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Biomedical subjects

J A Innes

Publications and source records attributed to J A Innes.

At least 19 recordsLinked to original sources

Respiratory heat and moisture loss is associated with eosinophilic inflammation in asthma.

Increased mucosal vascularity is a hallmark of airway inflammation in asthma. It was hypothesised that this would lead to a detectable increase in respiratory heat and moisture loss (RHML), which would reflect the degree of airway inflammation present. A total of 23 subjects with asthma and 18 healthy controls had RHML measured in a cross-sectional study. The measurements were made using a device that combines temperature and humidity measurement during inspiration and expiration and allows precise control over inspirate conditions and ventilatory pattern. The subjects with asthma underwent parallel measurements of exhaled nitric oxide, sputum eosinophil percentage and exhaled breath condensate pH. Mean+/-SD RHML was elevated in patients with asthma (98.1+/-7.3 J.L(-1)) compared with control subjects (91.9+/-4.5 J.L(-1)). RHML measurement in asthma correlated with sputum eosinophil percentage. This novel correlation between thermal and cellular measurements in asthma suggests that both of these noninvasive indices are sensitive to the degree of underlying chronic airway inflammation.

Adult↗

Effects of breathing pattern and inspired air conditions on breath condensate volume, pH, nitrite, and protein concentrations.

BACKGROUND: The effects of breathing pattern and inspired air conditions on the volume and content of exhaled breath condensate (EBC) were investigated. METHODS: Total exhaled water (TEW), EBC volume, pH, nitrite and protein concentrations were measured in three groups of 10 healthy subjects breathing into a condenser at different target minute ventilations (Vm), tidal volumes (Vt), and inspired air conditions. RESULTS: The volumes of both TEW and EBC increased significantly with Vm. For Vm 7.5, 15 and 22.5 l/min, mean (SD) EBC was 627 (258) microl, 1019 (313) microl, and 1358 (364) microl, respectively (p<0.001) and TEW was 1879 (378) microl, 2986 (496) microl, and 4679 (700) microl, respectively (p<0.001). TEW was significantly higher than EBC, reflecting a condenser efficiency of 40% at a target Vm of 7.5 l/min which reduced to 29% at Vm 22.5 l/min. Lower Vt gave less TEW than higher Vt (26.6 v 30.7 microl/l, mean difference 4.1 (95% CI 2.6 to 5.6), p<0.001) and a smaller EBC volume (4.3 v 7.6 microl/l, mean difference 3.4 (95% CI 2.3 to 4.5), p<0.001). Cooler and drier inspired air yielded less water vapour and less breath condensate than standard conditions (p<0.05). Changes in the breathing pattern had no effect on EBC protein and nitrite concentrations and pH. CONCLUSION: These results show that condensate volume can be increased by using high Vt and increased Vm without compromising the dilution of the sample.

Breath Tests↗

Chest physicians' and microbiologists' awareness and demand for drug monitoring in the treatment of TB.

There is a role for therapeutic drug monitoring (TDM) to achieve the optimum therapeutic concentration of anti-tuberculous drugs. This work aimed to determine the current awareness of TDM in TB control among chest physicians and to estimate the demand for this service. Responses from a sample of chest physicians in the West Midlands revealed that 60% were aware of TDM and 33% had used it. Responses were received from half of a UK group of microbiologists who reported a median of nine requests in the past year. It appeared that more was known about services for rifampicin and streptomycin than other first-line drugs. There appears to be a need for both increased awareness among potential service users and for coordination of assay services.

Antitubercular Agents↗

Airways in cystic fibrosis are acidified: detection by exhaled breath condensate.

