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Biomedical subjects

J P Seale

Publications and source records attributed to J P Seale.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing.

Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.

Adolescent↗
PubMed2005

Poor health is associated with episodic heavy alcohol use: evidence from a National Survey.

OBJECTIVES: The objective of this study was to examine the relationship between self-rated health and episodic heavy drinking in a representative sample of American adults. We also sought to determine ethnic and gender differences in the association between self-rated health and episodic heavy drinking. METHODS: Data (n=4649) from the Third US National Health and Nutrition Examination Survey were utilized for this investigation. Episodic heavy drinking was defined as the consumption of five or more and four or more alcoholic beverages on one occasion for men and women, respectively. Poor health was defined as answering fair or poor to the question: "Would you say your health in general is excellent, very good, good, fair or poor?" Odds ratio from the logistic linear regression analysis was used to estimate the risk for poor health that was associated with episodic heavy drinking. Statistical adjustments were made for age, hypertension, diabetes, current smoking, body mass index and race/ethnicity. RESULTS: Overall, episodic heavy drinking was associated with increased odds of poor self-rated health in men and women. In men, episodic heavy drinking was independently associated with 1.28 (95% CI: 1.07-1.82) increased odds of poor health. The corresponding value in women was 1.86 (95% CI: 1.05-2.28). In men, being Black was associated with approximately two-fold (OR=1.96; 95% CI: 1.33, 2.89), and being Hispanic was associated with approximately four-fold (OR=3.59; 95% CI: 2.50, 5.14) increased odds of poor self-rated health relative to being White. The corresponding odds ratios in women were 2.97 (95% CI: 1.90, 4.64) and 5.18 (95% CI: 3.23, 8.30). Associations were greater among blacks (adjusted OR=2.41; 95% CI: 1.81-3.22) and Hispanics (adjusted OR=4.15; 95% CI: 3.12-5.52) than among whites. CONCLUSIONS: Poor health is associated with episodic heavy alcohol consumption. Public health strategies to curb alcohol abuse may improve self-reported health status in these at-risk populations.

Adult↗
PubMed2002

Effects of terbutaline in combination with mannitol on mucociliary clearance.

Beta2-agonists and osmotic agents stimulate mucociliary clearance (MCC) via different mechanisms which could potentially interact. The effects of inhaling terbutaline in combination with mannitol on MCC were investigated in nine healthy (aged 19+/-1 yrs) and 11 mild (aged 21+/-4 yrs) asthmatic subjects. Using 99mTc-sulphur colloid radioaerosol and a gamma camera, MCC was studied on four separate days with each of the following interventions: 1) terbutaline or its placebo inhaled 10 min before mannitol (in random, double blind); 2) terbutaline inhaled 5 min after mannitol; and 3) terbutaline inhaled 10 min before the control for mannitol. Lung images were collected over a period of 120 min postintervention and over 150 min in total. The mannitol-induced increase in clearance was transiently inhibited by terbutaline pretreatment and transiently enhanced when terbutaline was administered after mannitol both in asthmatic and healthy subjects. The order of administration of mannitol and terbutaline did not affect the total clearance of radioactive mucus over 140 min from the start of intervention in both groups. The pathways through which terbutaline and mannitol increase mucociliary clearance may transiently interact in an inhibitory or synergistic way, depending on the order of administration. However, this did not affect the overall increase in mucociliary clearance over 140 min.

Administration, Inhalation↗
PubMed2001

Quantification of epimeric budesonide and fluticasone propionate in human plasma by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry.

A highly sensitive and selective liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry assay was developed and validated for simultaneous determination of epimeric budesonide (BUD) and fluticasone propionate (FP) in plasma. The drugs were isolated from human plasma using C18 solid-phase extraction cartridges, and epimeric BUD was acetylated with a mixture of 12.5% acetic anhydride and 12.5% triethylamine in acetonitrile to form the 21-acetyl derivatives following the solid-phase extraction. Deuterium-labelled BUD acetate with an isotopic purity >99% was synthesized and used as the internal standard. The assay was linear over the ranges 0.05-10.0 ng/ml for epimeric BUD, and 0.02-4.0 ng/ml for FP. The inter- and intra-day relative standard deviations were <14.3% in the assay concentration range.

