The feasibility and impact of implementing a computer-guided consultation to target health inequality in Asthma.

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management. Patients on asthma registers in Greater Manchester Primary Care Networks were identified and underwent remote review by nursing staff using the CGC linked directly to the GP clinical system. Three-hundred thirty-eight patients (mean age 59 (SD 17) years; 60% Female) were reviewed. The CGC reported the patient's asthma control to be "Good" in 22%, "Partial" in 6% and "Poor" in 72%. ACT scores were significantly higher in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. The number of steroid courses and hospital admissions in the previous 12 months was significantly lower in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. Nineteen percent were found not to have a personalised asthma management plan during CGC review, which was alerted by the CGC and subsequently, all but 3 patients had this created on review completion (McNemar's test; p < 0.001). 5% were found not to have been prescribed regular inhaled steroid therapy resulting in the operator being alerted by the CGC in all cases. Overall, 44% underwent alteration in asthma therapy following the CGC review with 82% of these representing treatment escalation. An end-to-end digital service solution is feasible for Asthma within primary care and the utilisation of a CGC when conducting primary care asthma reviews increases implementation of guideline-level management thus addressing healthcare inequality while enabling identification of "high risk" asthma patients and guiding appropriate therapy escalation and de-escalation.

Hyperglycaemia as a predictor of outcome during non-invasive ventilation in decompensated COPD.

RATIONALE: Hyperglycaemia predicts a poor outcome in Intensive Care Unit (ICU) patients. Whether this is true for respiratory failure necessitating non-invasive ventilation (NIV) is not known. OBJECTIVES: To determine whether hyperglycaemia within 24 h of admission independently predicts outcome of NIV during acute decompensated ventilatory failure complicating chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: Patients with COPD presenting with acute hypercapnic respiratory failure at University Hospital Aintree between June 2006 and September 2007 and receiving NIV within 24 h of admission were studied prospectively. Random blood glucose levels were measured before NIV administration. RESULTS: 88 patients (mean baseline pH 7.25, PaCO(2) 10.20 kPa, and PaO(2) 8.19 kPa) met the inclusion criteria, with NIV normalising arterial pH off therapy in 79 (90%). After multivariate logistic regression, the following predicted outcome: baseline respiratory rate (OR 0.91; 95% CI 0.84 to 0.99), random glucose > or = 7 mmol/l (OR 0.07; 95% CI 0.007 to 0.63) and admission APACHE II (Acute Physiology and Chronic Health Evaluation II) score (OR 0.75; 95% CI 0.62 to 0.90). The combination of baseline respiratory rate (RR) <30 breaths/min and random glucose <7 mmol/l increased prediction of NIV success to 97%, whilst use of all three factors was 100% predictive. CONCLUSIONS: In acute decompensated ventilatory failure complicating COPD, hyperglycaemia upon presentation was associated with a poor outcome. Baseline RR and hyperglycaemia are as good at predicting clinical outcomes as the APACHE II score. Combining these variables increases predictive accuracy, providing a simple method of early risk stratification.

Lessons from the implementation of a home telecare service.

We conducted a qualitative evaluation of the introduction of a telenursing service. The service used an analogue videophone linked with a physiological monitoring device, which allowed the transmission of data between the patient's home and the hospital. A researcher kept a detailed diary of day-to-day activity for the first year of the project. Computer software for qualitative data analysis was used to code the text and the analysis followed the principles of constant comparison. The diary entries documented how the commercially available equipment was adapted to suit the organization and content of the nurses' work. The nurses made a number of suggestions to improve the user-friendliness of the equipment. The technology, the existing home care service (the comparison arm of the study) and the randomized controlled trial itself all underwent continuous change. The traditional randomized control design of trial has limitations in this situation, and there is a need for more realistic trial designs.

Inhaled corticosteroids (budesonide): the cornerstone of asthma therapy--what are the options?

