimize lung injury in the neonatal period are warranted to maximize lung health in later life. Pediatr Pulmonol. 2008; 43:224,235. © 2008 Wiley-Liss, Inc. [source] Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats is associated with increased acetylcholine-induced airway contractilityACTA PHYSIOLOGICA, Issue 3 2009L. K. Sciesielski Abstract Aim:, We have recently reported that hypoxia stimulates transcription of the TrkB neurotrophin receptor in cultured cells via stabilization of hypoxia-inducible factor-1,. Here we investigated whether the expression of TrkB and other neurotrophin receptors is oxygen-sensitive also in vivo, and explored the functional consequences of an oxygen-regulated TrkB expression. Methods:, Rats were exposed either to 21% O2 or 8% O2 for 6 h and TrkB was analysed by reverse transcription real-time PCR, in situ mRNA hybridization, and immunological techniques. The importance of the brain-derived neurotrophic factor (BDNF)-TrkB pathway in the control of mechanical airway function was assessed on isolated tracheal segments from normoxic and hypoxic rats. Results:,TrkB transcripts were increased approx. 15-fold in the lungs of hypoxic rats, and the respiratory epithelium was identified as the site of enhanced TrkB expression in hypoxia. The TrkB ligand, BDNF, significantly increased the contractile response to acetylcholine (ACh) of isolated tracheal segments from hypoxic but not from normoxic rats. This effect of BDNF was prevented by pre-incubation of the tissue specimens with the tyrosine kinase inhibitor K252a and by mechanical removal of the TrkB containing airway epithelium. Likewise, the nitric oxide (NO) synthase inhibitor l -NAME abrogated the influence of BDNF on ACh-induced contractions of isolated tracheal segments from hypoxic rats. Conclusion:, These results demonstrate that systemic hypoxia stimulates expression of the TrkB neurotrophin receptor in the airway epithelium. Furthermore, activation of TrkB signalling by BDNF in hypoxia enhances mechanical airway contractility to ACh through a mechanism that requires NO. [source] Effects of unilateral laser-assisted ventriculocordectomy in horses with laryngeal hemiplegiaEQUINE VETERINARY JOURNAL, Issue 6 2006P. ROBINSON Summary Reasons for performing study: Recent studies have evaluated surgical techniques aimed at reducing noise and improving airway function in horses with recurrent laryngeal neuropathy (RLN). These techniques require general anaesthesia and are invasive. A minimally invasive transnasal surgical technique for treatment of RLN that may be employed in the standing, sedated horse would be advantageous. Objective: To determine whether unilateral laser-assisted ventriculocordectomy (LVC) improves upper airway function and reduces noise during inhalation in exercising horses with laryngeal hemiplegia (LH). Methods: Six Standardbred horses were used; respiratory sound and inspiratory transupper airway pressure (Pui) measured before and after induction of LH, and 60, 90 and 120 days after LVC. Inspiratory sound level (SL) and the sound intensities of formants 1, 2 and 3 (F1, F2 and F3, respectively), were measured using computer-based sound analysis programmes. In addition, upper airway endoscopy was performed at each time interval, at rest and during treadmill exercise. Results: In LH-affected horses, Pui, SL and the sound intensity of F2 and F3 were increased significantly from baseline values. At 60 days after LVC, Pui and SL had returned to baseline, and F2 and F3 values had improved partially compared to LH values. At 90 and 120 days, however, SL increased again to LH levels. Conclusions: LVC decreases LH-associated airway obstruction by 60 days after surgery, and reduces inspiratory noise but not as effectively as bilateral ventriculocordectomy. Potential relevance: LVC may be recommended as a treatment of LH, where reduction of upper airway obstruction and respiratory noise is desired and the owner wishes to avoid risks associated with a laryngotomy incision or general anaesthesia. [source] Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves)EQUINE VETERINARY JOURNAL, Issue 5 2000C. A. Jackson Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function. [source] Lack of Clinical Efficacy of a Phosphodiesterase-4 Inhibitor for Treatment of Heaves in HorsesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2006Jean-Pierre Lavoie Phosphodiesterase-4 (PDE 4) enzyme inhibitors have been shown to have anti-inflammatory properties in various animal disease processes and therefore could be effective drugs for the treatment of equine airway diseases. The purpose of this study was to evaluate the