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1.  Is opiate action in cough due to sedation? 
Opiates have been used for cough suppression for centuries. It is unclear whether this antitussive action is due to their known sedative effects. We aimed to assess correlation between cough suppression and opiate usage.
We performed a post hoc analysis of two published trials with three opioids. In study one, patients with chronic cough were treated with 4 weeks of modified release morphine sulphate (5 mg twice daily) or placebo in a double-blinded placebo-controlled fashion. Cough suppression was assessed subjectively by the Leicester Cough Questionnaire and objectively by citric acid aerosol (CAA) induced cough challenge. In study 2, normal volunteers were given single doses of placebo, codeine 30 mg or dextromethorphan 50 mg and cough suppression assessed using the CAA-induced cough challenge. Sedation was contemporaneously assessed by direct questioning.
There were 14 episodes of patient-reported sedation; 2 with modified release morphine sulphate, 9 with codeine and 3 with dextromethorphan. There was no correlation between change in the Leicester Cough Questionnaire or the CAA-induced cough challenge and reported sedation.
This observational study suggests that sedation is unlikely to underlie the antitussive properties of these opioids. Eliciting the mechanism of these medications in cough may be a target for future tailored drug development.
PMCID: PMC4131504  PMID: 25177477
antitussive; codeine phosphate; cough therapies dextromethorphan; morphine sulphate (MST); sedation
2.  Comparison of the effect of high-dose inhaled budesonide and fluticasone on adrenal function in patients with severe chronic obstructive pulmonary disease 
Annals of Thoracic Medicine  2012;7(3):140-144.
Chronic obstructive pulmonary disease (COPD) is a leading cause of respiratory-related morbidity and mortality. Inhaled steroids are frequently used in patients with moderate to severe disease and may lead to adrenal suppression.
The aim of this study was to compare the effect of inhaled budesonide/formoterol with inhaled fluticasone/salmeterol in severe COPD.
It was a prospective open-label crossover study of 22 patients. Adrenal suppression was measured by overnight urinary cortisol/creatinine ratio. The measurements were taken while patients were on either combination for at least 4 weeks.
A total of 12 patients completed the study. The mean age was 64 years (8 males, 4 females). The mean FEV1 was 1 L (range, 0.5-1.8). There was no significant difference in adrenal suppression measured by overnight urinary cortisol/creatinine ratio (budesonide 5.2 ± 4.3, fluticasone 4.7 ± 3.1; 95% CI -2.2 to 1.2; P = 0.52) and urinary cortisol concentration (budesonide 51 ± 53, fluticasone 43 ± 31 [nmol/l]; 95% CI -35 to 20; P = 0.56).
Inhaled budesonide and fluticasone have no significantly different effect on adrenal function in moderate to severe COPD. The adverse event profile of high-dose inhaled steroids should not influence the choice of medication.
PMCID: PMC3425045  PMID: 22924071
Adrenal suppression; COPD; cortisol-creatinine ratio; inhaled corticosteroids
3.  Validation of the ERS standard citric acid cough challenge in healthy adult volunteers 
Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive agent, single and dose response. A definitive method for measuring cough sensitivity needs to be established.
The ERS guidelines recommend the KoKo DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of this citric acid (CA) cough challenge and previously established Mefar dosimeter (MD) protocol.
39 (female 26) volunteers mean age (40.4 yrs) were randomised to either KD or MD. Intra-day and inter-day reproducibility was compared.
We calculated the concentration of citric acid evoking 2 coughs (C2).
The geometric mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209 (151,288) mM respectively.
The mean KD C2 was not significantly different. (F = 0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated significant variability (F = 7.85, P < 0.001)
Measuring mean log C2 at baseline and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2 at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC = 0.41
Administering CA from KD offers a reproducible cough challenge in healthy volunteers. The results correlate well with the MD challenge but offer greater intra-day and inter-day reproducibility.
Trial Registration
Current controlled trials ISRCTN98385033
PMCID: PMC2925329  PMID: 20698995

Results 1-3 (3)