Androstadienes↗
PubMed2001

Impaired vascular responses to nitroglycerin in subjects with coronary atherosclerosis.

To study smooth muscle function in atherosclerosis, we calculated dose-response curves in patients with coronary artery disease and in controls by measuring changes in brachial artery diameter after incremental sublingual doses of nitroglycerin. The doses required to produce a 50% maximal dilator response were significantly higher in patients with coronary artery disease than in controls (p <0.002), suggesting smooth muscle dysfunction in atherosclerosis.

Adult↗
PubMed2001

Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol.

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD(15) was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV(1) with fexofenadine was 20.8 +/- 5.4% and not different from placebo (20.1 +/- 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to mannitol and the PD(15) was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0.35). The total dose of mannitol delivered and the final percent reduction in FEV(1) with montelukast were 171 +/- 142 mg and 21 +/- 4% and for placebo were 182 +/- 144 mg and 20 +/- 5% (p = 0.35, p = 0.59, respectively). However, recovery of FEV(1) to baseline was faster with montelukast, with the area under the percent reduction FEV(1)-versus-time curve reduced (220 +/- 121% change.min) compared with placebo (513 +/- 182% change.min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.

Acetates↗
PubMed2001

Clinical pharmacokinetics of inhaled budesonide.

The corticosteroid budesonide is a 1:1 racemic mixture of 2 epimers, (22R)- and (22S)-, and is available in 3 different inhaled formulations for the management of asthma: a pressurised metered dose inhaler (pMDI), a dry powder inhaler (DPI) and a solution for nebulised therapy. Inhaled corticosteroids such as budesonide reach the systemic circulation either by direct absorption through the lungs (a route that is much more important than previously recognised) or via gastrointestinal absorption of drug that is inadvertently swallowed. Although the pharmacokinetics of budesonide have been extensively investigated following oral and intravenous administration, relatively few studies have defined the systemic disposition of budesonide after inhalation. Drug deposition in the lungs depends on the inhaler device: 15% of the metered dose of budesonide reached the lung with a pMDI compared with 32% with a breath-actuated DPI. In patients with asthma (n = 38) receiving different doses of budesonide by DPI (Turbuhaler), the pharmacokinetic parameters peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were dose-dependent after both single dose and repeat dose (3 weeks) administration: time to Cmax (tmax) was short (0.28 to 0.40 hours) and the elimination half-life approximately 3 hours. Both AUC and Cmax were linearly related to budesonide dose. In a small group of healthy male volunteers (n = 9), the pharmacokinetics of budesonide 1,600 microg twice daily via pMDI were assessed on the fifth day of administration. Mean model-independent parameters for (22R)-budesonide were as follows: Cmax 1.8 microg/L, tmax 0.46 hours, elimination half-life 2.3 hours and oral clearance 163 L/h, and there were no enantiomer-specific differences in drug disposition. Budesonide undergoes fatty acid conjugation within the lung, but very limited pharmacokinetic data are available to define the pulmonary absorption characteristics. There is evidence from a population analysis that the pulmonary absorption of budesonide is prolonged and shows wide interindividual variation. Further pharmacokinetic studies are required to define the time-course of budesonide absorption through the lung in specific patient groups, and to investigate the effect of new inhaler devices (especially chlorofluorocarbon-free pMDIs) on the pharmacokinetic profile and systemic drug exposure.

Administration, Inhalation↗
PubMed2000

Comparative kinetics of metabolism of beclomethasone propionate esters in human lung homogenates and plasma.

The systemic availability of inhaled beclomethasone dipropionate (BDP) is the net result of the absorption of the glucocorticoid from the lower respiratory and gastrointestinal tracts, and metabolism in the lung, plasma, and other sites. The metabolism kinetics of BDP and its active metabolite, beclomethasone 17-monopropionate (17-BMP), in human lung 1000 x g supernatant (HLu) and human plasma (HP) at 37 degrees C were compared. The effect of MgCl(2) and/or an NADPH-generating system on the decomposition of BDP and 17-BMP in HLu was also investigated. The concentrations of BDP and its metabolites were determined by HPLC with UV detection at 242 nm. Kinetics of decomposition of BDP and 17-BMP in HLu and HP were qualitatively and quantitatively different. The decomposition of BDP in HLu involved only hydrolysis. In comparison, three reactions are involved following incubation of BDP in HP; namely, hydrolysis, transesterification, and loss of hydrogen chloride. The hydrolysis of BDP and 17-BMP in HLu seem to be inhibited appreciably by MgCl(2) with the NADPH-generating system. Effective activation of BDP in HLu, in combination with transesterification of 17-BMP in HP, might favor a high ratio of local antiinflammatory activity to systemic side effects following inhalation of BDP.

