Biomedical subjects

E H Walters

Publications and source records attributed to E H Walters.

At least 73 records · Page 4Linked to original sources

PubMed2001

Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma.

BACKGROUND: We have previously shown that airway macrophages (AMs) from atopic nonasthmatic subjects, but not atopic asthmatic subjects, inhibit T-cell IL-5 production during an allergen-dependent interaction. However, the mechanisms responsible for the IL-5-modulating effect of the AMs are less clear. OBJECTIVES: The aim of the present study was to define the roles of B7 and CD40 costimulatory signals delivered by AMs in regulating T-cell IL-5 responses in an allergen-stimulated coculture system. METHODS: Peripheral blood CD4(+) T cells and AMs were cocultured under different conditions. RESULTS: Compared with those from well-matched atopic nonasthmatic subjects, AMs from atopic asthmatic subjects demonstrated a significantly lower expression of B7-1 and CD40, but not B7-2 and HLA-DR, after either fresh isolation or coculture with allergen-reactive CD4(+) T cells. Lower IL-12 production by the AMs from asthmatic subjects was also observed under the same conditions. Allergen-related T-cell IFN-gamma and IL-5 production was inhibited by the addition of either neutralizing B7-1 or B7-2 antibody to the cocultures in both atopic groups. In contrast, IL-5 production was significantly increased by the addition of blocking CD40 antibody, whereas IL-12 production by the AMs was inhibited. Anti-IL-12 mAb enhanced IL-5 production in the cocultures from atopic nonasthmatic subjects, whereas a dose-dependent suppressive effect of recombinant human IL-12 on IL-5 production was seen in atopic asthmatic subjects. CONCLUSION: In this coculture model system, lower IL-12 production by AMs and higher IL-5 production by CD4(+) T cells in atopic asthmatic subjects compared with that found in atopic nonasthmatic subjects are related to the lower expression of CD40 rather than B7-1 signals on the AMs from these patients.

Antibodies, Monoclonal↗

PubMed2001

The usefulness of competitive PCR: airway gene expression of IL-5, IL-4, IL-4delta2, IL-2, and IFNgamma in asthma.

BACKGROUND: Asthma has been described as an eosinophilic bronchitis driven by interleukin(IL)-4 and IL-5. The quantification of cytokine mRNA levels in airway samples has been confounded by housekeeping gene expression which differs between and within asthmatics and controls. METHODS: The usefulness of competitive reverse transcriptase-polymerase chain reaction (RT-PCR) that is independent of housekeeping gene expression for quantitating the mRNA for interferon (IFN)gamma, IL-2, IL-5, IL-4 and its receptor antagonist encoding splicing variant IL-4delta2 was determined in a cross sectional study of 45 normal control subjects and 111 with asthma. RESULTS: Atopic controls and atopic asthmatic subjects expressed more IL-5 than non-atopic controls (p<0.02) in bronchoalveolar lavage (BAL) cells, but not in biopsy specimens. IL-5 mRNA expression in BAL cells from asthmatic subjects using inhaled corticosteroids (ICS) was significantly lower than those not receiving ICS (p=0.04). IL-2 mRNA levels differed with steroid use in biopsy specimens but not in BAL cells. IFNgamma, IL-4, and IL-4delta2 mRNA levels did not differ between any groups and were not affected by steroid use. IL-4 and IL-4delta2 mRNA levels were positively correlated (p<0.0001), suggesting coordinated transcription. CONCLUSIONS: While the signal differentiation of competitive PCR in asthma may rival that of in situ hybridisation and immunohistochemistry, the method is expensive and wasteful of material.

Adult↗

PubMed2001

What is evidence-based medicine and the role of the systematic review: the revolution coming your way.

The practice of evidence-based medicine involves the critical application of current best evidence to the care of individual patients. This process requires clinicians to be able to efficiently locate, critically appraise and appropriately apply the best available evidence to particular clinical scenarios. The current volume of medical and scientific literature is unmanageable and traditional approaches to continuing education cannot fully address the information needs of practicing clinicians in the era of evidence-based medicine. Review articles are useful resources but traditional narrative reviews often include a selective summary of research findings mixed with personal opinion. Systematic reviews have many advantages over traditional narrative reviews; importantly, the use of systematic and explicit methods mean that bias in identifying, selecting and summarizing the evidence is minimized. For systematic reviews where meta-analysis can be performed, the quantitative synthesis of data from different studies can provide additional information. Systematic reviews are retrospective studies and like all research may be susceptible to bias. Furthermore some methodological issues related to meta-analysis have yet to be resolved. The strengths and limitations of systematic reviews are discussed in this article and useful resources for locating high quality systematic reviews are outlined. Clinical judgement and experience have a pivotal role in the practice of evidence-based medicine and clinicians must rely on this judgement when deciding how and when to apply the results of systematic reviews to particular patients.

