Biomedical subjects

J A Nightingale

Publications and source records attributed to J A Nightingale.

9 recordsLinked to original sources

PubMed2004

Do selective topical beta antagonists for glaucoma have respiratory side effects?

BACKGROUND/AIMS: Topical beta antagonists are prescribed for glaucoma in approximately 500 000 people in the United Kingdom. The authors have previously shown that topical beta antagonists are associated with an excess incidence of airways obstruction. They examined whether selective topical beta antagonists are associated with excess airways obstruction. METHODS: A historical cohort study was performed to determine the incidence of airways obstruction in subjects with no previous history of airways obstruction, following treatment with topical beta antagonists for glaucoma for the period 1993-7. Cases were defined as having received a first prescription of a drug specifically used in the management of airways obstruction. RESULTS: For selective topical beta antagonists 12 of 324 treated subjects developed airways obstruction, compared with 112 of 9094 controls (adjusted hazard rate 3.0 (95% confidence interval (95% CI) 1.6 to 5.4)). For non-selective topical beta antagonists, the corresponding figures were 69 of 2321 subjects compared with the same control group (adjusted hazard rate 2.2 (1.6 to 3.0)). There was no significant difference between groups (p = 0.47, chi(2)), both being associated with a significantly increased risk of airways obstruction. CONCLUSION: Selective topical beta antagonists do appear to have an excess risk of airways obstruction in this population setting and should be subject to the same prescribing caveats as unselective topical beta antagonists.

Adrenergic beta-Antagonists↗

PubMed2000

No effect of inhaled budesonide on the response to inhaled ozone in normal subjects.

Inhalation of ozone in normal subjects causes a neutrophilic inflammatory response in the airways. Pretreatment with inhaled corticosteroids reduces the inflammatory response to inhaled ozone in dogs. We undertook a double-blind, randomized, placebo-controlled, crossover study to investigate the effects of 2 wk of treatment with inhaled budesonide 800 microg twice daily or placebo prior to ozone exposure in humans. Fifteen (six male; mean age, 31.1 +/- 2.1 yr) healthy nonsmokers were exposed to 400 parts per billion (ppb) ozone for 2 h with intermittent exercise. Spirometry, exhaled carbon monoxide (CO) and nitric oxide (NO) levels, measurement of methacholine reactivity, and collection of exhaled air condensate and induced sputum samples were performed at baseline, preexposure, and at intervals up to 24 h postexposure. Ozone exposure led to significant decreases in spirometry and increased methacholine reactivity and sputum neutrophils and myeloperoxidase (MPO). There were no changes in exhaled NO and CO levels, or exhaled breath nitrite after ozone exposure. There were no differences in any of the parameters after treatment with budesonide compared with placebo, and no differences in the response to ozone between treatment groups. We conclude that a high dose of inhaled corticosteroid does not protect against the effects of ozone exposure in normal subjects.

Administration, Inhalation↗

PubMed2000

Airway inflammation after controlled exposure to diesel exhaust particulates.

Epidemiologic evidence suggests a link between morbidity and mortality and levels of particulate matter in the atmosphere. We studied the inflammatory response to inhalation of diesel exhaust particulates (DEP) in normal volunteers. DEP were collected from the exhaust of a stationary diesel engine and were resuspended in an exposure chamber. Ten nonsmoking healthy volunteers were exposed for 2 h at rest to a controlled concentration of DEP (monitored at 200 microg/m(3) particulate matter of less than 10 microm aerodynamic diameter [PM(10)]) or air in a double-blind, randomized, crossover study. Exposures were followed by serial spirometry and measurement of pulse, blood pressure, exhaled carbon monoxide (CO), and methacholine reactivity, as well as sputum induction and venesection for up to 4 h after exposure, and a repeat of all these procedures at 24 h after exposure. There were no changes in cardiovascular parameters or lung function following exposure to DEP. Levels of exhaled CO were increased ater exposure to DEP, and were maximal at 1 h (air: 2.9 +/- 0.2 ppm [mean +/- SEM]; DEP: 4.4 +/- 0.3 ppm; p < 0.001). There was an increase in sputum neutrophils and myeloperoxidase (MPO) at 4 h after DEP exposure as compared with 4 h after air exposure (neutrophils: 41 +/- 4% versus 32 +/- 4%; MPO: 151 ng/ml versus 115 ng/ml, p < 0.01), but no change in concentrations of inflammatory markers in peripheral blood. Exposure to DEPs at high ambient concentrations leads to an airway inflammatory response in normal volunteers.

