PubMed Health⌕ Search

Biomedical subjects

S Rennard

Publications and source records attributed to S Rennard.

At least 19 recordsLinked to original sources
PubMed2004

COPD exacerbations: the importance of a standard definition.

Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition. A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation. To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined. Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult. New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool. Improvements in data recording will also contribute to the accuracy of data retrieval and assessment. If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.

Ambulatory Care↗
PubMed2002

Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey.

To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000. From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified. The mean age of the subjects was 63.3 yrs and 44.2% were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of <65 yrs reported work loss in the past year) and frequent use of health services (13.8% of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects' perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8% described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground). This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe.

Age Distribution↗
PubMed2001

Alternative mechanisms for long-acting beta(2)-adrenergic agonists in COPD.

beta(2)-Adrenergic agonists are commonly used as bronchodilators to treat patients with COPD. In addition to prolonged bronchodilation, long-acting beta(2)-agonists (LABAs) exert other effects that may be of clinical relevance. These include inhibition of airway smooth-muscle cell proliferation and inflammatory mediator release, as well as nonsmooth-muscle effects, such as stimulation of mucociliary transport, cytoprotection of the respiratory mucosa, and attenuation of neutrophil recruitment and activation. This review details the possible alternative mechanisms of action of the LABAs, salmeterol and formoterol, in COPD.

Adrenergic beta-Agonists↗
PubMed1998

Expression of epithelial markers in nocturnal asthma.

BACKGROUND: Although the airway epithelium participates in inflammation and repair, the circadian expression of epithelial cell markers involved in these processes has not been investigated. OBJECTIVE: We sought to determine whether expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM and 4 AM in a random order 1 week apart, with brushing of the proximal and distal airways. The percentage of cells staining for a particular marker was determined. RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways was significantly greater in control subjects as compared with asthmatic subjects (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0% to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0% [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0% to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly greater in patients with NA as compared with patients with NNA and control subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range, 13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51 in the distal airways correlated with the degree of airway obstruction (r = -0.57, P = .001). Control subjects exhibited significant circadian variation in the expression of HLA-DR in the proximal airways and CD54 in the distal airways. CONCLUSION: The increased CD51 at night in patients with NA may be related to increased airway inflammation and repair processes in response to injury. The circadian changes in CD54 and HLA-DR in control subjects require further study to determine their significance. (J Allergy Clin

Adult↗
PubMed1998

Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma.

BACKGROUND: Airway inflammation is a hallmark of asthma, therefore current treatment recommendations include the use of inhaled glucocorticosteroids (GCS). However, there is little evidence that the effects of inhaled GCS are dose dependent. OBJECTIVES: The objective of this study was to assess the efficacy and safety of a second-generation GCS, budesonide, delivered by Turbuhaler, in adults with chronic asthma. METHODS: In a 12-week, randomized, double-blind, multicenter, parallel-group study, 473 subjects 18 to 70 years of age received either placebo or budesonide (200, 400, 800, or 1600 microg total daily dose) administered twice daily. Primary efficacy end points were mean change from baseline for FEV1 and morning peak expiratory flow. Safety was assessed by reported adverse events and by a cosyntropin-stimulation test. RESULTS: The mean baseline FEV1 was 63% to 66% of predicted normal value between groups. All doses of budesonide were more effective than placebo (p < 0.001). The mean changes in morning peak expiratory flow were 12, 22, 27, and 30 L/min in the 200, 400, 800, and 1600 microg budesonide total daily dose groups, respectively, and -27 L/min for the placebo group. A statistically significant dose-response effect for the mean change from baseline over the 12-week study was seen for both morning peak expiratory flow and FEV1. Budesonide-treated subjects also demonstrated significant reduction in asthma symptoms and bronchodilator use compared with placebo. There were no clinically significant differences in treatment-related adverse experiences among groups. CONCLUSIONS: Budesonide administered by Turbuhaler exhibited a dose response and was effective at low doses. It was well tolerated and significantly more effective than placebo.

Adolescent↗
PubMed1998

The CD14 molecule participates in regulation of IL-8 and IL-6 release by bronchial epithelial cells.

