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Biomedical subjects

P W Ind

Publications and source records attributed to P W Ind.

At least 19 recordsLinked to original sources
PubMed1998

Nebulized glyceryl trinitrate exerts acute bronchodilator effects in patients with acute bronchial asthma.

Glyceryl trinitrate (GTN) is a potent smooth muscle relaxant and vasodilator. There are conflicting reports regarding its efficacy as a bronchodilator. The aim of this study was to examine whether nebulized GTN has bronchodilating effects in patients with acute bronchial asthma. We studied 18 patients (five female, 13 male) who were admitted to the hospital with acute severe asthma on two occasions, administering either 6 mg nebulized GTN or placebo (saline) in a double-blind, randomized, crossover fashion. Bronchial response was assessed by measurement of peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). A systematic effect of this dose of GTN was demonstrated by a mean increase in heart rate of 38.1% (SEM=7.6%) after GTN administration from supine to erect posture, compared with 10.2% (SEM=1.8%) after placebo (P<0.005). Systolic blood pressure decreased by 8.7% (SEM=1.1%) after GTN, compared with 4.0% (SEM=2.1%) after placebo (P<0.05). Diastolic blood pressure did not change significantly. Baseline PEF, FEV1 and FVC did not differ on the two experimental days; however, acute bronchodilating effects were seen: PEF (l/min); 368 (21) pre-GTN, 411 (22) post-GTN and 384 (23) post-placebo (P<0.001). FEV1 (l); 2.12 (0.13) pre-GTN, 2.46 (0.15) post-GTN and 2.25 (0.16) post-placebo (P<0.001). FVC (l); 3.31 (0.17) pre-GTN, 3.75 (0.2) post-GTN and 3.54 (0.2) post-placebo (P<0.001). In conclusions, nebulized GTN has bronchodilating effects in patients with acute bronchial asthma. The exact mechanism of bronchodilation is not known, but it may be due to local effect on bronchial smooth muscles through nitric oxide or by systemic vasodilatation which leads to a decrease in pulmonary artery pressure and pulmonary vascular resistance, or an increase in systemic catecholamine release.

Acute Disease↗
PubMed1998

Bronchoalveolar lavage causes decrease in PaO2, increase in (A-a) gradient value and bronchoconstriction in asthmatics.

The aims of this study were to (1) record the changes of (arterial oxygen partial pressure) PaO2, (arterial carbon dioxide partial pressure) PaCO2, (percentage saturation of haemoglobin with oxygen in arterial blood) SaO2 and alveolar-arterial (A-a) oxygen gradiant resulting from bronchoalveolar lavage (BAL) in asthmatic and normal subjects; (2) measure changes in forced expiratory volume in 1 s (FEV1), vital capacity forced (FVC) associated with BAL; and (3) assess possible predictive factors for the degree of hypoxaemia and impairment of spirometry resulting from BAL. Bronchoscopy and BAL (150 ml) were performed in 24 asthmatics and 15 healthy subjects. Serial arterial blood samples (radial artery) were obtained in all subjects: T1 and before T2 after local anaesthesia; T3 at end of bronchoscopy; T4 after BAL and 5 min, 15 min, 1 h, 2 h, 8 h and 24 h (T5-T10) after the procedure, FEV1 and FVC were measured immediately before and 5 min afer bronchoscopy. Baseline PaO2 was lower in asthmatics (10.2 +/- 0.8 kPa) than in healthy subjects (10.8 +/- 0.8). Both groups showed a significant decrease in PaO2, and a significant widening in (A-a) oxygen tension gradiant at T3-9, with respect to T1 (P < 0.05). PaO2 reached a significantly lower value in asthmatics (7.1 +/- 0.6 kPa) than in HS (7.7 +/- 0.5; P < 0.05). In asthmatics, FEV1, FVC and the ratio FEV1/FVC decreased significantly after BAL (P < 0.001). In healthy subjects, FEV1 and FVC decreased significantly (P < 0.001), whereas FEV1/FVC did not. The fall in FEV1 after BAL was significantly greater in asthmatics (32.4 +/- 10.0%) than in healthy subjects (17.7 +/- 4.6; P < 0.001). Severity of asthma, basline FEV1 or initial PaO2 did not predict the degree of hypoxaemia or the fall of FEV1. It is concluded that BAL causes more severe hypoxaemia and a greater decrease in FEV1 in asthmatics compared to healthy subjects, strongly supporting the recommendation of special caution and careful monitoring when BAL is undertaken in asthmatics.