Clinical Competence↗

PubMed2000

The epidemic of asthma: too much allergen or not enough infection?

Asthma has generally been thought to result from exposure to allergens in infancy leading to atopy, and eventually to airway hyperresponsiveness. There is now evidence that implicates absence of childhood infections as a factor in development of asthma. Childhood infections seem to be important in normal maturation of the immune system, with asthma a manifestation of a persistent "immature" immune system.

Adolescent↗

PubMed2000

Limited (information only) patient education programs for adults with asthma.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education. OBJECTIVES: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information. MAIN RESULTS: Eleven trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but perceived asthma symptoms did improve after limited asthma education (odds ratio 0.40, 95% confidence interval 0.18 to 0.86). In one study, limited asthma education was associated with reduced emergency department visits (weighted mean difference -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18). REVIEWER'S CONCLUSIONS: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma. However the use of information in the emergency department may be effective, but this needs to be confirmed.

Adult↗

PubMed2000

Self-management education and regular practitioner review for adults with asthma.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. This review was conducted to examine the strength of evidence supporting Step 6 of the Australian Asthma Management Plan: "Educate and Review Regularly"; to test whether health outcomes are influenced by education and self-management programmes. OBJECTIVES: The objective of this review was to assess the effects of asthma self-management programmes, when coupled with regular health practitioner review, on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised trials of self-management education in adults over 16 years of age with asthma. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. MAIN RESULTS: Twenty-five trials were included. Self-management education was compared with usual care in 22 studies. Self-management education reduced hospitalisations (odds ratio 0.57, 95% confidence interval 0.38 to 0.88); emergency room visits (odds ratio 0.71, 95% confidence interval (0.57 to 0.90); unscheduled visits to the doctor (odds ratio 0.57, 95% confidence interval 0.40 to 0.82); days off work or school (odds ratio 0.55, 95% confidence interval 0.38 to 0. 79); and nocturnal asthma (odds ratio 0.53, 95% confidence interval 0.39 to 0.72). Measures of lung function were little changed. Self-management programmes that involved a written action plan showed a greater reduction in hospitalisation than those that did not (odds ratio 0.35, 95% confidence interval 0.18 to 0.68). People who managed their asthma by self-adjustment of their medications using an individualised written plan had better lung function than those whose medications were adjusted by a doctor. REVIEWER'S CONCLUSIONS: Training in asthma self-management which involves self-monitoring by either peak expiratory flow or symptoms, coupled with regular medical review and a written action plan appears to improve health outcomes for adults with asthma. Training programmes which enable people to adjust their medication using a written action plan appear to be more effective than other forms of asthma self-management.

Adult↗

PubMed2000

Inhaled short acting beta2-agonist use in asthma: regular vs as needed treatment.

BACKGROUND: Inhaled beta2-adrenergic agonists delivered by inhalation are very widely used in asthma. There has been much controversy of the use and possible consequences of the use of these agents for regular, as opposed as-needed use in asthma. OBJECTIVES: This review to assessed the clinical trial evidence to test whether using regular use of short-acting beta2-agonists reduced asthma control and pulmonary function; worsened symptoms, airway reactivity and quality of life; and increased the rate of exacerbations. SEARCH STRATEGY: A search was carried out of the Cochrane Airways Group "Asthma and Wheez* RCT" register using the terms: regular AND [beta agonist OR bronchodilator OR salbutamol OR albuterol Or terbutaline OR isoproterenol OR reproterol OR fenoterol]. Bibliographies of existing trials were searched and primary trial authors and pharmaceutical companies were approached for additional trials. SELECTION CRITERIA: Randomised controlled trials in which the short-acting beta2-agonist was given regularly in the experimental group, together with an inhaled bronchodilator for relief of symptoms ('rescue use'). The control group consisted of matching placebo inhaled regularly, with an inhaled bronchodilator for as-needed 'rescue use'. DATA COLLECTION AND ANALYSIS: Data were extracted and quality assessments were made by both reviewers. Parallel group and cross-over trials were analysed separately. Where possible data were pooled using a fixed effects model. MAIN RESULTS: Over 800 abstracts were identified, following a review, 60 papers were requested for full assessment by both reviewers. 34 trials from 30 papers met the entry criteria. Data from 31 outcomes were analyzable. There was little difference between the treatments for nearly all outcomes. In cross-over studies, evening peak flow was better with regular treatment, weighted mean difference (WMD) 13.1 l/min (95% confidence interval 24.3, 1.9). In contrast, the FEV1 was better with as-needed treatment (WMD 157 ml (95% CI: 123, 192). Bronchial hyper reactivity was slightly better in the as-needed group, standardised mean difference 0.23, 95% CI: 0.52, 1.12. REVIEWER'S CONCLUSIONS: These results support current guidelines. There is little advantage in using short-acting beta2-agonists regularly, and potentially some small clinical disadvantage.