efficacy and adverse effects of the PDE 4 inhibitor L-826,141 in horses with heaves. In a blinded parallel design, horses with heaves exposed daily to moldy hay were given a placebo for 14 days and then administered either L-826,141 (n = 6; loading dose of 1 mg/kg IV followed by 0.5 mg/kg IV q48h) or dexamethasone (n = 6; 0.04 mg/kg IV q24h) from days 15 to 29 (study 1). Pulmonary function and bronchoalveolar (BAL) cytology were evaluated weekly from baseline (day 0) to 29 days. In study 2, horses were treated with L-826,141 (1.0 mg/kg IV q24h) for 8 days. Although ex vivo lipopolysaccharide-induced tumor necrosis factor (TNF)-, and LTB4 production by fresh blood were inhibited up to 90% after repeated administrations of L-826,141, this treatment failed to improve lung function. In contrast, dexamethasone (positive control) treatment resulted in significant improvement in lung mechanics and airway function in all horses. Neither drug had a significant effect on BAL total cell counts and differential cytology. Administration of the PDE 4 inhibitor L-826,141 for up to 14 days to horses with heaves was not associated with an improvement in airway function or inflammation. These findings suggest that the PDE 4 enzyme is not a key mediator of lung inflammation in heaves. [source] Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitisALLERGY, Issue 1 2008B. Sastre Background:, Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC4) and bronchoprotective (prostaglandin E2; PGE2) lipid mediators. Methods:, We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE2, and LTC4 were measured by enzyme immunoassays. Results:, The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon , (IFN-,), IL-2, vascular endothelial growth factor and transforming growth factor , were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-, and tumor necrosis factor , (TNF-,) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE2 concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 ± 612 pg/ml) when compared with asthmatic (7.54 ± 2.14 pg/ml) and healthy subjects (4 ± 1.3 pg/ml). Conclusion:, This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE2 production in the airways. [source] The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti-inflammatory therapiesALLERGY, Issue 10 2007L.-P. Boulet Allergen bronchoprovocation tests have been used for more than two decades in the investigation of respiratory allergic diseases such as asthma and rhinitis. These bronchial challenges are now well standardized and can offer key information on the therapeutic potential of new agents and on their anti-inflammatory effects on the airways. Both standard and low-dose allergen provocations are safe when performed by experienced investigators and do not lead to persistent worsening of asthma or change in airway function. The evaluation of new therapeutic agents by these methods can also provide important information on the mechanisms of development and persistence of airway diseases. [source] Airway function in infants treated with inhaled nitric oxide for persistent pulmonary hypertensionPEDIATRIC PULMONOLOGY, Issue 3 2008Aparna U. Hoskote MD Abstract Rationale Inhaled nitric oxide (iNO), used for treatment of persistent pulmonary hypertension of newborn (PPHN), is an oxygen free radical with potential for lung injury. Deferring ECMO with iNO in these neonates could potentially have long-term detrimental effects on lung function. We studied respiratory morbidity (defined as occurrence of respiratory infections requiring treatment, episodes of wheezing, and/or need for ongoing medications following discharge) and airway function at 1 year postnatal age in term neonates treated with iNO but not ECMO for PPHN, and compared data from similar infants recruited to the UK ECMO Trial randomized to receive ECMO or conventional management (CM). Methods Maximal expiratory flow at FRC (V'maxFRC) was measured in infants treated with iNO for PPHN (oxygenation index ,25) at birth. Results V'maxFRC was measured in 23 infants and expressed as z -scores, to adjust for sex and body size and compared to data from 71 (46 ECMO, 25 CM) infants studied at a similar age in the ECMO Trial. Respiratory morbidity was low in iNO group. V'maxFRCz -score was lower than predicted in all groups (P,<,0.001), with no significant difference between those treated with iNO [mean (SD) z -score: ,1.65 (1.2)] and those treated with ECMO [,1.59 (1.2)] or CM [,2.1(1.0)]. Within iNO, ECMO and CM groups; 26%, 37% and 56%, respectively, had V'maxFRCz -scores below normal. Conclusions Respiratory outcome at 1 year in iNO treated neonates with moderately severe PPHN is encouraging, with no apparent increase in respiratory morbidity when compared to the general population. Sub-clinical reductions in airway function are evident at 1 year, suggesting that continuing efforts to minimize lung injury in the neonatal period are warranted to maximize lung health in later life. Pediatr Pulmonol. 