The clinical value of corticosteroids in treating asthma has long been recognised. Major advances in the use of these drugs came with the introduction of inhaled corticosteroids (ICS) and the recognition that even mild asthma has an inflammatory component. ICS are now considered as first-line therapy in all asthma treatment guidelines. Over the past decade there has been clarification of the dose-response relationship with ICS and confirmation of the general long-term efficacy and safety of these drugs in both adults and children. Recent work has focused on simplifying dosing regimens and investigating flexibility of dosing. Moreover, ICS can be used in combination with other agents such as long-acting inhaled beta(2)-agonists to provide effective asthma control in patients with persistent asthma not adequately controlled on ICS alone. Thus, ICS remain the cornerstone of modern asthma therapy.

"Hospital at home" versus hospital care in patients with exacerbations of chronic obstructive pulmonary disease: prospective randomised controlled trial.

OBJECTIVES: To compare "hospital at home" and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease. DESIGN: Prospective randomised controlled trial with three months' follow up. SETTING: University teaching hospital offering secondary care service to 350 000 patients. PATIENTS: Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment. INTERVENTIONS: Nurse administered home care was provided as an alternative to inpatient admission. MAIN OUTCOME MEASURES: Readmission rates at two weeks and three months, changes in forced expiratory volume in one second (FEV(1)) from baseline at these times and mortality. RESULTS: 583 patients with chronic obstructive pulmonary disease referred for admission were assessed. 192 met the criteria for home care, and 42 refused to enter the trial. 100 were randomised to home care and 50 to hospital care. On admission, FEV(1) after use of a bronchodilator was 36.1% (95% confidence interval 2.4% to 69.8%) predicted in home care and 35.1% (6.3% to 63. 9%) predicted in hospital care. No significant difference was found in FEV(1 )after use of a bronchodilator at two weeks (42.6%, 3.4% to 81.8% versus 42.1%, 5.1% to 79.1%) or three months (41.5%, 8.2% to 74.8% versus 41.9%, 6.2% to 77.6%) between the groups. 37% of patients receiving home care and 34% receiving hospital care were readmitted at three months. No significant difference was found in mortality between the groups at three months (9% versus 8%). CONCLUSIONS: Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease.

The role of telecare in the management of exacerbations of chronic obstructive pulmonary disease in the home.

We examined home care as an alternative to hospital admission in exacerbations of chronic obstructive pulmonary disease (COPD). We performed a pilot study to investigate the feasibility of using telecommunications technology to assist in the support of acutely ill patients with exacerbations of COPD at home. Realtime, interactive video, via an analogue video-phone, was used to allow patients in their own homes to obtain nursing support from a nurse located at a distant base station. Six individuals, four male and two female, had video-phones installed in their homes by members of the nursing intervention team. The age range was 52-72 years, mean 61.5. These patients used the system on 18 occasions. Experience in home telecare, via interactive video, has been limited to provision of ongoing support for relatively stable individuals with chronic illness. This pilot project represents the first attempt at providing home telecare in the UK to those experiencing an acute exacerbation of their chronic illness, who would otherwise have merited acute hospital admission.

Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.

BACKGROUND: The role of oral corticosteroids in treating patients with exacerbations of chronic obstructive pulmonary disease (COPD) remains contentious. We assessed in a prospective, randomised, double-blind, placebo-controlled trial the effects of oral corticosteroid therapy in patients with exacerbations of COPD requiring hospital admission. METHODS: We recruited patients with non-acidotic exacerbations of COPD who were randomly assigned oral prednisolone 30 mg once daily (n=29) or identical placebo (n=27) for 14 days, in addition to standard treatment with nebulised bronchodilators, antibiotics, and oxygen. We did spirometry and recorded symptom scores daily in inpatients. Time to discharge and withdrawals were noted in each group. We recalled patients at 6 weeks to repeat spirometry and collect data on subsequent exacerbations and treatment. Hospital stay was analysed by intention to treat and forced expiratory volume in 1 s (FEV1) according to protocol. FINDINGS: FEV1 after bronchodilation increased more rapidly and to a greater extent in the corticosteroid-treated group: percentage predicted FEV1 after bronchodilation rose from 25.7% (95% CI 21.0-30.4) to 32.2% (27.3-27.1) in the placebo group (p<0.0001) compared with 28.2% (23.5-32.9) to 41.5% (35.8-47.2) in the corticosteroid-treated group (p<0.0001). Up to day 5 of hospital stay, FEV1 after bronchodilation increased by 90 mL daily (50.8-129.2) and by 30 mL daily (10.4-49.6) in the placebo group (p=0.039). Hospital stays were shorter in the corticosteroid-treated group. Groups did not differ at 6-week follow-up. INTERPRETATION: These data provide evidence to support the current practice of prescribing low-dose oral corticosteroids to all patients with non-acidotic exacerbations of COPD requiring hospital admission.

Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure. METHODS: Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 < 8 kPa and PaCO2 > 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours. RESULTS: In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2. CONCLUSIONS: NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD.

Effect of inhaled thiorphan, a neutral endopeptidase inhibitor, on the bronchodilator response to inhaled atrial natriuretic peptide (ANP).

BACKGROUND: The hormone atrial natriuretic peptide (ANP) causes bronchodilation and partially protects against direct and indirect bronchial challenges. Both in vitro and in vivo studies have found that the protective effect of ANP against bronchoconstriction is enhanced by inhibition of the enzyme neutral endopeptidase (NEP). It was hypothesised that pretreatment with thiorphan, an NEP inhibitor, might enhance the bronchodilator response to inhaled ANP. METHODS: In a randomised double blind placebo controlled crossover study, six asthmatic patients (one woman) of mean (SD) age 47.3 (3.8) years and forced expiratory volume in one second (FEV1) 1.91 (0.42) 1, 55 (3.8)% predicted, were studied. All were shown at screening to have at least a 25% improvement in FEV1 to inhaled salbutamol. On five study visits the patients received either thiorphan 1 mg (in 2 ml) followed by ANP 5 mg or placebo (saline), or placebo (saline) followed by ANP (5 mg), placebo or salbutamol 5 mg. Spirometric parameters were measured after each inhalation and thereafter for the next two hours. RESULTS: ANP alone caused a bronchodilator response up to 15 minutes when compared with placebo or thiorphan alone with a mean (SE) change in FEV1 of 16.8 (8.1)% and 16.1 (6.8)% at 10 and 15 minutes from baseline, respectively. Prior inhalation of thiorphan prolonged the duration of the bronchodilator effect of ANP up to 60 minutes with a mean (SE) change in FEV1 of 23.1 (3.4)% at 60 minutes. There was no difference in the maximum degree of bronchodilation following the administration of ANP alone compared with the combination of thiorphan and ANP. The degree and duration of the bronchodilator response produced by ANP, or the combination of the NEP inhibitor and ANP, were less than that produced by salbutamol. CONCLUSIONS: These results confirm that, at least in part, the bronchodilator response to inhaled ANP is modulated by NEP. Analogues of ANP which are stable to NEP may have greater bronchodilator activity than ANP in the treatment of asthma.

Effect of hypoxia and beta 2-agonists on the activity of the renin-angiotensin system in normal subjects.

1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized beta 2-agonists. The contribution of other possible stimuli such as hypoxia is unknown. The present study examined the effect of hypoxia alone and also combined with beta 2-agonists on the activity of the renin-angiotensin system. 2. In a double-blind crossover study, eight healthy subjects were randomized to inhale a hypoxic (FiO2 = 12%) or normoxic mixture for a period of 30 min, with either nebulized salbutamol (5 mg) or placebo administered into the circuit after 10 min. Plasma renin, angiotensin II and serum angiotensin-converting enzyme were measured at baseline and at intervals up to 2 h. Pulse rate and oxygen saturation were monitored continuously throughout the study. 3. After hypoxia alone, there was no change in the levels of plasma renin or angiotensin II. When salbutamol was added to the hypoxic mixture, there was a significant rise in plasma renin and angiotensin II [mean (SEM) maximal increase in angiotensin II of 5.6 (2.9) pg/ml and renin of 15.5 (6.3) mu-units/ml at 60 min, P < 0.05 compared with normoxia]. When salbutamol was administered in the normoxic mixture, plasma renin and angiotensin II also increased but this effect was similar to the effect of salbutamol in the hypoxic mixture. Serum angiotensin-converting enzyme levels were unaffected by hypoxia or salbutamol. 4. We conclude from these results that there is activation of the renin-angiotensin system in healthy subjects by salbutamol, but not hypoxia. (ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inhaled atrial natriuretic peptide and a neutral endopeptidase inhibitor on histamine-induced bronchoconstriction.