Adrenergic beta-Agonists↗

PubMed2000

Corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations occur quite commonly in patients with chronic obstructive pulmonary disease (COPD). Corticosteroid drugs, either parenteral or oral, are used commonly in this setting. OBJECTIVES: To determine the effect of corticosteroids, administered either parenterally or orally, on the outcome in patients with acute exacerbations of COPD. SEARCH STRATEGY: An initial search was carried out using the Cochrane Airways Group COPD register with additional studies sought in the bibliographies of randomised controlled trials and review articles. Authors of identified randomised controlled trials were contacted for other published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids, administered either parenterally or orally, with appropriate placebo. Other interventions were standardised e.g. bronchodilators, antibiotics. Studies of acute asthma were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted by one reviewer and sent to authors for verification. All trials were combined for analysis where possible. MAIN RESULTS: We identified 7 studies that fulfilled the inclusion criteria. Outcomes were varied and few were common to all studies. The most commonly reported outcome, the FEV1 between 6 - 72 hours after treatment, showed no significant difference between corticosteroid and placebo treatment. Treatment failure (defined as re-attendance in the emergency department, need for oral steroids or hospitalisation) and quality of life did show a statistically significant benefit for corticosteroid treatment, but the number of studies reporting these outcomes was small and there was significant heterogeneity between them REVIEWER'S CONCLUSIONS: Treatment with oral or parenteral corticosteroids in outpatients may decrease the number of patients requiring further treatment or hospitalisation, but otherwise it has no significant effect on the outcome of acute exacerbations of chronic obstructive airways disease. Further research is required to determine the place of corticosteroid treatment in acute exacerbations of chronic obstructive airways disease.

Acute Disease↗

PubMed2000

The anti-inflammatory profile of inhaled corticosteroids combined with salmeterol in asthmatic patients.

Inhaled corticosteroid (ICS) therapy such as fluticasone propionate (FP) is effective in moderate-to-severe asthma, but for patients on ICS who still experience symptoms, treatment guidelines recommend either increasing the dose of ICS or adding a long-acting beta2-agonist such as salmeterol or formoterol. Several studies have now shown that adding salmeterol provides greater clinical benefit than increasing the dose of ICS, raising the question of whether salmeterol has an additive or complementary anti-inflammatory effect to that of ICS. Recent studies on bronchial biopsies and bronchoalveolar lavage from asthmatic patients treated with either salmeterol. FP or placebo in addition to low-dose ICS have demonstrated that addition of salmeterol produces independent or additional reductions in several pro-inflammatory cells, cytokines and cell adhesion molecules compared with FP. Such complementary anti-inflammatory effects may explain the improved control of asthma symptoms and exacerbations observed when salmeterol is added to low-dose ICS therapy, and may help to modify the long-term sequelae of asthma. These findings also indicate, contrary to earlier speculation, that salmeterol does not have a pro-inflammatory effect or mask persistent airway inflammation. This review presents the results of recent studies and suggests possible mechanisms for the additional antiinflammatory effects of salmeterol.

Administration, Inhalation↗

PubMed2000

The expression of the myogenic regulatory factors in denervated and normal muscles of different phenotypes.

