Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily.

Background: It has been proposed that the pH of airway lining fluid may regulate the fractional exhaled concentration of nitric oxide (FE NO ) in respiratory disease. Methods: FE NO , exhaled breath condensate (EBC) pH, and EBC concentrations of nitrite plus nitrate (NO 2 / NO 3 ) were compared in 12 subjects with stable asthma, 18 with stable cystic fibrosis (CF), and 15 healthy control subjects. Eight of the CF patients were studied on a separate occasion at the start of a pulmonary exacerbation. Results: FE NO was significantly greater in asthmatic subjects than in control subjects (mean 35 v 9 ppb, p,0.001). EBC pH, however, was similar in the asthmatic and control groups (median 5.82 v 6.08, p = 0.23). Levels of NO 2 /NO 3 were on average higher in EBC samples from asthmatic subjects, but the difference was not significant. In patients with stable CF both the FE NO (mean 4 ppb, p,0.001) and EBC pH (median 5.77, p = 0.003) were lower than in the control group. Levels of EBC NO 2 /NO 3 (median 29.9 mM; p = 0.002) in patients with stable CF, in contrast, were significantly higher than in control subjects. During CF exacerbations, EBC pH was further reduced (median 5.30, p = 0.017) but FE NO and NO 2 /NO 3 were unchanged.Conclusions: These findings demonstrate a dissociation between EBC pH and FE NO in inflammatory airways disease.

TRPV1 is a modulator of noxious stimuli known to be important in the cough reflex. We have compared the expression of TRPV1 in normal human airways and those from patients with chronic cough and found that there is up regulation in airways smooth muscle in disease. This increased expression appears to be intracellular and we have therefore examined the role of intracellular rat and human TRPV1 activity was found using intracellular calcium signalling with human intracellular TRPV1 being located in a thapsigargin insensitive compartment. Increase in TRPV1 activity may have a role in the airway hypersensitivity seen in chronic cough.

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Nitric oxide (NO) is synthesized from L-arginine in the human respiratory tract by enzymes of the NO synthase (NOS) family. Levels of NO in exhaled air are increased in asthma, and measurement of exhaled NO has been advocated as a noninvasive tool to monitor the underlying inflammatory process. However, the relation of NO to disease pathophysiology is uncertain, and in particular the fundamental question of whether it should be viewed primarily as beneficial or harmful remains unanswered. Exogenously administered NO has both bronchodilator and bronchoprotective properties. Although it is unlikely that NO is an important regulator of basal airway tone, there is good evidence that endogenous NO release exerts a protective effect against various bronchoconstrictor stimuli. This response is thought to involve one or both of the constitutive NOS isoforms, endothelial NOS (eNOS) and neuronal NOS (nNOS). Therefore, inhibition of these enzymes is unlikely to be therapeutically useful in asthma and indeed may worsen disease control. On the other hand, the high concentrations of NO in asthma, which are believed to reflect upregulation of inducible NOS (iNOS) by proinflammatory cytokines, may produce various deleterious effects. These include increased vascular permeability, damage to the airway epithelium, and promotion of inflammatory cell infiltration. However, the possible effects of iNOS inhibition on allergic inflammation in asthma have not yet been described and studies in animal models have yielded inconsistent findings. Thus, the evidence to suggest that inhibition of iNOS would be a useful therapeutic strategy in asthma is limited at present. More definitive information will require studies combining agents that potently and specifically target individual NOS isoforms with direct measurement of inflammatory markers.

AimsInhaled corticosteroids (ICS) are the cornerstone of asthma treatment. At high doses they can give rise to systemic side-effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression. This effect may depend on the delivery system, which in turn alters drug deposition and adsorption. We hypothesized that adrenal suppression depends on the rate of steroid absorption rather than the total steroid dose received. MethodsEight healthy adult males were recruited for a randomized double-blind placebo controlled trial. Adrenocortical suppression ability was demonstrated by a 30% suppression of early morning cortisol following 1 mg dexamethasone. Subjects then attended in the evening on two occasions receiving 500 µ g of intravenous beclomethasone monopropionate (17-BMP) for either 15 min or 2 h. Overnight urinary cortisol : creatinine (C : C) ratio was measured before and after the infusion and an 08.00 h serum cortisol was measured following the infusion. ResultsMean C : C pre and post 15 min infusion was 5.97 and 3.22 ( P = 0.005). Mean C : C pre and post 2 h infusion was 6.31 and 4.15 ( P = 0.004). Delta C : C and mean 08.00 h cortisol for 15 min and 2 h infusion was 2.74 and 2.16 and 425 nmol l − 1 and 400 nmol l − 1 , respectively ( P = NS). ConclusionsThe rate of infusion of 17-BMP seemed to have little effect on the degree of adrenal suppression. Individual C : C ratios were reproducible. Differences in absorption of ICS are unlikely to explain observed differences in HPA axis suppression.

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