BACKGROUND: The loss of cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride conductance does not fully explain the diverse pathologies evident in patients with cystic fibrosis (CF). Bicarbonate (HCO(3)(-)) secretion is also impaired in CFTR expressing tissues and CFTR is thought to regulate HCO(3)(-) secretion at the apical membrane of epithelial cells. We hypothesised that the epithelial lining fluid (ELF) of patients with CF would be acidified and that this may be worsened during an infective exacerbation due to the increased inflammatory burden. METHODS: pH and nitrite levels in exhaled breath condensate (EBC) from 12 healthy non-smoking controls and 30 patients with CF (11 of whom were in an infective exacerbation) were measured. A further nine patients were studied before and after intravenous antibiotic treatment for an exacerbation of CF. RESULTS: The pH of EBC was significantly lower in patients with stable CF than in controls (5.88 (0.32) v 6.15 (0.16), p=0.017), and was further reduced in CF patients with an exacerbation (5.32 (0.38), p=0.001) compared with stable CF patients. EBC pH increased significantly following antibiotic treatment from 5.27 (0.42) to 5.71 (0.42), p=0.049). Nitrite levels in EBC were increased in CF patients with an exacerbation compared with control subjects (4.4 (4.0) micro m v 1.6 (1.6) micro m p=0.047). No correlation was found between EBC pH and nitrite levels. CONCLUSIONS: These findings support the hypothesis that airway acidification occurs in CF. This acidity is in part a function of inflammation as the pH of the EBC of patients increased significantly with treatment of an exacerbation, although not to control levels. Acidic pH of the ELF may play a role in the pathophysiology of CF lung disease and requires further investigation.

Adult↗

Short term variability of single breath carbon monoxide transfer factor.

BACKGROUND: When monitoring patients with chronic lung disease it is important to distinguish genuine changes in gas transfer over time from natural variability. This study aims to define the coefficient of repeatability for routine measurements of single breath transfer factor (TCO) and transfer coefficient (KCO). METHODS: Sixty eight subjects (32 with emphysema, 36 healthy volunteers) had TCO measured twice at a mean (SD) interval of 7.5 (1.3) days. On each occasion a standard protocol (conforming to BTS guidelines) was followed, comprising duplicate measurements satisfying standard technical criteria. The mean of these duplicates was recorded. For the pooled data changes in TCO and KCO between study days were expressed as coefficient of repeatability. RESULTS: The coefficient of repeatability was +/-1.60 mmol/min/kPa for TCO and +/-0.24 mmol/min/kPa/l for KCO. Correcting TCO and KCO for prevailing barometric pressure or carboxyhaemoglobin level made no significant difference to the results. CONCLUSIONS: The quoted limits for variability in gas transfer over time are valid for a wide range of clinically relevant values. Changes in TCO and KCO greater than these limits are unlikely to arise from natural variation.

Adult↗

The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre.

The authors have observed that some patients with acute exacerbations of asthma do not have substantially higher levels of exhaled nitric oxide (NO). The study examined whether this could be explained by the effect of airway calibre on exhaled NO. Exhaled NO, height and forced expiratory volume in one second (FEV1) were measured in 12 steroid-naive asthmatics and 17 normal subjects. For comparison, another group of patients with airways disease (34 cystic fibrosis patients) were also studied. In 20 asthmatics (on various doses of inhaled steroids, 0-3,200 microg x day-1), exhaled NO was measured before and after histamine challenge (immediately after reaching the provocative concentration causing a 20% fall in FEV1) and in 12 of these patients, also after nebulized salbutamol to restore FEV1 to baseline. Studies were also conducted to examine possible confounding effects of repeated spirometry (as would occur in histamine challenge) and nebulized salbutamol alone in exhaled NO levels. Exhaled NO was measured using a single exhalation method with a chemiluminescence analyser at a constant flow rate and mouth pressure. There was a significant correlation between FEV1 and exhaled NO in steroid naive asthmatics (r=0.9, p<0.001) and cystic fibrosis patients (r=-0.48, p<0.05) but not in normal subjects (r=-0.13, p=0.61). Exhaled NO decreased significantly after histamine challenge and returned to baseline after bronchodilation by nebulized salbutamol (mean+/-SEM: 23.6+/-3.6 parts per billion (ppb) (prehistamine), 18.2+/-2.7 ppb (posthistamine) and 23.6+/-3.8 ppb (postsalbutamol) p=0.001). Repeated spirometry and nebulized salbutamol did not affect exhaled NO measurements significantly. Exhaled nitric oxide levels appear to be lower in circumstances of smaller airway diameter. Hence, within a subject nitric oxide levels may be artefactually decreased during bronchoconstriction. This may be caused by increased airflow velocity in constricted airways when the exhalation rate is kept constant.

Adult↗

Laboratory assessment of fitness to fly in patients with lung disease: a practical approach.