The nerve is known to play a pivotal role in the diversification of muscle fibre types postnatally. Reducing neuronal activity in a slow muscle such as the soleus by denervation, switches on genes associated with a fast muscle phenotype. On the other hand, denervating a fast muscle such as the extensor digitorum longus (EDL) induces the conversion of fast fibres to a 'slower' contractile phenotype. The myogenic regulatory factors (MRFs) are proposed as the regulators of muscle phenotype as MyoD and myogenin have been shown to differentially accumulate in fast and slow muscle upon the induction of fibre type transformation. The denervation model has been used in the present study to induce changes in MRF expression in the muscles of the lower hindlimb which have distinct phenotypic characteristics. The level of MRF expression in pairs of denervated and innervated soleus, EDL, tibialis anterior (TA), plantaris and gastrocnemius muscles has been determined by Northern analysis and compared. The present study has shown that each muscle responds differently to denervation with respect to the increases in MRF expression. Fast muscles responded very quickly to denervation by increasing the level of MRF transcripts while slow muscles did not show significant increases in expression after 48 h denervation. The innervated EDL (fast) and soleus (slow) muscle differed with respect to the level of MRF-4 expressed, MRF-4 being expressed at higher levels in the slow muscle compared to the fast, suggesting that MRF-4 is important in the maintenance of a slow muscle phenotype. Moreover, MRF-4 and myogenin show the greatest fold increases in expression in the fast muscles examined. MyoD and Myf 5 show less dramatic increase in expression in response to denervation but exhibit the greatest fold increases in the fast muscles compared to slow.

Animals↗

PubMed2000

Bronchoalveolar lavage fluid urea as a measure of pulmonary permeability in healthy smokers.

The effects of cigarette smoking on blood to airway pulmonary permeability to the low-molecular-weight solute urea were investigated, in an attempt to evaluate its use as a dilution marker for bronchoalveolar lavage (BAL) studies. Five healthy normal smokers who smoked a cigarette 10 min prior to undergoing a 3 x 60 mL bronchoalveolar lavage (BAL), and five nonsmokers who also underwent BAL but without cigarette smoke exposure were studied. Five minutes before bronchoscopy, 4 MBq 3H-water and 1 MBq 14C-urea were injected intravenously and biochemical urea assays and an indirect radiotracer method were used to evaluate permeability. It was shown that the smoking group had less urea in their BAL supernatants compared to nonsmokers the results using the radiotracer method being significant (p<0.005). Using both methods, it was shown that levels of urea increased in sequentially aspirated aliquots in both groups. The median directly assayed levels of urea in the smokers rose as follows: aliquot 1 0.05 micromol x mL(-1), (range 0.03-0.14), aliquot 2 0.10 micromol x mL(-1) (0.07-0.17), aliquot 3 0.12 micromol x mL(-1) (0.06-0.23) (p<0.05). This led to significantly increased calculated levels of epithelial lining fluid in the sequential aliquots (p<0.05). In addition, there were large but variable amounts of labelled water detected in both subject groups indicating a complex interaction between the BAL procedure and the circulation. Changing urea measurements during the bronchoalveolar lavage procedure confound the use of the urea (epithelial lining fluid) method for normalizing dilution factors. The use of epithelial lining fluid determinations in smokers ignores the additional and probably complex permeability changes. The present data suggest that acute exposure to cigarette smoke in smokers may decrease blood to airway permeability.

Adult↗

PubMed2000

Asthma is more prevalent in rural New South Wales than metropolitan Victoria, Australia.

OBJECTIVE: The aim of this study was to compare the prevalence of adult respiratory symptoms and conditions in a rural setting with a metropolitan setting. METHODOLOGY: We used cross-sectional population surveys of respiratory health using the European Respiratory Health Survey screening questionnaire. A random sample of 4455 eligible young adults aged 20-44 years, from electoral rolls in south-eastern metropolitan Melbourne, Victoria, and 4521 from rural south-western New South Wales were surveyed. RESULTS: Response rates of 72% (n=3194) and 69% (n=3121) were achieved in Melbourne and the Riverina, respectively. Respondents from the Riverina reported significantly higher prevalences of nocturnal dyspnoea (P<0.01), chronic bronchitis (P=0.03), an asthma attack in the previous 12 months (P<0.001), ever having had asthma (P<0.001) and doctor-diagnosed asthma (P<0.001) compared to those from Melbourne. However, among those with 'asthma attacks in the last 12 months', Melbourne respondents experienced a higher frequency of attacks (P<0.05). Riverina respondents reported a higher prevalence of smoking (P<0.05) and smoked more cigarettes on average (P<0.001) than Melbourne respondents. However, annoyance from air pollution was higher in Melbourne than in the Riverina. CONCLUSIONS: These results suggest that asthma is more prevalent in rural southern New South Wales than in Melbourne but follows a different pattern of exacerbations.

Adult↗

PubMed2000

Airway neutrophilia in stable and bronchiolitis obliterans syndrome patients following lung transplantation.