Analysis of Variance↗
PubMed1998

Circadian rhythm of cutaneous hypersensitivity reactions in nocturnal asthma.

BACKGROUND: Diurnal variation in mast cell discharge may play a central role in the early morning fall in peak expiratory flow rate (PEFR) in nocturnal asthmatic patients. METHODS: We tested the hypothesis that there is a circadian rhythm in mast cell response to allergen in 15 patients with nocturnal asthma by measuring the magnitude of cutaneous hypersensitivity reactions at 0600, 1200, 1800, and 2400 hours. Pre-admission, prick skin testing on the ventral aspect of the forearm to various allergens was performed. The allergen producing the largest wheal was tested at six sites on one forearm. Response was quantified after 20 minutes by measuring the area of the wheal produced using planimetry. Every six hours the skin testing was repeated at six new sites on alternating forearms. The average area of the six wheals was calculated and recorded at each time. The prick skin technique was used at all times. RESULTS: Maximal reactions occurred in 10 of the 15 patients at noon (P = .031, Friedman's two way analysis of variance). In these 10 patients wheal area at the time of maximum reactivity was on average 3.3-fold higher than at the time of minimum reactivity. The mean wheal areas for all 15 patients at 0600, 1200, 1800, and 2400 hours were 34 mm2, 42 mm2, 34 mm2, and 35 mm2 respectively. CONCLUSIONS: These observations support the concept of a circadian rhythm in mast cell activity in patients with severe nocturnal asthma.

Adult↗
PubMed1998

Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma.

In asthma, the acute increment of airway responsiveness caused by exposure to allergen is associated with influx of eosinophils into the airways. The relationship between chronic airway hyperresponsiveness and airway inflammation is unclear, as they do not change consistently following long-term anti-inflammatory treatments. We studied 71 patients with chronic asthma and allergic sensitization to perennial allergens. Airway responsiveness was determined by inhalation of methacholine, and airway inflammation was quantified by induced sputum (n = 28) or bronchoalveolar lavage (n = 43) and bronchial biopsy (n = 20). The relationships between airway responsiveness and the numbers of different inflammatory cells were assessed by multiple regression analysis. No significant correlations were found between the degree of airway responsiveness and the numbers of inflammatory cells in sputum or bronchoalveolar lavage or bronchial biopsy. By contrast, baseline lung function was inversely related to the numbers of eosinophils and directly related to the numbers of macrophages. The eosinophil cationic protein contents of either sputum or bronchoalveolar lavage were significantly correlated with the percentages of eosinophils but not with airway responsiveness. We suggest that other factors (e.g., airway wall remodeling or autonomic dysfunction) may be responsible for most of the interindividual variability of airway responsiveness in asthma.

Adult↗
PubMed1998

Comparison of two methods of processing induced sputum: selected versus entire sputum.

Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8%; p < 0.01), and higher levels of ECP (548 versus 105 microg/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects.

Adult↗
PubMed1997

Attenuation of propranolol-induced bronchoconstriction by frusemide.

BACKGROUND: Inhaled propranolol causes bronchoconstriction in asthmatic subjects by an indirect mechanism which remains unclear. Inhaled frusemide has been shown to attenuate a number of indirectly acting bronchoconstrictor challenges. The aim of this study was to investigate whether frusemide could protect against propranolol-induced bronchoconstriction in patients with stable mild asthma. METHODS: Twelve asthmatic subjects were studied on three separate days. At the first visit subjects inhaled increasing doubling concentrations of propranolol (0.25-32 mg/ml), breathing tidally from a jet nebuliser. The provocative concentration of propranolol causing a 20% reduction in FEV1 (PC20FEV1 propranolol) was determined from the log concentration-response curve for each subject. At the following visits nebulised frusemide (4 ml x 10 mg/ml) or placebo (isotonic saline) was administered in a randomised, double blind, crossover fashion. FEV1 was measured immediately before and five minutes after drug administration. Individual PC20FEV1 propranolol was then administered and FEV1 was recorded at five minute intervals for 15 minutes. Residual bronchoconstriction was reversed with nebulised salbutamol. RESULTS: Frusemide had no acute bronchodilator effect but significantly reduced the maximum fall in FEV1 due to propranolol: mean fall 18.2% after placebo and 11.8% after frusemide. The median difference in maximum % fall in FEV1 within individuals between study days was 3.6% (95% CI 1.2 to 11.7). CONCLUSIONS: Frusemide attenuates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and the present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.

