Sarah Jefferies

Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta‐analysis

Cite this as: S. Eyers, M. Weatherall, S. Jefferies and R. Beasley, Clinical & Experimental Allergy, 2011 (41) 482–489.

Randomised placebo-controlled study of the effect of paracetamol on asthma severity in adults.

Objective To investigate the effect of regular paracetamol on bronchial hyper-responsiveness (BHR) and asthma control in adult asthma. Setting Single research-based outpatient clinic. Participants 94 adults with mild-to-moderate asthma received randomised treatment; 85 completed the study. Key inclusion criteria were age 18–65 years, forced expiratory volume in 1 s (FEV1) >70% predicted, provocation concentration of methacholine causing a 20% reduction in FEV1 (PC20) between 0.125 and 16 mg/mL. Key exclusion criteria included an asthma exacerbation within the previous 2 months, current regular use of paracetamol, use of high-dose aspirin or non-steroidal anti-inflammatory drugs, current or past cigarette smoking >10 pack-years. Interventions In a 12-week randomised, double-blind, placebo-controlled, parallel-group study, participants received 12 weeks of 1 g paracetamol twice daily or placebo twice daily. Primary and secondary outcome measures The primary outcome variable was BHR, measured as the PC20 at week 12. Secondary outcome variables included FEV1, fractional exhaled nitric oxide (FeNO) and asthma control questionnaire (ACQ) score. Results At 12 weeks, the mean (SD) logarithm base two PC20 was 1.07 (2.36) in the control group (N=54) and 0.62 (2.09) in the paracetamol group (N=31). After controlling for baseline PC20, the mean difference (paracetamol minus placebo) was −0.48 doubling dose worsening in BHR in the paracetamol group (95% CI −1.28 to 0.32), p=0.24. There were no statistically significant differences (paracetamol minus placebo) in log FeNO (0.09 (95% CI −0.097 to 0.27)), FEV1 (−0.07 L (95% CI −0.15 to 0.01)) or ACQ score (−0.04 (95% CI −0.27 to 0.18)). Conclusions There was no significant effect of paracetamol on BHR and asthma control in adults with mild-to-moderate asthma. However, the study findings are limited by low power and the upper confidence limits did not rule out clinically relevant adverse effects. Trial Registration Australia New Zealand Clinical Trials Registry Number: NZCTR12609000551291.

Use of nebulised magnesium sulphate as an adjuvant in the treatment of acute exacerbations of COPD in adults: a randomised double-blind placebo-controlled trial

Background Intravenous magnesium has been shown to cause bronchodilation in acute severe asthma and in small trials in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). There is also some evidence of benefit from nebulised magnesium in acute severe asthma. Our hypothesis was that adjuvant magnesium treatment administered via repeated nebulisation was effective in the management of AECOPD. Methods In this randomised double-blind placebo-controlled trial, we approached 161 patients with AECOPD presenting to the emergency departments at two New Zealand hospitals with a forced expiratory volume in 1 s (FEV1) <50% predicted 20 min after initial administration of salbutamol 2.5 mg and ipratropium 500 µg via nebulisation. Patients received 2.5 mg salbutamol mixed with either 2.5 ml isotonic magnesium sulphate (151 mg per dose) or 2.5 ml isotonic saline (placebo) on three occasions at 30 min intervals via nebuliser. The primary outcome measure was FEV1 at 90 min. Results 116 patients were randomised, 52 of whom were randomly allocated to the magnesium adjuvant group. At 90 min the mean (SD) FEV1 in the magnesium group (N=47) was 0.78 (0.33) l compared with 0.81 (0.30) l in the saline group (N=61) (difference −0.026 l (95% CI −0.15 to 0.095, p=0.67). No patients required non-invasive ventilation. There were 43/48 admissions to hospital in the magnesium group and 56/61 in the saline group (RR 0.98, 95% CI 0.86 to 1.10, p=0.69). Conclusions Nebulised magnesium as an adjuvant to salbutamol treatment in the setting of AECOPD has no effect on FEV1. Australian New Zealand Clinical Trials Registry ACTRN12608000167369.

Systematic review and meta-analysis of the effects of antipyretic medications on mortality in Streptococcus pneumoniae infections.

Aim To determine whether the use of antipyretic medications in the treatment of Streptococcus pneumoniae infection affects mortality in humans or animal models. Design A systematic search of Medline, Embase, and The Cochrane Register of Controlled Trials was undertaken to identify in vivo animal experiments or randomised, controlled trials in humans of antipyretic medication in S pneumoniae infection which reported mortality data. Meta-analysis was by inverse variance weighted method for odds ratios. Setting Antipyretics are recommended for the symptomatic treatment of various diseases caused by S pneumoniae. However, there is evidence that fever is a protective physiological response to infection, that treating fever secondary to infection may be harmful, and that some strains of S pneumoniae are temperature sensitive. Main outcome measures Mortality associated with antipyretic use in S pneumoniae infection. Results Four studies from two publications met the inclusion criteria and investigated the use of aspirin in animal models. The pooled estimate of mortality was an OR with aspirin treatment of 1.97 (95% CI 1.22 to 3.19). There were no suitable human studies identified. Conclusions A twofold increased risk of mortality was found with aspirin treatment in animal models of S pneumoniae infection. No relevant human studies were identified. It is difficult to generalise from animal models to clinical medicine, but based on these findings and the prevalence and severity of S pneumoniae infections worldwide, future study of the effects of antipyretic therapy in S pneumoniae infection in humans is recommended.

Randomized controlled trial of the effect of regular paracetamol on influenza infection

Anti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection.

Pandemic Influenza A(H1N1)2009 in Hospital Healthcare Workers in New Zealand

We evaluated A/H1N1 influenza in healthcare workers (HCWs) and in a flu room during the 2009 pandemic. The flu room aided HCW care and management by facilitating rapid diagnosis and treatment. Absence of fever was common, and symptoms were nonspecific. A higher rate of H1N1 occurred in HCWs deployed in acute services.

High flow or titrated oxygen for obese medical inpatients: a randomised crossover trial

Objective: To compare the effects on transcutaneous carbon dioxide tension (Ptco2) of high concentration and titrated oxygen therapy in medical inpatients with morbid obesity who were not selected for a pre‐existing diagnosis of obesity hypoventilation syndrome.