Adolescent↗
PubMed2000

Metabolism kinetics of beclomethasone propionate esters in human lung homogenates.

PURPOSE: The purposes of this study were to characterize the kinetics of beclomethasone dipropionate (BDP) and its 17-monopropionate ester (17-BMP) in human lung 1000g supernatant (HLu) at 37 degrees C, and to analyze the interindividual variability in the metabolism of BDP in HLu. METHODS: The concentrations of BDP and its metabolites were determined by HPLC with UV detection at 242 nm. Kinetics of BDP and 17-BMP decomposition were characterized by least-squares fitting of rate equations. RESULTS: The active metabolite 17-BMP was rapidly formed following the incubation of BDP in HLu. Kinetics of BDP and 17-BMP in HLu were nonlinear owing to product inhibition and enzyme saturation. A model taking into account the product inhibition provides a kinetic basis for understanding the in vivo behavior of BDP and its metabolites in human lung. There was approximately a 3.5-fold difference in the initial half-life of BDP in HLu observed in seven subjects. CONCLUSIONS: An effective activation of BDP was demonstrated in HLu through the rapid formation of 17-BMP. Kinetics of BDP and 17-BMP in HLu were well characterized by the nonlinear kinetic model. Interindividual difference in the initial half-life of BDP was due mainly to esterase metabolizing activity rather than binding affinity.

Adolescent↗
PubMed2000

Pharmacokinetics of epimeric budesonide and fluticasone propionate after repeat dose inhalation--intersubject variability in systemic absorption from the lung.

AIMS: Pharmacokinetic variability is likely to be a significant factor contributing to the interindividual differences in dose requirements, anti-inflammatory response and side-effects with inhaled corticosteroids (ICS), but there is limited information about the disposition of ICS during regular dosing with a pressurized metered dose inhaler (pMDI). This study uses a mixed effects modelling approach to quantify and compare the interindividual variability in pharmacokinetics of epimeric budesonide (BUD) and fluticasone propionate (FP) after repeat-dose inhalation. METHODS: This pharmacokinetic substudy was part of a previously published open-label, randomised, placebo-controlled, 7-period crossover study to evaluate the short-term effects on plasma cortisol levels of inhaled BUD (400, 800, 1600 microg twice daily) and FP (375, 750, 1000 microg twice daily) via pMDI in a group of healthy male volunteers. On the fifth day of each high-dose treatment period (BUD 1600 microg twice daily and FP 1000 microg twice daily), venous blood samples were collected in nine subjects prior to the last dose and at 15 min, 30 min, 1, 2, 4, 6 and 8 h postdose for measurement of plasma drug concentrations to determine the pharmacokinetics of epimeric BUD and FP following inhalation. Non-compartmental analysis and a mixed effects model were used to characterize the disposition profiles. RESULTS: Both drugs had a rapid absorption half-life (BUD 10 min vs FP 11.3 min), but quite different elimination half-lives (BUD 2.4 h vs FP 7.8 h). Although there were intraindividual differences in the handling of the 22R-and 22S-epimers of BUD, there were no consistent pharmacokinetic differences between the two enantiomers in the group as a whole. Consistent with previous reports of FP's higher volume of distribution (V) and lower systemic bioavailability (F), the V/F ratio was lower for BUD than FP (498 l vs 8100 l). The parameter with the greatest interindividual variability for both BUD and FP was the rate of systemic absorption from the lung. CONCLUSIONS: This is the first report describing the pharmacokinetics of epimeric BUD and FP after repeat dose inhalation via pMDI. Three observations may be of clinical relevance: (1) there is considerable intersubject variability in the rate of absorption of both drugs from the lung; (2) in some individuals there was a long t(1/2),z for BUD, resulting in higher and more sustained plasma drug levels in the 4-12 h postdose period than would be predicted from single-dose pharmacokinetic data; and (3) there is evidence of diurnal variation in FP pharmacokinetics, with higher-than-expected plasma drug concentrations in the morning compared with the evening.