BACKGROUND: The bronchiolitis obliterans syndrome (BOS) remains the major constraint on the long term success of lung transplantation. Neutrophils have been associated with fibrosing lung conditions and have been noted to be increased in the bronchoalveolar lavage (BAL) fluid of patients with BOS. METHODS: This study was undertaken to examine neutrophil accumulation in the BAL fluid, airway wall and lung parenchyma, as well as levels of interleukin (IL)-8 in the BAL fluid, in normal controls and lung transplant recipients with and without BOS. Bronchoscopic examination included endobronchial biopsy (EBB), BAL fluid, and transbronchial biopsy (TBB) sampling. Tissue neutrophils were identified by neutrophil elastase staining on 3 microm paraffin biopsy sections and quantified by computerised image analyser. IL-8 levels were measured in unconcentrated BAL fluid by ELISA. RESULTS: Compared with controls, airway wall neutrophilia was increased in both stable lung transplant recipients and those with BOS (p<0.05). BAL neutrophils and IL-8 levels were also increased in both groups of transplant recipients compared with controls (p<0.01), the levels being significantly higher in the BOS group (p<0.01). Neutrophil numbers in the lung parenchyma were not significantly different between the two groups of lung transplant recipients. CONCLUSION: Increased levels of neutrophils are present in the airway wall and BAL fluid of lung transplant recipients with and without BOS. BAL fluid levels of IL-8 are also increased, raising the possibility that neutrophils and/or IL-8 may play a part in the pathogenesis of BOS following lung transplantation.

Adult↗

PubMed2000

MRF-4 exhibits fiber type- and muscle-specific pattern of expression in postnatal rat muscle.

The crucial role played by the myogenic regulatory factors (MRFs) in the development of skeletal muscle has been well characterized. The continued expression of these factors in skeletal muscle of the postnatal animal has led to the suggestion that they may play a role in the regulation of muscle fiber phenotype. The few studies that have examined the expression of MRF-4 in postnatal muscle have been carried out at the whole muscle level. These studies demonstrated that this factor is expressed at a higher level than any other MRF but suggested that this was not affected by muscle phenotype. In this study, the expression of the MRF-4 transcript has been examined at the cellular level by in situ hybridization. It was observed that in the mixed fiber type muscle the gastrocnemius, MRF-4 was preferentially expressed in slow muscle fibers, but in the slow postural soleus, no fiber type specificity was observed. These observations suggest that MRF-4 may play a role in the regulation of muscle fiber phenotype in the postnatal animal.

Animals↗

PubMed2000

Airway distensibility in healthy and asthmatic subjects: effect of lung volume history.

Anatomic dead space (VD) is known to increase with end-inspiratory lung volume (EILV), and the gradient of the relationship has been proposed as an index of airway distensibility (DeltaVD). The aims of this study were to apply a rapid method for measuring DeltaVD and to determine whether it was affected by lung volume history. VD of 16 healthy and 16 mildly asthmatic subjects was measured at a number of known EILVs by using a tidal breathing, CO(2)-washout method. The effect of lung volume history was assessed by using three tidal breathing regimens: 1) three discrete EILVs (low/medium/high; LMH); 2) progressively decreasing EILVs from total lung capacity (TLC; TLC-RV); and 3) progressively increasing EILVs from residual volume (RV; RV-TLC). DeltaVD was lower in the asthmatic group for the LMH (25.3 +/- 2.24 vs. 21.2 +/- 1.66 ml/l, means +/- SE) and TLC-RV (24. 3 +/- 1.69 vs. 18.7 +/- 1.16 ml/l) regimens. There was a trend for a lower DeltaVD in the asthmatic group for the RV-TLC regimen (23.3 +/- 2.19 vs. 18.8 +/- 1.68 ml/l). There was no difference in DeltaVD between groups. In conclusion, mild asthmatic subjects have stiffer airways than normal subjects, and this is not obviously affected by lung volume history.

Adult↗

PubMed2000

Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure.