2008; 43:224,235. © 2008 Wiley-Liss, Inc. [source] Correlation of tracheal smooth muscle function with structure and protein expression during early development,PEDIATRIC PULMONOLOGY, Issue 5 2007Aaron B. Cullen MD Abstract With increased survival of premature infants, understanding the impact of development on airway function and structure is imperative. Airway smooth muscle plays a primary role in the modulation of airway function. The purpose of this study is to correlate the functional maturation of airway smooth muscle during the perinatal period with structural alterations at the cellular, ultrastructural, and molecular levels. Length-tension and dose-response analyses were performed on tracheal rings acquired from preterm and term newborn lambs. Subsequent structural analyses included isolated airway smooth muscle cell length, electron microscopy, and myosin heavy chain isoform expression measurements. Functionally the compliance, contractility, and agonist sensitivity of the tracheal rings matured during preterm to term development. Structurally, isolated cell lengths and electron microscopic ultrastructure were not significantly altered during perinatal development. However, expression of myosin heavy chain isoforms increased significantly across the age range analyzed, correlating with the maturational increase in smooth muscle contractility. In conclusion, the developmental alterations in tracheal function appear due, in part, to enhanced smooth muscle myosin heavy chain expression. Pediatr Pulmonol. 2007; 42:421,432. © 2007 Wiley-Liss, Inc. [source] Airway function measurements and the long-term follow-up of survivors of preterm birth with and without chronic lung diseasePEDIATRIC PULMONOLOGY, Issue 6 2006Indra Narang MRCPCH Abstract This seventh paper in a review series on different aspects of chronic lung disease following preterm birth focuses on the current knowledge of respiratory symptoms, airway function, airway hyperresponsiveness, and exercise capacity from childhood to adulthood. This paper further considers the long-term implications of these studies for both future research and clinical practice. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Lung function tests in neonates and infants with chronic lung disease: Lung and chest-wall mechanicsPEDIATRIC PULMONOLOGY, Issue 4 2006Monika Gappa MD This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which differentiate the tissue and airway components of respiratory mechanics, are likely to require further development before they can be of clinical significance. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Lung Function Tests in Neonates and Infants with Chronic Lung Disease: Forced Expiratory ManeuversPEDIATRIC PULMONOLOGY, Issue 3 2006Sooky Lum PhD Abstract This fourth paper in a review series on the role of lung function testing in infants and young children with acute neonatal disorders and chronic lung disease of infancy (CLDI) addresses measurements of forced expiration using rapid thoraco-abdominal compression (RTC) techniques and the forced deflation technique. Following orientation of the reader to the subject area, we focus our comments on the areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. All studies on infants and young children with CLDI using forced expiratory or deflation maneuvers demonstrated that forced flows at low lung volume remain persistently low through the first 3 years of life. Measurement of maximal flow at functional residual capacity (V,maxFRC) is the most commonly used method for assessing airway function in infants, but is highly dependent on lung volume and airway tone. Recent studies suggested that the raised volume RTC technique, which assesses lung function over an extended volume range as in older children, may be a more sensitive means of discriminating changes in airway function in infants with respiratory disease. The forced deflation technique allows investigation of pulmonary function during the early development of CLDI in intubated subjects, but its invasive nature precludes its use in the routine setting. For all techniques, there is an urgent need to establish suitable reference data and evaluate within- and between-occasion repeatability, prior to establishing the clinical usefulness of these techniques in assessing baseline airway function and/or response to interventions in subjects with CLDI. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Peripheral airway function in childhood asthma, assessed by single-breath He and SF6 washout,PEDIATRIC PULMONOLOGY, Issue 4 2003Henrik K. Ljungberg MD Abstract To assess whether the peripheral airways are involved in pediatric asthma, 10 asthmatic children (aged 8,15 years), hyperresponsive to dry-air hyperventilation challenge (DACh), performed spirometry and a vital capacity He/SF6 single-breath washout test at rest, after DACh, and after beta2 -therapy. The normalized phase III slopes (SnIII) of the expired He and SF6 concentrations served as measures of overall ventilation inhomogeneity, and the (SF6,,,He) SnIII difference served to indicate where along the peripheral airways obstruction occurs. While a greater increase in the He vs. SF6 slope indicates that obstruction has occurred in the vicinity of the acinar entrance, the reverse suggests obstruction deeper in the intraacinar airways. The mean (SD) fall in FEV1 after DACh was 35 (14)%. Both He and SF6 SnIII increased significantly (P,<,0.05) after the challenge, and were restituted after beta2 -therapy (P,<,0.05). After DACh, SnIII increased more for He than for SF6, resulting in a negative (SF6,,,He) SnIII difference (P,<,0.01), which was restituted after beta2 -therapy (P,<,0.05). Even though there was no correlation between baseline FEV1 and the magnitude of the subsequent fall in this parameter after DACh (r2,=,0.04; n.s.), a strong correlation was found between the (SF6,,,He) SnIII difference at rest and its change after DACh (r2,=,0.81; P,<,0.001). We conclude that airways close to the acinar entrance participate in the airway response to DACh in asthmatic children. The magnitude of this peripheral airway response is related to the severity of resting peripheral airway dysfunction. Pediatr Pulmonol. 2003; 36:339,347. © 2003 Wiley-Liss, Inc. [source] Roflumilast: clinical benefit in patients suffering from COPDTHE CLINICAL RESPIRATORY JOURNAL, Issue 4 2010Charlotte Suppli Ulrik Abstract Background and aims:, Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality and is characterised by persistent airway inflammation, which leads to impaired airway function, quality of life and intermittent exacerbations. In spite of recent advances in the treatment of COPD, new treatment options for COPD are clearly necessary. The oral phosphodiesterase-4 (PDE4) inhibitor roflumilast represents a new class of drugs that has shown efficacy and acceptable tolerability in preclinical and short-term clinical studies in patients with COPD. Methods and results:, The available long-term clinical studies reviewed here suggest that the clinical efficacy of roflumilast is likely because of the suppression of airway inflammation and not through bronchodilation. Furthermore, the clinical studies have shown a modest improvement in airway function, including FEV1, and a reduction in frequency and severity of COPD exacerbations, as well as a positive effect on several patient-reported outcomes. The clinical benefit of roflumilast appears to be greatest in patients with more symptomatic and severe disease who experience exacerbations. The most common adverse effects are gastrointestinal events, primarily diarrhoea, nauseas and weight loss. Conclusion:, Roflumilast is beneficial for maintenance treatment of patients with severe and symptomatic COPD and with a history of frequent acute exacerbations as an add-on to treatment with long-acting bronchodilators. It may have a role as an alternative to inhaled corticosteroids in more symptomatic COPD patients with frequent exacerbations, although direct comparisons are currently lacking. Please cite this paper as: Ulrik CS and Calverley PMA. Roflumilast: clinical benefit in patients suffering from COPD. Clin Respir J 2010; 4: 197,201. [source] Mechanical ventilatory constraints during incremental cycle exercise in human pregnancy: implications for respiratory sensationTHE JOURNAL OF PHYSIOLOGY, Issue 19 2008Dennis Jensen The aim of this study was to identify the physiological mechanisms of exertional respiratory discomfort (breathlessness) in pregnancy by comparing ventilatory (breathing pattern, airway function, operating lung volumes, oesophageal pressure (Poes)-derived indices of respiratory mechanics) and perceptual (breathlessness intensity) responses to incremental cycle exercise in 15 young, healthy women in the third trimester (TM3; between 34 and 38 weeks gestation) and again 4,5 months postpartum (PP). During pregnancy, resting inspiratory capacity (IC) increased (P < 0.01) and end-expiratory lung volume decreased (P < 0.001), with no associated change in total lung capacity (TLC) or static respiratory muscle strength. This permitted greater tidal volume (VT) expansion throughout exercise in TM3, while preserving the relationship between contractile respiratory muscle effort (tidal Poes swing expressed as a percentage of maximum inspiratory pressure (PImax)) and thoracic volume displacement (VT expressed as a percentage of vital capacity) and between breathlessness and ventilation . At the highest equivalent work rate (HEWR = 128 ± 5 W) in TM3 compared with PP: , tidal Poes/PImax and breathlessness intensity ratings increased by 10.2 l min,1 (P < 0.001), 8.8%PImax (P < 0.05) and 0.9 Borg units (P < 0.05), respectively. Pulmonary resistance was not increased at rest or during exercise at the HEWR in TM3, despite marked increases in mean tidal inspiratory and expiratory flow rates, suggesting increased bronchodilatation. Dynamic mechanical constraints on VT expansion (P < 0.05) with associated increased breathlessness intensity ratings (P < 0.05) were observed near peak exercise in TM3 compared with PP. In conclusion: (1) pregnancy-induced increases in exertional breathlessness reflected the normal awareness of increased and contractile respiratory muscle effort; (2) mechanical adaptations of the respiratory system, including recruitment of resting IC and increased bronchodilatation, accommodated the increased VT while preserving effort,displacement and breathlessness, relationships; and (3) dynamic mechanical ventilatory constraints contributed to respiratory discomfort near the limits of tolerance in late gestation. [source] The definition and diagnosis of AsthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2009F. E. Hargreave Summary The diagnosis of asthma depends on what we mean by the word. Its definition continues to be controversial because there is no single genetic or environmental cause. Addressed from a descriptive point of view, the disease components include airway inflammation, symptoms, variable airflow limitation and chronic airflow limitation. The essentialist definition conveys the message that asthma is a separate disease entity, fails to identify a primary defining characteristic which separates it from other diseases and is long winded. These disadvantages are overcome by the nominalist definition of asthma in which the word ,asthma'refers to an abnormality of airway function, specifically to wide variations in airflow limitation over short periods of time. In patients with asthma the other components of airway disease need to be considered. These have separate nominalist definitions and especially include different types of bronchitis for airway inflammation and chronic obstructive pulmonary disease for chronic airflow limitation. What is present will vary between and within patients. The accurate diagnosis of asthma and of other components of disease all require objective measurements. Currently spirometry and airway responsiveness should be available to the general practitioner, who sees milder disease, and additional quantitative sputum cell counts in specialist practice, where moderate to severe disease is more prevalent. Such measurements characterize the patient, identify heterogeneity and allow treatment to be personalized. [source] Role of STAT6 and SMAD2 in a model of chronic allergen exposure: a mouse strain comparison studyCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009J. A. Hirota Summary Background Asthma is a disease characterized by variable and reversible airway obstruction and is associated with airway inflammation, airway remodelling (including goblet cell hyperplasia, increased collagen deposition and increased smooth muscle mass) and increased airway responsiveness. It is believed that airway inflammation plays a critical role in the development of airway remodelling, with IL-13 and TGF-,1 pathways being strongly associated with the disease progression. Mouse models of asthma are capable of recapitulating some components of asthma and have been used to look at both IL-13 and TGF-,1 pathways, which use STAT6 and SMAD2 signalling molecules, respectively. Objectives Using brief and chronic models of allergen exposure, we utilized BALB/c and C57Bl/6 to explore the hypothesis that observed differences in responses to allergen between these mouse strains will involve fundamental differences in IL-13 and TGF-,1 responses. Methods The following outcome measurements were performed: airway physiology, bronchoalveolar lavage cell counts/cytokine analysis, histology, immunoblots and gene expression assays. Results We demonstrate in BALB/c mice an IL-13-dependent