The soluble form of the leukocyte membrane antigen CD14 is known to increase the sensitivity of endothelial and epithelial cell lines to bacterial lipopolysaccharide (LPS). This molecule also directly induces cytokine production in monocytes. Here, the effect of sCD14 and LPS on the release of IL-6 and IL-8 by human bronchial epithelial cells (HBECs) was studied. Soluble CD14 induced cytokine production both in the presence and absence of LPS. In addition, neither sCD14 nor anti-CD14 monoclonal antibody which blocks the interaction of LPS with CD14 had any effect on the binding of LPS to HBECs. These data suggest that sCD14 may induce the release of IL-6 and IL-8 from HBECs. However, the binding of LPS to bronchial epithelium appears to be mediated by CD14-independent mechanisms.

Bronchi↗
PubMed1997

Smoking cessation is associated with an increase in exhaled nitric oxide.

STUDY OBJECTIVES: Nitric oxide (NO), a gas produced by cells lining the respiratory tract, has been reported to be decreased in the exhaled air of cigarette smokers. We hypothesized that smoking cessation would result in an increase in exhaled NO. DESIGN: Comparison of exhaled NO measured from nonsmokers, cigarette smokers, and smokers after smoking cessation. SETTING: University outpatient smoking cessation clinic. PATIENTS OR PARTICIPANTS: Twenty-five cigarette smokers and 23 normal, nonsmokers. INTERVENTIONS: Exhaled NO was measured by three techniques: (1) a peak oral method; (2) a mean oral method; and (3) a nasal method. The smokers were given nicotine patches and instructed to return after 1 and 8 weeks. The exhaled NO determinations were repeated on each visit. MEASUREMENTS AND RESULTS: Compared with nonsmokers, smokers had decreased NO levels measured by all three methods (p<0.05, each comparison). Nineteen smokers returned after 1 week. Fourteen were successfully abstinent from cigarettes and their exhaled NO increased compared with baseline (p<0.01 for each method) but not in the five subjects who had not successfully quit smoking (p>0.05 for each method). Ten subjects returned after 8 weeks. The exhaled NO levels increased further and were not significantly different from the normal nonsmokers for the peak oral and nasal NO methods (p>0.2), but were still lower than the normal nonsmoker mean oral NO (p=0.018). CONCLUSIONS: These data demonstrate that smoking cessation is associated with an increase in exhaled NO.

Administration, Cutaneous↗
PubMed1996

Efficient vasoactive intestinal polypeptide hydrolyzing autoantibody light chains selected by phage display.

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The activity was bound by immobilized anti-kappa-chain antibody. A control recombinant L chain displayed no catalytic activity. Hydrolysis of VIP by the catalytic L chains was saturable and consistent with Michaelis-Menten kinetics. The turnover of the L chains was moderate (0.22 and 2.21/min) and their Km values indicated comparatively high affinity recognition of VIP[111 and 202 nM), producing catalytic efficiencies comparable to or greater than trypsin. Unlike trypsin, the L chains did not display detectable cleavage of casein, suggesting a catalytic activity specialized for VIP. Comparisons of the nucleotide sequences of the L chain cDNA with their putative germ-line counterparts suggested the presence of several replacement mutations in the complementarity determining regions (CDRs). These observations suggest: (a) Retention or acquisition of catalytic activity by the L chains is compatible with affinity maturation of antibodies; and (b) The autoimmune L chain repertoire can serve as a source of substrate-specific and efficient catalysts.

Amino Acid Sequence↗
PubMed1990

Functional loss of chemotactic factor inactivator in the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is often characterized by a neutrophilic alveolitis, which may be mediated in part by the neutrophil chemoattractant, C5a. Chemotactic factor inactivator (CFI) can decrease C5a-directed neutrophil chemotaxis. Thus, a loss of CFI activity in the ARDS lung could lead to an increased ability of C5a to attract neutrophils. Lung CFI levels were measured antigenically and functionally in bronchoalveolar lavage (BAL) fluid obtained from 29 patients with ARDS and in 14 normal control subjects. Antigenic levels of CFI were found to be markedly elevated in ARDS BAL fluid (1,855 +/- 437 ng/ml) compared with that in normal BAL (29 +/- 10 ng/ml, p less than 0.005), but, in contrast, CFI functional activity was markedly decreased in ARDS BAL fluid compared with that in normal BAL fluid (31 +/- 7% inhibition versus 76 +/- 5% inhibition, p less than 0.01). Furthermore, although purified CFI readily inhibited the ability of C5a to attract neutrophils (92% inhibition), this activity was decreased when BAL fluid from patients with ARDS was incubated with CFI (47 +/- 10%, p less than 0.01). These findings suggest that patients with ARDS are functionally deficient in CFI, leading to an increased ability of C5a to attract neutrophils.