Adrenergic beta-Antagonists↗
PubMed1997

Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma.

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of < or = 1:4.

Administration, Inhalation↗
PubMed1997

Pulmonary and cardiac beta-adrenoceptor density in vivo in asthmatic subjects.

To examine whether there is a primary deficit in beta-adrenoceptor density in asthma, pulmonary and cardiac beta-receptor density was determined in vivo with positron emission tomography (PET) in 10 male asthmatic subjects (36 +/- 8 yr of age) and compared with that in 30 age-matched normal male subjects (36 +/- 8 yr of age). Pulmonary beta-receptor density was 10.3 +/- 1.8 pmol/g tissue for the asthmatic group and 10.9 +/- 1.9 for the normal group. Cardiac beta-receptor density was 9.1 +/- 3.3 pmol/g for the asthmatic group and 8.8 +/- 2.3 pmol/g for the normal group. There was no difference in either pulmonary or cardiac beta-receptor density between the two groups. In addition, an inverse relationship was observed between FEV1 % predicted and pulmonary beta-receptor density in asthmatic subjects. In conclusion, beta-receptor numbers are normal in untreated asthmatic subjects.

Adult↗
PubMed1997

Induced sputum to assess airway inflammation: a study of reproducibility.

BACKGROUND: Infiltration of the airways mucosa with activated inflammatory cells appears to be a major factor in the pathogenesis of asthma and other airway diseases. Examination of sputum provides a direct method to investigate airway inflammation non-invasively. OBJECTIVES: The aim of the present study was to evaluate the reproducibility of cell counts on cytospins and fluid phase (eosinophil cationic protein, ECP) measurements in a selected portion of induced sputum. We aimed to confirm the validity of the tecnique by comparing measurements between stable asthmatics, allergic rhinithis and healthy subjects. METHODS: Sputum was induced with hypertonic saline (4.5%) twice within one week in 53 stable asthmatics, 16 subjects with seasonal rhinitis (out of the pollen season), and 19 healthy subjects. Reproducibility was examined within sample (two different plugs of the same sample) between sample (two specimens of induced sputum obtained within one week) and between examiners on stable subjects taking into account sample size, number of examinations per patients and Confidence Interval (CI) of the estimates. RESULTS: We have found that the method is highly reproducible within sample and between examiners for all types of cells and fluid phase measurements of ECP. It is reproducible between sample for eosinophils, macrophages, neutrophils and ECP, but not for lymphocytes and weakly for epithelial cells. Sputum from asthmatics, in comparison with the sputum of healthy subjects and subjects with rhinitis had higher eosinophils (asthmatics: 12.2% +/- 12.9, rhinitis: 0.4 +/- 0.8, normals: 0.4 +/- 0.7 (%) and ECP (asthmatics: 827 +/- 491 microg/L, rhinitis: 127 +/- 82 normals: 157 +/- 203). No significant differences were found between healthy subjects and subjects with rhinitis. Eosinophil counts were inversely correlated with FEV1 (r = -0.37) expressed as percentage of predicted, but not significantly correlated with PC20 methacholine (r = -0.28) or blood eosinophils (r = 0.26). CONCLUSIONS: The importance of this study is the confirmation, within important statistical guidelines for a study of reproducibility, that the methods examined are reproducible and valid.

Adult↗
PubMed1996

Anti-leukotriene intervention: is there adequate information for clinical use in asthma?