phosphorylation of STAT6, nuclear localized in inflammatory cells, which is associated with indices of airway remodelling and development of airway dysfunction. In BALB/c mice, phosphorylation of SMAD2 is delayed relative to STAT6 activation and also involves an IL-13-dependent mechanism. In contrast, despite an allergen-induced increase in IL-4, IL-13 and eosinophils, C57Bl/6 demonstrates a reduced and distinct pattern of phosphorylated STAT6, no SMAD2 phosphorylation changes and fail to develop indices of remodelling or changes in airway function. Conclusion The activation of signalling pathways and nuclear translocation of signalling molecules downstream of IL-13 and TGF-,1 further support the central role of these molecules in the pathology and dysfunction in animal models of asthma. Activation of signalling pathways downstream from IL-13 and TGF-,1 may be more relevant in disease progression than elevations in airway inflammation alone. [source] Persistence of rhinovirus RNA after asthma exacerbation in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2005S. Kling Summary Background Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. Objective We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). Methods Patients aged 4,12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. Results Fifty children with acute asthma (mean age±SD, 7.4±2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4±16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. Conclusion RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections. [source] Allergic rhinitis: more than just a stuffy noseACTA PAEDIATRICA, Issue 7 2009Magnus P Borres Abstract Allergic rhinitis is more than just sneezing and an itchy nose. Complications of this disease are numerous and can have a significant impact, both mentally and physically. That is why it is important not only to detect, investigate and treat allergic rhinitis but also to actively identify potential complications. Mental functions such as learning, sleep and activity levels can deteriorate, and the eustachian tubes, sinuses and airway functions can be affected. Otitis, sinusitis and asthma are overrepresented among individuals who suffer from allergic rhinitis. This article highlights how allergic rhinitis can affect cognitive functions, and what consequences this can have on school performance, work and quality of life. Conclusion:, Health professionals and school personnel need to increase their awareness of the ramifications of this disease and actively work to prevent deterioration in both academic achievement and workplace productivity. [source] Nitric oxide evaluation in upper and lower respiratory tracts in nasal polyposisCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2008C. Delclaux Summary Background A decrease in nasal nitric oxide (NO) and an increase in exhaled NO have been demonstrated in patients with nasal polyposis (NP). Objectives The aims were to evaluate the flux of NO from the three compartments of the respiratory tract, namely, upper nasal, lower conducting and distal airways, and to search for relationships between NO parameters and indexes of upper and lower disease activity (bronchial reactivity and obstruction). The effect of medical treatment of polyposis was also evaluated. Methods Seventy patients with polyposis were recruited. At baseline, pulmonary function tests (spirometry, plethysmography, bronchomotor response to deep inspiration using forced oscillation measurement of resistance of respiratory system, methacholine challenge, multiple flow rates of exhaled NO and nasal NO measurements) were performed together with an assessment of polyposis [clinical, endoscopic and computed tomography (CT) scores]. Results Statistical relationships were demonstrated between nasal NO flux and severity scores (clinical: ,=,0.31, P=0.015; endoscopic: ,=,0.57, P<0.0001; CT: ,=,0.46, P=0.0005), and between alveolar NO concentration and distal airflow limitation (FEF25,75, ,=,0.32, P=0.011). Thirty-six patients were assessed after 11 [7,13] (median [interquartile]) months of medical treatment, demonstrating an improvement in clinical and endoscopic scores, an increase in nasal NO flux, a decrease in NO flux from conducting airways, an improvement in the mild airflow limitation (forced expiratory volume in 1 s, FEF25,75, even in non-asthmatic patients) and a decrease in the bronchoconstrictor effect of deep inspiration. Conclusions The medical treatment of NP improves both airway reactivity and obstruction, whatever the presence of asthma, suggesting a functional link between upper and lower airway functions. [source] | |||||||||||||||||||||||||