Biomedical subjects
Alyn H Morice
Publications and source records attributed to Alyn H Morice.
Sex-related differences in cough reflex sensitivity in patients with chronic cough.
Among patients attending specialist cough clinics there is an excess of females, but the reason for this sex difference is unknown. We tested the hypothesis that the sensitivity of the cough reflex is greater in female compared with male patients with chronic cough. Inhalation cough challenges with capsaicin and citric acid were performed in a large group of patients with chronic cough. The concentrations of tussive agent causing two (C2) and five (C5) coughs were calculated. Measurements of capsaicin cough reflex sensitivity (median [interquartile range]) were significantly lower for female patients compared with male patients (C2: 1.9 [0.5 to 5.5] versus 5.3 [2.2 to 11.5] micro M, p = 0.0026; C5: 8.6 [2.2 to 34.0] versus 51.2 [7.2 to > 100] micro M, p = 0.0007). Similarly for citric acid challenge, values were significantly lower for female compared with male patients (C2: 53.5 [17.3 to 145.4] versus 118.1 [41.4 to 381.7] mM, p = 0.0064; C5: 300.0 [97.1 to > 1,000] versus 830.4 [300.0 to > 1,000] mM, p = 0.032). There were significant correlations between capsaicin and citric acid C2 values (r(s) = 0.54, p < 0.0001) and C5 values (r(s) = 0.57, p < 0.0001). These findings indicate a sex difference in cough sensitivity in patients with chronic cough, as previously reported in healthy volunteers. This may explain the female preponderance in cough clinics.
Epidemiology of cough.
Patients with cough may be conveniently divided into those with acute, usually viral, illness and those with chronic cough. Acute cough represents the largest single cause of consultation in primary care, whereas chronic cough is one of the commonest presentations in respiratory medicine. The world-wide market in cough treatments is several billion dollars. In both syndromes, cough sensitivity is upregulated, but the inflammation giving rise to cough is localised to the larynx and large airways in acute cough. Whilst this is also true of cough-predominant asthma, the origin of cough in chronic disease may also lie in the oesophagus, nose or sinuses leading to errors in diagnosis and treatment.
A widely available method for the assessment of aerosol delivery in cystic fibrosis.
Whilst nebulisers are commonly used in the treatment of cystic fibrosis (CF), nebulised aerosol lung deposition in individual patients is not routinely assessed in clinical practice. The present study was designed to evaluate whether a comparative measurement of aerosol lung deposition from nebulisers using a widely available scintigraphic method could be employed to assist the selection of the best system for individual patients. Lung deposition of the radiolabelled aerosol from the Pari LC Plus (Pari Medical Ltd) nebuliser and the HaloLite Adaptive Aerosol Delivery (AAD) system (Profile Therapeutics Ltd) was measured using planar scintigraphy in 10 healthy volunteers and 6 CF patients. The HaloLite AAD delivered on average 2.1 times (P=0.003) as much aerosol to the lungs compared with Pari LC Plus. Only two subjects had higher lung deposition from Pari LC Plus than HaloLite AAD system. There was marked inter-individual variation in the deposition pattern in CF patients. The aerosol deposition from HaloLite AAD had higher central distribution than that obtained with the Pari LC Plus. The overall intersubject variability of the delivered dose was 56% with Pari LC Plus and 24% with HaloLite AAD (P<0.05). The measurement of aerosol deposition from nebulisers can be performed using a simple and widely available methodology, and may improve nebuliser selection in CF patients.
Pulmonary vasodilatory action of testosterone: evidence of a calcium antagonistic action.
Recent evidence supports a beneficial effect of testosterone on the cardiovascular system. Testosterone acts as a coronary vasodilator and reduces myocardial ischemia in men with coronary heart disease. The aim of the current study was to determine whether testosterone has a similar vasodilatory action in the pulmonary circulation and to characterize the underlying mechanism of action. The vasodilatory action of testosterone was studied in pulmonary arteries (n = 132, mean internal diameter = 344 +/- 8 microm) isolated from male rats (n = 48, mass = 396 +/- 7 g) mounted in a small vessel wire myograph and loaded to a tension equivalent to 17.5 mm Hg. Micromolar concentrations of testosterone induced dilatation in pulmonary arteries preconstricted with prostaglandin F2alpha (100 microM) within seconds of application. Dilatation to testosterone was similar in vessels treated with N-gamma-nitro-l-arginine methyl ester (l-NAME) (10 microM) or vehicle (5 microl distilled water), -38.2 +/- 2.9%, and -38.1 +/- 3.4%, respectively, and in vessels treated with indomethacin (10 microM), flutamide (10 microM), or vehicle (5 microl ethanol), -35.5 +/- 2.8%, -43.2 +/- 3.6%, and -35.7 +/- 4.6%, respectively (all p > 0.05). Maximal dilatation to testosterone occurred following preconstriction with agents that activated voltage-gated calcium channels such as prostaglandin F2alpha (-34.6 +/- 5.0%), BAY K8644 (-32.9 +/- 8.7), or potassium chloride (-26.7 +/- 1.5%), compared with calcium-independent protein kinase C activation by phorbol dibutyrate (-14.7 +/- 1.6%) or capacitative calcium entry via thapsigargin (-5.1 +/- 0.9%). This study demonstrates that testosterone induces pulmonary dilatation via a mechanism that is independent of the classic androgen receptor and also of the release of nitric oxide or dilator prostaglandins. The data support a calcium antagonistic action for testosterone in the pulmonary circulation, primarily against voltage-gated calcium channels.
Measurement of gastric emptying in gastroesophageal reflux-related chronic cough.
STUDY OBJECTIVES: Gastroesophageal reflux (GER) is one of the most common causes of chronic cough, but the mechanisms of GER-related cough are not well-understood. We tested the hypothesis that gastric emptying is delayed in patients with GER-related chronic cough. DESIGN: We studied 12 patients (7 women; mean age, 53 years; age range, 37 to 68 years) with GER-related chronic cough and a control group of 27 asymptomatic healthy volunteers (16 women; mean age, 37 years; age range, 18 to 62 years). Gastric emptying scintigraphy was performed, and the time at which 50% of the radiolabeled material had left the stomach (T(1/2)) was calculated. RESULTS: There was no statistically significant difference in T(1/2) values between healthy volunteers and subjects with GER-related cough (99 +/- 26 min vs 86 +/- 20 min, respectively; difference between the means, 13 min [95% confidence interval, -4 to 30 min]; p = 0.13). CONCLUSIONS: Gastric emptying was not delayed in patients with GER-related chronic cough. The measurement of gastric emptying did not therefore provide further insights into the mechanisms of GER-related cough or clinically relevant information that would assist in patient management.