The reduced ability of inhaled compared with intravenous atrial natriuretic peptide (ANP) to modify bronchial reactivity and tone may be due to degradation of the peptide by neutral endopeptidase (NEP) within the airways. To test this hypothesis, we have examined the effect of thiorphan, an NEP inhibitor, on the protection afforded by inhaled ANP against histamine-induced bronchoconstriction in 10 mildly asthmatic patients. Pretreatment with ANP alone attenuated the bronchoconstrictor response to histamine with a mean (SEM) maximum percent fall in FEV1 after histamine of 15.9 (2.9) (p < 0.05) compared with 24 (2.9) after placebo and 24 (4) after pretreatment with thiorphan alone. Prior inhalation of thiorphan greatly enhanced the ANP effect: the mean maximum percent fall after this combination was 5.1 (2.3) (p < 0.01, compared with ANP alone). Our results suggest that airway NEP is important in modulating the effect of inhaled ANP. It may be possible to exploit the guanylyl cyclase pathway, by which ANP acts, in the treatment of asthma by the administration of ANP analogues stable to neutral endopeptidase.

Effect of a novel potent platelet-activating factor antagonist, modipafant, in clinical asthma.

Platelet-activating factor (PAF), proposed as an important inflammatory mediator in asthma, reproduces several of the features of asthma, such as microvascular leakage, mucus secretion, bronchoconstriction, and possibly increased airway responsiveness. Modipafant (UK-80,067) is the (+)-enantiomer of UK-74,505, a potent and specific PAF antagonist. We have assessed the effect of modipafant over 28 d in adult subjects with moderately severe asthma in a placebo-controlled parallel group study. A total of 218 patients with asthma were enrolled into the single-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr) entered the double-blind treatment phase after demonstrating symptomatic asthma in the final week of the single-blind run-in phase. Patients could take up to 1600 micrograms inhaled corticosteroid and an inhaled beta 2 agonist as rescue medication. A total of 59 patients with asthma took modipafant (one 50 mg capsule twice daily), and 61 took matched placebo. There was no significant difference between placebo and modipafant in diurnal variation in PEF, morning and evening PEF, clinic FEV1, rescue bronchodilator usage, symptom score, or airway responsiveness. We previously showed that the racemate UK-74,505 had no effect on antigen challenge, and this study shows that the active (+)-enantiomer modipafant has no effect in chronic asthma. This suggests that PAF is not an important mediator in asthma.

Effect of inhaled atrial natriuretic peptide on methacholine induced bronchoconstriction in asthma.

We have previously demonstrated that intravenous and inhaled atrial natriuretic peptide (ANP) significantly inhibits histamine induced bronchoconstriction in asthmatic patients. The current study was designed to determine whether inhaled ANP was also able to inhibit the effects of methacholine. Eight atopic asthmatic patients (five women) were studied: mean (SD) age 38.2 (8.3) years flow expiratory volume per second (FEV1) 2.97 (0.60) litres, equivalent to 92 (13) % of the predicted. Each had demonstrated at least mild bronchial hyperreactivity to inhaled methacholine at screening (geometric mean PC20 1.02 mg/ml; range 0.11-6.54 mg/ml). Patients attended for 3 study days and after baseline spirometry received 3.5 ml saline (placebo), 0.1 mg ANP or 1 mg ANP (ANP dissolved in 3.5 ml saline) in a randomized, double-blind manner via a Mizer aerosol conservation device. Aerosolization took approximately 9 min and FEV1 was repeated at 0.5, 1.5 and 3 min after completion. Immediately thereafter each patient received a 2 min inhalation of methacholine at a dose individually calculated to give a 25% fall in FEV1 (as extrapolated at their initial screening visit) and the FEV1 was followed over the next 20 min. Mean (SEM)% FEV1 did not change significantly after ANP being -4.3 (1.7), -3.2 (2.7) and -2.4 (1.2) after placebo, 0.1 mg ANP and 1 mg ANP respectively. The mean (SEM) maximum fall in FEV1 after methacholine was as follows: placebo 26.9 (5.7)%, 0.1 mg ANP 18.2 (4.3)% and 1.0 mg 11.2 (2.7)% (P < 0.05 placebo vs 1 mg ANP). These results demonstrate that ANP offers significant protection against methacholine induced bronchoconstriction in asthmatic patients.