Administration, Inhalation↗
PubMed2000

Differential potency of beclomethasone esters in-vitro on human T-lymphocyte cytokine production and osteoblast activity.

Beclomethasone dipropionate is an inhaled corticosteroid, used for the treatment of asthma. It is metabolised to 17-beclomethasone monopropionate, which has greater affinity for corticosteroid receptors than the parent compound, and to beclomethasone. We investigated the potency of beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone (compared with dexamethasone as a reference steroid) in two different human cell types, peripheral blood mononuclear cells and osteoblasts. We found that beclomethasone dipropionate, 17-beclomethasone monopropionate (EC50 10(-14) M) and beclomethasone (EC50 approx. 10(-12) M) were much more potent than dexamethasone (EC50 10(-8) M) in inhibiting interleukin-5 production by peripheral blood mononuclear cells. In contrast, beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone were equipotent with dexamethasone (EC50 range 0.3-1.2 x 10(-9) M) in affecting several functional assays of osteoblasts (e.g. alkaline phosphatase activity and osteocalcin synthesis). These results show that the relative bioactivities of corticosteroids vary between different human cell types, and that affinities observed in receptor binding assays are not necessarily predictive of the bioactivity in cell populations, such as peripheral blood mononuclear cells and osteoblasts, which are putatively relevant to efficacy and side effects respectively.

Administration, Topical↗
PubMed2000

Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro.

Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.

Analysis of Variance↗
PubMed2000

Optimizing the erythromycin breath test for use in cancer patients.

The erythromycin breath test (EBT) is a putative in vivo probe for drug metabolism by cytochrome P450 3A4 (CYP3A4). Because many anticancer drugs are metabolized by this system, we sought to further develop the EBT as a tool for predicting the clearance, in cancer patients, of drugs metabolized by CYP3A4. Sixteen adult patients with incurable cancer were studied. The EBT was performed on day 1 and breath sampled after the i.v. injection of 4 microCi of 14C-erythromycin. The breath 14CO2 flux (CERt) was estimated at 11 time points over 2 h. On day 2, the EBT was repeated midway through a 10-min infusion of 100 mg of erythromycin lactobionate, and the plasma pharmacokinetics of erythromycin were determined. The infusion of 100 mg of erythromycin did not modify the EBT results significantly. The values of the conventional EBT parameter CER20 min obtained on day 1 were comparable for most subjects (0.03-0.06% dose/min), with the exception of an individual receiving the known CYP3A4 inducers dexamethasone and phenytoin who returned a value of 0.14% dose/min. There was no significant correlation between any of the conventional EBT parameters and erythromycin clearance. However, two parameters reflecting early emergence of breath radioactivity (1/TMAX and CER3 min/CERMAX) correlated significantly with erythromycin clearance (P = 0.005 and 0.006, respectively). Novel parameters derived from the EBT are significantly correlated with the clearance of erythromycin even in the presence of confounding factors, such as metastatic liver disease, altered protein binding, and comedication. These parameters may enable dose optimization of cytotoxics metabolized by CYP3A4.

Adult↗
PubMed1999

Tissue- and isoform-specific effects of aging in rats on protein kinase C in insulin-sensitive tissues.

