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(1/213) Risk factors for death from asthma, chronic obstructive pulmonary disease, and cardiovascular disease after a hospital admission for asthma.

BACKGROUND: Patients with asthma have an increased risk of death from causes other than asthma. A study was undertaken to identify whether severity of asthma, its treatment, or associated co-morbidity were associated with increased risk of death from other causes. METHODS: Eighty five deaths from all causes occurring within three years of discharge from hospital in a cohort of 2242 subjects aged 16-64 years admitted for asthma were compared with a random sample of 61 controls aged <45 years and 61 aged >/=45 years from the same cohort. RESULTS: Deaths from asthma were associated with a history of clinically severe asthma (OR 6.29 (95% CI 1.84 to 21.52)), chest pain (OR 3.78 (95% CI 1.06 to 13.5)), biochemical or haematological abnormalities at admission (OR 4.12 (95% CI 1.36 to 12.49)), prescription of ipratropium bromide (OR 4.04 (95% CI 1.47 to 11.13)), and failure to prescribe inhaled steroids on discharge (OR 3.45 (95% CI 1.35 to 9.10)). Deaths from chronic obstructive pulmonary disease (COPD) were associated with lower peak expiratory flow rates (OR 2.56 (95% CI 1.52 to 4.35) for each 50 l/min change), a history of smoking (OR 5.03 (95% CI 1.17 to 21.58)), prescription of ipratropium bromide (OR 7.75 (95% CI 2.21 to 27.14)), and failure to prescribe inhaled steroids on discharge (OR 3.33 (95% CI 0.95 to 11.10)). Cardiovascular deaths were more common among those prescribed ipratropium bromide on discharge (OR 3.55 (95% CI 1.05 to 11.94)) and less likely in those admitted after an upper respiratory tract infection (OR 0.21 (95% CI 0.05 to 0.95)). Treatment with ipratropium bromide at discharge was associated with an increased risk of death from asthma even after adjusting for peak flow, COPD and cardiovascular co-morbidity, ever having smoked, and age at onset of asthma. CONCLUSIONS: Prescription of inhaled steroids on discharge is important even for those patients with co-existent COPD and asthma. Treatment with ipratropium at discharge is associated with increased risk of death from asthma even after adjustment for a range of markers of COPD. These results need to be tested in larger studies.  (+info)

(2/213) Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia.

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.  (+info)

(3/213) Changes in airway resistance induced by nasal or oral intermittent positive pressure ventilation in normal individuals.

Nasal intermittent positive-pressure ventilation (nIPPV) is used for the treatment of respiratory failure in patients with neuromuscular disease. The aim of the present study was to demonstrate that nIPPV may activate nose receptors, the consequence of which being reflex changes in lung resistance. The changes in interrupter resistances (Rint) in response to nIPPV were tested before and after local anaesthesia of the nasal mucosa in normal subjects. They were compared to the Rint changes induced by oral intermittent positive-pressure ventilation (oIPPV) in the same individuals. Rint was measured during 10-min periods of nIPPV or oIPPV at a constant rate (15 L x min(-1)), but at two different stroke volumes (0.8 and 1.2 L). Inspired temperature and relative humidity were held constant. nIPPV with 1.2 L (17 mL x kg(-1)) significantly increased the Rint value (+22%). This effect disappeared after nose anaesthesia or after inhalation of a cholinergic antagonist. oIPPV never changed Rint, even though the associated hypocapnia was present and more accentuated than during nIPPV. Adding CO2 to the inspired gas during nIPPV and oIPPV trials suppressed the Rint changes. The present study suggests the existence of a nasopulmonary bronchoconstrictor reflex elicited through the stimulation of nasal mechanoreceptors, their activity being markedly influenced by the changes in expired CO2 concentration.  (+info)

(4/213) Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways.

1. In this study we have evaluated the pharmacological profile of the muscarinic antagonist glycopyrrolate in guinea-pig and human airways in comparison with the commonly used antagonist ipratropium bromide. 2. Glycopyrrolate and ipratropium bromide inhibited EFS-induced contraction of guinea-pig trachea and human airways in a concentration-dependent manner. Glycopyrrolate was more potent than ipratropium bromide. 3. The onset of action (time to attainment of 50% of maximum response) of glycopyrrolate was similar to that obtained with ipratropium bromide in both preparations. In guinea-pig trachea, the offset of action (time taken for response to return to 50% recovery after wash out of the test antagonist) for glycopyrrolate (t1/2 [offset]=26.4+/-0.5 min) was less than that obtained with ipratropium bromide (81.2+/-3.7 min). In human airways, however, the duration of action of glycopyrrolate (t1/2 [offset]>96 min) was significantly more prolonged compared to ipratropium bromide (t1/2 [offset]= 59.2+/-17.8 min). 4. In competition studies, glycopyrrolate and ipratropium bromide bind human peripheral lung and human airway smooth muscle (HASM) muscarinic receptors with affinities in the nanomolar range (K1 values 0.5-3.6 nM). Similar to ipratropium bromide, glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide. 5. These results suggest that glycopyrrolate bind human and guinea-pig airway muscarinic receptors with high affinity. Furthermore, we suggest that the slow dissociation profile of glycopyrrolate might be the underlying mechanism by which this drug accomplishes its long duration of action.  (+info)

(5/213) An empirical comparison of the St George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ) in a clinical trial setting.

