A half doubling dose change in bronchial hyperresponsiveness in a population represents an important difference

Abstract Background The prevalence of asthma has increased over recent decades and the reasons for this are poorly understood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness (BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference in BHR for an individual is accepted to be around one doubling dose, the minimum important change in a population is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and cholesterol, a change that is not clinically important in an individual may be extremely important in public health terms. Findings To assess the potential impact of a small absolute change in BHR across a population, we modelled the effect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population. We calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR by 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe asthma, this would be highly significant in public health terms. Conclusions We propose that a one half doubling dose worsening in BHR across a population may represent an important change. </jats:sec

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study

OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling 'a lot better' compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (-6.4, 95% CI -9.4 to -3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results

Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a secondary analysis of data from a randomised controlled trial

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94 (0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents : analyses from Phase Three of the ISAAC programme

We are grateful to the children and parents who participated in ISAAC Phase Three and the coordination and assistance by the school staff is sincerely appreciated. The authors also acknowledge and thank the many funding bodies throughout the world that supported the individual ISAAC centres and collaborators and their meetings.Background: Exposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between exposure and asthma in childhood and adolescents. Aims:To examine the association between maternal and paternal smoking and symptoms of asthma, eczema and rhinoconjunctivitis. Methods: Parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including maternal smoking in the child’s first year of life, current maternal smoking (and amount) and paternal smoking. Adolescents aged 13-14 years self completed the questionnaires on these symptoms and whether their parents currently smoked. Results: In the 6-7-year age group there were 220 407 children from 75 centres in 32 countries. In the 13-14- year age group there were 350 654 adolescents from 118 centres in 53 countries. Maternal and paternal smoking was associated with an increased risk of symptoms of asthma, eczema and rhinoconjunctivitis in both age groups, although the magnitude of the OR is higher for symptoms of asthma than the other outcomes. Maternal smoking is associated with higher ORs than paternal smoking. For asthma symptoms there is a clear dose relationship (1e9 cigarettes/day, OR 1.27; 10-19 cigarettes/day, OR 1.35; and 20+ cigarettes/day, OR 1.56). When maternal smoking in the child’s first year of life and current maternal smoking are considered, the main effect is due to maternal smoking in the child’s first year of life. There was no interaction between maternal and paternal smoking. Conclusions: This study has confirmed the importance of maternal smoking, and the separate and additional effect of paternal smoking. The presence of a dose-response effect relationship with asthma symptoms suggests that the relationship is causal, however for eczema and rhinoconjunctivitis causality is less certain.peer-reviewe

Maternal post-natal tobacco use and current parental tobacco use is associated with higher body mass index in children and adolescents: an international cross-sectional study

Background: We investigated whether maternal smoking in the first year of life or any current parental smoking is associated with childhood or adolescent body mass index (BMI). Methods: Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6-7 years completed questionnaires about their children's current height and weight, whether their mother smoked in the first year of the child's life and current smoking habits of both parents. Adolescents aged 13-14 years completed questionnaires about their height, weight and current parental smoking habits. A general linear mixed model was used to determine the association between BMI and parental smoking. Results: 77,192 children (18 countries) and 194 727 adolescents (35 countries) were included. The BMI of children exposed to maternal smoking during their first year of life was 0.11 kg/m2 greater than those who were not (P = 0.0033). The BMI of children of currently smoking parents was greater than those with non-smoking parents(maternal smoking: +0.08 kg/m2 (P = 0.0131), paternal smoking: +0.10 kg/m2 (P < 0.0001)). The BMI of female adolescents exposed to maternal or paternal smoking was 0.23 kg/m2 and 0.09 kg/m2 greater respectively than those who were not exposed (P < 0.0001). The BMI of male adolescents was greater with maternal smoking exposure, but not paternal smoking (0.19 kg/m2, P < 0.0001 and 0.03 kg/m2, P = 0.14 respectively). Conclusion: Parental smoking is associated with higher BMI values in children and adolescents. Whether this is due to a direct effect of parental smoking or to confounding cannot be established from this observational study

The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis

Background: Patterns of inhaled β2-agonist therapy use during severe asthma exacerbations before hospital attendance are poorly understood. Aims: To assess β2-agonist use prior to hospital attendance. Methods: We undertook an exploratory post hoc analysis of data from a 6-month clinical trial of 303 patients randomised to combination budesonide/formoterol inhaler according to a Single combination inhaler as Maintenance And Reliever Therapy regimen (‘SMART’) or fixed-dose budesonide/formoterol with salbutamol as reliever (‘Standard’). Patterns of β2-agonist use for 14 days before hospital attendance with a severe asthma exacerbation were determined by electronic monitoring of inhaler use. Results: There were 22 hospital attendances in 16 patients during the study. Seven and nine hospital attendances were eligible for analysis in the SMART and Standard groups, respectively. In both regimens, β2-agonist use increased before hospital attendance, with a median (range) maximum daily number of actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95) salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the day of maximal salbutamol use. There was delay in obtaining medical review despite high β2-agonist use, in 9/16 patients. Different patterns of use were observed, including repeated days of no inhaled corticosteroid despite marked salbutamol use, which occurred in 3/9 patients in the Standard group. Conclusions: Delay in obtaining medical review in association with high β2-agonist use is common in patients before hospital presentation with severe exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled corticosteroid therapy during severe exacerbations