Adult↗

PubMed1999

Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects.

BACKGROUND: Nitric oxide (NO) may have a role in the pathophysiology of tissue injury in response to inhaled ozone in animals. METHODS: A double blind, randomised, placebo controlled, crossover study was undertaken to investigate the effects of inhaled ozone in 10 normal and 10 atopic asthmatic volunteers. Subjects were exposed to 200 ppb ozone or clean air for four hours with intermittent exercise, followed by hourly measurement of spirometric parameters and exhaled NO for four hours. Nasal NO and methacholine reactivity were measured and exhaled breath condensate and induced sputum samples were collected four and 24 hours after exposure. RESULTS: Exposure to ozone caused a fall in forced expiratory volume in one second (FEV(1)) of 7% in normal subjects (p<0.05) and 9% in asthmatic subjects (p<0.005). There was a 39% increase in sputum neutrophils at four hours in normal subjects (p<0.05) and a 35% increase at four hours in asthmatic subjects, remaining high at 24 hours (p<0.005 and p<0.05, respectively). There were no differences between normal and asthmatic subjects. There were no changes in methacholine reactivity, exhaled or nasal NO, nitrite levels in exhaled breath condensate, or sputum supernatant concentrations of interleukin 8, tumour necrosis factor alpha, or granulocyte-macrophage colony stimulating factor in either group. CONCLUSIONS: Exposure to 200 ppb ozone leads to a neutrophil inflammatory response in normal and asthmatic subjects but no changes in exhaled NO or nitrite levels.

Adult↗

PubMed1999

Differential effect of formoterol on adenosine monophosphate and histamine reactivity in asthma.

Short-acting beta2-agonists provide greater protection against bronchoconstriction induced by adenosine 5'-monophosphate (AMP) than by direct-acting bronchoconstrictors such as histamine and methacholine. AMP is thought to cause bronchoconstriction via release of mediators from mast cells, which suggests that these drugs stabilize mast cells in vivo. This in vivo property has not yet been demonstrated for long-acting beta2-agonists. We undertook a double-blind, randomized, placebo-controlled, cross-over study to investigate the effects of a single dose of formoterol inhaled via Turbuhaler (12 micrograms) and of albuterol inhaled via Turbuhaler (200 micrograms) on airway responsiveness to AMP and histamine in 16 subjects with mild atopic asthma. Albuterol reduced airway responsiveness to AMP and histamine by 4.1 +/- 0.5 and 3.5 +/- 0.4 doubling doses, respectively. In contrast, formoterol caused a greater protective effect against AMP than against histamine challenge, decreasing airway responsiveness by 6.0 +/- 0.8 and 4.2 +/- 0.4 doubling doses, respectively (p < 0.05). Thus, the long-acting beta2-agonist formoterol appears to have a mast cell-stabilizing effect in vivo in mild asthma.

Adenosine Diphosphate↗

PubMed1999

Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.

Administration, Inhalation↗

PubMed1998

Augmented enterocystoplasty for neurogenic bladder associated with renal transplantation: appearance on Tc-99m MAG3 renal transplant scan.

Enterocystoplasty (bladder augmentation) is a method of increasing bladder capacity in patients with small or neurogenic bladders in order to prevent vesicoureteral reflux. In patients with poorly compliant bladders, enterocystoplasty, which consists of a segment of detubularized small bowel or a portion of the stomach attached to the bladder, often helps to reduce the intravesicular pressures, thus reducing the likelihood of infection. It is also useful in treating bladder dysfunction in children with end-stage renal disease who require renal transplantation. Radiographic evaluation of patients with a renal transplant and augmented bladder often can be confusing, and may suggest a urine leak or hematoma. We report a patient with a renal transplant, bladder augmentation, and rising serum creatinine who underwent renal scintigraphy and ultrasonography.