BACKGROUND: The Chronic Respiratory Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) are the two most widely used quality of life questionnaires in chronic obstructive pulmonary disease (COPD). A study was undertaken to compare directly the self-administered version of the CRQ and the SGRQ with respect to feasibility, internal consistency, validity, and sensitivity to changes resulting from bronchodilator therapy. METHODS: One hundred and forty four patients with moderate or severe COPD were randomly assigned to receive three months of treatment with either salmeterol, salmeterol + ipratropium bromide, or placebo. Quality of life was measured at baseline and after 12 weeks of treatment. RESULTS: The proportions of missing values per patient were low for both questionnaires (0.54% for the CRQ and 2% for the SGRQ). The internal consistency was good for both questionnaires (Cronbach's alpha coefficients >/= 0.84 for the CRQ and >/= 0.76 for the SGRQ). Factor analysis confirmed the original domain structure of the CRQ but not of the SGRQ. Correlations with forced expiratory volume in one second (FEV(1)) % predicted and peak expiratory flow rate (PEFR) were low for both questionnaires but better for the SGRQ than for the CRQ. The ability to discriminate between subjects with different levels of FEV(1) was somewhat better for the SGRQ. The correlations with symptom scores were comparable for both questionnaires. Cross sectionally, the scores of the two questionnaires were moderately to highly correlated (coefficients ranged from 0.35 to 0.72). Longitudinally, these correlations were lower (coefficients ranged from 0.17 to 0.54) but were still significant. The CRQ total and emotions score and the SGRQ symptoms score were the most responsive to change. The SGRQ symptoms domain was the only domain where the improvement in patients receiving combination treatment crossed the threshold for clinical relevance. CONCLUSIONS: Since this analysis of reliability, validity, and responsiveness to change did not clearly favour one instrument above the other, the choice between the CRQ and the SGRQ can be based on other considerations such as the required sample size or the availability of reference values.  (+info)

(6/213) Laser Doppler flowmetry as a measure of extrinsic colonic innervation in functional bowel disease.

BACKGROUND: In functional disorders it is unknown whether disturbed function is due to an intrinsic gut abnormality or altered extrinsic innervation. AIMS: To study whether measurement of mucosal blood flow could be used as a quantitative direct measure of gut extrinsic nerve autonomic activity in patients with idiopathic constipation. METHODS: Seventy two patients with idiopathic constipation and 26 healthy volunteers had rectal mucosal blood flow measurements by a laser Doppler flowmetry probe applied 10 cm from the anus. Measurements were made at rest and after inhaled placebo and ipratropium 40 microg. RESULTS: Constipated subjects had lower baseline rectal blood flow than controls. Patients with slow transit had lower mucosal blood flow than normal transit. The number of retained markers on x-ray was inversely correlated with blood flow. Ipratropium reduced blood flow compared with placebo, reduced it less in constipated patients than controls, and reduced it less in patients with slow compared with normal transit. Constipated patients, not controls, showed a significantly attenuated RR interval (the interval between successive R waves on the ECG) variability, and blood flow correlated with vagal function. CONCLUSIONS: Laser Doppler mucosal flowmetry is a gut specific, quantitative measure of extrinsic autonomic nerve activity. The technique has shown that patients with idiopathic constipation have impaired extrinsic gut nerve activity, and this is more notable in those with slow transit. The degree of slow transit correlates with the degree of impaired extrinsic innervation.  (+info)

(7/213) Lack of association between ipratropium bromide and mortality in elderly patients with chronic obstructive airway disease.

BACKGROUND: Ipratropium is commonly used for the management of elderly patients with obstructive airway disease. However, a recent report suggested that its use might be associated with a significant increase in mortality. A study was therefore conducted to compare all-cause mortality rates between users and non-users of ipratropium in elderly patients with either asthma or chronic obstructive pulmonary disease (COPD). METHODS: A retrospective cohort study was performed using linked data from the Canadian Institute for Health Information, the Ontario Drug Benefit Program, the Ontario Health Insurance Plan, and the Ontario Registered Persons database. A total of 32 393 patients were identified who were aged 65 years or older and who had been discharged from hospital with asthma or COPD between 1 April 1992 and 31 March 1997. All-cause mortality rates were compared between those treated and those not treated with ipratropium following discharge from hospital. RESULTS: In total, 49% of patients received ipratropium within 90 days of discharge. After adjusting for age, sex, comorbidity, use of health services, and other airway medications there was no significant association in patients with COPD between the use of ipratropium and mortality (relative risk (RR) 1.03; 95% confidence interval (CI) 0.98 to 1.08). In patients with asthma, however, there was a slight increase in the relative risk of mortality associated with the use of ipratropium (RR 1.24; 95% CI 1.11 to 1.39). A dose-response increase in the mortality rate was not observed with increasing use of ipratropium in either COPD or asthma. CONCLUSIONS: The use of ipratropium in patients with COPD was not associated with an increase in mortality. However, in asthma there was a small increase in the mortality rate. Since asthmatic patients who received ipratropium had greater use of other airway medications and health services, the difference in mortality rate between users and non-users may be a reflection of unmeasured differences in asthma severity.  (+info)

(8/213) A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.

BACKGROUND: A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: 288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV(1)) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 microg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV(1) and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV(1) and FVC), and 0.5, 1, 2, 3, 4, 5, and 6 hours after inhalation of the study drug on days 1, 8, 50, and 92. RESULTS: During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV(1) levels and in trough and average FVC levels. The trough FEV(1) response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01 to 0. 07) for ipratropium. The trough FVC response on days 8, 50, and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV(1) than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients). CONCLUSIONS: Tiotropium in a dose of 18 microg inhaled once daily using the HandiHaler was significantly more effective than 40 microg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.  (+info)