Management of chronic airflow obstruction: differences in practice between respiratory and general physicians.

An audit of inpatient care of diseases characterized by chronic airflow obstruction namely chronic bronchitis, emphysema and chronic obstructive airways disease (ICD Code Nos. 490-2 & 496) was performed and the practice of respiratory and general physicians compared. One hundred cases were sampled at random from 279 cases admitted to hospitals serving the West of Glasgow in 1988. Fifty cases were selected from those admitted under the care of respiratory physicians and 50 from those under general physicians; 89 were suitable for analysis. The main outcome measurements consisted of the use of routine respiratory investigations, comparison of the use of standard therapies during the admission and at discharge, length of stay, inpatient deaths, follow up and readmission rates. The groups were similar in age, smoking history, gender and there was no significant difference in admission arterial blood gas values. The pulse rate on admission was higher in the general group (102 beats per min) in comparison to the respiratory group (91 beats per min) (P < 0.004). A similar use of chest radiograph and arterial blood gas analysis was noted between the groups. Ninety-six per cent of respiratory patients had either spirometry or peak expiratory flow measured compared to 62% in the general group (P = 0.0001). No significant differences were noted in the use of antibiotics, bronchodilators, corticosteroids, oxygen or respiratory stimulants. The mean length of stay was similar. Two patients (4%) in the respiratory group compared with seven (18%) in the general group died during the admission (P = 0.01); there were no further early deaths at 1 month from discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a disease of asthmatic patients which may follow a protracted course and result in chronic lung damage such as central bronchiectasis. In asthma uncomplicated by allergic bronchopulmonary aspergillosis, in particular in asthmatic patients with immediate hypersensitivity type skin reactions to Aspergillus fumigatus, the incidence of bronchiectasis is uncertain. METHODS: Computed tomographic (CT) scans were performed in 17 asthmatic patients of mean (SE) age 60.1 (2.5) years, FEV1 49.4 (5.8)% predicted with allergic bronchopulmonary aspergillosis (all with current or previous positive precipitins to A fumigatus) and in 11 asthmatic patients of mean (SE) age 49.5 (5.8) years, FEV1 75.5 (6.5)% predicted, skin test positive for A fumigatus, but without the clinical or serological features of allergic bronchopulmonary aspergillosis (non-allergic bronchopulmonary aspergillosis group). RESULTS: Bronchial dilatation was more common in the group with allergic bronchopulmonary aspergillosis, affecting 14 patients compared with two in the non-allergic bronchopulmonary aspergillosis group. Evidence of bronchiectasis was found in 43 of a possible 102 lobes of patients with allergic bronchopulmonary aspergillosis, compared with three of a possible 66 in the non-allergic bronchopulmonary aspergillosis group. Bronchial wall thickening was common to both, affecting 16 and nine patients respectively. Pleural thickening on CT scanning was common in the group with allergic bronchopulmonary aspergillosis, being noted in 14 patients compared with only three in the non-allergic bronchopulmonary aspergillosis group. CONCLUSIONS: Bronchiectasis is common in allergic bronchopulmonary aspergillosis but occurs only occasionally in asthmatic patients with a positive skin test to A fumigatus but without other features of the disease.

No effect of the oral neutral endopeptidase inhibitor candoxatril, on bronchomotor tone and histamine reactivity in asthma.