Various mediators of inflammation have been suggested as being important in the pathogenesis of asthma. These include histamine, acetylcholine, bradykinin, adenosine, prostaglandins D2 and F2 alpha, thromboxane A2, leukotrienes, PAF and, more recently, various cytokines. Intervention in the action of these mediators is proposed to offer therapeutic benefit, and recent advances in drug therapy have centred on two main approaches. Specific and potent leukotriene antagonists and inhibitors of leukotriene biosynthesis have emerged, and their effects against allergen challenge, cold-air- and exercise-induced bronchospasm and aspirin-sensitive asthma have been evaluated. A small number of studies have also been conducted in clinical asthma, with both acute and long-term (up to 20 weeks) efficacy studies being reported. A considerable degree of inter-individual variation is seen in the degree of protection afforded by leukotriene intervention. The extent to which inhibiting one set of inflammatory mediators can be expected to attenuate the asthmatic response can be questioned. As yet, there is no way of distinguishing leukotriene-related asthma from other types. It is likely, however, that leukotriene intervention may be useful in some patients with specific forms of the disease; for example, aspirin-sensitive asthma. Leukotriene intervention is unlikely to replace inhaled corticosteroids in the treatment of asthma, and its position in the guidelines for the management of asthma remain unclear thus far.

Asthma↗
PubMed1996

In vivo quantification of human pulmonary beta-adrenoceptors: effect of beta-agonist therapy.

In human subjects, chronic beta2-agonist dosing reduces mononuclear leukocyte (MNL) beta-adrenoceptor numbers. The aim of this study was to investigate whether this downregulation also occurs in the lung. Seven healthy male subjects were treated for 2 wk with oral (up to 16 mg/d) and inhaled (up to 1.6 mg/d) albuterol (salbutamol in Europe). Pulmonary maximal beta-adrenoceptor binding capacity (Bmax) was determined in vivo using positron emission tomography (PET) and the beta-receptor antagonist ligand, 11C-labeled CGP-12177, before and after the 2-wk chronic dosing. MNL Bmax was also measured, using a radioligand binding assay and 3H-labeled CGP-12177. Bronchodilator responses to the beta2-agonist were determined after each PET scan by measuring the change in specific airway conductance (SGaw) after increasing doses of inhaled albuterol. Pulmonary and MNL Bmax fell by 22% +/- 14% (p < 0.05) and 42% +/- 19% (p < 0.05) respectively. The changes in pulmonary and MNL Bmax were correlated (r = 0.9, p < 0.05). There was also a reduction in the bronchodilator response to inhaled albuterol. In a further six subjects, pulmonary and MNL Bmax did not change during an acute infusion of albuterol (2 to 4 microg/kg/h). The reduction in pulmonary beta-adrenoceptor numbers after chronic albuterol dosing may be predictable from the changes observed in circulating MNL cells.

Administration, Inhalation↗
PubMed1995

Intradermal actions of hypertonic saline involve neural and vascular mechanisms.

The aim of this study was to investigate whether the wheal and flare responses to intradermal injection of hypertonic (4.5%) saline (HTS) were inhibited by local injection of 1% lignocaine. Eight normal subjects were studied on one occasion. Lignocaine (0.125 ml) was infiltrated at four sites on one forearm and normal saline on the other. Five minutes later, duplicate intradermal injections of 30 microliters of histamine (22.5 nmol ml-1), substance P (1 nmol ml-1), HTS and normal saline were given coded and in random order, one of each pair to each forearm. Lignocaine inhibited flare responses to histamine, substance P and HTS by 56% (P < 0.01), 78% (P < 0.01) and 77% (P < 0.05) respectively suggesting similar involvement of an axon reflex. Wheal to histamine was inhibited by 31% (P < 0.02) and to substance P by 33% (P < 0.05) but not to HTS. This suggests that the mechanism of wheal response to HTS differs from that of histamine and substance P.

Anesthetics, Local↗
PubMed1995

Determination of the minimum dose of lactose drug carrier that can be sensed during inhalation.

Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy volunteers without respiratory symptoms inhaled seven different doses of lactose and a placebo (empty) dose through the four place Diskhaler device, in order to determine the lowest dose that could be reliably sensed. The minimum dose for which all subjects reported taste or feel sensations was 10 mg. This has implications regarding the amount of carrier used in future drug delivery systems.

Administration, Inhalation↗
PubMed1995

Effects of intradermal injection of atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of alpha-human ANP in normal humans. Eight normal subjects received five 30 microliters injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 +/- 0.6 (mean +/- s.e. mean) compared with 0.42 +/- 0.17 cm2, but much less than to histamine 9.86 +/- 0.97 or to substance P 12.5 +/- 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 +/- 0.08 compared with 0.18 +/- 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 +/- 0.06 or to substance P 1.05 +/- 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.

Adult↗