To identify patients with respiratory disease, who may be at risk of developing respiratory distress during commercial air travel, a hypoxia inhalation test (HIT) can be performed. This paper reports our experience of using such a test combined with an interpretation algorithm in a routine respiratory function laboratory. Twenty-eight patients were studied. Baseline oxygen saturation (Sa,O2) was measured using a pulse oximeter. If Sa,O2 was < 90% no HIT was performed and the patient was assessed as unfit for air travel. If baseline Sa,O2 was > or = 90% an HIT was performed by the patient breathing through a 35% Venturi mask supplied with 100% nitrogen which reduced inspiratory oxygen fraction to 15.1+/-0.2%. Results were interpreted using a locally derived algorithm, and validation was attempted using a questionnaire to investigate subsequent symptoms during travel. All patients tolerated the assessment well. Twenty-two patients were assessed as "fit to fly" with a further two patients "fit to fly with supplemental O2". Four patients were considered unfit to fly. Hypoxic response could not be predicted from either forced expiratory volume in one second, or pretest saturation. Validation of such protocols is difficult, but the hypoxia inhalation test may be a useful tool for predicting hypoxia during air travel in patients with chronic respiratory disease.

Aerospace Medicine↗

Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. EDICI.

Inefficient inhaler technique is a common problem resulting in poor drug delivery, decreased disease control and increased inhaler use. The aim of this study was to assess patients' use of different inhaler devices and to ascertain whether patient preference is indicative of ease of use and whether current inhaler use has any influence on either technique or preference. We also wished to define the most appropriate method of selecting an inhaler for a patient, taking into account observed technique and device cost. One hundred patients received instruction, in randomized order, in the use of seven different inhaler devices. After instruction they were graded (using predetermined criteria) in their inhaler technique. After assessment patients were asked which three inhalers they most preferred and which, if any, they currently used. Technique was best using the breath-actuated inhalers; the Easi-Breathe and Autohaler, with 91% seen to have good technique. The pressurized metered dose inhaler (pMDI) fared poorly, in last position with only 79% of patients showing good technique, despite being the most commonly prescribed. The Easi-Breathe was by far the most popular device with the patients. The Autohaler came in second position closely followed by the Clickhaler and Accuhaler. The majority of patients (55%) currently used the pMDI but the pMDI did not score highly for preference or achieve better grades than the other devices. Only 79% of patients tested could use the pMDI effectively even after expert instruction yet it continues to be commonly prescribed. This has important repercussions for drug delivery and hence disease control. Prescribing a patient's preferred device increases cost but can improve efficiency and therefore be cost effective in the long term. Using an inexpensive device (pMDI) when technique is good and the patient's preferred inhaler device when not is one way to optimize delivery and may even reduce cost.

Adult↗

Emergency pre-hospital management of patients admitted with acute asthma.

BACKGROUND: Little is known about the management of acute asthma prior to hospital admission. Pre-hospital treatment of patients referred to hospital with acute asthma was therefore studied in 150 patients divided into three groups: those in the Edinburgh Emergency Asthma Admission Service (EEAAS) who can contact an ambulance and present directly to respiratory services when symptoms arise (n = 38), those under continuing supervision at a hospital respiratory outpatient clinic (n = 54), and those managed solely in primary care (n = 58). METHODS: Standardised admission forms detailing aspects of pre-hospital management, case records, GP referral letters, and ambulance patient transport forms were analysed. RESULTS: In each group airflow obstruction had improved upon arrival at hospital, the effect being most marked in patients transported by ambulance (p<0. 001) and in those receiving nebulised beta(2) agonists prior to admission (p<0.005). However, 25% of patients arrived without having nebulised beta(2) agonists and 37% without having glucocorticoids. EEAAS patients were least likely to receive nebulised beta(2) agonists before arrival at hospital (p<0.05). This observation was attributable to a tendency for these patients to travel to hospital by car rather than by ambulance. CONCLUSIONS: There is an important shortfall in administration of bronchodilators and glucocorticoids for acute asthma before arrival at hospital. Ambulances equipped with nebulised bronchodilators provide the optimal mode of transport to hospital for patients with acute asthma. In Edinburgh ambulances are not being used by a significant proportion of the population with asthma, possibly because of the mistaken belief that personal transport arrangements reduce journey time to hospital.