Aminopeptidases↗
PubMed1988

Mechanisms of neutrophil recruitment to the lung by grain dust exposure.

Inhalation of grain dusts can cause symptoms of both acute and chronic bronchitis, which has been associated with a neutrophilic inflammatory response in the lung. Since this influx of neutrophils may potentially result in bronchial injury, mechanisms of neutrophil recruitment to grain dust were examined. Sterile, aqueous grain dust extracts were prepared from settled dusts of grain sorghum, corn, oats, and soybeans. The extracts were evaluated for their ability to directly attract human neutrophils using a blindwell neutrophil chemotaxis assay. Each extract was found to possess significant chemotactic activity compared to control (p less than 0.01). To evaluate if the dusts could attract neutrophils indirectly by activating humoral inflammatory mechanisms, the grain dust extracts were evaluated for their ability to activate the complement system. When incubated with normal human serum, each of the grain dusts caused cleavage of the complement proteins C3 and properdin factor B (PFB). Importantly, the grain dust extracts lead to the generation of C5a, a potent neutrophil chemoattractant generated by complement activation. Since activation of the alveolar macrophage to release chemotactic activity represents an additional indirect mechanism of neutrophil recruitment, an extract from grain sorghum dust was evaluated for its ability to stimulate guinea pig and human alveolar macrophages to release neutrophil chemotactic activity. The results demonstrate that supernatants obtained from alveolar macrophages cultured in the presence of grain sorghum dust extract possessed increased chemotactic activity compared to controls (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1988

The role of surveillance bronchoscopy and bronchoalveolar lavage prior to heart transplantation.

All patients had an elevated bronchitis score over that of normal controls. The cause of this bronchitis is likely multifactorial and was not uniformly predicted by bronchial neutrophil counts, current smoking history, or PFT abnormality. All patients had, in addition to high bronchitis score, evidence of increased bronchial neutrophils and/or PFT abnormality or cancer. These findings lead to a change in management prior to heart transplantation.

Adult↗
PubMed1981

Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema.

This study suggests one mechanism by which alveolar macrophages accumulate in the lung in pulmonary emphysema: elastin fragments generated at the diseased sites are potent chemoattractants for monocytes, the precursors of the macrophages. The most chemotactic elastin fragments have a molecular weight between 10,000 and 50,000 and are active at concentrations as low as 3 nanograms per milliliter. By comparison, elastin fragments with higher molecular weights and desmosines are active at concentrations greater than 0.3 microgram per milliliter. In addition, preincubation of monocytes with the 10,000- to 50,000-dalton elastin impairs the ability of the cells to migrate toward elastin fragments but not toward activated serum. Fragments of tropoelastin are not chemotactic for monocytes. Because elastin, but not tropoelastin, contains lysyl-derived cross-links, these structures may be the active chemotactic site on the elastin fragments.

Cells, Cultured↗
PubMed1980

Synthesis of fibronectin, laminin, and several collagens by a liver-derived epithelial line.

We have investigated the ability of ARL-6 cells, a cell line derived from rat liver, to synthesize various collagens and two glycoproteins of the extracellular matrix, fibronectin, and laminin. Using immunofluorescence, we detected types I, II, and IV collagen plus laminin and fibronectin. Antibodies to types I and III collagen and to fibronectin were associated with most cells and showed a similar distribution. Type IV collagen and laminin were found in thin filaments associated with a small proportion of the cells. Chemical studies showed that ARL-6 cells synthesize predominantly types I and III collagens. The level of collagen synthesis was greatly affected by the presence of exogenous fibronectin added to the cells in the media. Cells maintained in fibronectin-free serum synthesized much less collagen. These studies indicate that liver-derived cells can synthesize a variety of connective tissue proteins and that collagen synthesis by these cells is enhanced by the presence of fibronectin.

Animals↗