Neutral endopeptidase (NEP) is found in many tissues in man, including the lung. Metabolism by NEP is one of the main mechanisms for the clearance of atrial natriuretic peptide (ANP), a hormone that causes bronchodilation and reduces nonspecific bronchial reactivity in man. Candoxatril, an oral NEP inhibitor has been shown to elevate circulating ANP levels. We have sought to determine whether the administration of candoxatril will alter bronchomotor tone (forced expiratory volume in one second (FEV1)) and histamine reactivity. Ten male asthmatic patients with stable asthma were enrolled (mean (SD) age 32 (10) yrs; FEV1 92 (11)% predicted) in a randomized, double-blind, placebo-controlled study. On each study day, after baseline spirometry, patients received 200 mg of candoxatril or placebo. Spirometry was repeated at half hourly intervals. After 2 h a histamine inhalation test was performed. There was no significant difference in FEV1 values at baseline or at 2 h post-dosing between active and placebo study days, with mean (SEM) FEV1 at baseline and 2 h of 3.71 (0.29) l and 3.85 (0.29) l on the placebo day, and 3.89 (0.27) l and 4.05 (0.82) l on the active day, respectively. The geometric mean (range) provocative concentration of histamine producing a 20% fall in FEV1 (PC20) on the placebo day and active day did not differ significantly, being 1.17 (0.25-25.8) and 0.93 (0.13-32) mg.ml-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function.

BACKGROUND: The activity of the renin-angiotensin system in asthma has not been studied previously and the effect of angiotensin II (AII) on bronchomotor tone in vivo is unknown. METHODS: Plasma levels of renin and AII levels were measured in 20 patients with acute severe asthma, nine with mild asthma, 10 with severe chronic asthma, and 16 normal volunteers. The effect of AII, given as an intravenous infusion, on bronchomotor tone was also investigated in eight mild asthmatic patients. RESULTS: In acute severe asthma plasma levels of renin [median (interquartile range)] were elevated on days 1, 2, and 5 after admission [48.7 (24-79), 44.2 (15-75), and 45.5 (21-70) microU/ml, respectively]. Plasma AII levels were significantly elevated at day 5 [56 (12-109) pg/ml]. In the second study a bronchoconstrictor response to intravenous AII was seen with a mean (SE) maximal fall in FEV1 of 0.34 (0.13) litres or 12.4 (3.3)% from baseline following the high dose infusion of AII (8 ng/kg/min) with a corresponding plasma AII concentration of 121.3 pg/ml. CONCLUSIONS: The renin-angiotensin system is activated in acute asthma and AII causes bronchoconstriction in vivo in man. These observations suggest that in some patients AII may contribute to bronchoconstriction during acute severe asthma.

Ultrasound assessment of normal hemidiaphragmatic movement: relation to inspiratory volume.

BACKGROUND: Traditionally the radiological assessment of diaphragmatic movement has relied on fluoroscopy. Ultrasound scanning has recently been shown to be a sensitive and reproducible method of assessing hemidiaphragmatic movement in normal subjects. A study was undertaken to examine how movement of the diaphragm measured by ultrasound scanning relates to inspired lung volumes measured by spirometric testing. METHODS: Ultrasound examinations were performed on 14 normal volunteers using a 3.5 MHz sector transducer (Acuson 128). A fixed skin position on each lateral chest wall between the anterior clavicular and midaxillary line was selected symmetrically to obtain a longitudinal plane of each hemidiaphragm including the maximal renal bipolar length, allowing identification of the adjacent posterior aspect of the diaphragm. Craniocaudal excursions of the posterior part of each hemidiaphragm on successive respiratory cycles were recorded on videotape and compared with spirometric measurements recorded simultaneously on a water bath spirometer. Measurements were made in the sitting and supine position and were repeated on a separate occasion (at least two weeks apart) in 10 subjects by the same operator to assess reproducibility. RESULTS: The relation between inspired volume and hemidiaphragmatic movement was found to be linear. The gradient of these observed linear relations (hemidiaphragmatic excursion (mm)/inspired volume (1)) was calculated and their distribution for each hemidiaphragm followed a normal distribution irrespective of position. The 95% confidence limits of the right to left ratio of these gradients in the supine position were 0.53 and 1.7. Change of posture from the supine to the sitting position reduced the gradient. The technique had acceptable reproducibility with coefficients of variation for the supine position of 7.5% and 11.7% for right and left hemidiaphragm respectively. CONCLUSION: Ultrasound scanning is a simple, non-invasive and reproducible means of assessing hemidiaphragmatic movement, yielding quantitative information which relates to inspired lung volumes.