Acute Disease↗

Atopy influences exhaled nitric oxide levels in adult asthmatics.

STUDY OBJECTIVE: To examine whether atopy influences exhaled nitric oxide (NO) levels in adults with established asthma. SETTING: Specialist respiratory unit in a university teaching hospital. PATIENTS: Twenty-eight asthmatics (mean FEV(1), 85.7%) receiving short-acting inhaled bronchodilators and a range of inhaled steroids (0 to 4,000 microg/d). INTERVENTIONS: Subjects were studied on two occasions, 5 to 7 days apart, between September and March. MEASUREMENTS AND RESULTS: On the first day, FEV(1), exhaled NO, and histamine challenge were performed. On the second day, exhaled NO, total IgE, and skin-prick testing to six common allergens were conducted. Exhaled NO was measured with the single exhalation method. We found exhaled NO levels to correlate positively with total IgE (r = 0.43, p = 0.02) and number of positive skin-prick tests (p = 0. 002). By contrast, there was no significant correlation between exhaled NO and FEV(1) or the provocative concentration causing a 20% fall in FEV(1). Subanalyses of steroid-treated and steroid-naive patients in this group revealed the same findings. CONCLUSION: Exhaled NO levels in asthmatics correlate more closely with atopy than with bronchial hyperreactivity and lung function.

Administration, Inhalation↗

Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n-of-1 trials. Scottish Cystic Fibrosis Group.

Nebulized recombinant human deoxyribonuclease (DNase) reduces sputum viscosity and improves lung function in some cystic fibrosis patients, but individual responses are unpredictable. The aim of this study was to investigate how DNase can be targeted to those cystic fibrosis patients who would benefit most. The Scottish Cystic Fibrosis Group agreed on a randomized, double-blind, placebo-controlled n-of-1 assessment protocol. Patients underwent a maximum of three 4-week assessment periods (2 weeks saline, 2 weeks DNase each). Measurements performed at hospital (exercise, oximetry and spirometry) and home (symptom scores) were used to derive a scoring system to discriminate maximally between DNase and placebo effects. The data on 89 4-week assessments in 52 patients were reported. Twenty-four patients have completed the assessment process (12 responders and 12 nonresponders) to date. Forced expiratory volume in one second (FEVI) was the best discriminator of response, rising by >200 mL after DNase in 33 of 89 (37%) assessments compared with 3 of 89 (3%) after saline. N-of-1 trials, while laborious, permitted genuine treatment effects to be quantified within individuals with confidence, permitting appropriate treatment targeting. This provides a model of how other new expensive therapies may be introduced to maximize patient benefit.

Adolescent↗

Expired hydrogen peroxide in breath condensate of cystic fibrosis patients.

Stimulated inflammatory cells release large amounts of hydrogen peroxide (H2O2). Breath condensate H2O2 has been shown to be elevated in stable asthmatic children, chronic obstructive pulmonary disease and intubated adult respiratory distress syndrome. In cystic fibrosis airways, where neutrophilic inflammation dominates, it is postulated that H2O2 in breath condensate would be elevated and may be used as a marker of airways inflammation. Expired breath condensate was collected from 16 clinically stable cystic fibrosis (CF) patients (mean age 25.3 yrs, mean forced expiratory volume in one second (FEV1) 50.2%) and 14 normal subjects (mean age 29.9 yrs). Total plasma leukocyte, neutrophil, monocyte and eosinophil counts and lung function were also measured on the day of collection. A method of breath condensate collection excluding the confounding factors of nasal air and saliva contamination was validated and used and H2O2 measured fluorometrically using an optimized assay. The median level of H2O2 concentration in breath condensate of CF patients was lower than that in normal subjects (0.064 versus 0.089 microM), but this did not reach statistical significance (p = 0.20, Mann-Whitney rank sum test). Within the CF group, there was no correlation between H2O2 concentration and lung function. Expired breath condensate H2O2 is not elevated in patients with cystic fibrosis, and is thus not a suitable marker of airways inflammation in these patients. Possible explanations include physical barriers to its detection caused by viscous airways secretions, reaction with other reactive species or increased antioxidant activity caused by trapping of positively charged antioxidants in negatively charged airways secretions.

Adult↗