Adult↗

PubMed1998

Effect of repeated sputum induction on cell counts in normal volunteers.

BACKGROUND: Sputum induction is becoming more commonly used to assess airway inflammation. Since it is a relatively non-invasive procedure it may be useful for repeated measurements over a short period of time. METHODS: To assess the repeatability of the method over a 24 hour period, eight healthy, non-smoking, non-atopic subjects (four men) of mean age 30 years underwent sputum induction, repeated at eight hours and 24 hours. Sputum was induced by inhalation of 3.5% saline. Absolute and differential counts of inflammatory cells were performed on the whole sputum after dilution in Hank's balanced salt solution containing 1% dithiothreitol to solubilise the mucus content of the samples. RESULTS: There was a significant rise in the percentage of neutrophils in the eight hour sample compared with the baseline (57%, range 25-94% at eight hours compared with 28%, range 19-60%: median difference 26%). The median baseline percentage of macrophages was 55% (range 26-69%) which fell to 38% (range 3-56%: median difference 22%) at eight hours and 19% (range 14-59%: median difference 25%) at 24 hours. There was no significant change in the differential counts of eosinophils, lymphocytes or columnar epithelial cells, nor in any of the absolute cell counts, at any time point. CONCLUSIONS: Sputum induction may have limited utility in serial assessment of neutrophilic airway inflammation in normal subjects within a 24 hour period.

Adult↗

PubMed1998

Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects.

BACKGROUND: Inhalation of lipopolysaccharide (LPS) causes an inflammatory response in the lungs. To explore this response, inflammatory indices were measured in induced sputum from atopic asthmatic patients and compared with atopic and non-atopic subjects after inhalation of LPS. METHODS: The effects of inhaled LPS (60 micrograms) or placebo (0.9% saline) were examined in a randomised, double blind, crossover trial in 11 non-atopic normal subjects, seven atopic, non-asthmatic individuals, and eight atopic, asthmatic patients. Sputum was induced by inhalation of 3.5% saline before the test inhalation and again at six hours and 24 hours. Spirometry (forced expiratory volume in one second (FEV1), forced vital capacity (FVC)), heart rate, blood pressure, and temperature were recorded before challenge and at intervals until eight hours, and at 24 hours after challenge. RESULTS: There was no change in cardiovascular parameters or spirometry with either exposure in any group. In the asthmatic patients only, inhalation of LPS caused a rise in temperature, with a peak of 0.6 degree C at seven hours, which was significantly higher than following placebo inhalation (p < 0.05). In normal subjects, LPS caused a significant rise in absolute neutrophil counts at 24 hours compared with placebo (median 1.1 x 10(6) cells/ml after LPS; median 0.2 x 10(6) cells/ml after placebo, p < 0.01), but no change in differential counts. In asthmatic patients, LPS caused a significant rise in differential neutrophil counts at six hours compared with placebo (median 88% after LPS; median 56% after placebo, p < 0.05), but no change in absolute cell counts at any time point. There was no change in neutrophil counts in the atopic subjects. There was a significant rise in sputum interleukin 8 (IL-8) concentrations in normal subjects at six hours compared with placebo (mean placebo 1.1 ng/ml; LPS 3.0 ng/ml, p < 0.05) and in asthmatics at 24 hours (mean placebo 2.0 ng/ml, LPS 6.9 ng/ml, p < 0.05). There were no changes in sputum concentrations of tumour necrosis factor alpha or granulocyte macrophage colony stimulating factor at any time. CONCLUSIONS: Inhalation of LPS causes a neutrophilic inflammation with increases in IL-8 in both normal and asthmatic subjects.

Administration, Inhalation↗