Given that the apnea-ventilation cycle length during central sleep apnea (CSA) with congestive heart failure (CHF) is approximately 70 s, we hypothesized that rapidly responsive peripheral CO(2) ventilatory responses would be raised in CHF-CSA and would correlate with the severity of CSA. Sleep studies and single breath and rebreathe hypercapnic ventilatory responses (HCVR) were measured as markers of peripheral and central CO(2) ventilatory responses, respectively, in 51 subjects: 12 CHF with no apnea (CHF-N), 8 CHF with obstructive sleep apnea (CHF-OSA), 12 CHF-CSA, 11 CSA without CHF ("idiopathic" CSA; ICSA), and 8 normal subjects. Single breath HCVR was equally elevated in CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (0.58 +/- 0.09 [mean +/- SE] and 0. 58 +/- 0.07 versus 0.23 +/- 0.06, 0.25 +/- 0.04, and 0.27 +/- 0.02 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Similarly, rebreathe HCVR was elevated in both CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (5.80 +/- 1.12 and 3.53 +/- 0. 29 versus 2.00 +/- 0.25, 1.44 +/- 0.16, and 2.14 +/- 0.22 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Furthermore, in the entire CHF group, single breath HCVR correlated with central apnea-hypopnea index (AHI) (r = 0.63, p < 0.001) and percentage central/total apneas (r = 0.52, p = 0.022). Rebreathe HCVR correlated with awake Pa(CO(2)) (r = -0.61, p < 0.001), but not with central AHI or percentage central/total apneas independent of its relationship with single breath HCVR. In conclusion, in subjects with CHF, raised central CO(2) ventilatory response predisposes to CSA promoting background hypocapnia and exposing the apnea threshold to fluctuations in ventilation, whereas raised and faster-acting peripheral CO(2) ventilatory response determines the periodicity and severity of CSA.

Analysis of Variance↗

PubMed2000

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by increased exhaled nitric oxide levels and epithelial inducible nitric oxide synthase.

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by airway inflammation and development of progressive airway narrowing and fibrosis. We have previously shown that in stable lung transplant recipients (LTR), mean eNO levels were not elevated but were still related to the degree of airway neutrophilia within the group. The hypothesis now tested is that in BOS, eNO levels are increased in association with even greater airway neutrophilia and enhanced expression of inducible (iNOS) nitric oxide synthase in the bronchial epithelium. We determined eNO levels in 40 LTR in four groups: well and "stable": LTR (n = 20), BOS (n = 8), bacterial airway infection (BI, n = 6), and acute rejection (AR, n = 6). Following bronchoscopic sampling, we performed a quantitative assessment of iNOS and constitutive nitric oxide synthase (cNOS) expression in endobronchial biopsies by immunohistochemistry. Mean +/- SEM eNO levels in BOS and BI were significantly higher than in stable LTR (20 +/- 1.2 parts per billion [ppb] and 24.7 +/- 1.7 ppb versus 12.5 +/- 0.9 ppb; p < 0.01 for both). In AR, eNO levels (13.4 ppb +/- 0.5) were not different in stable LTR (p = 0.34). When compared with stable LTR, there was increased expression of iNOS in the bronchial epithelium and generally in the lamina propria (LP) in patients with BOS and BI. In AR, iNOS expression was increased but only in the LP in a perivascular distribution. Expression of cNOS was reduced in BOS but not in BI and AR compared with the stable group. Using regression analysis, only iNOS expression in the bronchial epithelium (r(2) = 0.77; p < 0.0001) and %BAL neutrophils (r(2) = 0. 79; p < 0.0001) were positively related to eNO in stable LTR and BOS. We conclude that epithelial iNOS appears to be the major source of eNO. Exhaled NO levels also appear to reflect the degree of airway neutrophilia in both stable LTR and BOS groups. This suggests that serial eNO measurements may be able to predict the early development of BOS.

Acute Disease↗

PubMed2000

Bronchoalveolar lavage cellular profiles in lung transplantation: the effect of inhaled corticosteroids.

UNLABELLED: Bronchiolitis Obliterans Syndrome (BOS) remains a major cause of long term morbidity and mortality in lung transplantation, and occurs despite significant immunosuppression. Airway inflammation is thought to precede the development of BOS. OBJECTIVES: To examine the effect of inhaled corticosteroids on airway inflammation and the development of BOS in lung transplant recipients. METHODS: 30 patients were recruited and randomised in a double blind fashion to receive either 750 micrograms Fluticasone propionate (FP) twice daily or an identical appearing placebo for 3 months. BAL cell counts and differentials were performed at time 0 and after 3 months treatment. Lung function was assessed at each time point using spirometry. RESULTS: 24 patients were felt to be stable and free from infection at both time points and thus included in the analysis. There was a significant reduction in total cell count in BAL fluid after treatment with 3 months FP compared to 3 months placebo, however no change in cell differentials nor lung function was found. DISCUSSION: Despite a reduction in total cell numbers in BAL fluid, lung function was not altered over the 3 months of treatment. It may be that longer treatment is required to see an effect.

Administration, Inhalation↗