The mechanisms responsible for the age-related decline in insulin sensitivity have not been clearly identified, but activation of the diacylglycerol/protein kinase C (PKC) signalling pathway (often confined to individual isoforms of PKC) has recently been implicated in the pathogenesis of other insulin-resistant states in both humans and animal models. Fasting serum glucose, insulin and triacylglycerol (triglyceride) concentrations, and results of oral glucose tolerance tests, were compared in groups of 6-week-old (n=8) and 6-month-old (n=8) Sprague-Dawley rats. Insulin-responsive tissues (liver, soleus muscle and epididymal fat pad) were collected to compare levels of diacylglycerol, PKC enzyme activity and protein expression of individual PKC isoforms in cytosol and membrane fractions. The older group were heavier (556+/-14 g, compared with 188+/-7 g) and relatively insulin-resistant and hyperinsulinaemic (477+/-73 pM compared with 293+/-51 pM; P<0.05) compared with young rats; they also had greater areas under the serum glucose (old, 20. 3+/-1.1; young, 17.3+/-0.7 mmol.h(-1).l(-1)) and insulin (old, 1254+/-76; young, 721+/-113 mmol.h(-1).l(-1)) profiles following an oral glucose tolerance test, and significantly higher fasting triacylglycerol levels (old, 1.24+/-0.06 mM; young, 0.92+/-0.07 mM; P<0.01). There were no age-related differences in diacylglycerol levels or PKC activity in muscle and liver, but membrane-associated PKC activity was 2.5-fold higher in the adipose tissue of older rats (101+/-19 compared with 40+/-5 pmol.min(-1).mg(-1) protein; P<0.05) due to increased translocation of PKC-beta(I), -beta(II) and -epsilon. Thus insulin resistance due to normal aging is associated with tissue- and isoform-specific changes in diacylglycerol/PKC signalling. In contrast with diabetes and dietary-induced insulin resistance, there were no changes in diacylglycerol/PKC signalling in skeletal muscle and liver, but isoform-specific translocation and higher PKC activity in adipose tissue may blunt the insulin-mediated inhibition of lipolysis and contribute to the increased triacylglycerol levels observed in older animals.

Adipose Tissue↗
PubMed1999

Perception of bronchodilation in subjects with asthma and smokers with airflow limitation.

Perception of the efficacy of bronchodilators in relieving airflow obstruction is a likely determinant of compliance with treatment in patients prescribed these drugs on an 'as needed' basis. This study aimed to determine whether bronchodilator-induced improvements in lung function are associated with improvements in breathing difficulty in subjects with asthma or smokers with airflow limitation. Twenty smokers with airflow limitation and 16 subjects with previously physician-diagnosed asthma received salbutamol (200 micrograms) and ipratropium bromide (80 micrograms). Spirometry and lung volumes were measured before and 40 min after bronchodilator. Subjects recorded changes in 'difficult breathing' on a visual analogue scale (VAS). After bronchodilator, forced expiratory volume in 1 s (FEV1) increased by 23.0 +/- 6.4% of baseline (mean +/- 95% CI) in smokers, and by 25.2 +/- 8.5% in the asthmatics, while VAS improved by 31 +/- 23% in smokers and 45 +/- 25% in asthmatics. However, these changes were not significantly correlated in either smokers (r = -0.04) or asthmatics (r = 0.15). In the asthmatic subjects, good perceivers (> 25% improvement in VAS) had greater improvements in lung volumes, as percentage predicted, than did poor perceivers. In the smokers, changes in lung function did not differ significantly between good and poor perceivers. Improvement in FEV1, as percentage predicted, was significantly correlated with improvement in VAS in good perceivers (asthma: r = 0.78, P < 0.01; smokers: r = 0.68, P < 0.05), but not in poor perceivers. Asthmatic subjects had good perception of improvements in lung function. However, in smokers with airflow limitation there is little correlation between improvement in lung function and sensation of breathing difficulty. In these subjects symptoms appear to be an unreliable guide for 'as needed' use of bronchodilators.

Aged↗
PubMed1999

Fulminant psittacosis requiring mechanical ventilation and demonstrating serological cross-reactivity between Legionella longbeachae and Chlamydia psittaci.

Chlamydia psittaci infection typically causes a mild respiratory illness in humans. Severe respiratory failure requiring mechanical ventilation or intensive care therapy is an uncommon development. The aetiological agents causing severe community acquired pneumonia often remain undetermined. Serological tests may aid in diagnosis. We present two cases of fulminant psittacosis, one demonstrating early cross-reactivity with Legionella longbeachae.

Adult↗
PubMed1999

Do subjects with asthma have greater perception of acute bronchoconstriction than smokers with airflow limitation?

OBJECTIVE: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction. METHODOLOGY: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%. RESULTS: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 +/- 0.04, 0.03 +/- 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes. CONCLUSIONS: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.

Aged↗