Modulation of the effect of atrial natriuretic peptide in human and bovine bronchi by phosphoramidon.

1. We have previously shown that atrial natriuretic peptide causes bronchodilatation and reduces bronchial reactivity when administered intravenously or by inhalation to asthmatic patients. We wished to determine the direct effect of exogenously applied atrial natriuretic peptide on isolated airway and the role of proteases important in atrial natriuretic peptide degradation in other organ systems. 2. The ability of atrial natriuretic peptide (alpha-human atrial natriuretic peptide 28-amino acid) to relax precontracted tissues and to protect against methacholine-induced contraction was studied in human and bovine tissue. The role of neutral endopeptidase-24.11 and other proteases in regulating the effect of atrial natriuretic peptide on bronchial smooth muscle was also examined by studying the influence of phosphoramidon, a protease inhibitor, whose actions include the inhibition of neutral endopeptidase-24.11, and the protease inhibitors leupeptin, aprotinin and soybean trypsin inhibitor on the airway response to atrial natriuretic peptide. 3. In human and bovine tissue atrial natriuretic peptide (10(-6) mol/l) caused a slight relaxation of methacholine-contracted tissue [mean (SEM) percentage inhibition of contraction of 13.2 (3.02)% and 9.41 (2.63)% respectively] and evoked a significant rightward shift of the cumulative concentration-response curve to methacholine [pD2 5.15 (0.23) and 4.85 (0.1) compared with control values of 6.14 (0.1) and 5.85 (0.16), respectively]. 4. Phosphoramidon potentiated atrial natriuretic peptide-induced relaxation of methacholine-induced tone and the ability of atrial natriuretic peptide to protect against methacholine-induced contraction. The combination of leupeptine, aprotinin and soybean trypsin inhibitor did not significantly alter the bronchial response to atrial natriuretic peptide in either human or bovine tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchodilator, cardiovascular, and cyclic guanylyl monophosphate response to high-dose infused atrial natriuretic peptide in asthma.

Atrial natriuretic peptide (ANP) has bronchodilator and vasodilator properties thought to be mediated through the generation of cyclic guanylyl monophosphate (cGMP). The current study was designed to examine the effects of infused ANP on respiratory (FEV1), cardiovascular (blood pressure and pulse), and metabolic (plasma cGMP) function in asthmatic patients. Eight patients with a mean +/- SD age of 45.6 +/- 8.2 yr and mean FEV1 of 56.4 +/- 15.4% of predicted were studied using a randomized double-blind crossover design. On one study day after baseline measurements (FEV1, blood pressure, pulse, and plasma cGMP), ANP was infused for 20-min periods at 5 pmol/kg/min and at 25 pmol/kg/min; a placebo (saline) inhalation was then administered. On the other day the placebo infusion was followed by inhalation of 5 mg albuterol. Measurements were repeated at the end of each 20-min period. The highest rate of ANP infusion increased the FEV1 by 0.50 +/- 0.09 L compared with 0.09 +/- 0.05 after the placebo infusion (p < 0.001). The increase in FEV1 produced by ANP plus placebo inhalation (0.50 +/- 0.28 L) was similar to that produced by placebo infusion plus albuterol inhalation (0.61 +/- 0.30 L). There was no clinically significant fall in systolic or diastolic blood pressure (torr) at the 25 pmol/kg/min infusion rate. The mean basal cGMP was 602 +/- 242 fmol/ml and increased to 5,883 +/- 1,460 and 21,182 +/- 2,509 with the two rates of ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)